marine drugs

Review
An Overview on Antimicrobial Potential of Edible Terrestrial
Plants and Marine Macroalgae Rhodophyta and
Chlorophyta Extracts
Silvia Lomartire 1 and Ana M. M. Gonçalves 1,2, *

1 University of Coimbra, MARE—Marine and Environmental Sciences Centre/ARNET-Aquatic Research

Network, Department of Life Sciences, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal
2 Department of Biology, CESAM—Centre for Environmental and Marine Studies, University of Aveiro,
3810-193 Aveiro, Portugal
* Correspondence: amgoncalves@[Link]; Tel.: +351-239-240-700 (ext. 262-286)

Abstract: Antibiotics are used to prevent and treat bacterial infections. After a prolonged use of
antibiotics, it may happen that bacteria adapt to their presence, developing antibiotic resistance
and bringing up health complications. Nowadays, antibiotic resistance is one of the biggest threats
to global health and food security; therefore, scientists have been searching for new classes of
antibiotic compounds which naturally express antimicrobial activity. In recent decades, research
has been focused on the extraction of plant compounds to treat microbial infections. Plants are
potential sources of biological compounds that express several biological functions beneficial for our
organism, including antimicrobial activity. The high variety of compounds of natural origin makes it
possible to have a great bioavailability of antibacterial molecules to prevent different infections. The
antimicrobial activity of marine plants, also called seaweeds or macroalgae, for both Gram-positive
and Gram-negative, and several other strains infective for humans, has been proven. The present
review presents research focused on the extraction of antimicrobial compounds from red and green
macroalgae (domain Eukarya, kingdom Plantae). Nevertheless, further research is needed to verify
the action of macroalgae compounds against bacteria in vitro and in vivo, to be involved in the
Citation: Lomartire, S.; Gonçalves,
production of safe and novel antibiotics.
A.M.M. An Overview on
Antimicrobial Potential of Edible
Keywords: bioactive compounds; Rhodophyta; Chlorophyta; antimicrobial resistance; natural antibi-
Terrestrial Plants and Marine
Macroalgae Rhodophyta and
otics; seaweeds
Chlorophyta Extracts. Mar. Drugs
2023, 21, 163. [Link]
10.3390/md21030163
1. Introduction
Academic Editor: Marcelo
The advent of antibiotic resistance, which has become a barrier in the treatment of
D. Catarino
numerous types of diseases caused by bacterial infections, has made infectious diseases one
Received: 5 January 2023 of the global leading causes of death cases [1,2]. Antibiotic resistance occurs for different
Revised: 24 February 2023 reasons: bacteria neutralize antibiotics by pumping them out of cells or changing the
Accepted: 25 February 2023 structure of their cell walls to minimize the entering of the drug within bacterial cells [3].
Published: 28 February 2023 Antibiotic resistance is due especially to the overuse and misuse of antibiotics in human
and animal health and the lack of development of new antibiotics that minimize resistance.
The research for new bioactive compounds is one of the solutions to overcome this
problem [4,5]. Natural products are a source of secondary metabolites with a variety of
Copyright: © 2023 by the authors.
structures and bioactivity. Moreover, natural products have high availability and may
Licensee MDPI, Basel, Switzerland.
exhibit similar properties to synthetic antibiotics but, additionally, they could prevent drug
This article is an open access article
distributed under the terms and
resistance [4,6]. Originally, a limited group of marine species, including sponges, mollusks,
conditions of the Creative Commons
tunicates, and macroalgae, were the main targets of marine wildlife exploitation for natural
Attribution (CC BY) license (https:// bioactive compounds [7]. These were demonstrated to form a wide variety of unusual
[Link]/licenses/by/ molecular structures, including prostaglandins, polyketides, and halogenated terpenes that
4.0/). present interesting biological activities [8–10]. This variety of bioactive structures is thought

Mar. Drugs 2023, 21, 163. [Link] [Link]

Mar. Drugs 2023, 21, 163 2 of 35

to be a component of these species’ defense, survival, and predation strategies [11]. Marine
natural products are examples of novel and varied chemotypes that can be used as models
to find and create therapeutic medicines. These genetically encoded molecules are typically
highly complex and can be challenging to replicate in laboratories. Moreover, most of the
time, chemicals are limited due to the low yield isolated from the source organism, but
thanks to sophisticated NMR technologies and dereplication techniques they are able to
reproduce more bioactive compounds of interest [12].
Penicillin was discovered by Alexander Fleming in the 1920s from a culture of the
fungus Penicillium notatum [13]. Out of the 162 antibacterial agents approved by the U.S.
Food and Drug Administration from 1981 to 2019, about 50% are or derive from natural
sources [14], and most compounds have a microbial source rather than a plant source [15].
Nevertheless, in most in vitro studies carried out in recent years, the antibacterial
properties of plant extracts have been confirmed [16–20].
It is also important to develop further studies regarding the combination of natural
products with common antibiotics on multidrug-resistant bacteria. Nascimento et al. [21]
showed the beneficial effects of mixing the antibiotic methicillin with natural extracts. The
authors investigated extracts of clove, jambolan, pomegranate, and thyme. The synergistic
effect of antibiotic compounds prevented the development of Klebsiella pneumoniae and
Pseudomonas aeruginosa, bacteria both resistant to 19 different antibiotics. Anacardic acid
and totarol have also been combined with methicillin and have demonstrated positive
results in suppressing strains of Staphylococcus aureus resistant to methicillin [21].
This review collects the investigations carried out to evaluate the antimicrobial activity
of edible plants and macroalgae extracts, particularly focusing on Rhodophyta (red algae)
and Chlorophyta (green algae), as they are classified in kingdom Plantae; therefore, no
brown algae are considered in the present review [22].
Macroalgae extracts present several biological activities; among them, antibacterial ac-
tivity is widely exhibited in plants and macroalgae [23–26]. To live in harsh environmental
conditions and to fight back predators, macroalgae naturally developed secondary metabo-
lites with a wide diversity of structural and biological properties. Additionally, differences
in the inhibitory action of macroalgae extracts against microorganisms largely depend on a
number of variables, including habitat and location of collection, macroalga developmental
stage, ecological characteristics (irradiance and nutrients), and seasonality [27]. The an-
tibacterial activity of macroalgae inhibited the growth of a wide array of bacteria; therefore,
the incorporation of these compounds could reduce the use of the synthetic compounds
that have caused antimicrobial resistance. From several investigations, red algae present a
higher diversity of secondary metabolites than brown and green algae. The chemistry of
Rhodophyta is dominated mainly from halogenated compounds, which exhibited diverse
biological activities including anti-bacterial, antifungal, anti-inflammation, cytotoxic, and
insecticidal activity [28,29].
Macroalgal metabolites are significantly different from terrestrial plant extracts; indeed,
this is inspiring for scientists to explore new classes of bioactive compounds that can be
involved in antibiotic development and research.
Even though the antimicrobial effects of plants and algal extracts as well as isolated
phytochemical compounds are undeniable, more clinical studies should be carried out to
determine the optimal conditions under which these compounds could be safely consumed
alone or in combination with conventional antibiotics.
The present review mainly collects literature regarding antimicrobial assays in vitro per-
formed with extracts of terrestrial edible plants, and macroalgae, in particular Rhodophyta
and Chlorophyta, belonging to the Plantae kingdom. The research methodology consists of
research on Google Scholar and PubMed web search engines of recent literature using the
keywords “antimicrobial assays of edible plants”; “red algae with antimicrobial activity”;
“green algae with antimicrobial activity”; “antimicrobial resistance”; etc. From the articles
of interest, the authors select the useful bibliography suitable for the review scope. The
considered publications are between the years 2018 and 2023, as the authors wanted to
Mar. Drugs 2023, 21, 163 3 of 35

focus on the most recent investigations. This review contains 144 references: 12 are related
to plant extracts with antimicrobial activity (counting 25 plant extracts), 10 and 14 articles
investigate Rhodophyta and Chlorophyta, respectively, counting 13 red and 17 green algae
extracts exhibiting antibacterial properties.

2. Causes of Antimicrobial Resistance

Antimicrobial resistance is a major global concern for people and animals’ health.
According to a report by the Organization for Economic Co-operation and Development
(OECD), if there is no stop to antibiotic resistance, it may result in an increase in the number
of deaths of 2.4 million people in Europe, Australia, and North America by 2050, with 90,000
or 1.3 million of deaths expected in Europe. According to the most recent assessments,
antibiotic resistance is “one of the biggest risks to modern medicine”. Currently, sepsis
brought by bacteria strains resistant to antibiotics results in 44,000 deaths every year in the
UK [30].
Thomson [31] reports that Western sub-Saharan Africa had the highest rate of mortality
directly attributed to AMR among the 21 GBD geographic regions, with 27.3 per 100,000
deaths. It is more likely to have highest death mortality rate due to antimicrobial resistance
in low-income areas compared to wealthy nations, as both the prevalence of resistance and
the number of infections with resistant bacteria are higher. Multidrug-resistant bacteria
are accountable for antibiotic resistance, due to the development, dissemination, and
persistence of the bacteria [32]. Antibiotics that are supplied over the counter which leads
to their overuse, increased worldwide travel, inadequate sanitation/hygiene conditions,
and the release of non-metabolized antibiotics or residues into the environment through
manure/feces are a few of the possible reasons for antimicrobial resistance. These elements
add to the genetic selection pressure that leads to the spread of bacterial illnesses that are
resistant to a variety of treatments. Darwinian selection forced bacteria to develop a robust
defense against the damaging impacts of antimicrobial agents. The majority of antibiotics
are naturally manufactured by microbes such as saprophytic bacteria or fungi, while some,
such as fluoroquinolones and sulphonamides, are entirely synthetic [33].
Antibiotic misuse is severely discouraged; however, there are still too many prescrip-
tions written worldwide. According to several studies, from 30% to 50% of the cases,
treatment indications, agent selection, and antibiotic medication length are ineffective;
therefore, antimicrobial resistance is accentuated [34–36]. One of the causes of microbial
resistance is the lack of monitoring of resistance development. The first report on antimi-
crobial resistance was published by the World Health Organization (WHO) in 2014, and it
included data gathered from nine bacterial infections/antibiotic combinations that caused
more health complications. Data showed that just 129 of the 194 studied countries had
given information, and only 22 of those had information on all nine infection–antibiotic
resistance combinations [37]. Surveillance is fundamental to monitor the status of an-
tibiotics to be efficient against the interest bacterial strains. Mostly in many developing
countries, poor quality of available antibiotics is the reason for having microbial resistance;
tropical conditions and no possibility to store the antibiotics at the right temperature, in
addition to a lack of proper transport methods, affect the quality of the antibiotics [38]. The
easy availability of antibiotics is also reflected in their overuse, contributing to microbial
resistance. Lastly, clinical misdiagnosis and antibiotic misuse also contribute to antibiotic
resistance due to the excessive use of antibiotics when not clinically indicated [39].
The main mechanisms by which microorganisms exhibit resistance to antimicro-
bials [40] are shown in Figure 1. There is a change in the permeability of the bacterial
cell wall (1) due to the modification of the cell wall proteins; therefore, the antibiotic cannot
go beyond the cell wall. Next, there is target site alteration (2), which frequently results
from a bacterial gene’s spontaneous mutation. Minor changes to the target molecule can
have a significant impact on antibiotic action since antibiotic interactions with targets are
typically rather specific (2). With an increased activity of the efflux pumps, the proteins
present in the cytoplasmic membrane discharge the antibiotics outside the bacterial wall
 beyond the cell wall. Next, there is target site alteration (2), which frequently results from
a bacterial gene’s spontaneous mutation. Minor changes to the target molecule can have
Mar. Drugs 2023, 21, 163 a significant impact on antibiotic action since antibiotic interactions with targets are typi- 4 of 35
cally rather specific (2). With an increased activity of the efflux pumps, the proteins pre-
sent in the cytoplasmic membrane discharge the antibiotics outside the bacterial wall and
maintain intracellular
and maintain concentrations
intracellular low (3)low
concentrations [41].
(3)Moreover, the inactivation
[41]. Moreover, of the anti-
the inactivation of the
biotic through the bond with a phosphate group (4) reduces the ability of the antibiotic
antibiotic through the bond with a phosphate group (4) reduces the ability of the antibiotic to
bind withwith
to bind bacterial ribosomes
bacterial [42]. [42].
ribosomes Bacterial ribosomes
Bacterial are the
ribosomes aremajor bacterial
the major targets
bacterial for
targets
antibiotics, since since
for antibiotics, drugsdrugs
inhibitinhibit
ribosome function
ribosome by interfering
function in messenger
by interfering RNA trans-
in messenger RNA
lation or by or
translation blocking the formation
by blocking the formationof bacterial peptide
of bacterial bonds
peptide bondsand proteins,
and proteins,inhibiting
inhibiting
peptidyl
peptidyltransferase.
transferase.

Figure
[Link]
Mechanism ofof
antimicrobial resistance.
antimicrobial resistance.(1)(1)
Impermeability; (2)(2)
Impermeability; Modification; (3)(3)
Modification; Pumping
Pumping
out; (4) Inactivation.
out; (4) Inactivation.

[Link]
AnOverview
OverviewofofTerrestrial
TerrestrialPlants’
Plants’Antibacterial
AntibacterialActivity.
Activity
After
Afterthe thediscovery
discoveryofofpenicillin
penicillinand andthetheextension
extensionof ofits
its therapeutic
therapeutic use,use, other anti-
antibi-
biotics werecreated
otics were createdforforthe
thedaily
dailytreatment
treatmentof ofinfections,
infections,leading
leadingtotoan anincrease
increaseininthetheclinical
clin-
usage
ical usageof both
of bothnatural andand
natural chemical
chemicalantibiotics. However,
antibiotics. However, mostmostbacteria now now
bacteria have have
increased
in-
resistance
creased to different
resistance antibiotics
to different after the
antibiotics overuse
after of these
the overuse treatments
of these [43]. This
treatments [43]. is oneisof
This
theof
one reasons for the for
the reasons growing interest in
the growing researching
interest natural antimicrobial
in researching compounds
natural antimicrobial with
com-
pounds with low-risk in antimicrobial resistance, affordable, and comparable to syntheticin
low-risk in antimicrobial resistance, affordable, and comparable to synthetic antibiotics
the treatment
antibiotics in theoftreatment
bacterial infections
of bacterial [44].
infections [44].
ToToovercome
overcomethe thecrisis
crisisof
ofantibiotic
antibiotic resistance, extracts
extracts fromfromedible
edibleplants
plantshavehavebeen
beenin-
vestigated to
investigated todetermine
determinetheir
theirantimicrobial
antimicrobialactivity, since
activity, since natural
naturalproducts
products offer
offera promising
a prom-
source
ising of antibacterial
source chemicals
of antibacterial that could
chemicals help to
that could fill to
help thefill
drug
the discovery
drug discoverypipeline [45–47].
pipeline
Due to the diverse and abundant plant biodiversity, there are numerous
[45–47]. Due to the diverse and abundant plant biodiversity, there are numerous antibac- antibacterial com-
pounds available in nature. Each plant evolved sophisticated
terial compounds available in nature. Each plant evolved sophisticated defense mecha-defense mechanisms to fight
bacteria,
nisms utilizing
to fight a variety
bacteria, of different
utilizing a varietyand unique secondary
of different and unique compounds
secondary[48]. compounds
[48]. Currently, studies have been carried out on the use of edible plants to cure bacterial
infections
Currently,(Table 1). Gonelimali
studies have beenetcarried
al. [49] out
evaluated
on the the
useantimicrobial
of edible plants potential
to cureofbacterial
ethanolic
and water extracts of aromatic plants widely used in cooking. Thymus
infections (Table 1). Gonelimali et al. [49] evaluated the antimicrobial potential of known vulgaris, etha-
as thyme,
nolic and water Rosmarinus
extractsofficinalis
of aromatic(rosemary), Syzygium
plants widely usedaromaticum
in cooking. (clove),
Thymus Hibiscus
andvulgaris,
sabdariffa
known (roselle)Rosmarinus
as thyme, demonstrated antimicrobial
officinalis activity
(rosemary), againstaromaticum
Syzygium food pathogens andand
(clove), spoilage
Hi-
microorganisms, including Bacillus cereus, S. aureus, Escherichia coli,
biscus sabdariffa (roselle) demonstrated antimicrobial activity against food pathogens and Salmonella enteritidis,
Vibrio parahaemolyticus,
spoilage microorganisms,and P. aeruginosa.
including Bacillus cereus, S. aureus, Escherichia coli, Salmonella en-
The water extracts for all four plants, except for T. vulgaris, exhibited the highest
teritidis, Vibrio parahaemolyticus, and P. aeruginosa.
inhibition activity for B. cereus. The T. vulgaris water extract had a zone inhibition of
The water extracts for all four plants, except for T. vulgaris, exhibited the highest in-
13.9 ± 1.3 mm against V. parahaemolyticus, while the ethanolic extract was the most effective
hibition activity for B. cereus. The T. vulgaris water extract had a zone inhibition of 13.9 ±
against B. cereus with an inhibition zone of 17.3 ± 0.7 mm. The R. officinalis ethanolic extract
displayed a high inhibition zone against S. aureus (19.8 ± 0.4 mm), while B. cereus and P.
aeruginosa were highly inhibited from the ethanolic extract of S. aromaticum and H. sabdariffa,
respectively, with inhibition zones of 18.2 ± 3.2 mm and 23.4 + 1.4 mm. The minimum
inhibitory concentration (MIC) of these extracts has been reported in Table 1 [49].
Mar. Drugs 2023, 21, 163 5 of 35

The antimicrobial properties of thyme have also been proven by Burt et al. [50]; the au-
thors considered that its antibacterial activity may be due to the hydrophobic bonding and
hydrogen bonding between thymol, a phenol present in thyme which presents antibacterial
activity, and the membrane proteins of cells, changing the permeability of the membranes
and avoiding the entrance of the bacteria into the cells.
Glycyrrhiza glabra L., also known as liquorice, has been widely used for its medical
properties. The first report of its medicinal use comes from Greeks, who recommended it
for the treatment of gastric and peptic ulcers. In Asia and Europe, the extract is used in the
treatment of psoriasis. It is used in traditional Chinese medicine to treat gastrointestinal
disorders and oral ulcers [51], hepatitis, and heart disease [52,53]. Its extract is suitable as
an adjuvant for inhibiting the growth of colon cancer cells such as prostate cancer [54] and
gastric cancer [55]. Liquorice is a traditional medicinal herb that grows in different parts of
the world. It is a very sweet, moist, soothing herb that detoxifies and protects the liver, and
it also has powerful anti-inflammatory applications in arthritis and mouth ulcers.
The results of Gupta et al. [56] indicate the potential use of liquorice as antitubercular
agent through systemic experiments. The antimycobacterial activity of the root ethanolic
extract of G. glabra L. was observed at 500 µg/mL against Mycobacterium tuberculosis H37Ra
and H37Rv strains.
According to the result of the research conducted by Jafari-Sales et al. [57], S. aureus,
B. cereus, E. coli, and P. aeruginosa were affected from the methanolic extracts of G. glabra
L. in both the agar well diffusion and dilution test techniques. S. aureus had the greatest
response, whereas P. aeruginosa demonstrated the weakest response, as we see from the MIC
values in Table 1. As a result, it is reasonable to assume that the G. glabra L. extract can be
used to treat diseases caused by pathogenic bacteria and may be ideal for the formulation
of natural antibiotics.
The antimicrobial effects of ethanolic extracts of five herbal plants, namely guava
(Psidium guajava), sage (Salvia officinalis), rhamnus (Ziziphusspina christi), mulberry (Morus
alba), and olive (Olea europaea) leaves were investigated to evaluate the growth inhibition
of S. aureus, E. coli, Pasteurella multocida, B. cereus, and S. enteritidis. The results show that
Psidium guajava inhibited S. aureus and P. multocida growth. Salvia officinalis exhibited a
high growth inhibition for S. aureus, E. coli, and S. enteritidis. O. europaea resulted to be
powerful against B. cereus, E. coli, and S. enteritidis growth. M. alba has been detected to
have antibacterial potency against B. cereus and P. multocida. Therefore, this investigation
confirms the idea to involve natural herbal extracts in antibiotic development [58].
The chemical composition and antimicrobial activities of nine wild edible Mediter-
ranean species, namely Reichardia picroides, Hymenonema graecum, Sonchus oleraceus, Scolymus
hispanicus, Hedypnois cretica, Picris echioides, Urospermum picroides, Taraxacum sp., and Tarax-
acum officinale, were investigated. The human pathogenic microorganisms that were tested
include Salmonella typhimurium, Listeria monocytogenes, E. coli, B. cereus, and S. aureus. For
each examined species, significant antibacterial activity was detected against B. cereus and
S. typhimurium. With the exception of the Taraxacum species, flavonoids were the most
prevalent phenolic compounds based on their chemical makeup in all the species.
Additionally, by commercial culture techniques and planning the growing season, the
production of the investigated species may be enhanced and their commercial value could
be boosted in the pharmaceutical and nutraceutical fields. Research on the antibacterial activ-
ities of plant extracts revealed encouraging findings that may be applied to the food processing
sector as substitute food preservatives or food products with antimicrobic properties.
Therefore, these species could be viewed as useful components of nutritious diets that
improve consumer welfare while also ensuring year-round availability [59].
The antibacterial properties of plant extracts are influenced by the extraction tech-
niques. Five Thai edible plant leaf extracts, including Anacardium occidentale L., Garcinia
cowa, Glochidion wallichianum, Careya sphaerica, and Gnetum gnemon var. temerum, were
explored by Junsathian et al. [60] for their total phenolic content (TPC), total flavonoid
content (TFC), antioxidant, and antimicrobial properties. The authors performed different
Mar. Drugs 2023, 21, 163 6 of 35

extraction methods, such as ethanol extraction (EE), microwave-assisted extraction (MAE),

and ultrasonic-assisted extraction (UAE). Compared to the UAE and EE techniques, the
MAE leaf extracts of G. wallichianum had the highest extraction yield. The antioxidant and
antibacterial activity of TPC and TFC were greater in the MAE-extracted C. sphaerica and
A. occidentale L. samples. All extracts that had undergone MAE processing, with the excep-
tion of A. murica extracts, which may have required higher concentrations to show activity,
had the greatest MIC and zones of inhibition against Gram-positive and Gram-negative
bacterial strains. Consequently, MAE is a promising technique for obtaining bioactive
substances. These results suggest that MAE enhanced the antioxidant and antibacterial
efficiency of the leaf extracts in comparison to EE and UAE. The aforementioned extracts
could be used as natural food additives to stop food from becoming spoiled by bacteria.
Therefore, the uses of common and edible plants in pharmaceutical field are numerous,
as we can see in numerous published papers and literature reviews [61–64].

Table 1. Antimicrobial activity of edible terrestrial plants (“–“ = no antimicrobial activity revealed;
“1GP” = 1st growing period; “2GP” = 2nd growing period).

Minimum
Inhibitory Inhibition Zone
Terrestrial Plant Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Staphylococcusaureus 1.56 mg/mL 16.00
Bacillus subtilis 1.56 mg/mL 15.00
Ethanolic extract
Escherichia coli 1.56 mg/mL 12.00
Pseudomonas aeruginosa 1.56 mg/mL 14.00
Staphylococcusaureus <1.56 mg/mL 14.00
Anacardium Bacillus subtilis <1.56 mg/mL 16.00 [60]
occidentale UAE
Escherichia coli 1.56 mg/mL 14.00
Pseudomonas aeruginosa 1.56 mg/mL 15.00
Staphylococcusaureus 0.78 mg/mL 17.00
Bacillus subtilis <1.56 mg/mL 16.00
MAE
Escherichia coli 1.56 mg/mL 15.00
Pseudomonas aeruginosa 1.56 mg/mL 16.00
Staphylococcusaureus <1.56 mg/mL 17.00
Bacillus subtilis <1.56 mg/mL 17.00
Ethanolic extract
Escherichia coli 3.12 mg/mL 11.00
Pseudomonas aeruginosa 1.56 mg/mL 13.00
Staphylococcusaureus <1.56 mg/mL 17.00
Careya sphaerica Bacillus subtilis <1.56 mg/mL 16.00 [60]
UAE
Escherichia coli 3.12 mg/mL 15.00
Pseudomonas aeruginosa 1.56 mg/mL 14.00
Staphylococcusaureus <1.56 mg/mL 18.00
Bacillus subtilis <1.56 mg/mL 17.00
MAE
Escherichia coli 1.56 mg/mL 16.00
Pseudomonas aeruginosa 1.56 mg/mL 16.00
Mar. Drugs 2023, 21, 163 7 of 35

Table 1. Cont.

Minimum
Inhibitory Inhibition Zone
Terrestrial Plant Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Staphylococcusaureus 3.12 mg/mL 14.00
Bacillus subtilis 1.56 mg/mL 11.00
Ethanolic extract
Escherichia coli 12.5 mg/mL 11.00
Pseudomonas aeruginosa 12.5 mg/mL 12.00
Staphylococcusaureus <1.56 mg/mL 14.00

Garcinia cowa Bacillus subtilis <1.56 mg/mL 16.00 [60]

UAE
Escherichia coli 12.5 mg/mL 11.00
Pseudomonas aeruginosa 12.5 mg/mL 13.00
Staphylococcusaureus 0.78 mg/mL 14.00
Bacillus subtilis <1.56 mg/mL 16.00
MAE
Escherichia coli 12.5 mg/mL 11.00
Pseudomonas aeruginosa 12.5 mg/mL 12.00
Staphylococcusaureus <1.56 mg/mL 16.00
Bacillus subtilis <1.56 mg/mL 14.00
Ethanolic extract
Escherichia coli 6.25 mg/mL 10.00
Pseudomonas aeruginosa 3.12 mg/mL 13.00
Staphylococcusaureus <1.56 mg/mL 14.00
Glochidion Bacillus subtilis <1.56 mg/mL 15.00 [60]
wallichianum UAE
Escherichia coli 3.12 mg/mL 15.00
Pseudomonas aeruginosa 6.25 mg/mL 13.00
Staphylococcusaureus 0.78 mg/mL 14.00
Bacillus subtilis <1.56 mg/mL 15.00
MAE
Escherichia coli 3.12 mg/mL 15.00
Pseudomonas aeruginosa 3.12 mg/mL 13.00
Mycobacteriumtuberculosis
500 mg/mL -
H37Ra
Glycyrrhiza glabra Ethanolic extract [56]
Mycobacteriumtuberculosis
500 mg/mL -
H37Rv
Staphylococcusaureus 6.25 mg/mL 10 ± 1.34
Bacilluscereus 12.5 mg/mL 7±1 [57]
Glycyrrhiza glabra Methanolic extract
Escherichiacoli 50 mg/mL 6 ± 1.22
Pseudomonas aeruginosa 100 mg/mL -
Staphylococcusaureus 50.00 mg/mL 10.00
Bacillus subtilis 25.00 mg/mL -
Ethanolic extract
Escherichia coli 50.00 mg/mL 9.00
Gnetum gnemon var. Pseudomonas aeruginosa 50.00 mg/mL 9.00 [60]
temerum
Staphylococcusaureus 50 mg/mL 10.00
Bacillus subtilis 12.5 mg/mL -
UAE Escherichia coli 50 mg/mL 10.00
Pseudomonas aeruginosa 25 mg/mL 10.00
Mar. Drugs 2023, 21, 163 8 of 35

Table 1. Cont.

Minimum
Inhibitory Inhibition Zone
Terrestrial Plant Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Staphylococcusaureus 12.5 mg/mL 11.00
Bacillus subtilis 6.25 mg/mL -
MAE
Escherichia coli 50 mg/mL 11.00
Pseudomonas aeruginosa 25 mg/mL 10.00
Bacilluscereus 2GP: 0.15 mg/mL -
Staphylococcusaureus 2GP: 0.60 mg/mL -
Listeria monocytogenes 2GP: 0.45 mg/mL -
Hedypnois cretica Methanolic extract [59]
Escherichiacoli 2GP: 0.20 mg/mL -
Enterobactercloacae 2GP: 0.30 mg/mL -
Salmonella typhimurium 2GP: 0.30 mg/mL -
Ethanolic extract 5 (% w/v) 22.2 + 0.8
Bacillus cereus
Water extract 0.625 (% w/v) 17.0 + 1.1
Ethanolic extract 2.5 (% w/v) 21.5 + 2.1
Staphylococcus aureus
Water extract 2.5 (% w/v) 15.7 + 1.0
Ethanolic extract 5 (% w/v) 21.1 + 1.3
Escherichia coli
Hibiscus sabdariffa Water extract 5 (% w/v) 15.6 + 1.2 [49]
Ethanolic extract 5 (% w/v) 20.2 + 1.7
Salmonella enteritidis
Water extract 10 (% w/v) 14.0 + 1.9
Ethanolic extract 2.5 (% w/v) 20.3 + 1.8
Vibrio parahaemolyticus
Water extract 5 (% w/v) 15.9 + 1.7
Ethanolic extract 2.5 (% w/v) 23.4 + 1.4
Pseudomonas aeruginosa
Water extract 5 (% w/v) 13.9 + 1.9
1GP: 0.20 mg/mL
Bacilluscereus -
2GP: 0.20 mg/mL
1GP: 0.60 mg/mL
Staphylococcusaureus -
2GP: 0.60 mg/mL
1GP: 0.60 mg/mL
Listeria monocytogenes -
Hymenonema graecum Methanolic extract 2GP: 0.60 mg/mL [59]
1GP: 0.60 mg/mL
Escherichiacoli -
2GP: 0.60 mg/mL
1GP: 0.45 mg/mL
Enterobactercloacae -
2GP: 0.60 mg/mL
1GP: 0.30 mg/mL
Salmonella typhimurium -
2GP: 0.30 mg/mL
Staphylococcusaureus - 10.5 ± 1.15
Bacilluscereus 2500 µg/mL 14.75 ± 0.15
Morus alba Ethanolic extract Escherichiacoli - 7.5 ± 0.15 [58]
Pasteurellamultocida 1250 µg/mL 15.42 ± 0.15
Salmonella enteritidis 625 µg/mL 12.02 ± 0.05
Mar. Drugs 2023, 21, 163 9 of 35

Table 1. Cont.

Minimum
Inhibitory Inhibition Zone
Terrestrial Plant Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Staphylococcusaureus 625 µg/mL 12.02 ± 2.05
Bacilluscereus 5000 µg/mL 16.62 ± 1.05
Olea europaea Ethanolic extract Escherichiacoli 2500 µg/mL 16.72 ± 0.55 [58]
Pasteurellamultocida 625 µg/mL 9.12 ± 0.05
Salmonella enteritidis 5000 µg/mL 18.02 ± 0.05
1GP: 0.075 mg/mL
Bacilluscereus -
2GP: 0.15 mg/mL
1GP: 0.45 mg/mL
Staphylococcusaureus -
2GP: 0.30 mg/mL
1GP: 0.60 mg/mL
Listeria monocytogenes -
Picris echioides Methanolic extract 2GP: 0.30 mg/mL [59]
1GP: 0.45 mg/mL
Escherichiacoli -
2GP: 0.15 mg/mL
1GP: 0.30 mg/mL
Enterobactercloacae -
2GP: 0.20 mg/mL
1GP: 0.60 mg/mL
Salmonella typhimurium -
2GP: 0.20 mg/mL
Staphylococcusaureus 1250 µg/mL 15.62 ± 1.15
Bacilluscereus - 10.05 ± 0.15
Psidium guajava Ethanolic extract Escherichiacoli 625 µg/mL 10.55 ± 0.15 [58]
Pasteurellamultocida 5000 µg/mL 18.02 ± 0.95
Salmonella enteritidis 625 µg/mL 10.12 ± 0.55
1GP: 0.15 mg/mL
Bacilluscereus -
2GP: 0.15 mg/mL
1GP: 0.30 mg/mL
Staphylococcusaureus -
2GP: 0.30 mg/mL
1GP: 0.30 mg/mL
Listeria monocytogenes -
Reichardia picroides Methanolic extract 2GP: 0.30 mg/mL [59]
1GP: 0.15 mg/mL
Escherichiacoli -
2GP: 0.30 mg/mL
1GP: 0.30 mg/mL
Enterobactercloacae -
2GP: 0.30 mg/mL
1GP: 0.30 mg/mL
Salmonella typhimurium -
2GP: 0.60 mg/mL
Mar. Drugs 2023, 21, 163 10 of 35

Table 1. Cont.

Minimum
Inhibitory Inhibition Zone
Terrestrial Plant Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Ethanolic extract 5 (% w/v) 19.8 ± 0.8
Bacillus cereus
Water extract 1.25 (% w/v) 13.9 ± 1.2
Ethanolic extract 1.25 (% w/v) 19.8 ± 0.4
Staphylococcus aureus
Water extract 20 (% w/v) 12.7 ± 0.4
Ethanolic extract 5 (% w/v) 21.1 ± 0.9
Escherichia coli
Rosmarinus officinalis Water extract 20 (% w/v) 12.5 ± 0.7 [49]

Ethanolic extract Salmonella enteritidis 2.5 (% w/v) 20.7 ± 1.2

Ethanolic extract - -
Vibrio parahaemolyticus
Water extract - -
Ethanolic extract - -
Pseudomonas aeruginosa
Water extract - -
Staphylococcusaureus 5000 µg/mL 17.05 ± 1.05
Bacilluscereus 625 µg/mL 16.45 ± 1.05
Salvia officinalis Ethanolic extract Escherichiacoli 2500 µg/mL 19.25 ± 0.65 [58]
Pasteurellamultocida - 9.05 ± 1.05
Salmonella enteritidis 2500 µg/mL 16.25 ± 0.75
Bacilluscereus 2GP: 0.10 mg/mL -
Staphylococcusaureus 2GP: 0.30 mg/mL -
Listeria monocytogenes 2GP: 0.20 mg/mL -
Scolymus hispanicus Methanolic extract [59]
Escherichiacoli 2GP: 0.10 mg/mL -
Enterobactercloacae 2GP: 0.15 mg/mL -
Salmonella typhimurium 2GP: 0.15 mg/mL -
1GP: 0.20 mg/mL
Bacilluscereus -
2GP: 0.15 mg/mL
1GP: 0.45 mg/mL
Staphylococcusaureus -
2GP: 0.30 mg/mL
1GP: 0.45 mg/mL
Listeria monocytogenes -
Sonchus oleraceus Methanolic extract 2GP: 0.60 mg/mL [59]
1GP: 0.45 mg/mL
Escherichiacoli -
2GP: 0.30 mg/mL
1GP: 0.60 mg/mL
Enterobactercloacae -
2GP: 0.30 mg/mL
1GP: 0.45 mg/mL
Salmonella typhimurium -
2GP: 0.30 mg/mL
Mar. Drugs 2023, 21, 163 11 of 35

Table 1. Cont.

Minimum
Inhibitory Inhibition Zone
Terrestrial Plant Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Ethanolic extract 2.5 (% w/v) 18.2 ± 3.2
Bacillus cereus
Water extract 0.313 (% w/v) 15.1 ± 0.9
Ethanolic extract 2.5 (% w/v) 16.7 ± 1.0
Staphylococcus aureus
Water extract 5 (% w/v) 13.6 ± 1.3
Ethanolic extract 2.5 (% w/v) 17.4 ± 0.8
Escherichia coli
Syzygium aromaticum Water extract 5 (% w/v) 13.2 ± 1.6 [49]
Ethanolic extract 5 (% w/v) 15.1 ± 1.4
Salmonella enteritidis
Water extract 5 (% w/v) 12.2 ± 1.1
Ethanolic extract 0.625 (% w/v) 14.7 ± 2.0
Vibrio parahaemolyticus
Water extract 2.5 (% w/v) 13.1 ± 1.8
Ethanolic extract 5 (% w/v) 17.0 ± 0.5
Pseudomonas aeruginosa
Water extract 10 (% w/v) 13.2 ± 1.4
1GP: 0.037 mg/mL
Methanolic extract Bacilluscereus -
2GP: 0.20 mg/mL
1GP: 0.30 mg/mL
Staphylococcus aureus -
2GP: 0.90 mg/mL
1GP: 0.30 mg/mL
Listeria monocytogenes -
Taraxacum officinale 2GP: 0.90 mg/mL [59]
1GP: 0.15 mg/mL
Escherichiacoli -
2GP: 0.30 mg/mL
1GP: 0.15 mg/mL
Enterobactercloacae -
2GP: 0.30 mg/mL
1GP: 0.15 mg/mL
Salmonella typhimurium -
2GP: 0.60 mg/mL
1GP: 0.075 mg/mL
Methanolic extract Bacilluscereus -
2GP: 0.075 mg/mL
1GP: 0.60 mg/mL
Staphylococcusaureus -
2GP: 0.30 mg/mL
1GP: 0.45 mg/mL
Enterobactermonocytogenes -
Taraxacum sp. 2GP: 0.45 mg/mL [59]
1GP: 0.20 mg/mL
Escherichiacoli -
2GP: 0.90 mg/mL
1GP: 0.20 mg/mL
Enterobactercloacae -
2GP: 0.20 mg/mL
1GP: 0.20 mg/mL
Salmonella typhimurium -
2GP: 0.30 mg/mL
Mar. Drugs 2023, 21, 163 12 of 35

Table 1. Cont.

Minimum
Inhibitory Inhibition Zone
Terrestrial Plant Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Ethanolic extract 5 (% w/v) 17.3 ± 0.7
Bacillus cereus
Water extract 5 (% w/v) 13.8 ± 1.1
Ethanolic extract 5 (% w/v) 15.9 ± 0.3
Staphylococcus aureus
Water extract 2.5 (% w/v) 12.2 ± 0.7
Ethanolic extract 10 (% w/v) 15.9 ± 0.3
Escherichia coli
Thymus vulgaris Water extract 5 (% w/v) 12.2 ± 0.7 [49]

Water extract Salmonella enteritidis 5 (% w/v) 11.8 ± 1.4

Water extract 2.5 (% w/v) 13.9 ± 1.3
Vibrio parahaemolyticus
Ethanolic extract 10 (% w/v) 14.3 ± 0.1
Water extract - -
Pseudomonas aeruginosa
Ethanolic extract - -
1GP: 0.15 mg/mL
Bacilluscereus -
2GP: 0.15 mg/mL
1GP: 0.90 mg/mL
Staphylococcusaureus -
2GP: 0.90 mg/mL
1GP: 0.90 mg/mL
Listeria monocytogenes -
Urospermum picroides Methanolic extract 2GP: 0.30 mg/mL [59]
1GP: 0. 90 mg/mL
Escherichiacoli -
2GP: 0.45 mg/mL
1GP: 0.45 mg/mL
Enterobacter cloacae -
2GP: 0.60 mg/mL
1GP: 0.45 mg/mL
Salmonella typhimurium -
2GP: 0.30 mg/mL
Staphylococcusaureus 625 µg/mL 11.82 ± 2.5
Bacilluscereus 625 µg/mL 13.52 ± 2.1
Ziziphusspina christi Ethanolic extract Escherichiacoli - 10.02 ± 0.05 [58]
Pasteurellamultocida - 8.52 ± 2.5
Salmonella enteritidis 625 µg/mL 12.82 ± 2.5

Not only terrestrial plants possess bioactive compounds with interesting properties.
In recent decades, research on marine plants and algae as well as biological compounds
has been carried out, with impressive outcomes that demonstrate the potential therapeutic
activity of compounds of marine origin.

4. Antimicrobial Activity from Rhodophyta and Chlorophyta Extracts

Macroalgae are aquatic photosynthetic organisms (mainly marine) belonging to the
domain Eukarya. Macroalgae are mainly divided into three groups: red algae (Rhodophyta)
and green algae (Chlorophyta), which are classified in kingdom Plantae, and brown algae
(Ochrophyta, class Phaeophyceae), belonging to kingdom Chromista [22]. Therefore, as
terrestrial plants, macroalgae possess interesting biological activities that could be involved
in the development of natural and innovative antibiotics [65]. Macroalgae’s biological
activities can vary among phyla [66]. In the following section, antimicrobial tests for
Rhodophyta and Chlorophyta extracts are considered.
 bial tests for Rhodophyta and Chlorophyta extracts are considered.

4.1. Rhodophyta
Two different extracts of Gracilaria corticata and Gracilaria edulis (methanolic
Mar. Drugs 2023, 21, 163 methyl sulfoxide (DMSO) extracts), were investigated against pathogenic 13 of 35
bacteria
E. coli, Bacillus subtilis, B. cereus, S. aureus, Photobacterium sp., and Pseudomonas flu
[67]. All tested extracts exhibited antimicrobial activity against these pathogenic
4.1. Rhodophyta
(Table 2), and GC-MS analysis has revealed the presence of numerous bioactive m
Two different extracts of Gracilaria corticata and Gracilaria edulis (methanolic and
lites such
dimethyl as sulphurous
sulfoxide acid, 2-ethylhexyl
(DMSO) extracts), isohexyl
were investigated againstester, eugenol,
pathogenic benzene,
bacteria such and p
as E. coli, Bacillus subtilis, B. cereus, S. aureus, Photobacterium sp., and Pseudomonas fluo- of eug
acid in both red macroalgae. Jasna et al. [68] reported high concentrations
the clove
rescens [67]. extract,
All testedwhich
extractsproves
exhibited itsantimicrobial
potential for antibacterial
activity against theseandpathogenic
antioxidant pro
bacteria
The antibacterial mechanism of action of eugenol consists of thebioactive
(Table 2), and GC-MS analysis has revealed the presence of numerous disruption of
metabolites such as sulphurous acid, 2-ethylhexyl isohexyl ester, eugenol, benzene, and
structure by the incorporation within the lipopolysaccharides layer of the bacter
phthalic acid in both red macroalgae. Jasna et al. [68] reported high concentrations of
membrane,
eugenol in thewhich leads which
clove extract, to theproves
intracellular components’
its potential release
for antibacterial and and the death of
antioxidant
teria [69].The
properties. It may be possible
antibacterial mechanismthat ofthe same
action mechanism
of eugenol ofofactions
consists happened
the disruption of with
the cell structure
corticata and [Link]
the incorporation
extracts. within the lipopolysaccharides layer of the bacteria’s
cell membrane, which leads to the intracellular components’ release and the death of the
S. aureus and E. coli growth reductions have been shown by testing these pat
bacteria [69]. It may be possible that the same mechanism of actions happened with the G.
bacteriaand
corticata against
G. edulisGrateloupia
extracts. turuturu ethanolic and polysaccharide extracts. The
show that both
S. aureus and [Link]
coli growth revealed
reductions antibacterial
have been shown activity, withthese
by testing polysaccharides
pathogenic ex
higher against
bacteria antimicrobial
Grateloupiaactivity.
turuturuThe FTIR-ATR
ethanolic analysis made
and polysaccharide it possible
extracts. to charact
The results
show that both extracts revealed antibacterial activity, with polysaccharides
turuturu polysaccharides, concluding that they are composed by a hybrid kappa/i exhibiting
higher antimicrobial activity. The FTIR-ATR analysis made it possible to characterize
rageenan (Figure 2) with traces of agar, in both phases of the life cycle. This sugge
G. turuturu polysaccharides, concluding that they are composed by a hybrid kappa/iota
these compounds
carrageenan (Figure 2)maywith be responsible
traces for this
of agar, in both phasesactivity; therefore,
of the life cycle. Thisthis red alga ma
suggests
pharmaceutical
that these compounds interest,
may besince it wasfor
responsible possible to observe,
this activity; therefore,both in the
this red algaethanolic
may be extra
of pharmaceutical interest, since it was possible to observe, both in the
polysaccharides extracts, the ability to inhibit the growth of two different bacteria ethanolic extracts
and polysaccharides extracts, the ability to inhibit the growth of two different bacterial
[70].
strains [70].

Figure 2. Structure of k-carrageenan molecule.

Figure 2. Structure of k-carrageenan molecule.
Methanolic extracts of G. edulis and Hypnea valentiae were tested against human
bacterial pathogens Klebsiella oxytoca, E. coli, S. aureus, P. aeruginosa, B. subtilis, Serratia
Methanolic
sp., and extracts
Salmonella sp. of [Link]
The G. edulis edulis and Hypneadisplayed
compound valentiaeawere tested
maximum of 23against
mm hum
terial
of pathogens
inhibition Klebsiella
zone against oxytoca,
B. subtilis E. H.
and the coli, S. aureus,
valentiae P. aeruginosa,
polyphenol [Link]
subtilis, aSerratia
maximum of 17 mm of inhibition zone against K. oxytoca (Table
Salmonella sp. The G. edulis polyphenol compound displayed a maximum 2). Polyphenols from red of 23
algae carry potential assets, as they may have a strong pharmaceutical value in the future.
inhibition zone against B. subtilis and the H. valentiae polyphenol compound disp
Biochemical analysis revealed the presence of flavonoids, saponins, tannin, and steroids in
maximum
both red algae,ofwhile
17 mm [Link] zone
edulis revealed againstand
phenolics [Link]
oxytoca [71].
(Table 2). Polyphenols f
algae Thecarry potential
objective of theassets,
study of asFreitas
they may
et [Link]
[72] isa to
strong pharmaceutical
evaluate the antioxidantvalue
and in the
Biochemicalactivity
antimicrobial analysis revealed
of twelve red the presence
seaweed species ofcommonly
flavonoids, saponins,
found tannin, and
on Portuguese
shores,
in bothnamely Porphyra
red algae, whileumbilicalis,
only [Link] ciliatum, phenolics
edulis revealed Osmundea pinnatifida, Chondrus
and alkaloids [71].
crispus, Sphaerococcus coronopifolius, Plocamium cartilagineum, Corallina officinalis, Ellisolandia
The objective of the study of Freitas et al. [72] is to evaluate the antioxidant a
elongata, Amphiroa rigida, Jania rubens, Mesophyllum lichenoides, and Liagora viscida. All of
microbial
them possessactivity of antimicrobial
interesting twelve red properties,
seaweed species commonly
and in Table found
2 are reported on Portuguese
the MIC and
namely Porphyra
inhibition zone diameterumbilicalis,
of the edibleCeramium
seaweeds P. ciliatum, Osmundea
umbilicalis, pinnatifida,
O. pinnatifida, Chondrus
and C. crispus.
P. umbilicalis presents, by far, the highest phenol content when compared to the other
studied algae, as well as a high scavenging ability. These results likely indicate strong
Mar. Drugs 2023, 21, 163 14 of 35

antioxidant activity, as it is known that seaweeds are able to develop antioxidant shielding
mechanisms and strategies to withstand highly oxidative environments [72].
The study of Bhuyar et al. [73] demonstrates that different extracts (water and ethanol)
of red alga K. alvarezii were more efficient against B. cereus but not against E. coli, as disc
diffusion assay results indicated.
Among edible seaweeds, Pyropia orbicularis [74] and Asparagopsis taxiformis both inhib-
ited S. aureus and E. coli, with Klebseilla sp., K. pneumoniae, Pseudomonas fluorescens, Vibrio
proteolyticus, and Streptococcus sp. Bacillus subtilis demonstrating a high inhibition zone [75]
(Table 2).

Table 2. Antimicrobial activity of Rhodophyta species (“nd” = not determined; “–“ = no antimicrobial
activity revealed).

Minimum
Inhibitory Inhibition Zone
Rhodophyta Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Staphylococcus aureus 0.5 mg/mL >15
Serratia sp. 0.5 mg/mL -
Klebseilla sp. 0.5 mg/mL >1
Salmonella sp. 0.5 mg/mL -
Escherichia coli 0.5 mg/mL >10
Asparagopsistaxiformis Methanolic extract Klebseilla pneumonia 0.5 mg/mL >1 [75]

Pseudomonas aeruginosa 0.5 mg/mL -

Pseudomonas fluorescens 0.5 mg/mL >10
Vibrio proteolyticus 0.5 mg/mL >1
Streptococcus sp. 0.5 mg/mL 10
Bacillussubtilis 0.5 mg/mL 10
Chondrus crispus Bacillus subtilis 12.5 mg/mL - [72]
Salmonella enterica 12.5 mg/mL >10
Klebsiella pneumoniae 50 mg/mL >11
Listeria monocytogenes 50 mg/mL 11
Enterobacter aerogenes 25 mg/mL >11
Proteus mirabilis 50 mg/mL >11
Vibrio
nd >11
Gelidium sp. Water extract parahaemolyticus [76]
Vibrio alginolyticus nd 13
Bacillus licheniformis 25 mg/mL 11
Bacillus cereus 0.625 mg/mL >11
Bacillus subtilis 3.125 mg/mL >10
Escherichia coli 50 mg/mL >13
Pseudomonas putida - -
Pseudomonas fluorescens - -
Mar. Drugs 2023, 21, 163 15 of 35

Table 2. Cont.

Minimum
Inhibitory Inhibition Zone
Rhodophyta Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Escherichia coli 100 µg/mL 7 ± 0.01
Photobacterium sp. 100 µg/mL 6 ± 0.04
Methanolic extract Pseudomonas fluorescens 100 µg/mL 8 ± 0.1
Staphylococcus aureus 100 µg/mL 4 ± 0.10
Bacillus subtilis 100 µg/mL 8 ± 0.01
Gracilaria corticata [67]
Escherichia coli 100 µg/mL 5 ± 0.10
Photobacterium sp. 100 µg/mL 4 ± 0.30
Dimethyl sulfoxide
Pseudomonas fluorescens 100 µg/mL 4 ± 0.05
(DMSO) extract
Staphylococcus aureus 100 µg/mL 6 ± 0.05
Bacillus subtilis 100 µg/mL 5 ± 0.12
Escherichia coli 100 µg/mL 3 ± 0.01
Photobacterium sp. 100 µg/mL 1 ± 0.00
Methanolic extract Pseudomonas fluorescens 100 µg/mL 3 ± 0.05
Staphylococcus aureus 100 µg/mL 3 ± 0.05
Gracilaria edulis Bacillus subtilis 100 µg/mL 3 ± 0.03 [67]

Escherichia coli 100 µg/mL 4.5 ± 0.01

Dimethyl sulfoxide Photobacterium sp. 100 µg/mL 4 ± 0.01
(DMSO) extract
Pseudomonas fluorescens 100 µg/mL 4 ± 0.10
Staphylococcus aureus 100 µg/mL 3 ± 0.00
Klebsiella oxytoca 0.3 mg/mL 21
Escherichia coli 0.3 mg/mL 19
Staphylococcus aureus 0.3 mg/mL 18
Gracilaria edulis Methanolic extracts Pseudomonas aeruginosa 0.3 mg/mL 16 [71]
Bacillus subtilis 0.3 mg/mL 23
Serratia sp. 0.3 mg/mL 20
Salmonella sp. 0.3 mg/mL 22
Staphylococcus aureus 10 mg/mL -
Ethanolic extract
Escherichia coli 10 mg/mL -
Grateloupia turuturu [70]
Polysaccharides Staphylococcus aureus 7.5 mg/mL -
(carrageenan) Escherichia coli 7.5 mg/mL -
Klebsiella oxytoca 0.3 mg/mL 17
Escherichia coli 0.3 mg/mL 12
Staphylococcus aureus 0.3 mg/mL 14
Hypnea valentiae Methanolic extract [71]
Pseudomonas aeruginosa 0.3 mg/mL 11
Bacillus subtilis 0.3 mg/mL 15
Serratia sp. 0.3 mg/mL 13
Salmonella sp. 0.3 mg/mL 16
Mar. Drugs 2023, 21, 163 16 of 35

Table 2. Cont.

Minimum
Inhibitory Inhibition Zone
Rhodophyta Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Escherichia coli - -
Ethanolic extract
Bacillus cereus 0.5 mg/mL <10
Kappaphycus alvarezii [73]
Escherichia coli - -
Hot water extract
Bacillus cereus 0.5 mg/mL <10
Osmundea pinnatifida Bacillus subtilis 1.56 mg/mL - [72]
Porphyra umbilicalis Aqueous extract Bacillus subtilis 3.13 mg/mL - [72]
Staphylococcus aureus 250 mg/mL nd
Pyropiaorbicularis Methanolic extract [74]
Escherichia coli 500 mg/mL

The in vitro activity of the Gelidium sp. flour extract was evaluated against the most
common pathogenic and spoilage bacteria. From the results, it emerged that P. fluorescens
and Pseudomonas putida exhibited resistance to components of algal flour extract. Only
B. subtilis and Salmonella enterica were inhibited by the lowest MIC. The highest level
of inhibition was observed both for Gram-negatives such as Enterobacteriaceae (E. coli,
Enterobacter aerogenes, and K. pneumoniae) and proteobacteria (Vibrio alginolyticus).
Due to the simplicity of the extraction methodology and the abundancy of Gelidium
sp., further research is envisaged to optimize the extraction of the used compounds and to
analyze the molecules involved in antimicrobial action [76].
Red algae are the main producers of halogenated compounds, which exhibited di-
verse biological activities including antibacterial, antifungal, anti-inflammatory, insecticidal,
and carcinogenic effects. Along with several interesting amino acid, acetate, and nucleic
acid derivatives, red algae also synthesize terpenoid, polyether, and acetogenin com-
pounds [28,29]. For example, the halogenated sesquiterpene alcohol, elatol, is commonly
found in Laurencia sp., and known for its potent antibacterial activity. The compound was
isolated for the first time in Laurencia microcladia, collected in the Southern Brazilian coast,
and tests showed the antiherbivore and antimicrobial activity of elatol [77].

4.2. Chlorophyta
Caulerpa racemosa and Caulerpa lentillifera, also known as “sea grapes”, are green sea-
weeds commonly found in different parts of the world. They are widely used as whole
food, but they also possess interesting therapeutic properties. It has been investigated
whether C. racemosa and C. lentillifera from Malaysia have antibacterial properties. Crude
extracts from seaweed were obtained using chloroform, methanol, and water. The authors
measured the total phenolic and flavonoid contents. Both seaweed extracts displayed
antibacterial abilities against neuropathogenic E. coli K1 and methicillin-resistant S. aureus
(MRSA). The results show that the C. racemosa chloroform extract had the highest total
phenolic content and the strongest antibacterial effect against MRSA, but it did not demon-
strate similar promising results against E. coli K1. The chloroform extract of C. lentillifera
gives a moderate antibacterial effect on MRSA but poorly on E. coli K1. In both species,
the methanol extracts only show a moderate antibacterial effect against both MRSA and
E. coli K1. A positive correlation has been revealed between the TPC and antibacterial
activity, suggesting that the antimicrobial action may be due to the presence of phenolics.
Both the C. racemosa and C. lentillifera water extracts promote the growth of the bacteria.
According to the study, C. racemosa chloroform extracts mostly contain polyunsaturated
and monounsaturated fatty acids, terpenes, and alkaloids. As a result, C. racemosa has the
potential to be an excellent source of new antibacterial compounds. Still, the mechanisms
Mar. Drugs 2023, 21, 163 17 of 35

of action of these compounds are unclear; therefore, further studies are needed along with
the improvement of isolation and purification techniques of bioactive compounds [78].
C. racemosa, along with Ulva intestinalis, have also been investigated to test their
antibacterial activity against Vibrio fluvialis. It appears that both exhibit antibacterial activity
against V. fluvialis bacteria, with C. racemosa exhibiting a higher activity [79].
Nagappan and Vairappan [80] evaluated the antibacterial properties of the green sea-
weed C. lentillifera and C. racemosa methanolic extracts against E. coli, S. aureus, Streptococcus
sp., Salmonella sp., and S. aureus. The higher MIC has been determined for C. racemosa
species against Streptococcus sp.
Ravikumar et al. [81] investigated Caulerpa cuppressoides, Enteromorpha intestinalis, and
Ulva lactuca antimicrobial activity. Tests were carried out considering different extraction
solvents, such as benzene, butanol, propanol, acetone, and water. The results reveal high
inhibitory activities against S. aureus, P. aeruginosa for C. cupressoides propanol extracts, while
for Streptococcus pyogens and E. coli with acetone extracts. E. intestinalis sees the highest
antimicrobial activity for K. pneumoniae from water extracts, while U. lactuca exhibited a
higher antimicrobial activity for butanol extracts against S. aureus and acetone extracts
tested for P. aeruginosa.
Ulva fasciata, U. lactuca, Cladophora vagabunda, Caulerpa taxifolia, Chaetomorpha anteninna,
and Chaetomorpha linum crude extracts were tested against E. coli clinical and labora-
tory strains, namely E. coli NCTC 10418, E. coli ATCC 25923, Proteus vulgaris, P. mirabilis,
P. aeruginosa, P. putida, Salmonella typhi clinical strain, Salmonella typhi NCTC 8385, Serratia
macerans, as well as K. pneumoniae, S. aureus ATCC 25922, B. subtilis, Streptococcus pneumoniae,
Enterobacter faecalis, and Mycobacterium aurum.
The highest activity against the bacterial strain was detected in the diethyl acetate
extract of C. antennina against S. aureus laboratory strain, while the highest inhibitory zone
against the Gram-negative bacterial species was observed in the dichloromethane/methanol
extract of C. taxifolia against E. coli strains. This alga presents the highest inhibitory activi-
ties among all the tested algae present in Table 3 that shows MIC and minimum zone of
inhibition performed with the disc diffusion method. U. fasciata exhibited broad-spectrum
antibacterial activity [82]. The effects of the methanol extracts of Ulva sp. against the
following multidrug-resistant bacteria isolated from patients in Saudi Arabia and Malaysia
were tested. The lowest MIC was for the 0.5 µg/mL extract of Ulva sp. against S. agalactiae
(group B), whereas S. saprophyticus exhibited more resistance to Ulva sp. with an MIC
of 16 µg/mL. This investigation conducted by Al-Zahrani et al. [83] is an example of the
potential for obtaining new sources of antimicrobial agents to develop new therapeutically
interesting molecules from easy cultivable seaweeds.
The results of Srikonga et al. [84], which evaluated the effects of the green seaweed
U. intestinalis methanolic, ethanolic, dichloromethane, and hexane extracts, demonstrated
antimicrobial activity against Gram-positive bacteria. The methanolic extracts exhibited
activity against B. cereus, MRSA, and S. aureus, while the ethanolic and dichloromethane
extracts affected only L. monocytogenes. All these four microbes are affected by the hexane
extract. For these species, the authors calculated the MIC, shown in Table 3. The extract of
Enteromorpha sp. had been tested by Swathi et al. [85] against P. aeruginosa, S. aureus, and
E. coli to analyze its antibacterial activity by the disc diffusion method. At the concentrations
of 150 g/mL and 200 g/mL, it produced a zone of clearance with diameters of 11 ± 0.2 mm
and 13 ± 0.2 mm, respectively, against P. aeruginosa. It exhibited inhibitory zones of
10 ± 0.2 mm, 16 ± 0.2 mm, and 18 ± 0.2 mm at the concentrations of 100 g/mL, 150 g/mL,
and 200 g/mL, respectively, for S. aureus and 11 ± 0.2 mm, 15 ± 0.2 mm, and 18 ± 0.2 mm,
respectively, against E. coli. This demonstrated the excellent antioxidant and antibacterial
properties of Enteromorpha sp. The bioactive compounds present in the green seaweed
extract of Enteromorpha compressa were tested for its antimicrobial activity against human
pathogens such as Klebsiella sp., Salmonella sp., S. aureus, and Proteus sp. Salmonella sp.
was found to be more susceptible to E. compressa ethanolic extracts compared with the
effect against other tested bacteria [86]. Phytochemical analysis confirmed the presence
 Mar. Drugs 2023, 21, 163 18 of 35

of phenols, alkaloids, flavonoids, steroids, and terpenoids that may be responsible for the
antibacterial activity.
Cadar et al. [87] investigated the extracts of U. lactuca to determine total polyphenols
content and antibacterial activity against S. aureus, Staphylococcus epidermidis, P. aeruginosa,
and E. coli. Ampicillin was used as a standard drug and control. The chloroform extract
demonstrated the largest inhibitory zone against S. aureus, comparable to that of conven-
tional ampicillin. The extract in n-hexane displayed the biggest inhibitory zone against
Staphylococcus epidermides and P. aeruginosa, comparable to the ampicillin control. The
extracts in n-hexane and chloroform produced the largest areas of inhibition in the case of
E. coli; however, they present low values compared to the ampicillin standard. The authors
deduced from the tests that ampicillin-like antibacterial activity was present in n-hexane
and chloroform extracts. Due to the presence of known bioactive chemical components that
promote this property, U. lactuca validates its potential for antimicrobial properties [87].
The Codium species have received the least attention from exploring the biological
activities of Chlorophyceae members for potential biomedical applications. C. intricatum
methanol extract was tested for antibacterial activity against a variety of bacterial infections.
It displayed a broad spectrum of inhibitory effects against MRSA and modest action against
B. cereus and L. monocytogenes in a research conducted by Arguelles et al. [88].
However, in other studies, such as Koz et al.’s [89] investigation, the antibacterial
activity of hexane, methanol, and dichloromethane of Codium fragile extracts against several
pathogenic bacteria were tested. All three extracts of C. fragile demonstrated a similar
weak antimicrobial activity on B. subtilis, MRSA, E. aerogenes, and E. coli compared with the
standard antibiotic tobramycin.
Mar. Drugs 2023, 21, x The antibacterial activity of methanolic extracts of C. bursa, C. tomentosum, C. dichoto-
mum, and C. fragile were tested against S. aureus, E. coli, K. pneumoniae, and E. faecalis. All
Codium extracts exhibited high inhibition against S. aureus, except for C. bursa, for which no
antibacterial activity was observed [90]. However, antimicrobial activity studies of Codium
sp. are limited and need to be further developed.
as anticancer [91], anticoagulant [92], antioxidant, antifungal, and antitu
Ulvan is a water-soluble sulphated polysaccharide (Figure 3) derived from marine
[93,94]. Ulvan
green seaweed, essentially
which contains
exhibits a wide range of rhamnose, xylose,
physiological and glucuronic
biological activities suchacid,
as iduro
anticancer [91],
sulphate anticoagulant
groups [93,95][92],
andantioxidant, antifungal,
its structure and antitumorcan
and properties activities
vary[93,94].
depending
Ulvan essentially contains rhamnose, xylose, glucuronic acid, iduronic acid, and sulphate
cies, place of cultivation, and method of extraction [96–100]. The study of V
groups [93,95] and its structure and properties can vary depending on algae species, place
[101] showed
of cultivation, andthe antibacterial
method activityThe
of extraction [96–100]. of study
ulvan of extracted from
Van Tran et al. [101] U. reticulata a
showed
P. aeruginosa, and Enterobacter cloacae. The highest inhibition activity was sho
the antibacterial activity of ulvan extracted from U. reticulata against E. coli, P. aeruginosa,
and Enterobacter cloacae. The highest inhibition activity was shown in E. cloacae, followed by
cae, followed by E. coli, and the lowest inhibitor activity was in P. aeruginosa
E. coli, and the lowest inhibitor activity was in P. aeruginosa [101].

Figure 3. Structure of ulvan molecule.

Figure 3. Structure of ulvan molecule.
However, ulvan extracted from U. lactuca demonstrates activity against other pathogenic
bacteria listed in Table 3 [102]. It is likely that the different antibacterial activities are due to
However,
molecular ulvanofextracted
weight, density charged groups,fromand [Link]
lactuca demonstrates activityit agains
of molecules. Therefore,
genic bacteria listed in Table 3 [102]. It is likely that the different
is necessary to investigate more deeply the factors influencing the antibacterial antibacteria
activity of
ulvan and its mechanisms of action.
due to molecular weight, density of charged groups, and morphology
Therefore, it is necessary to investigate more deeply the factors influencing
rial activity of ulvan and its mechanisms of action.

Table 3. Antimicrobial activity of Chlorophyta species (“nd” = not determined; “–“

Mar. Drugs 2023, 21, 163 19 of 35

Table 3. Antimicrobial activity of Chlorophyta species (“nd” = not determined; “–“ = no antimicrobial
activity revealed).

Minimum
Inhibitory Inhibition Zone
Chlorophyta Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Escherichia coli nd 6
Klebsiella pneumoniae nd 6
Benzene Pseudomonas aeruginosa nd 5
Streptococcus pyogens nd 6
Staphylococcus aureus nd 6
Escherichia coli nd 7
Klebsiella pneumoniae nd -
Butanol Pseudomonas aeruginosa nd 7
Streptococcus pyogens nd -
Staphylococcus aureus nd 6
Escherichia coli nd 7
Caulerpa cupressoides [81]
Klebsiella pneumoniae nd -
Propanol Pseudomonas aeruginosa nd 8
Streptococcus pyogens nd 7
Staphylococcus aureus nd 6
Escherichia coli nd 9
Klebsiella pneumoniae nd 6
Acetone Pseudomonas aeruginosa nd 5
Streptococcus pyogens nd 8
Staphylococcus aureus nd 7
Escherichia coli nd 6
Klebsiella pneumoniae nd 6
Water Pseudomonas aeruginosa nd -
Streptococcus pyogens nd -
Staphylococcus aureus nd -
Methicillin-resistant
Caulerpa lentillifera Water extract Staphylococcus aureus, 5 µg/mL nd [78]
Escherichia coli
136.50 ± 0.85
Escherichia coli nd
mg/mL
125.25 ± 3.78
Staphylococcus aureus nd
mg/mL
Caulerpa lentillifera Methanolic extract [80]
175.25 ± 0.23
Streptococcus sp. nd
mg/mL
140.50 ± 0.55
Salmonella sp. nd
mg/mL
Methicillin-resistant
Caulerpa racemosa Water extract Staphylococcus aureus, 5 µg/mL nd [78]
Escherichia coli
Mar. Drugs 2023, 21, 163 20 of 35

Table 3. Cont.

Minimum
Inhibitory Inhibition Zone
Chlorophyta Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Caulerpa racemosa Methanolic extract Vibrio fluvialis nd 9 ± 0.50 [79]
245.25 ± 2.11
Escherichia coli nd
mg/mL
225.50 ± 0.45
Staphylococcus aureus nd
Caulerpa racemosa var. mg/mL
Methanolic extract [80]
clavifera f. microphysa 450.75 ± 1.09
Streptococcus sp. nd
mg/mL
275. 20 ± 0.66
Salmonella sp. nd
mg/mL
360.50 ± 2.14
Escherichia coli nd
mg/mL
375.75 ± 0.07
Staphylococcus aureus nd
Caulerpa racemosa var. mg/mL
Methanolic extract [80]
laetevirens 450. 25 ± 0.42
Streptococcus sp. nd
mg/mL
345. 25 ± 0.35
Salmonella sp. nd
mg/mL
Chloroform/methanol Escherichia coli 640 µg/mL 7.33–10.67
Caulerpa taxifolia [82]
extract Staphylococcus aureus - 10.00–11.17
Chaetomorpha Chloroform/methanol Escherichia coli 640 µg/mL 7.33–10.67
[82]
anteninna extract Staphylococcus aureus 640 µg/mL 10.00–11.17
Chloroform/methanol Escherichia coli >640 µg/mL 7.33–10.67
Chaetomorpha linum [82]
extract Staphylococcus aureus - 10.00–11.17
Chloroform/methanol Escherichia coli 640 µg/mL 7.33–10.67
Cladophora vagabunda [82]
extract Staphylococcus aureus nd 10.00–11.17
Staphylococcus aureus nd ≥20
Escherichia coli nd <10
Codium dichotomum Methanolic extract [90]
Klebliella pneumoniae nd <10
Enterobacter faecalis nd <10
Staphylococcus aureus nd ≥20
Escherichia coli nd <10
Codium fragile Methanolic extract [90]
Klebliella pneumoniae nd <10
Enterobacter faecalis nd <10
Bacillus subtilis 250 µg/mL 6.5
Bacillus cereus 1000 µg/mL -
Staphylococcus
- -
epidermidis
Hexane extract
Staphylococcus aureus - -
Methicillin-resistant
- 6.5
Staphylococcus aureus
Enterobacter cloacae 1000 µg/mL 7
Enterobacter cloacae - -
Mar. Drugs 2023, 21, 163 21 of 35

Table 3. Cont.

Minimum
Inhibitory Inhibition Zone
Chlorophyta Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Escherichia coli 500 µg/mL -
Escherichia coli
500 µg/mL -
(Hemorrhagic, O157:H7)
Pseudomonas aeruginosa <50 µg/mL -
Proteus vulgaris 250 µg/mL -
Salmonella typhimurium - -
Candida albicans -
Bacillus subtilis 250 µg/mL 6.5
Bacillus cereus 500 µg/mL -
Staphylococcus
500 µg/mL -
epidermidis
Staphylococcus aureus 500 µg/mL -
Methicillin-resistant
- 7.5
Methanol extract Staphylococcus aureus
Enterobacter cloacae - 7
Escherichia coli - -
Escherichia coli
- -
(Hemorrhagic, O157:H7)
Pseudomonas aeruginosa 250 µg/mL -
Proteus vulgaris 250 µg/mL -
Salmonella typhimurium - -
Candida albicans - -
Bacillus subtilis - 6.5
Bacillus cereus - -
Staphylococcus
- -
epidermidis
Staphylococcus aureus - -
Methicillin-resistant
- -
Dichloromethane Staphylococcus aureus
extract Enterobacter cloacae - 7
Escherichia coli - 7
Escherichia coli
- -
(Hemorrhagic, O157:H7)
Pseudomonas aeruginosa - -
Proteus vulgaris - -
Salmonella typhimurium - -
Candida albicans - -
Mar. Drugs 2023, 21, 163 22 of 35

Table 3. Cont.

Minimum
Inhibitory Inhibition Zone
Chlorophyta Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Methicillin-resistant
250 µg/mL nd
Staphylococcus aureus
Bacillus cereus 500 µg/mL nd
Listeria monocytogenes 500 µg/mL nd
Streptococcus mutans - nd
Codium intricatum Methanol extract [88]
Pseudomonas aeruginosa - nd
Escherichia coli - nd
Enterobacter cloacae - nd
Salmonella typhimurium - nd
Aeromonas hydrophila - nd
Staphylococcus aureus nd ≥20
Escherichia coli nd <10
Codium tomentosum Methanolic extract [90]
Klebliella pneumoniae nd <10
Enterobacter faecalis nd <10
Salmonella sp. nd 15
Enteromorpha
Ethanolic extract Klebsiella sp. nd 10 [86]
compressa
Proteus sp. nd 5
Staphylococcus aureus nd 5
Pseudomonas aeruginosa 150 g/mL 11 ± 0.2
Methanol:acetone
Enteromorpha sp. Staphylococcus aureus 100 g/mL 10 ± 0.2 [85]
extract
Escherichia coli 100 g/mL 11 ± 0.2
Chloroform/methanol Escherichia coli 640 µg/mL 7.33–10.67
Ulva fasciata [82]
extract Staphylococcus aureus >640 µg/mL 10.00–11.17
Ulva intestinalis Methanolic extract Vibrio fluvialis nd 7 ± 0.56 [79]
Escherichia coli nd 6
Klebsiella pneumoniae nd -
Benzene Pseudomonas aeruginosa nd 6
Streptococcus pyogens nd 6
Staphylococcus aureus nd 6
Escherichia coli nd 7
Klebsiella pneumoniae nd 7
Ulva intestinalis [81]
Butanol Pseudomonas aeruginosa nd 6
Streptococcus pyogens nd 7
Staphylococcus aureus nd 6
Escherichia coli nd 6
Klebsiella pneumoniae nd -
Propanol Pseudomonas aeruginosa nd 7
Streptococcus pyogens nd 7
Staphylococcus aureus nd 7
Mar. Drugs 2023, 21, 163 23 of 35

Table 3. Cont.

Minimum
Inhibitory Inhibition Zone
Chlorophyta Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Escherichia coli nd -
Klebsiella pneumoniae nd -
Acetone Pseudomonas aeruginosa nd -
Streptococcus pyogens nd -
Staphylococcus aureus nd -
Escherichia coli nd 6
Klebsiella pneumoniae nd 10
Water Pseudomonas aeruginosa nd -
Streptococcus pyogens nd -
Staphylococcus aureus nd -
Escherichia coli nd -
Klebsiella pneumoniae nd -
Proteus mirabilis nd -
Pseudomonas aeruginosa nd -
Salmonella typhi nd -
Vibrio alginolyticus nd -
Methanolic extract
Vibrio harveyi nd -
Vibrio parahaemolyticus nd -
Bacillus cereus 1024 µg/mL 6.85 ± 0.17
Enterobacter faecalis nd -
Listeria monocytogenes -
Methicillin-resistant
>1024 µg/mL 12.71 ± 0.98
Staphylococcus aureus
Ulva intestinalis [84]
Staphylococcus aureus >1024 µg/mL 8.41 ± 0.56
Escherichia coli nd -
Klebsiella pneumoniae nd -
Proteus mirabilis nd -
Pseudomonas aeruginosa nd -
Salmonella typhi nd -

Ethanolic extract Vibrio alginolyticus nd -

Vibrio harveyi nd -
Vibrio parahaemolyticus nd -
Bacillus cereus nd -
Enterobacter faecalis nd -
Listeria monocytogenes >1024 µg/mL 7.96 ± 0.38
Mar. Drugs 2023, 21, 163 24 of 35

Table 3. Cont.

Minimum
Inhibitory Inhibition Zone
Chlorophyta Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Methicillin-resistant
nd -
Staphylococcus aureus
Staphylococcus aureus nd -
Escherichia coli nd -
Klebsiella pneumoniae nd -
Proteus mirabilis nd -
Pseudomonas aeruginosa nd -
Salmonella typhi nd -
Vibrio alginolyticus nd -
Dichloromethane
extract Vibrio harveyi nd -
Vibrio parahaemolyticus nd -
Bacillus cereus nd -
Enterobacter faecalis 1024 µg/mL -
Listeria monocytogenes nd 9.89 ± 0.24
Methicillin-resistant
nd -
Staphylococcus aureus
Staphylococcus aureus nd -
Escherichia coli nd -
Klebsiella pneumoniae nd -
Proteus mirabilis nd -
Pseudomonas aeruginosa nd -
Salmonella typhi nd -
Vibrio alginolyticus nd -
Hexane extract Vibrio harveyi nd -
Vibrio parahaemolyticus nd -
Bacillus cereus 256 µg/mL 7.28 ± 0.02
Enterobacter faecalis nd -
Listeria monocytogenes 1024 µg/mL 10.55 ± 0.29
Methicillin-resistant
256 µg/mL 16.4 ± 2.4
Staphylococcus aureus
Staphylococcus aureus 256 µg/mL 12.13 ± 0.16
Escherichia coli nd 6
Klebsiella pneumoniae nd 6
Benzene Pseudomonas aeruginosa nd 6 [81]
Ulva lactuca
Streptococcus pyogens nd 6
Staphylococcus aureus nd 6
Mar. Drugs 2023, 21, 163 25 of 35

Table 3. Cont.

Minimum
Inhibitory Inhibition Zone
Chlorophyta Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Escherichia coli nd 6
Klebsiella pneumoniae nd 7
Butanol Pseudomonas aeruginosa nd -
Streptococcus pyogens nd -
Staphylococcus aureus nd 8
Escherichia coli nd 6
Klebsiella pneumoniae nd 6
Propanol Pseudomonas aeruginosa nd 6
Streptococcus pyogens nd -
Staphylococcus aureus nd 7
Escherichia coli nd -
Klebsiella pneumoniae nd -
Acetone Pseudomonas aeruginosa nd 8
Streptococcus pyogens nd -
Staphylococcus aureus nd -
Escherichia coli nd -
Klebsiella pneumoniae nd -
Water Pseudomonas aeruginosa nd -
Streptococcus pyogens nd -
Staphylococcus aureus nd -
Chloroform/methanol Escherichia coli >640 µg/mL 7.33–10.67
Ulva lactuca [82]
extract Staphylococcus aureus 640 µg/mL 10.00–11.17
Staphylococcus aureus nd 10
Staphylococcus
nd 12
N–hexane extract epidermidis
Escherichia coli nd 11
Pseudomonas aeruginosa nd 12
Staphylococcus aureus nd 11
Ulva lactuca Staphylococcus [87]
nd 11
Chloroform extract epidermidis
Escherichia coli nd 11
Pseudomonas aeruginosa nd 10
Staphylococcus aureus nd 9
Staphylococcus
ethanol: water (1:1) nd 10
epidermidis
extract
Escherichia coli nd 9
Pseudomonas aeruginosa nd 9
Mar. Drugs 2023, 21, 163 26 of 35

Table 3. Cont.

Minimum
Inhibitory Inhibition Zone
Chlorophyta Extract Type Microbes Reference
Concentration Diameter (mm)
(MIC)
Staphylococcus aureus - -
Enterobacter faecalis - -
12.50 ± 0.0
Bacillus subtilis 15 ± 0.50
mg/mL
Polysaccharide
Ulva lactuca Listeria monocytogenes - - [102]
(ulvan)
25.00 ± 0.0
Pseudomonas aeruginosa 12 ± 0.10
mg/mL
Escherichia coli 6.25 ± 0.0 mg/mL 11 ± 0.21
Klebsiella pneumoniae 6.25 ± 0.0 mg/mL 12 ± 0.00
Bordetella pertussis - -
Bacillus cereus nd -
Enterobacter faecalis nd -
Enterobacter cloacae nd 20.00 ± 1.00
Polysaccharide
Ulva reticulata Staphylococcus aureus nd - [101]
(ulvan)
Escherichia coli nd 18 ± 0.5
Pseudomonas aeruginosa nd <18 ± 0.5
Vibrio harveyi nd -
Staphylococcus
16 µg/mL 29 ± 0.592
saprophyticus
Staphylococcus
4 µg/mL 26 ± 0.548
epidermidis
Streptococcus agalactiae
0.5 µg/mL 14 ± 0.592
(group B)
Enterobacter faecalis 2 µg/mL 21 ± 0.592
Ulva sp. Methanolic extract [83]
Stenotrophomonas
1 µg/mL 15 ± 0.592
maltophilia
Salmonella enterica 2 µg/mL 11 ± 0.592
Shigella sonnei 2 µg/mL 12 ± 0.592
Pproteus vulgaris 2 µg/mL 20 ± 0.592
Pproteus mirabilis - -
Enterobacter cloacae - -
Haemophilus influenzae - -

5. Antimicrobial Mechanisms of Action of Seaweeds Compounds

Seaweeds have been used as traditional medicines and potential sources of new thera-
peutic agents for a long time. Research and development continue to carry on investigations
of marine algae and their potential metabolites for human health. The development of
seaweed is supported by the facts that seaweeds are easy to collect, easily cultivated,
renewable, and they grow fast [103–105].
The chemical profile of seaweeds and their therapeutic efficacy are largely influenced
by a number of parameters such as species, physiological status, environmental variables
(location, climate, temperature, salinity), growth conditions, environmental contamination,
collecting period, thallus area, and epiphytic organisms [106,107]. Each seaweed species
 Mar. Drugs 2023, 21, 163 27 of 35

differs from another; thus, they all have their own unique characteristics. Moreover,
differences may be due to different methods of extraction, solvents used in extraction,
and different collecting seasons [108]. Macroalgae include a wide variety of taxonomic
groups with different metabolites exhibiting biological properties, synthetized by seaweeds
to overcome the harsh conditions in extreme environments [109]. Phenols, fatty acids,
Mar. Drugs 2023, 21, x carbohydrates, proteins, and other minor chemicals have been identified as the chemical 22 of 30
elements that give algae their antibacterial properties [110,111]. This section describes the
possible mechanisms of antimicrobial activity of natural compounds (Figure 4).

Figure Possible mechanisms

4. [Link]
Figure mechanisms of antimicrobial activity exhibited
of antimicrobial activity by antibioticsby
exhibited andantibiotics
natural compounds.
and natural
compounds.
Gram-negative bacteria are reportedly less sensitive to phenolic compounds’ bioac-
tivity than Gram-positive bacteria, probably as a result of variations in cell wall com-
Gram-negative bacteria are reportedly less sensitive to phenolic compounds’
position [112]. The mechanisms of action of seaweed metabolites have not been clearly
bioactivity than Gram-positive bacteria, probably as a result of variations in cell wall
elucidated. According to earlier research, some phlorotannin antibacterial effect may be
composition
connected to [112].
theirThe mechanisms
ability to integrate ofwith action of seaweed
microbial proteins, metabolites have not been
such as cell membranes
clearly
and enzymes, and cause cell disintegration by inhibiting the oxidative phosphorylationeffect
elucidated. According to earlier research, some phlorotannin antibacterial
may be connected
pathway to their ability
in microorganisms to Different
[113,114]. integrateinteractions,
with microbialincluding proteins, such as cell
those involving
membranes and enzymes,
microbial membrane and cause
permeability, enzymaticcell inactivation,
disintegration by to
binding inhibiting the oxidative
surface membranes,
and binding to surface
phosphorylation pathway sticky
in molecules, are thought
microorganisms to be involved
[113,114]. Differentin polyphenolic
interactions, antibac-
including
terial bioactivity [115]. The study case of Hierholtzer et al. [116]
those involving microbial membrane permeability, enzymatic inactivation, binding displayed disrupted outer to
membranes, exo-polysaccharide coagulation, separation of the cytoplasmic membrane
surface membranes, and binding to surface sticky molecules, are thought to be involved
from the cell envelope, and "blebbing" and debris of phlorotannin-coagulated components,
in polyphenolic antibacterial bioactivity [115]. The study case of Hierholtzer et al. [116]
after the interaction between germs and phlorotannins from Laminaria digitata. The crucial
displayed disrupted
phase involved with outer membranes,
the bactericidal exo-polysaccharide
action of phlorotannin is coagulation,
the disruption separation
of the cellof the
cytoplasmic
envelopes,membrane from the
so the researchers cell envelope,
concluded anddisruption
that this "blebbing" is and debris
linked withofthephlorotannin-
level of
coagulated components,
polymerization after the[116].
of the compounds interaction between germs and phlorotannins from
Laminaria digitata. Theare
Phlorotannins crucial
thought phase involved
to cause with
cell lysis as the bactericidal
a result action of phlorotannin
of their antibacterial activity.
Thedisruption
is the inclusion ofofhydroxyl
the cell groups in theso
envelopes, phlorotannin
the researchers molecule, which may
concluded thatbind
this to amide
disruption is
groups in the bacterial proteins, can further strengthen
linked with the level of polymerization of the compounds [116]. these interactions [117,118]. The -NH
groups of bacterial proteins presumably interact with aromatic rings and -OH groups of the
Phlorotannins are thought to cause cell lysis as a result of their antibacterial activity.
phloroglucinol monomer through hydrophobic interactions and H-bonds [112,117,119,120].
The inclusion of hydroxyl groups in the phlorotannin molecule, which may bind to amide
Depending on the species and time of year they are harvested, seaweeds are a promis-
groups in the of
ing source bacterial
[Link],
Brown algaecan further
usuallystrengthen
contain a low these interactions
quantity [117,118].
of proteins (3–15%The -
NHDW),groups
whileof bacterial proteins
an intermediate presumably
quantity is found interact
in greenwith aromatic
algae (9–33%rings DW),andand-OH groups
a high
of quantity
the phloroglucinol monomer through hydrophobic interactions
in red seaweeds (47% DW) [121]. Relevant proteins with antibacterial activity and H-bonds
[112,117,119,120]. Depending
are lectins or agglutinins; on the
these speciesare
substances andglycoproteins
time of year thattheycan aredetect
harvested, seaweeds
free sugars
are a promising source of proteins. Brown algae usually contain a low quantity of proteins
(3–15% DW), while an intermediate quantity is found in green algae (9–33% DW), and a
high quantity in red seaweeds (47% DW) [121]. Relevant proteins with antibacterial
activity are lectins or agglutinins; these substances are glycoproteins that can detect free
Mar. Drugs 2023, 21, 163 28 of 35

or glycoconjugates and interact with them in a reversible manner without altering their
structural integrity [122]. Lectins have been investigated as antibacterial, anti-inflammatory,
anti-adhesion, anti-cancer, and antimicrobial agents [122].
Fatty acids and monoglycerides that interact with bacterial cell membranes and have
antibacterial activity are identified as antimicrobial lipids [123]. Myristic, palmitic, oleic,
and eicosapentaenoic acids, which are linked to the antibacterial characteristics of algae,
are the most prevalent saturated and unsaturated fatty acids found in seaweed [124].
Seaweeds typically have low levels of lipids (0.4 to 5% DW basis); however, they do include
important lipids including glycolipids and polyunsaturated fatty acids such as omega-3
that have important biological features and health advantages [125]. Additionally, a range
of secondary metabolites and chemicals found in essential oils from various seaweeds are
known to slow down or prevent the growth of bacteria, yeast, and molds [126–130]. It
appears that the mechanism of action is due to the membrane-lytic response of fatty acids,
which results in membrane instability and defect formation and, as result, inhibits cell
development (bacteriostatic action) or even causes cell death. These molecules can also
interfere with two vital cellular processes for energy production: oxidative phosphorylation
(by reducing the membrane potential and proton gradient) and the electron transport
chain (by attaching to electron carriers or changing the integrity of the membranes). Fatty
acids can also directly disrupt membrane enzymes and obstruct the cell’s ability to absorb
nutrients [123].
Macroalgal polysaccharides’ antibacterial mechanisms of action are still not completely
understood. According to Zhao et al. [131], the antibacterial properties of fucoidan may
be connected to the amounts of glucuronic and sulfuric acids that are released when the
molecules depolymerize. The results announce that fucoidans have the ability to attach to
the proteins that assemble bacterial membranes, leading to membrane cell breakdown and
cell death [131]. Compared to Gram-positive bacteria, Gram-negative bacteria appear to be
less responsive to fucoidans antibacterial properties. This phenomenon was explained by
the existence of cell wall elements that could serve as a barrier to the antibacterial effects
of fucoidans [131]. The study of He et al. [132] suggested that the cell wall, cytoplasmic
membranes, and DNA may be the primary targets of antibacterial polysaccharides. These
results came out from investigating the antibacterial activities of seaweed polysaccharides
against bacteria that cause food spoilage and food poisoning, including Candida utilis,
S. aureus, B. subtilis, L. monocytogenes, and E. coli [132].
Among minor compounds, sterols are the most diverse in nature and have a variety
of features. The antibacterial properties of the sterol 24-propylidene cholest-5-en-3-ol iso-
lated from L. papillosa against a range of bacteria were determined by Kavita et al. [133].
Similar to this, earlier studies on macroalgal sterols noted their potent antibacterial prop-
erties [134–136]. Previous research revealed that the presence of sterols may impact the
morphological responses in the cell membranes when induced by antimicrobial lipids, and
therefore lead to the disruption of the bacterial membranes. However, the antimicrobial
mechanisms of action of these substances are still not entirely elucidated and further studies
need to be carried out [137].

6. Conclusions
As the present review shows, various plants and macroalgae developed several chem-
icals with antimicrobial activities. Moreover, due to the therapeutic efficacy of their active
ingredients, medicinal plants play a significant part in the restoration of damage caused
by microbial infection. Many plant products, including the entire plant, medicinal volatile
oils, extracts, etc., have been used as natural antibiotics for treating burns, respiratory tract
infections, boosting the immune system, lowering blood pressure, and other conditions
wherein microbes can infect and thrive inside or outside of the body once our immune
system is weak. Natural antibiotics are herbs and spices that can be found in nature
which have qualities that stop pathogens from functioning and spreading, with less severe
consequences than those of conventional antibiotics.
Mar. Drugs 2023, 21, 163 29 of 35

The necessity to replace synthetic antibiotic compounds with natural ones is due to
the action of synthetic antibiotics during their assumption; even though antibiotics kill
infectious bacteria, they also cause a significant amount of side effects by disturbing natural
functions of the body and destroying intestinal flora bacteria [138–140]. Herbal antibiotics
destroy bacteria as well, purify the blood, boost the immune system, and improve organ
system functions. They function by killing microorganisms and correcting body imbalances.
Additionally, most herbal antibiotics do not develop drug resistance and do not have the
bactericidal effect against beneficial bacteria which live in our body [141].
It is misleading to say that herbal medicines have no toxic effects at all, or any side
effects. There are cases where the uptake of large amounts of natural products in high
concentrations of herbal complements may badly influence our organisms [142,143]. For
example, taking garlic in high concentrations may enhance the risk of bleeding, so it is not
suggested for people having surgery or taking blood thinners [144]. Therefore, to avoid
unpleasant consequences, it is important to take medicine, herbal or synthetic, in proper
dosage and proper course of treatment.
Although there is evidence that natural plants and macroalgae extracts are a source
of antimicrobial chemicals, further research is required to understand the mechanisms
by which plant and macroalgal substances affect cells, as well as clinical trials. The phar-
macochemical profiles, pharmacological outcomes, and evaluations of the inclusion of
these natural chemicals in new antibiotics must be gathered. As we see through this
manuscript, the different types of extraction and solvents used influence the antimicrobial
activity. To reduce the occurrences of drug-resistant microorganisms, it is vital to go further
in the development of herbal medicines and find the best extraction methodology with
remunerative costs and yield. The use of herbal drugs as medicine has the potential to
provide biocompatible, less expensive, and effective herbal solutions and will increase the
probability of the discovery of new natural antibiotics. Further and more in-depth studies
are required to build an understanding on the mechanism of action, identify, and isolate
the specific compounds responsible for the desired effects and use them as an alternative to
synthetic drugs.

Author Contributions: Conception and design of the idea: S.L. and A.M.M.G.; writing and biblio-
graphic research: S.L. and A.M.M.G.; supervision and manuscript revision: A.M.M.G. All authors
have read and agreed to the published version of the manuscript.
Funding: This work is financed by national funds through FCT—Foundation for Science and Tech-
nology, I.P., within the scope of the projects LA/P/0069/2020 granted to the Associate Laboratory
ARNET, UIDB/04292/2020—granted to MARE—Marine and Environmental Sciences Centre and
UIDP/50017/2020+UIDB/50017/2020 (by FCT/MTCES) granted to CESAM—Centre for Environ-
mental and Marine Studies. This research was co-financed by the project AlgaMar4antivirus—Marine
MacroalgaE in the prevention and treatment of ANTIviral diseases (Coronavirus SARS-CoV-2)
(FA_07_2018_009), funded by the Blue Fund under Public Notice No. 7 /2018—Scientific Research
and Marine Technology. Silvia Lomartire thanks the Foundation for Science and Technology (FCT)
for the financial support granted through the doctoral grant [Link]. Ana M. M. Gonçalves
acknowledges the University of Coimbra for the contract IT057-18-7253.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.

References
1. Hoffman, P.S. Antibacterial Discovery: 21st Century Challenges. Antibiotics 2020, 9, 213. [CrossRef]
2. Breijyeh, Z.; Jubeh, B.; Karaman, R. Resistance of Gram-Negative Bacteria to Current Antibacterial Agents and Overcoming
Approaches to Resolve It. Molecules 2020, 25, 1340. [CrossRef] [PubMed]
3. Silhavy, T.J.; Kahne, D.; Walker, S. The Bacterial Cell Envelope. Cold Spring Harb. Perspect. Biol. 2010, 2, 1–17. [CrossRef]
4. Yuan, R.; Hou, Y.; Sun, W.; Yu, J.; Liu, X.; Niu, Y.; Lu, J.J.; Chen, X. Natural Products to Prevent Drug Resistance in Cancer
Chemotherapy: A Review. Ann. N. Y. Acad. Sci. 2017, 1401, 19–27. [CrossRef] [PubMed]
5. Liu, M.; El-Hossary, E.M.; Oelschlaeger, T.A.; Donia, M.S.; Quinn, R.J.; Abdelmohsen, U.R. Potential of Marine Natural Products
against Drug-Resistant Bacterial Infections. Lancet Infect. Dis. 2019, 19, e237–e245. [CrossRef]
Mar. Drugs 2023, 21, 163 30 of 35

6. Qin, Y. Health Benefits of Bioactive Seaweed Substances; Elsevier Inc.: Amsterdam, The Netherlands, 2018; ISBN 9780128133125.
7. Gerwick, W.H.; Moore, B.S. Lessons from the Past and Charting the Future of Marine Natural Products Drug Discovery and
Chemical Biology. Chem. Biol. 2012, 19, 85–98. [CrossRef] [PubMed]
8. Weinheimer, A.J.; Spraggins, R.L. The Occurrence of Two New Prostaglandin Derivatives (15-Epi-PGA2 and Its Acetate, Methyl
Ester) in the Gorgonian Plexaura homomalla Chemistry of Coelenterates. XV. Tetrahedron Lett. 1969, 10, 5185–5188. [CrossRef]
9. Masuda, M.; Abe, T.; Suzuki, T.; Suzuki, M. Morphological and Chemotaxonomic Studies on Laurencia Composita and L. okamurae
(Ceramiales, Rhodophyta). Phycologia 1996, 35, 550–562. [CrossRef]
10. Taylor, R.E. Tedanolide and the Evolution of Polyketide Inhibitors of Eukaryotic Protein Synthesis. Nat. Prod. Rep. 2008, 25,
854–861. [CrossRef]
11. Santos, J.D.; Vitorino, I.; Reyes, F.; Vicente, F.; Lage, O.M. From Ocean to Medicine: Pharmaceutical Applications of Metabolites
from Marine Bacteria. Antibiotics 2020, 9, 455. [CrossRef]
12. Liang, X.; Luo, D.; Luesch, H. Advances in Exploring the Therapeutic Potential of Marine Natural Products. Pharmacol. Res. 2019,
147, 104373. [CrossRef]
13. Singh, S.B.; Barrett, J.F. Empirical Antibacterial Drug Discovery-Foundation in Natural Products. Biochem. Pharmacol. 2006, 71,
1006–1015. [CrossRef] [PubMed]
14. Newman, D.J.; Cragg, G.M. Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. J.
Nat. Prod. 2020, 83, 770–803. [CrossRef] [PubMed]
15. Newman, D.J.; Cragg, G.M. Natural Products as Sources of New Drugs from 1981 to 2014. J. Nat. Prod. 2016, 79, 629–661.
[CrossRef] [PubMed]
16. Mostafa, A.A.; Al-Askar, A.A.; Almaary, K.S.; Dawoud, T.M.; Sholkamy, E.N.; Bakri, M.M. Antimicrobial Activity of Some Plant
Extracts against Bacterial Strains Causing Food Poisoning Diseases. Saudi J. Biol. Sci. 2018, 25, 361–366. [CrossRef] [PubMed]
17. Takó, M.; Beáta Kerekes, E.; Zambrano, C.; Kotogán, A.; Papp, T.; Krisch, J.; Vágvölgyi, C. Plant Phenolics and Phenolic-Enriched
Extracts as Antimicrobial Agents against Food-Contaminating Microorganisms. Antioxidants 2020, 9, 165. [CrossRef]
18. Manandhar, S.; Luitel, S.; Dahal, R.K. In Vitro Antimicrobial Activity of Some Medicinal Plants against Human Pathogenic
Bacteria. J. Trop. Med. 2019, 2019, 1895340. [CrossRef]
19. Alzoreky, N.S.; Nakahara, K. Antibacterial Activity of Extracts from Some Edible Plants Commonly Consumed in Asia. Int. J.
Food Microbiol. 2003, 80, 223–230. [CrossRef]
20. Fankam, A.G.; Kuete, V.; Voukeng, I.K.; Kuiate, J.R.; Pages, J. Antibacterial Activities of Selected Cameroonian Spices and Their
Synergistic Effects with Antibiotics against Multidrug-Resistant Phenotypes. Complement. Altern. Med. 2011, 11, 104. [CrossRef]
21. Nascimento, G.G.F.; Locatelli, J.; Freitas, P.C.; Silva, G.L. Antibacterial Activity of Plant Extracts and Phytochemicals on Antibiotic-
Resistant Bacteria. Brazilian J. Microbiol. 2000, 31, 247–256. [CrossRef]
22. Pereira, L. Macroalgae. Encyclopedia 2021, 1, 17. [CrossRef]
23. Bhuyar, P.; Rahim, M.H.A.; Sundararaju, S.; Ramaraj, R.; Maniam, G.P.; Govindan, N. Synthesis of Silver Nanoparticles Using
Marine Macroalgae Padina sp. and Its Antibacterial Activity towards Pathogenic Bacteria. Beni-Suef Univ. J. Basic Appl. Sci. 2020,
9, 1–15. [CrossRef]
24. Silva, A.; Silva, S.A.; Lourenço-Lopes, C.; Jimenez-Lopez, C.; Carpena, M.; Gullón, P.; Fraga-Corral, M.; Domingues, V.F.; Fátima
Barroso, M.; Simal-Gandara, J.; et al. Antibacterial Use of Macroalgae Compounds against Foodborne Pathogens. Antibiotics 2020,
9, 712. [CrossRef]
25. Kizhakkekalam, V.K.; Chakraborty, K. Marine Macroalgae-Associated Heterotrophic Firmicutes and Gamma-Proteobacteria:
Prospective Anti-Infective Agents against Multidrug Resistant Pathogens. Arch. Microbiol. 2020, 202, 905–920. [CrossRef]
26. Arguelles, E.D.L.R.; Monsalud, R.G.; Sapin, A.B. Chemical Composition and in Vitro Antioxidant and Antibacterial Activities of
Sargassum Vulgare c. Agardh from Lobo, Batangas, Philippines. J. Int. Soc. Southeast Asian Agric. Sci. 2019, 25, 112–122.
27. Salvador, N.; Gómez Garreta, A.; Lavelli, L.; Ribera, M.A. Antimicrobial Activity of Iberian Macroalgae. Sci. Mar. 2007, 71,
101–113. [CrossRef]
28. Maschek, J.A.; Baker, B.J. The Chemistry of Algal Secondary Metabolism. In Algal Chemical Ecology; Springer: Berlin/Heidelberg,
Germany, 2008; pp. 1–20. ISBN 9783540741800.
29. Ayyad, S.-E.N.; Al-Footy, K.O.; Alarif, W.M.; Sobahi, T.R.; Bassaif, S.A.; Makki, M.S.; Asiri, A.M.; Al Halawani, A.Y.; Bandria, A.F.;
Bandria, F.A.A. Bioactive C15 Acetogenins from the Red Alga Laurencia obtusa. Chem. Pharm. Bull. 2011, 59, 1294–1298. [CrossRef]
[PubMed]
30. OECD, (Organisation for Economic Co-operation and Development). Stemming the Superbug Tide: Just A Few Dollars More. In
OECD Health Policy Studies; OECD Publishing: Paris, France, 2018; pp. 1–12. ISBN 9789264307582.
31. Thompson, T. The Staggering Death Toll of Drug-Resistant Bacteria. Nature, 2022; Epub ahead print. [CrossRef]
32. Davies, J.; Davies, D. Origins and Evolution of Antibiotic Resistance. Microbiol. Mol. Biol. Rev. 2010, 74, 417–433. [CrossRef]
[PubMed]
33. Holmes, A.H.; Moore, L.S.P.; Steinbakk, M.; Regmi, S.; Karkey, A.; Guerin, P.J.; Piddock, L.J. V Understanding the Mechanisms
and Drivers of Antimicrobial Resistance. Lancet Infect. Dis. 2016, 387, 176–187. [CrossRef]
34. Ventola, C.L. The Antibiotic Resistance Crisis Part 1: Causes and Threats. Pharm. Ther. 2015, 40, 277–283.
35. Read, A.F.; Woods, R.J. Antibiotic Resistance Management. Evol. Med. Public Heal. 2020, 1, 147. [CrossRef]
36. Lushniak, B.D. Antibiotic Resistance: A Public Health Crisis. Surg. Gen. Perspect. 2014, 129, 314–316. [CrossRef]
Mar. Drugs 2023, 21, 163 31 of 35

37. World Health Orgnization Antimicrobial Resistance: Global Report on Surveillance. 2014. Available online: [Link]
int/iris/handle/10665/112642 (accessed on 8 February 2023).
38. Okeke, I.N.; Lamikanra, A.; Edelman, R. Socioeconomic and Behavioral Factors Leading to Acquired Bacterial Resistance to
Antibiotics in Developing Countries. Emerg. Infect. Dis. 1999, 5, 18–27. [CrossRef]
39. Chokshi, A.; Sifri, Z.; Cennimo, D.; Horng, H. Global Contributors to Antibiotic Resistance. J. Glob. Infect. Dis. 2019, 11, 36–42.
[CrossRef]
40. Malmir, S.; Bahreinian, M.; Zahiri Yeganeh, S.; Mirnejad, R.; Moosazadeh Moghaddam, M.; Saberi, F. Molecular Mechanisms of
Resistance to Conventional Antibiotics in Bacteria. Int. J. Med. Rev. 2018, 5, 118–129. [CrossRef]
41. Kapoor, G.; Saigal, S.; Elongavan, A. Action and Resistance Mechanisms of Antibiotics: A Guide for Clinicians. J. Anaesthesiol.
Clin. Pharmacol. 2017, 33, 300–305. [CrossRef]
42. Lambert, T. Antibiotics That Affect the Ribosome. OIE Rev. Sci. Technol. 2012, 31, 57–64. [CrossRef] [PubMed]
43. Sales, A.J.; Shadbad, N.N.; Kaleybar, V.P. The Investigation of the Antibacterial Effects of Ethanol Extract of Cichorium The
Investigation of the Antibacterial Effects of Ethanol Extract of Cichorium intybus L. on Antibiotic-Resistant Staphylococcus aureus
Strains. Bull. Environ. Pharmacol. Life Sci. 2018, 4, 161–164.
44. Cowan, M.M. Plant Products as Antimicrobial Agents. Clin. Microbiol. Rev. 1999, 12, 564–582. [CrossRef] [PubMed]
45. Porras, G.; Chassagne, F.; Lyles, J.T.; Marquez, L.; Dettweiler, M.; Salam, A.M.; Samarakoon, T.; Shabih, S.; Farrokhi, D.R.;
Quave, C.L. Ethnobotany and the Role of Plant Natural Products in Antibiotic Drug Discovery. Chem. Rev. 2021, 121, 3495–3560.
[CrossRef]
46. Anand, U.; Jacobo-Herrera, N.; Altemimi, A.; Lakhssassi, N. A Comprehensive Review on Medicinal Plants as Antimicrobial
Therapeutics: Potential Avenues of Biocompatible Drug Discovery. Metabolites 2019, 9, 258. [CrossRef]
47. Bereksi, M.S.; Hassaïne, H.; Bekhechi, C.; Abdelouahid, D.E. Evaluation of Antibacterial Activity of Some Medicinal Plants
Extracts Commonly Used in Algerian Traditional Medicine against Some Pathogenic Bacteria. Pharmacogn. J. 2018, 10, 507–512.
[CrossRef]
48. Zaynab, M.; Fatima, M.; Sharif, Y.; Zafar, M.H.; Ali, H.; Ali, K. Microbial Pathogenesis Role of Primary Metabolites in Plant
Defense against Pathogens. Microb. Pathog. 2019, 137, 103728. [CrossRef]
49. Gonelimali, F.D.; Lin, J.; Miao, W.; Xuan, J.; Charles, F.; Chen, M.; Hatab, S.R. Antimicrobial Properties and Mechanism of Action
of Some Plant Extracts Against Food Pathogens and Spoilage Microorganisms. Front. Microbiol. 2018, 9, 1639. [CrossRef]
50. Burt, S. Essential Oils: Their Antibacterial Properties and Potential Applications in Foods—A Review. Int. J. Food Microbiol. 2004,
94, 223–253. [CrossRef] [PubMed]
51. Saxena, S. Glycyrrhiza Glabra: Medicine over the Millennium. Nat. Prod. Radiance 2005, 4, 358–367.
52. Ikeda, K.; Murashima, N.; Chayama, K.; Tsubota, A.; Koida, I.; Suzuki, Y.; Kobayashi, M.; Kumada, H. The Long Term Efficacy of
Glycyrrhizin in Chronic Hepatitis C Patients. Am. Cancer Soc. 1997, 79, 1494–1500.
53. Baba, M.; Shigeta, S. Antiviral Activity of Glycyrrhizin against Varicella-Zoster Virus in Vitro. Antiviral Res. 1987, 7, 99–107.
[CrossRef]
54. Thirugnanam, S.; Xu, L.; Ramaswamy, K.; Gnanasekar, M. Glycyrrhizin Induces Apoptosis in Prostate Cancer Cell Lines DU-145
and LNCaP. Oncol. Rep. 2008, 20, 1387–1392. [CrossRef]
55. Lin, D.; Zhong, W.; Li, J.; Zhang, B.; Song, G.; Hu, T.; Lin, D.; Zhong, W.; Li, J.; Zhang, B. Involvement of BID Translocation
in Glycyrrhetinic Acid and 11-Deoxy Glycyrrhetinic Acid-Induced Attenuation of Gastric Cancer Growth Involvement of BID
Translocation in Glycyrrhetinic Acid and 11-Deoxy Glycyrrhetinic Acid-Induced Attenuation of Gastric C. Nutr. Cancer 2014, 66,
463–473. [CrossRef]
56. Gupta, V.K.; Fatima, A.; Faridi, U.; Negi, A.S.; Shanker, K.; Kumar, J.K.; Rahuja, N.; Luqman, S.; Sisodia, B.S.; Saikia, D.; et al.
Antimicrobial Potential of Glycyrrhiza glabra Roots. J. Ethnopharmacol. 2008, 116, 377–380. [CrossRef] [PubMed]
57. Jafari-sales, A.; Bolouri, P. Evaluation of the Antimicrobial Effects of Glycyrrhiza glabra L. on Some Gram Positive and Gram
Negative Pathogenic Bacteria in Laboratory. Jorjani Biomed. J. 2018, 6, 78–84. [CrossRef]
58. Hemeg, H.A.; Moussa, I.M.; Ibrahim, S.; Dawoud, T.M.; Alhaji, J.H.; Mubarak, A.S.; Kabli, S.A.; Alsubki, R.A.; Tawfik, A.M.;
Marouf, S.A. Saudi Journal of Biological Sciences Antimicrobial Effect of Different Herbal Plant Extracts against Different
Microbial Population. Saudi J. Biol. Sci. 2020, 27, 3221–3227. [CrossRef] [PubMed]
59. Petropoulos, S.A.; Fernandes, Â.; Tzortzakis, N.; Sokovic, M.; Ciric, A.; Barros, L.; Ferreira, I.C.F.R. Bioactive Compounds Content
and Antimicrobial Activities of Wild Edible Asteraceae Species of the Mediterranean Flora under Commercial Cultivation
Conditions. Food Res. Int. 2019, 119, 859–868. [CrossRef]
60. Junsathian, P.; Nakamura, S.; Katayama, S.; Rawdkuen, S. Antioxidant and Antimicrobial Activities of Thai Edible Plant Extracts
Prepared Using Different Extraction Techniques. Molecules 2022, 27, 6489. [CrossRef]
61. Zazharskyi, V.V.; Davydenko, P.; Kulishenko, O.; Borovik, I.V.; Brygadyrenko, V.V. Antimicrobial Activity of 50 Plant Extracts.
Biosyst. Divers. 2019, 27, 163–169. [CrossRef]
62. Kumar, S.; Kishore, Y.; Padhi, L.; Luyten, W. Antimicrobial Activity of Select Edible Plants from Odisha, India against Food-Borne
Pathogens. LWT Food Sci. Technol. 2019, 113, 108246. [CrossRef]
63. Hochma, E.; Yarmolinsky, L.; Khalfin, B.; Nisnevitch, M.; Ben-shabat, S.; Nakonechny, F. Antimicrobial Effect of Phytochemicals
from Edible Plants. Processes 2021, 9, 2089. [CrossRef]
Mar. Drugs 2023, 21, 163 32 of 35

64. Chibane, L.B.; Degraeve, P.; Ferhout, H.; Bouajila, J.; Oulahal, N. Plant Antimicrobial Polyphenols as Potential Natural Food
Preservatives. J. Sci. Food Agric. 2018, 99, 1457–1474. [CrossRef]
65. Rosaline, X.D.; Sakthivelkumar, S.; Rajendran, K.; Janarthanan, S. Screening of Selected Marine Algae from the Coastal Tamil
Nadu, South India for Antibacterial Activity. Asian Pac. J. Trop. Biomed. 2012, 2, S140–S146. [CrossRef]
66. Vallinayagam, K.; Arumugam, R.; Kannan, R.R.R.; Thirumaran, G.; Anantharaman, P. Antibacterial Activity of Seaweeds of
Pudumadam Coast Antibacterial Activity of Some Selected Seaweeds from Pudumadam Coastal Regions. Glob. J. Pharmacol.
2016, 3, 50–52.
67. Arulkumar, A.; Rosemary, T.; Paramasivam, S. Phytochemical Composition, In Vitro Antioxidant, Antibacterial Potential and
GC-MS Analysis of Red Seaweeds (Gracilaria corticata and Gracilaria edulis) from Palk Bay, India. Biocatal. Agric. Biotechnol. 2018,
15, 63–71. [CrossRef]
68. Ivanovic, J.; Dimitrijevic-brankovic, S.; Misic, D.; Ristic, M.; Zizovic, I. Evaluation and Improvement of Antioxidant and
Antibacterial Activities of Supercritical Extracts from Clove Buds. J. Funct. Foods 2012, 5, 416–423. [CrossRef]
69. Devi, K.P.; Nisha, S.A.; Sakthivel, R.; Pandian, S.K. Eugenol (an Essential Oil of Clove) Acts as an Antibacterial Agent against
Salmonella typhi by Disrupting the Cellular Membrane. J. Ethnopharmacol. 2010, 130, 107–115. [CrossRef]
70. Cardoso, I.; Cotas, J.; Rodrigues, A.; Ferreira, D.; Osório, N.; Pereira, L. Extraction and Analysis of Compounds with Antibacterial
Potential from the Red Alga Grateloupia turuturu. J. Mar. Sci. Eng. 2019, 7, 220. [CrossRef]
71. Mahendran, S.; Maheswari, P.; Sasikala, V.; Rubika, J.J.; Pandiarajan, J. In Vitro Antioxidant Study of Polyphenol from Red
Seaweeds Dichotomously Branched Gracilaria edulis and Robust Sea Moss Hypnea valentiae. Toxicol. Rep. 2021, 8, 1404–1411.
[CrossRef] [PubMed]
72. Freitas, M.V.; Inácio, L.G.; Ruas, A.; Silva, I.A.; Mouga, T.; Pereira, L.; Afonso, C. Antioxidant and Antimicrobial Properties of
Selected Red Seaweeds from Central Portugal. Appl. Sci. 2022, 13, 157. [CrossRef]
73. Bhuyar, P.; Rahim, M.H.; Sundararaju, S.; Maniam, G.P.; Govindan, N. Antioxidant and Antibacterial Activity of Red Seaweed:
Kappaphycus alvarezii against Pathogenic Bacteria. Glob. J. Environ. Sci. Manag. 2020, 6, 47–58.
74. García, V.; Uribe, E.; Vega-Gálvez, A.; Delporte, C.; Valenzuela-Barra, G.; López, J.; Pastén, A. Health-Promoting Activities of
Edible Seaweed Extracts from Chilean Coasts: Assessment of Antioxidant, Anti-Diabetic, Anti-Inflammatory and Antimicrobial
Potential. Rev. Chil. Nutr. 2020, 47, 792–800. [CrossRef]
75. Saim, S.; Sahnouni, F.; Bouhadi, D.; Kharbouche, S. The Antimicrobial Activity of Two Marine Red Algae Collected from Algerian
West Coast. Trends Pharmacol. Sci. 2021, 7, 233–242. [CrossRef]
76. Miranda, J.M.; Trigo, M.; Barros-Velázquez, J.; Aubourg, S.P. Antimicrobial Activity of Red Alga Flour (Gelidium sp.) and Its Effect
on Quality Retention of Scomber scombrus during Refrigerated Storage. Foods 2022, 11, 904. [CrossRef] [PubMed]
77. dos Santos Oliviera, A.; Veiga-santos, P.; Prado, B.; Filho, D.; Sudatti, D.B.; Pereira, R.C.; Nakamura, C.V.; De Londrina, U.E.;
Celso, R.; Cid, G.; et al. Effect of Elatol, Isolated from Red Seaweed Laurencia dendroidea, on Leishmania amazonensis. Mar. Drugs
2010, 8, 2733–2743. [CrossRef]
78. Yap, W.-F.; Tay, V.; Tan, S.-H.; Yow, Y.-Y.; Chew, J. Decoding Antioxidant and Antibacterial Potentials of Malaysian Green Seaweeds:
Caulerpa racemosa and Caulerpa lentillifera. Antibiotics 2019, 8, 152. [CrossRef]
79. Aftabuddin, S.; Akter, S.; Hossen, S.; Rahman, M.A. Antioxidant, Antibacterial and Cytotoxic Activity of Caulerpa racemosa
(Forsskål) J. Agardh and Ulva (Enteromorpha) intestinalis L. Bangladesh J. Sci. Ind. Res. 2020, 55, 237–244.
80. Nagappan, T.; Vairappan, C.S. Nutritional and Bioactive Properties of Three Edible Species of Green Algae, Genus Caulerpa
(Caulerpaceae). J. Appl. Phycol. 2014, 26, 1019–1027. [CrossRef]
81. Ravikumar, S.; Anburajan, L.; Ramanathan, G.; Kaliaperumal, N. Screening of Seaweed Extracts against Antibiotic Resistant Post
Operative Infectious Pathogens. Seaweed Res. Util. 2002, 24, 95–99.
82. Agbaje-Daniels, F.; Adeleye, A.; Nwankwo, D.; Adeniyi, B.; Seku, F.; Beukes, D. Antibacterial Activities of Selected Green
Seaweeds from West African Coast. EC Pharmacol. Toxicol. 2020, 4, 84–92.
83. Al-Zahrani, A.; Al-Haj, N.; Omer, H.; Al-Judaibi, A. Impact of Extracts of Marine Macroalgae on Multidrug-Resistant Bacteria. J.
Microbiol. Res. 2014, 4, 18–24. [CrossRef]
84. Srikong, W.; Bovornreungroj, N.; Mittraparparthorn, P.; Bovornreungroj, P. Antibacterial and Antioxidant Activities of Differential
Solvent Extractions from the Green Seaweed Ulva intestinalis. ScienceAsia 2017, 43, 88–95. [CrossRef]
85. Swathi, N.; Kumar, A.G.; Parthasarathy, V.; Sankarganesh, P. Isolation of Enteromorpha Species and Analyzing Its Crude Extract
for the Determination of in Vitro Antioxidant and Antibacterial Activities. Biomass Convers. Biorefinery 2022, 3, 1–10. [CrossRef]
86. Priya, N.; Kokila, M.; Janani, J. Comparative Phytochemical Studies and Antibacterial Activity of Green and Brown Seaweeds
Extract of Enteromorpha compressa and Padina pavonica. Int. J. Res. Eng. Sci. Manag. 2021, 4, 136–139.
87. Cadar, E.; Negreanu-Pirjol, T.; Negreanu-Pirjo, B.-S. Antioxidant and Antibacterial Potential of Ulva lactuca Species from Romanian
Black Sea Coast. Eur. J. Nat. Sci. Med. 2022, 8705, 26–38. [CrossRef]
88. Arguelles, E.D.L.R. Evaluation of Nutritional Composition and In Vitro Antioxidant and Antibacterial Activities of Codium
intricatum Okamura from Ilocos Norte (Philippines). Jordan J. Biol. Sci. 2020, 13, 375–382.
89. Koz, F.F.Y.; Yavasoglu, N.U.; Demirel, Z.; Sukatar, A.; Ozdemir, G. Antimicrobial Activities of Some Macroalgal Essential Oil
and Extracts from Antioxidant and Antimicrobial Activities of Codium fragile (Suringar) Hariot (Chlorophyta) Essential Oil and
Extracts. Asian J. Chem. 2009, 21, 1197–1209.
Mar. Drugs 2023, 21, 163 33 of 35

90. Ibtissam, C.; Hassane, R.; Jose, M.; Francisco, D.S.; Antonio, G.V.; Hassan, B.; Mohamed, K. Screening of Antibacterial Activity in
Marine Green and Brown Macroalgae from the Coast of Morocco. Afr. J. Biotechnol. 2009, 8, 1258–1262. [CrossRef]
91. Kaeffer, B.; Benard, C.; Lahaye, M.; Herve, M.B.; Cherbut, C. Biological Properties of Ulvan, a New Source of Green Seaweed
Sulfated Polysaccharides, on Cultured Normal and Cancerous Colonic Epithelial Cells. Planta Med. 1999, 65, 527–531. [CrossRef]
92. Mao, W.; Zang, X.; Li, Y.; Zhang, H. Sulfated Polysaccharides from Marine Green Algae Ulva conglobata and Their Anticoagulant
Activity. J. Appl. Phycol. 2006, 18, 9–14. [CrossRef]
93. Jiao, G.; Yu, G.; Zhang, J.; Ewart, H. Chemical Structures and Bioactivities of Sulfated Polysaccharides from Marine Algae. Mar.
Drugs 2011, 9, 196–223. [CrossRef]
94. Alves, A.; Sousa, R.A.; Reis, R.L. In Vitro Cytotoxicity Assessment of Ulvan, a Polysaccharide Extracted from Green Algae.
Phyther. Res. 2013, 27, 1143–1148. [CrossRef]
95. Quemener, B.; Lahaye, M.; Bobin-Dubigeon, C. Sugar Determination in Ulvans by a Chemical-Enzymatic Method Coupled to
High Performance Anion Exchange Chromatography. J. Appl. Phycol. 1997, 9, 179–188. [CrossRef]
96. Alves, A.; Sousa, R.A.; Reis, R.L. A Practical Perspective on Ulvan Extracted from Green Algae. J. Appl. Phycol. 2013, 25, 407–424.
[CrossRef]
97. Ray, B.; Lahaye, M. Cell-Wall Polysaccharides from the Marine Green Alga Ulva “rigida” (Ulvales, Chlorophyta). Extraction and
Chemical Composition. Carbohydr. Res. 1995, 274, 251–261. [CrossRef]
98. Lahaye, M.; Inizan, F.; Vigouroux, J. Carbohydrate Polymers NMR Analysis of the Chemical Structure of Ulvan and of Ulvan-Boron
Complex Formation. Carbohydr. Polym. 1998, 36, 239–249. [CrossRef]
99. Yaich, H.; Garna, H.; Besbes, S.; Paquot, M.; Blecker, C.; Attia, H. Food Hydrocolloids Effect of Extraction Conditions on the Yield
and Purity of Ulvan Extracted from Ulva lactuca. Food Hydrocoll. 2020, 31, 375–382. [CrossRef]
100. Thanh, T.T.T.; Quach, T.M.T.; Nguyen, T.N.; Vu Luong, D.; Bui, M.L.; Tran, T.T. Van Structure and Cytotoxic Activity of Ulvan
Extracted from Green Seaweed Ulva lactuca. Int. J. Biol. Macromol. 2016, 93, 695–702. [CrossRef] [PubMed]
101. Van Tran, T.T.; Truong, H.B.; Ha, N.; Tran, V.; Thu, T.M. Structure, Conformation in Aqueous Solution and Antimicrobial Activity
of Ulvan Extracted from Green Seaweed Ulva reticulata. Nat. Prod. Res. 2018, 32, 2291–2296. [CrossRef] [PubMed]
102. Ibrahim, M.I.A.; Amer, M.S.; Ibrahim, H.A.H.; Zaghloul, E.H. Considerable Production of Ulvan from Ulva lactuca with Special
Emphasis on Its Antimicrobial and Anti-Fouling. Appl. Biochem. Biotechnol. 2022, 194, 3097–3118. [CrossRef]
103. García-Poza, S.; Leandro, A.; Cotas, C.; Cotas, J.; Marques, J.C.; Pereira, L.; Gonçalves, A.M.M. The Evolution Road of Seaweed
Aquaculture: Cultivation Technologies and the Industry 4.0. Int. J. Environ. Res. Public Health 2020, 17, 6528. [CrossRef]
104. Kraan, S. Seaweed Resources, Collection, and Cultivation with Respect to Sustainability; Elsevier Inc.: Amsterdam, The Netherlands,
2020; ISBN 9780128179437.
105. Hayashi, L.; Cantarino, S.D.J.; Critchley, A.T. Challenges to the Future Domestication of Seaweeds as Cultivated Species: Understanding
Their Physiological Processes for Large-Scale Production; Elsevier Ltd.: Amsterdam, The Netherlands, 2020; Volume 95, ISBN
9780081027103.
106. Freile-Pelegŕn, Y.; Morales, J.L. Antibacterial Activity in Marine Algae from the Coast of Yucatan, Mexico. Bot. Mar. 2004, 47,
140–146. [CrossRef]
107. Trigui, M.; Gasmi, L.; Zouari, I.; Tounsi, S. Seasonal Variation in Phenolic Composition, Antibacterial and Antioxidant Activities
of Ulva rigida (Chlorophyta) and Assessment of Antiacetylcholinesterase Potential. J. Appl. Phycol. 2013, 25, 319–328. [CrossRef]
108. Kandhasamy, M.; Arunachalam, K.D. Evaluation of in Vitro Antibacterial Property of Seaweeds of Southeast Coast of India. Afr. J.
Biotechnol. 2008, 7, 1958–1961.
109. Garcia-Vaquero, M.; Hayes, M. Red and Green Macroalgae for Fish and Animal Feed and Human Functional Food Development.
Food Rev. Int. 2016, 32, 15–45. [CrossRef]
110. Holdt, S.L.; Kraan, S. Bioactive Compounds in Seaweed: Functional Food Applications and Legislation. J. Appl. Phycol. 2011, 23,
543–597. [CrossRef]
111. Pereira, R.C.; Costa, E.d.S.; Sudatti, D.B.; da Gama, B.A.P. Inducible Defenses against Herbivory and Fouling in Seaweeds. J. Sea
Res. 2017, 122, 25–33. [CrossRef]
112. Besednova, N.N.; Andryukov, B.G.; Zaporozhets, T.S.; Kryzhanovsky, S.P.; Kuznetsova, T.A.; Fedyanina, L.N.; Makarenkova, I.D.;
Zvyagintseva, T.N. Algae Polyphenolic Compounds and Modern Antibacterial Strategies: Current Achievements and Immediate
Prospects. Biomedicines 2020, 8, 342. [CrossRef]
113. Cherian, C.; Jannet Vennila, J.; Sharan, L. Marine Bromophenols as an Effective Inhibitor of Virulent Proteins (Peptidyl Arginine
Deiminase, Gingipain R and Hemagglutinin A) in Porphyromas Gingivalis. Arch. Oral Biol. 2019, 100, 119–128. [CrossRef]
[PubMed]
114. Lopes, G.; Pinto, E.; Andrade, P.B.; Valentão, P. Antifungal Activity of Phlorotannins against Dermatophytes and Yeasts:
Approaches to the Mechanism of Action and Influence on Candida albicans Virulence Factor. PLoS ONE 2013, 8, e72203. [CrossRef]
[PubMed]
115. Silva, A.; Silva, S.A.; Carpena, M.; Garcia-Oliveira, P.; Gullón, P.; Barroso, M.F.; Prieto, M.A.; Simal-Gandara, J. Macroalgae as a
Source of Valuable Antimicrobial Compounds: Extraction and Applications. Antibiotics 2020, 9, 642. [CrossRef] [PubMed]
Mar. Drugs 2023, 21, 163 34 of 35

116. Hierholtzer, A.; Chatellard, L.; Kierans, M.; Akunna, J.C.; Collier, P.J. The Impact and Mode of Action of Phenolic Compounds
Extracted from Brown Seaweed on Mixed Anaerobic Microbial Cultures. J. Appl. Microbiol. 2012, 114, 964–973. [CrossRef]
117. Bhowmick, S.; Mazumdar, A.; Moulick, A.; Adam, V. Algal Metabolites: An Inevitable Substitute for Antibiotics. Biotechnol. Adv.
2020, 43, 107571. [CrossRef]
118. Wang, Y.; Xu, Z.; Bach, S.J.; McAllister, T.A. Sensitivity of Escherichia Coli to Seaweed (Ascophyllum nodosum) Phlorotannins and
Terrestrial Tannins. Asian-Australasian J. Anim. Sci. 2009, 22, 238–245. [CrossRef]
119. Wei, Y.; Liu, Q.; Xu, C.; Yu, J.; Zhao, L.; Guo, Q. Damage to the Membrane Permeability and Cell Death of Vibrio parahaemolyticus
Caused by Phlorotannins with Low Molecular Weight from Sargassum thunbergii. J. Aquat. Food Prod. Technol. 2016, 25, 323–333.
[CrossRef]
120. Bogolitsyn, K.; Dobrodeeva, L.; Druzhinina, A.; Ovchinnikov, D.; Parshina, A.; Shulgina, E. Biological Activity of a Polyphenolic
Complex of Arctic Brown Algae. J. Appl. Phycol. 2019, 31, 3341–3348. [CrossRef]
121. Cabral, E.M.; Oliveira, M.; Mondala, J.R.M.; Curtin, J.; Tiwari, B.K.; Garcia-Vaquero, M. Antimicrobials from Seaweeds for Food
Applications. Mar. Drugs 2021, 19, 211. [CrossRef] [PubMed]
122. Singh, R.S.; Walia, A.K. Lectins from Red Algae and Their Biomedical Potential. J. Appl. Phycol. 2018, 30, 1833–1858. [CrossRef]
123. Yoon, B.K.; Jackman, J.A.; Valle-González, E.R.; Cho, N.J. Antibacterial Free Fatty Acids and Monoglycerides: Biological Activities,
Experimental Testing, and Therapeutic Applications. Int. J. Mol. Sci. 2018, 19, 1114. [CrossRef]
124. Ahmed, G.; Shoubaky, E. Active Ingredients Fatty Acids as Antibacterial Agent from the Brown Algae Padina pavonica and
Hormophysa triquetra. J. Coast. Life Med. 2014, 2, 535–542. [CrossRef]
125. Da Costa, E.; Melo, T.; Moreira, A.S.P.; Bernardo, C.; Helguero, L.; Ferreira, I.; Cruz, M.T.; Rego, A.M.; Domingues, P.; Calado, R.;
et al. Valorization of Lipids from Gracilaria sp. through Lipidomics and Decoding of Antiproliferative and Anti-Inflammatory
Activity. Mar. Drugs 2017, 15, 62. [CrossRef] [PubMed]
126. Stabili, L.; Acquaviva, M.I.; Biandolino, F.; Cavallo, R.A.; De Pascali, S.A.; Fanizzi, F.P.; Narracci, M.; Cecere, E.; Petrocelli, A.
Biotechnological Potential of the Seaweed Cladophora rupestris (Chlorophyta, Cladophorales) Lipidic Extract. N. Biotechnol. 2014,
31, 436–444. [CrossRef]
127. Patra, J.K.; Kim, S.H.; Baek, K.H. Antioxidant and Free Radical-Scavenging Potential of Essential Oil from Enteromorpha linza L.
Prepared by Microwave-Assisted Hydrodistillation. J. Food Biochem. 2015, 39, 80–90. [CrossRef]
128. Patra, J.K.; Das, G.; Baek, K.H. Chemical Composition and Antioxidant and Antibacterial Activities of an Essential Oil Extracted
from an Edible Seaweed, Laminaria japonica L. Molecules 2015, 20, 12093–12113. [CrossRef] [PubMed]
129. Patra, J.K.; Lee, S.W.; Park, J.G.; Baek, K.H. Antioxidant and Antibacterial Properties of Essential Oil Extracted from an Edible
Seaweed Undaria pinnatifida. J. Food Biochem. 2017, 41, e12278. [CrossRef]
130. Tiwari, B.K.; Valdramidis, V.P.; O’Donnell, C.P.; Muthukumarappan, K.; Bourke, P.; Cullen, P.J. Application of Natural Antimicro-
bials for Food Preservation. J. Agric. Food Chem. 2009, 57, 5987–6000. [CrossRef] [PubMed]
131. Zhao, Y.; Zheng, Y.; Wang, J.; Ma, S.; Yu, Y.; White, W.L.; Yang, S.; Yang, F.; Lu, J. Fucoidan Extracted from Undaria pinnatifida:
Source for Nutraceuticals/Functional Foods. Mar. Drugs 2018, 16, 321. [CrossRef]
132. He, F.; Yang, Y.; Yang, G.; Yu, L. Studies on Antibacterial Activity and Antibacterial Mechanism of a Novel Polysaccharide from
Streptomyces virginia H03. Food Control 2010, 21, 1257–1262. [CrossRef]
133. Kavita, K.; Singh, V.K.; Jha, B. 24-Branched ∆5 Sterols from Laurencia papillosa Red Seaweed with Antibacterial Activity against
Human Pathogenic Bacteria. Microbiol. Res. 2014, 169, 301–306. [CrossRef]
134. Ikekawa, N.; Morisaki, N.; Tsuda, K.; Yoshida, T. Sterol Compositions in Some Green Algae and Brown Algae. Steroids 1968, 12,
41–48. [CrossRef]
135. Prakash, S.; Sasikala, S.L.; Aldous, V.H.J. Isolation and Identification of MDR-Mycobacterium tuberculosis and Screening of Partially
Characterised Antimycobacterial Compounds from Chosen Marine Micro Algae. Asian Pac. J. Trop. Med. 2010, 3, 655–661.
[CrossRef]
136. Wächter, G.A.; Franzblau, S.G.; Montenegro, G.; Hoffmann, J.J.; Maiese, W.M.; Timmermann, B.N. Inhibition of Mycobacterium
tuberculosis Growth by Saringosterol from Lessonia nigrescens. J. Nat. Prod. 2001, 64, 1463–1464. [CrossRef]
137. Kawakami, L.M.; Yoon, B.K.; Jackman, J.A.; Knoll, W.; Weiss, P.S.; Cho, N.J. Understanding How Sterols Regulate Membrane
Remodeling in Supported Lipid Bilayers. Langmuir 2017, 33, 14756–14765. [CrossRef]
138. Eng, R.H.K.; Padberg, F.T.; Smith, S.M.; Tan, E.N.; Cherubin, C.E. Bactericidal Effects of Antibiotics on Slowly Growing and
Nongrowing Bacteria. Antimicrob. Agents Chemother. 1991, 35, 1824–1828. [CrossRef] [PubMed]
139. Kanauchi, O.; Mitsuyama, K.; Araki, Y.; Andoh, A. Modification of Intestinal Flora in the Treatment of Inflammatory Bowel
Disease. Curr. Pharm. Des. 2003, 9, 333–346. [CrossRef] [PubMed]
140. Takesue, Y.; Yokoyama, T.; Akagi, S.; Ohge, H.; Imamura, Y.; Murakami, Y.; Seuda, T. Changes in the Intestinal Flora After the
Administration of Prophylactic Antibiotics to Patients Undergoing a Gastrectomy. Surg. Today 2002, 35, 581–586. [CrossRef]
141. Basappa, K.; Gopal, J.V. Natural Alternatives to Antibiotic Agents. Asian J. Biomed. Pharm. Sci. 2013, 25, 1–4.
142. Setty, A.R.; Sigal, L.H. Herbal Medications Commonly Used in the Practice of Rheumatology: Mechanisms of Action, Efficacy,
and Side Effects. Semin. Arthritis Rheum. 2005, 34, 773–784. [CrossRef] [PubMed]
Mar. Drugs 2023, 21, 163 35 of 35

143. Niggemann, B.; Gruber, C. Side-Effects of Complementary and Alternative Medicine. Allergy 2003, 58, 707–716. [CrossRef]
144. Tattelman, E. Health Effects of Garlic. Complement. Altern. Med. 2005, 72, 103–106.

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual
author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to
people or property resulting from any ideas, methods, instructions or products referred to in the content.