Anthelmintic activity in various plants:

A Comprehensive review of
Traditional knowledge and Scientific evidence

ASSIGNMENT
SUBMITED
BY:
NAME: PRAMOD CHOUDHARY
CLASS: [Link]
SEMESTER: 1
YEAR: 2024-25
GUIDED BY: Dr. K.S.
SHAIKH
(H.O.D. Quality Assurance Techniques)
DEPARTMENT OF QUALITY ASSURANCE TECHNIQUES

1
 TABLE OF CONTENTS

Sr. Contents Pg. no.

No.
1. Introduction 3
2. Classes of synthetic anthelmintic 4
drugs
3. Methods for studying 6
anthelmintic activity
4. Plants studied for anthelmintic 7
activity
5. Method of extraction of 15
phytochemicals
6. Marketed preparations of herbal 17
anthelmintic agents
7. Plant Extracts Loaded in 18
Nanostructured Drug Delivery
Systems for Treating Parasitic
infections
8. Advantages 21
9. Limitations 21
10. Conclusion 22
11. References 22

2
ABSTRACT
Anthelmintic drugs are used to treat helminthiasis, a condition brought on by parasitic
worms known as helminths. These worms can infect both people and animals, resulting in a
variety of illnesses and health problems. In order to assess the effectiveness of various
medicinal plants as anthelmintics, researchers investigated alternatives to conventional
medicine and performed studies. In these investigations, several screening techniques and
strategies have been used to identify the potential anthelmintic activity of plant species.
These plants' extracts include bioactive substances that may disrupt the systems and
metabolism of the parasites, resulting in their anthelmintic activity. According to the
research so far, traditional medicinal herbs have the potential to produce entirely new,
powerful anthelmintic chemicals. In order to replace currently available synthetic
medications, which frequently have drawbacks and undesirable side effects, researchers are
actively exploring such herbal remedies.
Keywords: Anthelmintic, Herbal, Medicinal plants, Earthworms, Worm expulsion.
INTRODUCTION :
Natural remedies are available to treat all human ills and diseases that are related to them.
Compared to other animal species, humans tend to be more susceptible to disease.[1]The
socioeconomic conditions of Asian and African nations make it difficult for many peasants
and tribes living in far-flung regions and dense forests to pay or access modern medicine. In
some areas of a country like India, tribal people lack access to modern conveniences like
electricity, roads, and telecommunications, thus they must rely solely on their traditional
medical expertise to meet their daily needs.[2] Nowadays more people prefer to take charge
of their health through the use of herbal remedies for a number of reasons, including not
just to treat illnesses but also to avoid them. This is especially true for a variety of diseases
that can be treated at home.[3] A significant majority of the world's population is prone to
helminthic infections, which are among the most prevalent illnesses in humans. Plant based
remedies, especially in tropical developing nations like India, hold enormous potential as a
source of readily available, efficient anthelmintic drugs for people worldwide.[4]
Helminthiasis Disease
Any macroparasitic disease affecting both humans and other animals and characterized by
the presence of parasitic worms called helminths in a specific body region is referred to as
helminthiasis.[5] Today, helminth parasites make up the most prevalent infectious diseases,
affecting around one-third of the global population. and causing a wide range of painful
diseases and syndromes. Helminths are also common in cattle and result in significant losses
to agriculture. Helminths create long-lasting, chronic infections in both human and animal
hosts, along with considerable levels of host immune response downregulation. The goal of
eradicating helminth illnesses is still far off due to an absence of effective vaccines,
constrained pharmaceutical efficacy, evolving drug resistance, and rapid reintroduction in
situations where the spread cannot be stopped.[6]
Multicellular worms called helminths are classified into three taxonomic groups: cestode
tapeworms, nematode roundworms, and trematode flukes. [7] They frequently reside in the
gastrointestinal tracts of their hosts, but they can also enter other organs and result in
3
physiological harm there.[5]These parasites have remarkably varied life histories, including
direct faecal-oral transmission , growth via free-living stages, and reliance on invertebrate
vectors . Similar to parasites, helminths can enter the body by a number of different routes,
including contact with the skin (schistosomes and hookworms), bites from mosquitoes
(filarial worms), and, most commonly, the digestive tract.[7]
It may be wise to check for infection in other family members when one person is found to
be infected. Patients should be reminded to practice good personal cleanliness and to take
precautions while preparing food, but they should also be reassured that most helminths do
not typically spread easily within the home.[8]Clinical signs of helminthiasis include the
following four fundamental symptoms:
One may simply proactively avoid the disease if we are aware of the parasitic worms'
locations and the mode of transmission. Spread the word and educate people about the
importance of food culture. Clean your food well before eating it and drinking it. This is
especially important in residential regions where people have a practice of eating raw, rare,
and utilizing blood soup.[9] There is usually a rise in awareness but not always an alteration
in behaviour when individuals are educated about the illness and encouraged to take
preventive measures.[10]
Educational materials (posters, brochures, broadcasting, and video footage messages) are
among the traditional ways to spread health-related messages, but techniques used in the
private sector are currently being encouraged for their potential value in creating and
disseminating health-related messages.[11,12] Frequent medication therapy is the primary
method of infection control in regions with high rates of infection transmission, little
resources for disease prevention, and inadequate funding for sanitary facilities. Alternative
methods of administering drug treatment in society at large include: universal treatment,
which provides care to everyone in the community regardless of age, sex, infection status,
or other social characteristics; targeted treatment, which provides care to population groups
based on age, sex, or other social characteristics regardless of infection status; and
particular treatment, which administers care at each person's level.[13]
CLASSES OF SYNTHETIC ANTHELMINTIC DRUGS :
Anthelmintics are a diverse group of medications that are grouped into classes based on
similarities in their chemical structure and modes of action.
1. Benzimidazole
Thiabendazole is a broad-spectrum anthelmintic that was first identified in 1961. The
literature on benzimidazole compounds is broad and demonstrates a variety of biological
effects. The capacity of benzimidazoles to selectively bind with tubulin factor and
compromise the cytoskeleton accounts for their effectiveness as anthelmintics.[14] Through
this, the chemical basis of benzimidazole molecule resistance in parasitic nematodes has
been discovered. Haemonchus contortus, a worm, exhibited resistance to the benzimidazole
molecule, which is linked to the drug's presence of particular alleles of tubulin .[15]

4
 2. Ivermectin
It is an effective medication, and its discovery sparked the creation of ivermectin analogues
such as moxidectin, milbemycin oxime, doramectin, selamectin, abamectin, and
eprinomectin. Pharyngeal and body wall muscles are paralyzed by ivermectin.[16]
3. Emodepside
Cyclodepsipeptide molecule and semi-synthetic derivative emodepside. a substance
produced by fermenting Mycelia sterilia, a fungus. Recently, its anthelmintic properties and
discoveries were found.[17]
4. Piperazine
It is the most well-liked and frequently applied medication for the treatment of parasitic
illness. Piperazine was first used as an anthelmintic in the 1950s, and it is currently an active
ingredient in several over-the counter medications and treatments for paediatric thread
worm infections.[14]
5. Levamisole, Pyrantel and Morantel
These anti-helminthics are nicotinic receptor agonists that result in spastic muscular
paralysis and sustained activation of the excitatory nicotinic acetylcholine (nACh) receptors
on muscle.[18]
6. Paraherquamide

Penicillium paraherquei and Penicillium roqueforti, which produce the drugs

paraherquamide and marcfortine A, respectively, are both members of the oxindole alkaloid
family.[19] Parasitic nematodes undergo flaccid paralysis when exposed to paraherquamide
or its derivative, deoxyparaherquamide.[18]
7. Nitazoxanide

The pyruvate ferredoxin oxidoreductase inhibitor nitazoxanide is effective against a variety

of intestinal protozoa and helminths. Because putative targets for this substance include
anaerobic electron transport enzymes, its mode of action in nematodes has not been
determined.[20] Nitazoxanide stops population growth after seven days in culture by 33%.
Mebendazole and albendazole, in contrast, significantly slowed the growth (by over 90%).
As a result, as compared to other anthelmintic medications, this compound's effectiveness is
rather modest. [1]
Since there are currently no vaccinations in the market, controlling helminths must instead
rely on some effective medications, known as anthelmintics. However, because these drugs
are frequently misused, major drug resistance issues arise throughout the world,
necessitating the urgent need to isolate and find novel anthelmintic drugs.[21]
An ideal anthelmintic agent would be one that has a broad scope of action, provides a
significant number of cures with a single therapeutic dose, is not harmful to the host, and is
reasonably priced. None of the synthetic drugs on the market satisfies this criterion. There is

5
evidence that even the most widely used medications, can cause digestive issues, giddiness,
and nausea.[22] Tolerance of the infections to the current therapies and their expensive
price justifies the need to search for fresher anthelmintic compounds. Due to the fact that
many effective medications have their roots in traditional medical procedures, various
researchers have conducted studies to assess the purported anthelmintic efficiency of
folkloric medicinal plants.[4]
In order to find novel potential anthelmintic molecules and to determine their potential
mechanism(s) of action, researchers have evaluated the effectiveness of plant species
through a variety of screening procedures and approaches. These efforts have been
reviewed further.

Figure 1: Types of different helminths

Methods for Studying Anthelmintic Activity:
a) Most in vitro studies on the anthelmintic properties of plants, their oils, or their
extracts have been conducted based on their toxicities to earthworms. The majority
of compounds that are poisonous to earthworms cause an initial irritability or
agitation, which causes the worm to die. Anthelmintics possibly sometimes eject the
parasite due to this effect if their concentration does not increase enough to kill the
worm.
b) Hookworms, H. contortus, tapeworms, and/or A. lumbricoides have also been
utilized by certain researchers to assess the in vitro anthelmintic activity of various
plant materials..[23]
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 c) To assess the effectiveness of plant items against the eggs of Haemonchus contortus
or other trichostrongylids, a modified egg hatch assay is frequently utilized.
d) A modified version on the larval development assay (LDA) or larval motility assays,
which are frequently used to test a parasite's resistance to anthelmintics, have been
employed by some other researchers doing in vitro studies.[24]
e) In one of the anthelmintic activity investigation, worms from houseflies that mimic
parasitic pinworms found in humans were produced under laboratory settings,
revealing a novel technology. Using housefly worms and earthworms, researchers
examined the anthelmintic effects of several medications.[25]
f) The effectiveness of several plant materials as anthelmintics has additionally been
tested in vivo. The criteria for this kind of activities included the evacuation of worms
from their hosts or a decrease in the quantity of eggs per gram of faeces (EPG) that
the hosts with the infection passed when compared to animals that had been given
commercial anthelmintics. As an example, oral feeding of Indonesian papaya (Carica
papaya) decreased parasite burden up to 100% within seven days after treatment for
pigs who were infected with Ascaris suum. Similar to this, various other plant
extracts discovered with anthelmintic qualities were examined for their effectiveness
against gastrointestinal nematodes in experimentally infected sheep.[24]
Common phytochemicals found in plant containing potent anthelmintic activity
a) Alkaloids e.g. Palasonin
b) Isoflavones e.g. Genistein
c) Triterpenoids e.g. Ursolic acid
d) Polyphenols (Tannins and flavonoids), simple phenols (Phenolic acids)
e) Saponins
f) Organosulfides - Allicin, Isothiocyanates,
g) Thymoquinone
h) Cysteine proteinases.
Plants studied for anthelmintic activity:

Adhatoda vasica (Family- Acanthaceae)

Crude aqueous (CAE) as well as methanol extracts (CME) of A. vesica had an anthelmintic
impact on live Haemonchus contortus, as shown by the mortality of the test subjects,
according to in vitro tests. Sheep already infected with a variety of gastrointestinal
nematodes were given A. vesica roots as crude powder (CP), CAE, and CME for in vivo
experiments. Despite having anthelmintic efficacy against nematodes, it was discovered that
A. vesica roots did not compare to Levamisole.[26]
Aerva lanata Linn Juss (Family- Amaranthaceae)

According to the findings, both the methanolic and aqueous extract of Aerva lanata's aerial
parts exhibit anthelmintic activity when compared to the common medication. Each crude
extract demonstrated anthelmintic action in a dose-dependent manner at concentrations of
25, 50, and 100 mg/ml. Aerva lanata aerial parts extraction in methanol at a dosage of 100

7
mg/ml caused paralysis in 7.5 minutes and death in 11.16 minutes, whereas aqueous extract
against Pheritima postuma exhibited paralysis in 13.83 minutes and death in 18 minutes.
Piperazine citrate, the standard of reference, demonstrated identical results at 14.16 and
31.83 minutes, respectively. Given the paralysis's shortest duration (P) and death (D) with
100 mg/ml concentration. The reference medication, piperazine citrate, demonstrated the
same at 14.16 and 31.83 minutes, respectively. The traditional utilization of Aerva lanata's
aerial parts as an anthelmintic has been verified, since the extracts have demonstrated
action against Pheritima postuma.[27]
Annona squamosa (Family- Annonaceae)
A. squamosa has therapeutic qualities. Internal roots are used to treat spinal disorders. Bark
has a reputation for being a potent astringent. Fruits are regarded as good tonics in
Ayurveda; they enrich the blood, are employed as expectorants, promote muscular strength,
are cooling, lessen burning sensations and the tendency toward biliousness, are sedative to
the heart, and alleviate vomiting. According to the study's findings, Annona squamosa Linn
extracts of leaves had significantly higher anthelminthic activity than the standard the
standard.[28]
Artemisia Annua (family- Asteraceae)
A. annua produces monoterpenes and sesquiterpenes, including the well-known sesquiterpene
lactone artemisinin which is the main compound responsible for the anthelmintic activity of A.
annua. The mechanisms of action attributed to this metabolite include interference with parasite
transport proteins, disruption of parasite mitochondrial function, modulation of host immune
function and inhibition of angiogenesis [37]. Researches have shown that artemisinin drugs are
effective against Leishmania, Trypanosoma, Eimeria (coccidia), Fasciola, Trichostrongylus, Babesia,
Giardia and mainly Haemonchus [38]

Azadirachta indica (Family- Meliaceae)

In this work, neem (Azadirachta indica) extracts from the leaves were tested in the
laboratory with Fasciola spp. with albendazole, a commonly used dewormer, and nutritional
broth, which served as a negative control. A comparison with the average recorded mean,
the investigation identified the extract quantity which generated the highest effectiveness.
[29]
Butea monosperma (Lam.) (Family-Fabaceae)
The seeds have been shown to have anthelmintic activity and to be effective against
ascarids. One investigation discovered that the isolated seed ingredient palasonin, a lactone
(C16 H22O6), had considerable anthelmintic properties. [4] Palasonin appears to have an
impact on the parasite's system for generating energy because it hindered glucose uptake
and reduced the amount of glycogen in the presence of glucose. Additionally, lactic acid
levels considerably increased, indicating ATP generation was being inhibited. The findings
suggested that palasonin may exert its effects via impairing energy metabolism or by
changing the parasite's motor activity.[30]

8
Buchholzia coriaceae (Family- Capparidacea)
The anthelmintic abilities of Buchholzia coriaceae were genuine. With all of the worms
utilized in the study, the extracts demonstrated concentration-related anthelmintic activity,
with 100 mg/ml providing the shortest time for paralysis (P) and death (D). The findings
revealed that for all of the worm kinds studied, the plant leaves had greater activity than the
plant stems.[31]
Calotropis procera (Family-Apocynaceae)
Through in vitro and in vivo investigations, the anthelmintic activity of Calotropis (C.)
procera florals in contrast to levamisole was [Link] procera floral crude
aqueous and crude methanolic extracts both showed time-dependent anthelmintic efficacy
in vitro against Haemonchus contortus.[32]
Cassia tora L. (Family- Fabaceae)
According to research, the most effective C. tora extract is the ethyl acetate fraction since it
kills worms faster and paralyzes them more quickly than the methanolic extract. Both
extracts demonstrated anthelmintic properties that were concentration dependent. The
extracts showed efficacy against the worms utilized in the study, supporting the traditional
assertion that C. tora leaf is an anthelmintic.[33]
Coriandrum sativum (Family- Umbelliferae)
The aqueous and hydro-alcoholic extracts of Coriandrum sativum (Apiaceae) seeds were
tested for their in vitro anthelmintic properties. Additionally, the in vivo anthelmintic activity
of Coriandrum sativum's aqueous extract in sheep sick with Haemonchus contortus was
examined. At a concentration of less than 0.5 mg/ml, Coriandrum sativum's two extract
varieties fully prevented eggs from hatching. The ED50 of Coriandrum sativum's aqueous
extract was 0.12 mg/ml, whereas that of its hydro-alcoholic extract was 0.18 mg/ml. Among
aqueous and hydro-alcoholic extracts, there were no statistically noteworthy change (p >
0.05). In vitro tests against adult parasites indicated that the hydro-alcoholic extract was
more efficient than the aqueous one.[34]
Cucurbita maxima Duch. (Family-Cucurbitaceae)
The plant's seeds have a reputation in the Ayurvedic medical system as an anthelmintic,
particularly against tape worms. Evaluated in vivo and in vitro using extracts of the seeds.
Aqueous, alcoholic, and ether extracts in the in vitro trials were in decreasing order of
extract potency. According to the kymographic tests, the seed extracts work by causing a
reduction in motility, which results in momentary paralysis.[35]
Capparis decidua (Family-Capparidaceae)
It is a tiny, glabrous shrub that can be found in most of India. In the ancient medical system,
root bark has been shown to be effective for treating helminthes infections, rheumatoid
arthritis, cough, and asthma. The Pheretima posthuma (Annelida) has been employed as the
test animal using the ethanolic extract of root bark of C. decidua Edge because of its physical

9
and physiological similarity to the roundworm parasite. When the extract utilized in the
study was concentrated to a greater concentration of 100 mg/ml, the activity was
discovered to be dose-dependent and similar with piperazine citrate (10 mg/ml). [36]
Carica papaya Linn. (Family-Caricaceae)
Due to its morphological and physiological similarity to human intestinal round worm
parasites, the anthelmintic activity of the adult Indian earthworm Pheretima posthuma was
assessed.[37]In a different investigation, benzyl isothiocyanate, which was extracted from C.
papaya Linn. seed extract, was identified as the main anthelmintic agent after being viability
tested using Caenorhabditis worms.[38]
Embelia ribes Burm.f (Family- Myrsinaceae)
Vidanga is precious medicinal plant from myrsinaceae family. Having antihelminthic and
antiparasotic property. It is widely used against intestinal worm infestation including round
worms, thread worms, and tapeworms. This herb is very rejuvenating that provides good
health and energy to body. Rajnighantu describe Vidanga with light properties, pungent
taste, and hot potency. It used to make balance between vata and kapha. Vidanga is very
useful to improve anorexia and digestive fire. It reduces symptoms like nausea, vomiting,
flatulence, and abdominal pain. Vidanga is commonly used as krimighna (Antihelminthic),
kushtaghana (skin disorder)
Erythrina indica (Family- Papilionaceae)
At concentrations of 50 mg/ml and 100 mg/ml, ethanol, chloroform, and ethyl acetate
extracts of Erythrina indica leaves demonstrated considerable anthelmintic action against
Pheritima poshthuma. By attaching to free protein in the host animal's gastrointestinal
system or glycoprotein on the parasite's cuticle, tannins exerted anthelmintic action. By
decoupling oxidative phosphorylation, phenolic substances (tannins are poly phenolic
compounds) reduce the ability of helminth parasites to produce energy. A phytochemical
examination of the leaves of the Erythrina indica plant identified tannins as one of the
components. Erythrina indica's anthelmintic properties may result from one or both of the
aforementioned mechanisms.[39]
Eucalyptus globulus (Family Myrtaceae)
In accordance to the observations of the study by D. J. Taur, V. B. Kulkarni, and R. Y. Patil,
albendazole took 5.82 0.46 and 6.54 0.429 minutes to paralyze and kill P. posthuma, while
eucalyptus oil at an amount of 0.15 ml/ml takes 4.598 1.151 and 6.57 1.374 minutes to do
the same. Therefore, the current study comes to the conclusion that E. globulus oil has
anthelmintic potential since it contains phytoconstituents including borneol, linalool, cineol,
geranyl acetate, anethol, and saffrol.[40]
Evolvulus alsinoides Linn. (Family-Convolvulaceae)

As an effective aphrodisiac, anthelmintic, and brain stimulant, it is frequently used in

Ayurveda. An ethanolbased extract of the whole plant was examined to validate its
anthelmintic effect utilizing the adult Indian earthworms Pheretima posthuma as an

10
experiment animal. The extract immobilized the worms at all dose levels that were tested
before killing them. At a higher dosage of 100mg/ml, the ethanolic extract was found to be
more effective than the reference control Piperazine citrate.[41]
Gynandropsis gynandra (Family- Capparidaceae)
For many years, plants from this family have been utilized in traditional African
ethnomedicine, and different genera of plants have been documented for the treatment of
various illnesses. The G. gynandra leaf methanol extract was highly toxic to earthworms.
When compared to the reference medicine, which caused paralysis to last for 2 minutes and
an 8-minute duration to death, respectively.[31]
Hugonia mystax (Family- Linaceae)
Hugonia mystax leaves were dried for two weeks in the shade. Dried leaves were ground
into a coarse powder, sieved (#40), and kept at room temperature in an airtight container.
Then, dried powder was successively extracted with petroleum ether, chloroform, and
ethanol utilizing soxhlation extraction. In this bioassay, anthelmintic activity of all prototypes
were evaluated at doses of 25, 50, and 100 mg/ml. Hugonia mystax aerial parts' long-
standing reputation as an anthelmintic was validated by the action of the extracts over
Pheretima posthuma.[42]
Juglans regia L. (Juglandaceae)

It was found that all of the Juglans regia extracts responded favourably to a specific level of
anthelmintic activity. In comparison to the standard, acetone extract of plant material
shows noticeable activity at all dilutions. The least effective of the four extracts is ethanol
extract. More concentrated extracts have higher rates of death and paralysis. It indicates
that compared to lower dosages, paralysis and death occur less frequently at greater
concentrations. The crude extracts' phytochemical screening revealed the presence of
flavonoids and polyphenolic compounds.[43] The tannins known as chemically polyphenolic
substances have anthelmintic action.[44]
Melia azedarach Linn.(Family-Meliaceae)
This species of tree, which is native to Persia, India, and China, has been used for centuries
as a therapeutic and insect repellent herb all throughout the planet. Using piperazine
phosphate as the reference medication, the ethanol-based extract of drupes was examined
for its anthelmintic effectiveness against both the tapeworm Taenia Solium (Cestoda) & an
earthworm called Pheretima posthuma (Annelida).Both the tested tapeworm and the
earthworm were resistant to the extract. Furthermore, its efficacy against the tapeworm
Taenia Solium was superior compared to the use of piperazine phosphate.[45]
Mussaenda frondose (Family- Rubiaceae)

The anthelmintic activity was carried out as per the method of Ajaiyeoba et al. This study
has shown that the Mussaenda frondosa plant contains a large number of secondary
metabolites (phytocostituents). The ability of the plant extract to combat and demonstrates
how Mussaenda frondosa may be used to create novel, very effective anthelmintics.[46]

11
Murraya koenigii (Family- Rutaceae)
Using various doses (12.5, 25, 50 mg/ml) for aqueous and methanolic extracts, which
demonstrate to be dose-dependent, the in vitro investigation indicated anthelmintic
impacts of M. koenigii against Haemonchus contortus as obvious due to its paralytic
condition and/or mortality at eight-hour post treatment. Egg hatching was found to be only
mildly inhibited by
M. koenigii aqueous and methanolic extracts. M. koenigii shown strong anthelmintic
activity, it can be said.[47]
Neolamarckia cadamba (Family- Rubiaceae)
In accordance to the research, the extract caused the earthworms to die as well as be
paralyzed. The greatest concentration of the methanolic extract demonstrated substantial
anthelmintic activity since it caused paralysis and death more quickly than the medication
albendazole did. It is possible that the terpenoids and phenolic chemicals in N. cadamba's
fruit extract are what give it its anthelmintic properties. [48]
Nyctanthes arbor-tristis (Family- Oleaceae)
The chloroform-methanol extract included flavonoids, whereas the methanolic portion
revealed an inclusion of both tannins and flavonoids. The water-based extracts of
Nyctanthes arbor-tristis consisted of steroid plus carbohydrate content. The biological
components of Nyctanthes arbor-tristis have significant anthelmintic action, making them a
potential replacement for routinely prescribed and expensive anthelmintic medications for
the deworming of grazing animals.[49]
Punica granatum Linn. (Family-Punicaceae)

It is grown all over India and is known locally as Anar. In the indigenous system of medicine,
the plant's root and stem bark are employed as astringents and anthelmintics. Its stem
bark's alcoholic extract was tested for its purported anthelmintic properties. It was
discovered that the action was dose-dependent and prevented Haemonchus contortus eggs
from developing into filariform larvae.[50]
Psidium guajava (Family- Myrtaceae)
The testing of phytochemicals took place in accordance with accepted procedures. Minor
adjustments were made to the Ajaiyeoba EO et al. procedure for the anthelmintic assay.
Different extract concentrations were investigated in order to ascertain the experiment's
worms' paralysis and death times. It was discovered that Psidium guajava leaf ethanol
extract has strong anthelmintic activity at elevated concentrations (100 mg/ml). As a
standard reference, albendazole in the same concentration as the extract was employed,
and saline water served as the control. The results of the current studies support the ethno-
medical assertion that this herb has anthelmintic properties. It can be included into
medicine formulations and utilized in an alternate source for herbal anthelmintics.[51]

12
Spigelia anthelmia Linn (Family- Loganiaceae)
Spigelia anthelmia Linn (Loganiaceae) is frequently used by locals in South Western Nigeria
to get rid of worms. In South Western Nigeria, the Yoruba people refer to the plant as
"Aparan," (apa-kill, araworm), and "ewearan."[52] Spigelia anthelmia's aqueous component
had a respectable level of anthelmintic effectiveness. The extract's estimated median
effective dose (ED50) was 21 mg/kg body weight. According to the therapeutic index found
in this investigation, the extract is rather safe even at greater doses. This investigation
verified Spigelia anthelmia Linn's anthelmintic properties. Additionally, rats exposed to the
extract have considerable anthelmintic activity towards Nippostrongylus braziliensis.[53]
Spermacoce articularis L.f. (Family- Rubiaceae)

Preliminary phytochemical analysis of the leaves and stem of Spermacoce articularis L.f.
revealed the presence of tannins, flavonoids, carbs, the saponins steroids, and triterpenoids.
The methanolic extracts of the leaves, stems, and roots demonstrated anthelmintic activity
in a dosage-dependent manner; as the extracts' dose was raised, a progressive increase in
anthelmintic activity was noticed. At maximal dosages of 100 mg/ml, all Spermacoce
articularis L.f. extracts demonstrated considerable anthelmintic action in addition to
paralysis. The results of this study have demonstrated the presence of anthelmintic activity
in methanolic extracts of Spermacoce articularis L.f. leaves, stems, and roots at doses of
12.5, 25, 50, and 100 mg/ml.[54]
Trachyspermum ammi Linn. (Family-Apiaceae)
The ajowan seeds are used as diuretics, analgesics, anthelmintics, and asthma medications.
The herb's seed extract was evaluated for its anthelmintic effect on sheep in one study, and
it produced n oteworthy outcomes.[55]Using the egg hatch test (EHT) on Haemonchus
contortus eggs , the ovicidal effectiveness of the crudeaqueous and methanolic extracts
from
T. ammi Linn. seeds were assessed ed as well. The LC50 values for these compounds were
found to be 0.1698 and 0.1828 mg/ml, respectively.[56]
Trifolium repens Linn. (Family-Fabaceae)
In Indian Naga tribal folk medicine, it is a deworming treatment. The anticestodal
effectiveness of T. repens Linn. was evaluated utilizing testing Hymenolepis diminuta
infections in albino rats. At doses of 200 and 500 mg/kg, the herb's aerial shoot extract
reduced H. diminuta's mean faecal egg counts by 47.72 and 54.59% and its worm rate of
recovery by 60 and 40%, respectively. The advised cestocidal drug, praziquantel, lowered
the average faecal egg number by 65.90% & the worm rate of recovery by 26.67%.[57]
Trigonella foenum-graecum (Family- Leguminoceae)
Trigonella foenum-graecum, a plant that is commonly referred to as fenugreek, is a member
of the Leguminoceae family. The results of anthelmintic activity on the earthworm Phertima
prosthuma demonstrate that various concentrations of both aqueous and alcoholic extracts
caused the paralysis and death of earthworms when opposed to albendazole as a reference
medicine at the exact same concentration. When compared to the identical concentration
13
of

14
standard drug, an alcoholic extract at a concentration of 60 mg/ml took somewhat longer to
paralyze and slightly less time to kill earthworms.[58]
Zingiber officinale (Family- Zingiberaceae)
Ginger (Zingiber officinale) is among the most often utilized plants whose anthelmintic
abilities have been studied. In order to demonstrate the anthelmintic effects of Z. officinale
rhizome on diverse parasite species, certain in vitro experiments as well as in vivo
investigations have been conducted. In comparison to Mebendazole, this study shown that
adding 25g/kg of ginger powder to pig feed is far better at lowering the overall parasite load
of gastrointestinal nematodes.[59]

Figure 2: Plants with proven anthelmintic property

15
Method of extraction of phytochemicals
The basic principle is to grind the plant material (dry or wet) finer, which increases the
surface area for extraction thereby increasing the rate of extraction. Earlier studies reported
that solvent to sample ratio of 10:1 (v/w) solvent to dry weight ratio has been used as ideal
(Das et al, 2010) [22].
Extraction procedures
Plant tissue homogenization
Plant tissue homogenization in solvent has been widely used by researchers. Dried or wet,
fresh plant parts are grinded in a blender to fine particles, put in a certain quantity of
solvent and shaken vigorously for 5 - 10 min or left for 24 h after which the extract is
filtered. The filtrate then may be dried under reduced pressure and redissolved in the
solvent to determine the concentration. Some researchers however centrifuged the filtrate
for clarification of the extract (Das et al, 2010) [22].
Serial exhaustive extraction
It is another common method of extraction which involves in volves successive extraction
with solvents of increasing polarity from a non-polar (hexane) to a more polar solvent
(Methanol) to ensure that a wide polarity range of compound could be extracted. Some
researchers employ soxhlet extraction of dried plant material using organic solvent. This
method cannot be used for thermo labile compounds as prolonged heating may lead to
degradation of compounds [22].
Soxhlet extraction
Soxhlet extraction is only required where the desired compound has a limited solubility in a
solvent, and the impurity is insoluble in that solvent. If the desired compound has a high
solubility in a solvent then a simple filtration can be used to separate the compound from
the insoluble substance. The advantage of this system is that instead of many portions of
warm solvent being passed through the sample, just one batch of solvent is recycled. This
method cannot be used for thermo labile compounds as prolonged heating may lead to
degradation of compounds (Nikhal et al, 2010) [57].
Maceration
In maceration (For fluid extract), whole or coarsely powdered plant-drug is kept in contact
with the solvent in a stoppered container for a defined period with frequent agitation until
soluble matter is dissolved. This method is best suitable for use in case of the thermo labile
drugs (Ncube et al, 2008) [54].
Decoction
This method is used for the extraction of the water soluble and heat stable constituents
from crude drug by boiling it in water for 15 minutes, cooling, straining and passing
sufficient cold water through the drug to produce the required volume (Remington, 2008)
[64].

16
Infusion
It is a dilute solution of the readily soluble components of the crude drugs. Fresh infusions
are prepared by macerating the solids for a short period of time with either cold or boiling
water (Remington, 2008) [64].
Digestion
This is a kind of maceration in which gentle heat is applied during the maceration extraction
process. It is used when moderately elevated temperature is not objectionable and the
solvent efficiency of the menstrum is increased (Remington, 2008) [64].
Percolation
This is the procedure used most frequently to extract active ingredients in the preparation
of tinctures and fluid extracts. A percolator (A narrow, cone-shaped vessel open at both
ends) is generally used. The solid ingredients are moistened with an appropriate amount of
the specified menstrum and allowed to stand for approximately 4 h in a well closed
container, after which the mass is packed and the top of the percolator is closed. Additional
menstrum is added to form a shallow layer above the mass, and the mixture is allowed to
macerate in the closed percolator for 24 hr. The outlet of the percolator then is opened and
the liquid contained therein is allowed to drip slowly. Additional menstrum is added as
required, until the percolate measures about three-quarters of the required volume of the
finished product. The marc is then pressed and the expressed liquid is added to the
percolate. Sufficient menstrum is added to produce the required volume, and the mixed
liquid is clarified by filtration or by standing followed by decanting (Handa, et al, 2008) [26]
Sonication
The procedure involves the use of ultrasound with frequencies ranging from 20 kHz to 2000
kHz; this increases the permeability of cell walls and produces cavitation. Although the
process is useful in some cases, like extraction of rauwolfia root, its large-scale application is
limited due to the higher costs. One disadvantage of the procedure is the occasional but
known deleterious effect of ultrasound energy (more than 20 kHz) on the active
constituents of medicinal plants through formation of free radicals and consequently
undesirable changes in the drug molecules (Handa, et al, 2008) [26].

Figure 3: Classification of Helminths

17
 Figure 4: symptoms of helminthiasis

Marketed preparations of herbal anthelmintic agents:

Vidangarishta
In Ayurveda, Sandhana Kalpana is particular dosage form. In Sandhana Kalpana, Asava and
Arishta are included. Arishta are self-generated herbal fermentation formulation in traditional
medicinal system; they are considered as unique and valuable therapeutics in Ayurveda.
Through traditional knowledge in literature as well as in practice exists about Arishtas and
Asavas. There was great efforts to document, preserve and improve knowledge for the
betterment of mankind. Vidangarishta is prepared by traditional method with special
reference to Sharangdhara Samhita. This is alcoholic medicaments prepared by allowing the
decoction to undergoes fermentation with addition of honey. Vidangarishta keep for
fermentation about one month. After fermentation process is completed, was tested
according to both Ayurvedic and modern method. Vidangarishta commonly used for Krumi
(worm infection) Vyadhi.
Polyherbal syrup (Curcuma longa and Moringa oleifera)
A Polyherbal formulation, syrup is in clinical use for its anthelmintic activity for last few
decades. The current research work was under taken to evaluate the anthelmintic property
of some herbs and compare with the marketed formulation. Prepared Curcuma longa and
Moringa oleifera syrup show synergistic effect that’s why formulated syrup is more effective
than marketed albendazole syrup. Stability studies also concluded that the drug release
profile or other parameters did not alter significantly after the accelerated stability studies.
The study indicates that Polyherbal syrup i.e. Curcuma longa and Moringa oleifera will offer
an option which is more convenient, effective and cost effective as compared to the
marketed formulation. The 10 ml of herbal extracts 0.1 N HCL was taken into beaker and
diluted with solvent was transferred to 100 mL beaker containing 20 mL of 0.1 N HCl and
kept aside for 2 hours. This solution was then diluted up to 900 mL using phosphate buffer
(pH 6.8). The final
18
concentration in the solution was calculated to be 50 mg/mL. From these, 10 mL of diluted
aqueous decoction was transferred to petri plate containing earthworm and time taken to
paralysis and death of earthworm was recorded.
Plant Extracts Loaded in Nanostructured Drug Delivery Systems for Treating Parasitic
infections
Polymeric Nanoparticles
Polymeric nanoparticles (PNs) are divided into nanocapsules and nanospheres. On the one
hand, nanocapsules are formed by a polymeric coating around an aqueous or oily core into
which the drug can be dissolved in or adsorbed to the polymer coating. On the other,
nanospheres are polymer matrices in which the drug can be retained or adsorbed [32,33].
The sizes of PNs vary from 50 to 1,000 nm defined by the morphology and structure of the
polymer [34]. The decreasing particle size in the system improves dissolution and
solubilization due to the increased surface area [35].
Rajendran et al. (2013) studied extracts of the leaves of Ocimum sanctum incorporated in
PNs approximately 33 nm in size with the aim of improving antimicrobial therapy against
four bacteria—Gram-positive Bacillus subtilis and Staphylococcus aureus as well as Gram-
negative Escherichia coli and Pseudomonas aeruginosa—and two fungi—Aspergillus niger
and Penicillium spp. The system was prepared with the cation-induced and -controlled
gelification of alginate. In vitro antimicrobial activity demonstrated that when incorporated
in PNs, extracts exhibited significantly more microbial activity than extracts without PNs. For
example, PNs in extracts showed complete reduction against all micro-organisms except E.
coli (98%), whereas extracts obtained against Bacillus cereus, E. coli, P. aeruginosa, and S.
aureus achieved reductions of 72%, 81%, 92%, and 98%, respectively. Such promising results
of extracts in PNs indicate an important increase in the effectiveness of antimicrobial
therapy by reducing the side effects of traditional treatments [36].
Although the first choice for many patients is artemisinin-based therapy, the emergence
and spread of drug-resistant parasites have aggravated the incidence of malaria worldwide.
Another problem is that artemisinin, as a sesquiterpene lactone isolated from the plant
Artemisia annua L., has limited bioavailability and tolerability in humans [37].
Micelles
Micelles, especially polymeric micelles, are formed of polymers that impart specific
characteristics and have been studied for more than a decade as potential drug-carrying
nanosystems [62]. The type of intermolecular forces involved in their formation determines
the classification of micelles, of which generally three types exist: amphiphilic micelles
formed by hydrophobic interactions, polyion complex micelles resulting from electrostatic
interactions, and micelles stemming from metal complexation [63,64].
In the first category, polymeric micelles represent a collection of amphiphilic surfactant
molecules that self-assemble into shell structures with the hydrophilic block forming an
outer layer—that is, molecules with two distinct regions with opposite affinity as well as
hydrophilic and hydrophobic properties relative to a solvent [65].

19
 Polymeric micelles are the most promising candidates for use in NDDSs given their innate
characteristics for drug targeting, including an increase in drug solubility [65], the chemical
stabilization of active hydrophobic molecules for passive targeting with enhanced
permeability and retention effect [66,67], and small particle size (i.e., 10–100 nm), all of
which can facilitate favorable biodistribution and high structural stability [68]. Moreover,
micelles possess the additional advantage of being easily reproducible and synthetized on a
large scale [69]. The choice of drugs to be encapsulated depends on micelle geometry and
the hydrophobic character of the drugs encapsulated in the core [70].
A successful example of chemical drug encapsulation within pristine, lactosylated, and
mixed poly(ethylene oxide)– poly(propylene oxide) polymeric micelles might be that
described for the antiparasitic, antimicrobial, and immunomodulatory agent nitazoxanide.
Results with nitazoxanide demonstrated that the encapsulated drug actively targeted to
hepatocytes more efficiently than free drug compounds [71], which highlights new insights
into the treatment of liver-associated parasitic and viral infections
Nano- and Microemulsions
Nanoemulsions and microemulsions are submicron-sized emulsions for systemic delivery
formed by immiscible liquids and stabilized by using an appropriate surfactant. Also termed
biphasic oil in water (O/W) or water in oil (W/O) and multiphasic water in oil in water
(W/O/W). Nanoemulsions and microemulsions differ depending on the range of particle
sizes and their stability; microemulsions are approximately 10–100 nm and have
thermodynamic stability, whereas nanoemulsions are 100–500 nm and are kinetically
stable. Depending on the surfactant chosen, as well as the ratios of surfactant-to-
cosurfactant mixtures and the concentrations in which they are used, the final emulsion
formulation might present some side effects. Nevertheless, those systems have some
advantages compared to other drug delivery systems, including increased drug loading into
the particles, drug solubility and bioavailability, and drug protection from enzymatic
degradation. For those reasons, such NDDSs present great potential to deliver PEs as a
strategy for controlling different diseases, including bacterial and parasitic infections
[23,78].
Data from the literature have indicated better results when compounds are incorporated
into nano- and microemulsions, and recent findings underscore the usefulness of those
NDDS for plantderived compounds. Campana et al. (2017) formulated three microemulsions
in the range of 400–500 nm with essential oil of Cinnamomum cassia and Salvia officinalis.
Among their results, the microemulsions promoted an outstanding reduction in S. aureus
biofilms after 90 min of exposure, which could be important for disinfecting contaminated
surfaces [79]. In other work, researchers prepared a topical microemulsion containing
extracts of Quercus infectoria to be used against S. aureus, P. aeruginosa, and C. albicans.
The microemulsion developed using oil (i.e., Captex 200), surfactant (i.e., Tween 80®),
cosurfactant (i.e., PEG 600), distilled water, and extracts in different ratios showed
interesting results with agar diffusion [80].

20
Liquid Crystals
LCs combine the mechanical properties of solids (i.e., structural order, rigidity, and defined
bonds) and liquid-state materials (i.e., mobility and disordered as well as liquid regions) in a
unique material. That circumstance results in several advantages for developing
manufactured products containing herbal extracts for the pharmaceutical and cosmetic
sectors mainly due to their greater stability, better variation in the release profile, increased
the solubility of the substances, and protection from photo- and thermal degradation than
conventional emulsions [30,85,86].
LCs can be utilized as mucoadhesive systems—that is, systems capable of prolonging the
duration of contact between active substances and sites of action—to allow more effective
antimicrobial treatments [87–89]. Ramos et al. (2015), for example, reported using the
methanolic extract of scapes of Syngonanthus nitens (Bong.) Ruhland loaded in LCs with the
aim to improve the therapeutic efficacy against Candida krusei-associated vulvovaginal
candidiasis (VVC). The results demonstrated a hexagonal liquid crystalline mesophase with
higher mucoadhesive force (~12 MN) in pig vaginal mucosa. Furthermore, the in vitro test
revealed that PEloaded LCs increased the antifungal activity against C. krusei compared to
the extract alone. Last, an in vivo prophylaxis assay of VVC suggested that groups receiving
PE- loaded LCs were protected against the infectious stage [88].
Nanofibers
The study and development of polymeric nanofibers for medical applications have
increased in recent years due to the increasing variety of spinning techniques, including
electrospinning, solution blow spinning, centrifugal jet spinning, and electrohydrodynamic
direct writing. Each of these techniques has many advantages and disadvantages, which
explains the variability of the method of synthesis chosen for selected applications.
Consequently, a wide range of natural or synthetic polymers continue to be used to
synthesize nanofibers [95]. At the same time, several biocompatible polymers can be used
and, after processing, may present as fine acicular nanosized rods with diameters ranging
from 5 to 90 nm [96,97]. That process is interesting for the manufacturing of transdermal
systems for the treatment of wounds. Properties of thickness, external shape, number, and
size of pores standardized with morphological similarity to the natural extracellular matrix in
the skin, however, would enhance the healing process [98].
With such knowledge, Suganya et al. (2011) developed PCL– polyvinyl pyrrolidone (PVP)
nanofibers incorporated with extracts of Tecomella undulata (7.5% w/w) for wound healing.
In vitro drug release showed that, after 24 h, 40.9% of the extracts was released.
Liposomes

Liposomes are microscopic vesicles composed of one or more concentric lipid bilayers
containing internal aqueous space that allow the encapsulation of hydrophilic and lipophilic
substances as well as protect active principles from direct interactions with the constituents
of the biological environment [102,103]. Liposomes can be developed with one or more

21
membranes and can thus be classified as unilamellar or multilamellar, with particle sizes
ranging from 20 nm to 5,000 nm [104].
In recent years, research conducted to develop liposomes composed of plant species with
different pharmacological activities has expanded. To evaluate the potential anti-Leishmania
activity, a liposomal formulation of Curcuma longa was developed. Liposomes were
obtained by evaporating the solvent and incorporating 5.0 mg of hexane fractions from C.
longa extract, 20 mg of phosphatidylcholine, 2.6 mg of cholesterol, and 0.3 mg of Tween
20®, all dissolved in 10 mL of chloroform. In vitro assays exhibited the greater inhibition of
the promastigote forms for C. longa extract loaded in liposome (5.5 µg/mL-1 (IC50 / 48 h =
2.9 µg/mL-1) than the free fraction (125 µg/mL).
Advantage of Plant based anthelmintics over chemicals anthelmintics:

1. Synthetics anthelmintics are expensive whereas plant based anthelmintics are less
expensive.
2. Synthetics anthelmintics cause drug residues problem while plant based
anthelmintics are free from drug residues.
3. There is chance of drug resistance after prolonged use of synthetics anthelmintics
whereas in plant based anthelmintics have less chance of drug resistance.
4. Synthetics drugs are unavailable in rural areas whereas it is easily available.
5. Synthetics drugs cause environment pollution whereas plant based anthelmintics are
eco-friendly and promote biodiversity.
Limitation of plant based anthelminthics
 Seasonal availability of certain plants.
 Some plants has to be found in special habitats.
 Collecting, preparing and administering the ingredients, which is very time consuming.
 Ethano medicine does not follow western paradigms of scientific proof of efficacy.

Future prospects
 There is need to screening of medicinal plants with reference to the
phytoconstituents on the basis of research problem in livestock.
 The 80% population of developing countries depends upon herbal medicine so
marketing is too good
 To explore indigenous Traditional knowledge through medicine plants needs
government support and establishment of biotechnology industry for proper
implementation of herbal medicine
 Need of establishment and implementation of policy frame work for the regulation
and standardization of herbal medicines.

22
 CONCLUSION:
In conclusion, helminthiasis is a prevalent and challenging disease caused by parasitic worms
called helminths. It affects both humans and animals, causing a wide range of diseases and
health complications. The misuse of drugs has led to the emergence of drug resistance,
highlighting the need for the discovery of novel anthelmintic compounds.
Traditional medicinal plants have been extensively studied for their potential anthelmintic
properties. Various plant species have demonstrated promising results in in vitro and in vivo
studies, showing anthelmintic activity against different types of helminths. Some examples
of these plants include Adhatoda vesica, Aerva lanata, Azadirachta indica, Carica papaya,
Cassia tora, Cucurbita maxima, and many others. These plants contain bioactive compounds
that have the potential to paralyze or kill the parasites, making them potential sources for
the development of new anthelmintic drugs. Traditional medicinal plants offer a potential
alternative or complementary approach to conventional anthelmintic drugs.
Different screening methods have been employed to study the anthelmintic activity of plant
extracts, including tests on earthworms, hookworms, tapeworms, and other parasitic
worms. In vitro assays measure factors such as paralysis and death of the worms, while in
vivo experiments evaluate parameters like worm expulsion and reduction in the number of
eggs.
Further research and exploration of these plant species and their bioactive compounds are
needed to understand their mechanisms of action and develop safe and effective
anthelmintic treatments. It is important to consider traditional knowledge, conduct rigorous
scientific investigations, and ensure sustainable practices to harness the potential of
medicinal plants in the fight against helminthiasis.

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