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THE PHARMACOLOGICAL ACTIVITIES OF VARIOUS EXTRACTS FROM


TERMINALIA ARJUNA BARK: A REVIEW

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INTERNATIONAL JOURNAL OF CURRENT MEDICAL AND
PHARMACEUTICAL RESEARCH
ISSN: 2395-6429, Impact Factor: 4.656
Available Online at [Link]
Volume 5; Issue 12(A); December 2019; Page No. xxxxx-xxxx
DOI: [Link]
Research Article
THE PHARMACOLOGICAL ACTIVITIES OF VARIOUS EXTRACTS FROM TERMINALIA ARJUNA
BARK: A REVIEW
Z.M. Anka1* Vijender Singh1 Gunjan Singh1 and S.N. GIMBA2
1Department of pharmacy, School of Allied Health science, Sharda University, Greater Noida U.P, India
2Department of Clinical Research, School of Allied Health science, Sharda University, Greater Noida, U.P, India

ARTICLE INFO ABSTRACT


Article History: Medicinal plants have been a main source of therapeutic agents from ancient time to cure diseases.
xxxxxxxxx Terminalia arjuna (T. arjuna) is one of the most accepted and beneficial medicinal plants in
indigenous system of medicine for the treatment of various critical diseases. This comprehensive
review provides various aspects of its ethno-medical, phyto-chemical, pharmacognostical,
pharmacological and clinical significance to different diseases particularly in cardiovascular
conditions. The plant has a good safety outline when used in combination with other conventional
drugs. This review highlights various medicinal properties of T. arjuna through different studies such
as antioxidant, hypertensive, antiatherogenic, anti-inflammatory, anti-carcinogenic, anti-mutagenic
Key words: and gastro-productive effect.
Terminalia Arjuna, Medicinal
property, Phytochemistry, Coronary
artery disease, Triterpenoids.

Copyright © 2019 Z.M. Anka et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.

INTRODUCTION According to WHO, almost 80% of the world's population


depending on traditional medicine and in India 60% of the
Medicinal plants play an essential role in health care and are people in rural areas use herbal medicines.(WHO., 2002)
the major raw materials for both traditional and conventional During the last few years, use of herbal supplements increased
medicine preparations; still most of the people choose herbal from 2.5% to 12%.(Stickel et al., 2007) In recent years, there
medicines than conventional medicines.(WHO, 2002) They has also been an increasing demand for Nanoparticles derived
expanded attention due to their effectiveness, lack of current from medicinal plants like Terminalia family due to their
medical alternatives, increasing cost of modern medicines and applications in various fields of research like medicine,
cultural preferences.(Heinrich., 2000), (Tabuti et al., 2003) catalysis, energy and materials.(Gopinath et al., 2013),
Ethnobotanical studies are most important to expose the (Yallappa et al., 2013), (Edison et al., 2012)
ancient times and current culture about plants in the world and
reserving original knowledge of medicinal plants. The In the earliest India, medicinal plants were used to prevent
quantitative ethnobotanical studies were used to identify the different critical diseases and they would be the best source to
plant uses as food, (Pieroni., 2001) human health care obtain a variety of drugs. The Indian traditional medicine is
medicines,(Kim et al., 2013) veterinary medicine(Upadhyay et based on various systems such as Ayurveda, Siddha, Unanai,
al., 2011) and economically important.(Reyes-Garcia et al., etc. In recent years there has been an increasing awareness
2006) about the importance of medicinal plants. Herbal drugs are
easily accessible, secure, less pricey, efficient and have very
Around the world, the traditional knowledge system has rare side effects. The evaluation of new drugs, especially the
expanded chief importance in perspective with protection, phytochemical obtained materials has opened a vast area for
sustainable growth and search for new utilization patterns of research and helpful in making a transition from traditional to
plant resources. Traditional medicine system includes the modern medicine in India. Medicinal plants contain some
knowledge, skills and practices based on the presumptions, organic compounds which provide definite physiological
beliefs and experiences of folk communities to protect their action on the human body and these bioactive substances
health problems. Traditional herbal medicines are considered include tannins, alkaloids, carbohydrates, terpenoids, steroids,
to be of huge importance among different rural or native flavonoids, and phenols. (Sharma et al., 2012)
communities in many developing countries.(Gosh., 2003)

*Corresponding author: Z.M. Anka


Department of pharmacy, School of Allied Health science, Sharda University, Greater Noida U.P, India
International Journal of Current Medical And Pharmaceutical Research, Vol. 5, Issue, 11(A), pp. xxx-xxx, November, 2019

Even though numerous medicinal plants have been explained Arjunaghrita. This tree is usually an evergreen tree with new
in the Indian customary therapeutic system for treatment of leaves (reddish in color) appearing in the hot season (February
several diseases, very few plant products are nowadays utilized to April) before leaf fall.(Ali., 1994)
in the modern medical system to treat most of the diseases
Phytochemistry
particularly; cardiovascular diseases (CVD), ulcers, diabetes,
cough, excessive perspiration, asthma, tumor, inflammation The major constituents of T. arjuna in stem bark, root bark,
and skin disorders. Among the plants, one of the medicinal fruits, leaves and seeds are well characterized (Table 1). The
plants indigenous to India is Terminalia arjuna, (T. arjuna) preliminary phytochemical analysis of existing compounds in
commonly known as ‘Arjuna’, which has been used as a T. arjuna was carried out according to various standard
cardiotonic in heart failure, ischemic, cardiomyopathy, protocols as mentioned by (Harbone., 1998) in (Table 2), as
atherosclerosis, myocardium necrosis and has been used for bark was considered to be the most important constituent from
the treatment of different human diseases like blood diseases, the medicinal point of view, initially reported that the bark had
anemia, venereal and viral disease; and to continue excellent 34% ash content consisting entirely of pure calcium carbonate.
healthiness. It is used in the treatment of fractures, ulcers, Aqueous extract of T. arjuna is reported to have 23% calcium
hepatic and showed hypocholesterolemic, antibacterial, salts and 16% tannins. Organic extracts of T. arjuna bark were
antimicrobial, antitumoral, antioxidant, antiallergic and also prepared using the sequential methods with a number of
antifeedant, antifertility and anti- HIV activities.(Ram et al., organic solvents such as hexane, benzene, chloroform,
1997), (Bachaya et al., 2009), (phani kumar et al., 2013) acetone, dichloromethane, ethyl acetate, butanol, ethanol,
methanol and ether, etc., to extract various phytochemical
T. arjuna is reported that to possess strong hydrolipidemic
constituents. The chemical structures of available compounds
properties. It is trusted that the saponin glycosides in T. arjuna
were confirmed by various advanced techniques like HPLC,
may be responsible for its inotropic effects, while the
UPLC, LC-ESI-MS/MS analysis.(Singh et al., 2002),
flavonoids/phenolics may supply antioxidant activity as well
(Chitlange et al., 2009), (Kokkiripati et al., 2013) Polyphenols,
as vascular amplification activity, in this manner
flavonoids, tannins, triterpenoids, saponins, sterols and
authenticating the multiple activities of this plant for its cardio-
minerals are the major constituents of T. arjuna. Such amino
protective function.(Dwivedi., 2007), (Maulik et al., 2012),
acids like tryptophan, tyrosine, histidine and cysteine are also
(Kapoor et al., 2014)
the main ingredients in T. arjuna.(Row et al., 1970), (singh et
METHODOLOGY al., 1995), (Kandil et al., 1998) Extracts from T. arjuna bark
are:
Systematic literature searches were carried out and the
available information on various plants traditionally used for Terpenoids, Ursane Triterpenoids and Glycosides
cardiovascular disorders was collected via electronic search At first, an oleanane triterpenoid named, arjunin, and a lactone,
(using Pubmed, Sci- Finder, Scopus, Scirus, ScienceDirect, arjunetin were isolated from the benzene and ethanolic extracts
Google Scholar and Web of Science) and a library search for of its bark respectively.(Honda et al., 1976) initially confirmed
articles published in peer-reviewed journals and also locally that the presence of arjunic acid and arjungenin and latterly
available books. reported that two more glucosides namely arjunglucoside I and
Occurrences, Botanical Description and Ethnopharmacology II in the stem bark of T. arjuna. (Anjaneyulu et al., 1982)
confirmed that the presence of arjunoside III and IV, terminic
Terminalia arjuna is an ayurvedic plant with important acid, and a triterpene carboxylic acid by ethyl acetate
medicinal value. It is commonly known as Arjuna, Indradru, extraction of roots of T. arjuna. Hexane extraction of stem of
(Sharma et al., 2005) which is belongs to Combretaceae family T. arjuna authenticated that the presence of terminic acid and
comprising of nearly 200 species distributed around the world. b-sitosterol.(Anjaneyulu et al., 1983)
Nearly 24 species of Terminalia have been reported from
various parts of India, some selected species are T. arjuna, (Ali et al., 2003) has isolated another oleanane type triterpane,
Terminalia bellirica (use for treatment of respiratory tract terminoside A from the acetone fraction of the ethanolic
infection), Terminalia catappa (use for treatment of skin extract of T. arjuna's stem bark. The structure of this new
diseases, leprosy and scabies), Terminalia elliptica( use for compound was established as olean-1a,3b,22b-triol-12-en-28-
treatment of diarrhea), Terminalia mantaly (use for cancer oic acid-3b-D-glucopyranoside. It was exhibited that
treatment), Terminalia tomentosa (use for bronchitis terminoside A inhibits nitric oxide production and decreases
treatment), Terminalia ivorensis (use for treatment of dermal inducible nitric oxide synthase levels in lipopolysaccharide
diseases) etc. In India, T. arjuna is about 60-80 feet in height, stimulate macrophages. (Ali et al., 2003) Five ursane type
buttressed trunk and horizontally spreading crown and triterpene glucosyl ester including new one, 2a, 3b-
drooping branches distributed in India, Burma, Mauritius and dihydroyurs-12,18-dien-28-oic acid 28-O-b Dglucopyranosyl
Sri Lanka.(Kapoor et al 2014), (Chopra et al., 1958), ester, and four known ursane triterpene glycosyl esters namely,
(Nadkarni., 1976) 2a, 3b, 23-trihydroxyurs-12,18-dien-28-oic acid 28-O-b-D-
glucopyranosyl ester, quadranosie VIII, kajiichigoside and 2a,
T. arjuna is distributed throughout sub Indo-Himalayan tracts 3b, 23-trihydroxyurs-12, 19-dien-28-oic acid 28-O-b-
of Uttar Pradesh, Punjab, Deccan, South Bihar, Orissa,West Dglucopyranosyl ester were isolated from bark of T.
Bengal and Madhya Pradesh mainly along riverside, rivulets arjuna.(Wang et al., 2010) 3-O-b-D-glucopyranosyl-2a, 3b,
and ponds. It is known by its various vernacular names, the 19a-trihydroxyolean- 12-en-28-oic acid, 28-O-b-D-
most commonly used ones are Arjuna (Common Name), Arjun glucopyranoside and 2a, 19a-dihydroxy- 3-oxo-olean-12-en28-
(Hindi), Marudhu (Tamil and Malayalam), Tella Maddi oic acid 28-O-b-D-gluco-pyranoside are isolated from bark of
(Telugu), Arjhan (Bengali), Sadaru (Marathi), Sadado T. arjuna by (Choubey et al., 2001), (Upadhyay et al., 2001)
(Gujarati), Neer matti (Kannada) and some traditional through spectrochemical analysis.
formulations prescribe in the name of Arjunarishta and
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International Journal of Current Medical And Pharmaceutical Research, Vol. 5, Issue, 11(A), pp. xxx-xxx, November, 2019

(Patnaik et al., 2007) using chromatography technique isolated Table 1 Phytochemical Constituents of various Parts of
a triterpenoid glycoside from the bark of T. arjuna and Terminalia Arjuna
identified it is an olean- 3b, 22b-diol-12-en-28 b-D- Part used
glucopyranoside-oic acid. Chemical Constituents Reference
Major
Row et al24 Honda et al25
(Alam et al., 2008) isolated two more glycosides namely Stem bark
Triterpenoids
Singh et al26,27 Anjaneyulu et
Termiarjunoside I (olean-1a,3b,9a,22a-tetraol-12-en-28- al28 Singh et al29 Wang et al30
oicacid-3b-D-glucopyranoside) and Termiarjunoside II (Olean- Ursane triterpenoids
3a,5a, 25-triol-12-en-23,28- dioicacid-3b-D-glucophyranoside) Row et al24,31, Singh et
al26,27Honda et al25,32 Tripathi et
from the ethanolic extract of T. arjuna bark. Arjunglucoside IV Glycosides al34 Ali et al35,36 Wang et al34,37
and V, Arjunasides A-E were isolated from the ethanolic Patnaik et al38Alam et al39
extract of the stem bark of T. arjuna by (Wang et al., 2010) Ahmad et al40 Sharma et al33
Sharma et al33 Pettit et al41
Flavonoids and Phenolics Flavonoids and phenolics Anonymous42 Saha et al43
Wang et al30
Bark of T. arjuna contains a very high level of flavonoids, Tannins Takahashi et al44 Lin et al45
namely arjunolone, flavones, luteolin, baicaleiin, quercetin, Kuo et al46
kempferol, and pelargonidin evaluated with other medicinal Minerals and trace elements Dwivedi et al47
plants particularly having favorable effects on cardiovascular Anjaneyulu et al28 Anjaneyulu
diseases. The compound luteolin has been isolated from the Other compounds
et al48,49
butanolic fraction of T. arjuna and it has been found to have Roots Triterpenoids Singh et al26,27
antimutagenic and antibacterial activities. It inhibited gram Arjunic acid
Glycosides Upadhyay et al51
negative pathogen growth with a minimum inhibitory
concentration of 12.5 mg/disc. Aqueous extract of T. arjuna Fruits Triterpenoids and flavonoids Rastogi et al52
contains 70% polyphenols having a molecular weight greater Leaves and Pettit et al41,
Flavonoids and glycosides
than 3.5 kDa and they are confirmed by the HPLC and LCMS. seeds Yadava et al53
The aqueous extract contains flavon-3-ols, such as (+)-
catechin, (+)-gallocatechin and (-)-epigallocatechin; gallic Pharmacological and Clinical Studies
acid, ellagic acid and its derivatives such as 3-O-methyl ellagic Pharmacological studies
acid 4-O-b-Dxylopyranoside and 3-O-methyl ellagic acid 3-O-
rhamnoside. Cardioprotective potential of T. arjuna stem bark on the
molecular basis was evaluated by (Kokkiripati et al., 2013),
Various studies support the fact that bioflavonoids inhibit LDL using cell cultures of human monocytic (THP-1) and human
oxidation, endothelial activation and platelet aortic endothelial cells (HAECs). Inhibitory effect of alcoholic
aggregation.(Fuhrman et al., 2001), (Carluccio et al., 2003), (TAAE) and aqueous (TAWE) extracts of T. arjuna stem bark
(Ruff., 2003), (Martikainen et al., 2007) Due to the presence of was assessed on human 3-hydroxy- 3-methylglutaryl
free radical scavenging action of the various phenolic contents coenzyme A (HMG-CoA) reductase, lipoprotein lipase (LpL)
in T. arjuna, it acts as strong anti proliferative and anti-oxidant and lipid peroxidation in rat (Wistar) liver and heart
agent.(Baipai et al., 2005) There is an inversely relationship homogenates. TAAE and TAWE inhibited the lipid
between the high intake of dietary flavonoids and the risk of peroxidation and HMG-CoA reductase. Both the extracts
coronary artery disease (CAD), so possible account for intake attenuated H2O2 mediated ROS generation in THP-1 cells by
of high flavonoids content Tarjuna is beneficial effects in promoting catalase (CAT), glutathione peroxidase (GPx)
CAD. activities, and by sustaining cellular reducing power. TAAE
Tannins was highly effective in satisfying proinflammatory gene
transcripts in THP-1 cells and HAECs, whereas the response to
Tannins are known to enhance the synthesis of nitric oxide and TAWE depended on the type of transcript and cell type. Both
relax vascular segments pre-contracted with norepinephrine. In extracts decreased the levels of typical inflammatory marker
addition to a flavonoids variety of tannins have been isolated proteins, viz. LPS induced tumor necrosis factor (TNF)-a
from the bark of T. arjuna. Around fifteen types of tannins and secreted by THP-1 cells and TNF-a induced cell surface
their related compounds were isolated from the bark of T. adhesion molecules on HAECs, namely vascular cell adhesion
arjuna and their structures were elucidated with the help of molecule-1 (VCAM-1) and Eselectin. The marked effects on
spectral analysis. Hydrolyzable tannins are castalagin, cultured human monocytic and aortic endothelial cells
casuariin, casuarinin, punicalagin, pyrocatechols, punicallin, (HAEC) provide the biochemical and molecular basis for the
terchebulin and terflavin C were isolated from the bark of T. therapeutic potential of T. arjuna stem bark against
arjuna.(Lin et al., 2001) Tannins are considered to have cardiovascular diseases (CVD).
wound healing, astringent, hypotensive, antioxidant and
antimicrobial effects.(Kolodziej et al., 2005), (Chaudhari et Triterpenoids are essentially responsible for cardiovascular
al., 2006) properties. Alcoholic and aqueous bark extracts of T. arjuna,
arjunic acid, arjunetin and arjungenin were evaluated for their
Minerals and Amino Acids potential to inhibit CYP3A4, CYP2D6 and CYP2C9 enzymes
The bark of T. arjuna contains large amount of various in human liver microsomes by (Varghese et al., 2015) They
minerals and trace elements such as magnesium (4000 µg/g), have demonstrated that alcoholic and aqueous bark extract of
calcium (3133 µg/g), zinc (119 µg/g) and copper (19 T. arjuna showed effective inhibition of all three enzymes in
µg/g).(Dwivedi et al., 1989) It contains some amino acids human liver microsomes with IC50 values less than 35 µg/ml.
such as tryptophan, tyrosine, histidine and cysteine.(Singh et Enzyme kinetics studies suggested that the extracts of T.
al., 2002), (Kandil et al., 1998) arjuna showed rapidly reversible noncompetitive inhibition of

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International Journal of Current Medical And Pharmaceutical Research, Vol. 5, Issue, 11(A), pp. xxx-xxx, November, 2019

all three enzymes in human liver microsomes. They suggest endogenous antioxidant compounds of rat heart and also
strongly that T. arjuna extracts significantly inhibit the activity prevented oxidative stress associated with IRI of the
of CYP3A4, CYP2D6 and CYP2C9 enzymes. heart.(Gauthaman et al., 2001) Vascular complications are a
leading cause of mortality and morbidity in diabetic patients.
(Ahmad et al., 2014) investigated and highlighted the
Therapeutic potential of T. arjuna bark extract was examined
anticarcinogenic and antimutagenic potential of extracts of T.
in improving myocardial function in streptozotocin (STZ)
arjuna. They have used human lymphocyte culture and bone
induced diabetic rats. After 8 weeks of STZ administration,
marrow cells of albino mice as assay system. The parameters
rats showed a decline in left ventricular pressure (LVP),
of studied were included chromosomal aberrations (CA), sister
maximal rate of rise and fall in LVP (LV [dP/dt] max and LV
chromatid exchanges (SCEs) and cell growth kinetics (RI)
[dP/dt] min), cardiac contractility index (LV [dP/dt]
both in the presence and in the absence of exogenous
max/LVP), and a rise in LV end-diastolic pressure. Altered
metabolic activation system for in vitro experiment, whereas
lipid profile, oxidative stress, and increased levels of
total aberrant cells and the total frequencies of aberrations
endothelin 1 (ET-1), tumor necrosis factor-a (TNF-a), and
were taken for in vivo study. The role of T. arjuna extracts in
interleukin 6 (IL-6) along with histological changes in heart
reducing metaphase aberrations due to aflatoxin B1 (AFB1) is
and pancreas were observed in diabetic rats. T. arjuna
quite significant, the reduction varying from 23.49%, 42.47%,
significantly attenuated cardiac dysfunction and myocardial
and 59.65% down to 12.32%, 28.00%, and 36.88%
injury in diabetic rats. It also reduced oxidative stress, ET-1,
respectively at the highest dose T. arjuna for the three different
and inflammatory cytokine levels.(Khaliq et al., 2013)
durations viz., 24, 48 and 72 h. Similarly the number of sister
chromatid exchanges got reduced from a higher level of 15.00 (Sinha et al., 2008) has investigated the antioxidative
± 1.40 per cell to 7.70 ± 0.50 per cell with liver microsomal properties of an ethanol extract of the bark of T. arjuna
metabolic activation system mix at 48 h of treatment. The (TAEE) against sodium fluoride (NaF)-induced oxidative
replication index was enhanced from 1.33 to 1.55 in the in stress in the murine heart. NaF intoxication significantly
vitro experiment. Similar trends were noticed in the in vivo altered all the indices related to the prooxidante antioxidant
experiments that are effective reductions in clastogeny ranging status of the heart. In addition, the ferric reducing/antioxidant
from 15.22% to 54.82% from the mutagen treated positive power assay revealed that TAEE enhanced the cardiac
control and the total frequencies in aberrant cells got reduced intracellular antioxidant activity.
from 429 due to AFB1 to 141 due to 5th concentration of T.
Finally, they concluded that TAEE protects murine hearts from
arjuna extracts at 32 h of exposure. Arjungenin and its
NaF induced oxidative stress, probably via its antioxidant
glucoside are extracted from T. arjuna and exhibited a
properties.
moderate free radical scavenging activity on the superoxide
release from PMN cells. Arjungenin also exhibited greater (Parveen et al., 2012) examined the protective effect of T.
inhibitory action on the hypochlorous acid production from arjuna bark extract on left ventricular (LV) and baroreflex
human neutrophils.(Pawar et al., 2005) function in chronic heart failure and to elucidate the possible
mechanistic clues in its cardioprotective action. Fifteen days
(Viswanatha et al., 2010) investigated the antioxidant and
after isoproterenol administration, rats exhibited cardiac
antimutagenic activities of alcoholic extract of Tarjuna bark.
dysfunction, hypertrophy, and LV remodeling along with
The alcoholic extract of the stem bark of T. arjuna (ALTA) has
reduced baroreflex sensitivity. Prophylactic and therapeutic
shown potent antioxidant activity with EC50 in DPPH (2,2-
treatment with T. arjuna improved cardiac functions and
diphenyl-1-picryl-hydrate) assay, superoxide radical
baroreflex sensitivity. It has also attenuated hypertrophy and
scavenging activity and lipid peroxidation assay. In
fibrosis of the LV. T. arjuna exerts beneficial effect on LV
micronucleus test ALTA showed significant reduction in
functions, myocardial remodeling, and autonomic control in
percentage of micronucleus in both polychromatic erythrocytes
chronic heart failure possibly through maintaining endogenous
(PCE) and normochromatic erythrocytes (NCE) and also
antioxidant enzyme activities, inhibiting lipid peroxidation and
shown a significant reduction in P/N ratio.
cytokine levels. Diethyl ether, ethyl acetate and ethanol
(Singh et al., 2008) investigated the effects of butanolic extractions of T. arjuna exerted hypolipidemic and
fraction of T. arjuna bark on Doxorubicin (Dox) induced antioxidative effects at two different dose levels of 175 and
cardiotoxicity using in vivo study with male Wistar rats and 350 mg/kg body weight in Poloxamer (PX)-407 induced
they found that T. arjuna bark has protective effects against hyperlipidemic albino Wistar rats. The results suggested that
Dox-induced cardiotoxicity and may have potential as a the ethanolic fraction of T. arjuna possesses the potent
cardioprotective agent. properties of being an antioxidant and hypolipidemic than
other fractions.(Subramaniam et al., 2011)
Dried pulverized bark of T. arjuna was administered orally to
Wistar albino rats (120-150 g) in two doses (500 and 750 (Kumar et al., 2009) evaluated the effects of T. arjuna bark
mg/kg in 2% carboxy methyl cellulose (CMC)), 6 days per extract on myocardial fibrosis and oxidative stress induced by
week for 12 weeks. The determination of baseline changes in chronic b-adrenoceptor stimulation. Because myocardial
cardiac endogenous antioxidant compounds [superoxide fibrosis and oxidative stress accompany a number of cardiac
dismutase (SOD), reduced glutathione (GSH) and catalase disorders such as hypertrophic cardiomyopathy, hypertensive
(CAT)] or the hearts were subjected to oxidative stress heart disease and cardiac failure. Aqueous extract of T. arjuna
associated with in vitro ischemic-reperfusion injury (IRI). bark was evaluated at 63, 125 and 250 mg/kg given orally for
Significant rise in myocardial thiobarbituric acid reactive antifibrotic and antioxidant effects in rats given the selective b-
substance (TBARS) and loss of SOD, GSH and CAT occurred adrenoceptor agonist isoprenaline for 28 days. The T. arjuna
in the vehicle-treated hearts subjected to in vitro IRI. Hearts of bark extract significantly prevented the isoprenaline induced
rats were significantly protected from oxidative stress, when increase in oxidative stress and decline in endogenous
subjected to in vitro IRI. The crude bark of TA augments antioxidant level and also prevented fibrosis.
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International Journal of Current Medical And Pharmaceutical Research, Vol. 5, Issue, 11(A), pp. xxx-xxx, November, 2019

(Gauthaman et al., 2005) studied that oral administration of T. and myeloperoxidase (MPO) in gastric mucosa. The levels of
arjuna for 12 weeks in rabbits caused augmentation of DNA, protein bound carbohydrate complexes-hexose,
myocardial antioxidants; superoxide dismutase (SOD), hexosamine, sialic acid, fucose in gastric mucosa and gastric
catalase (CAT) and glutathione (GSH) along with induction of juice and the levels of RNA in gastric mucosa were assessed.
heat shock protein72 (SHP72). In vivo ischemic-reperfusion The stomach tissues were used for adherent mucus content and
injury induced oxidative stress, tissue injury of heart and also for the histological examination. A significant reduction
hemodynamic effects were prevented in the T. arjuna treated in lesion index was observed in ulcer induced animals treated
rabbit hearts. with T. arjuna (DIC + TA) compared to ulcerated rats (DIC).
A significant increase was observed at pH, NP-SH, GSH,
Alcoholic extract of T. arjuna bark and its extracts were
enzymic antioxidants, protein bound carbohydrate complexes,
evaluated for DNA protection, protein oxidation and free
adherent mucus content, nucleic acid with a significant
radical scavenging activity. Ethanolic extract of T. arjuna bark
decrease in volume of gastric juice, free and total acidity,
(TAA) and its fractions, including dichloromethane (TAD),
pepsin concentration, acid output, LPO levels and MPO
ethyl acetate (TAE), butanol (TAB) and water (TAW) has
activities in DIC + TA rats compared to DIC rats. It is proved
significant antioxidant activity and potential to prevent protein
that T. arjuna could act as a gastroprotective agent probably
oxidation, DNA damage protection by pBR 322 DNA and
due to its free radical scavenging activity and cytoprotective
SCGE (Single cell gel electrophoresis) assay. The potent
nature.
antioxidative activity and DNA protection ability of T. arjuna
bark extracts might be endorsed with phenolic/flavonoid Clinical Studies
compounds. A significant correlationwas also observed
Recently, (Kapoor et al., 2014) investigated the therapeutic
between free radical scavenging activity, in vitro DNA damage
potential of T. arjuna on the inflammatory markers in subjects
activity and the total phenolic/flavonoid content.(Phani Kumar
with stable coronary artery disease (CAD). In a placebo-
et al., 2013)
controlled, randomized double-blind study, 116 patients with
Physicochemical property and inotropic effect of the aqueous stable CAD who were on standard cardiac medications for
extract of T. arjuna bark (TAAqE) were investigated by more than three months were enrolled and received either
(Oberoi et al., 2011) on adult rat ventricular myocytes in placebo or 500 mg of T. arjuna from Himalayan Herbal
comparison with extracts prepared sequentially with organic Healthcare, Bangalore, India twice a day in addition to
extracts. They found that TAAqE decoctions exerted positive receiving the conventional treatment. A significant decrease in
inotropy, accelerated myocyte relaxation and increased serum triglycerides as well as in various inflammatory
caffeine-induced contraction concentration dependently. cytokines such as hsCRP, IL-18 (P < 0.001), IL-6 and TNF-a
TAAqE-induced cardiotonic action via enhancing SR function, (P < 0.05) was observed at 3 months in patients who were on
a unique action minimizing the occurrence of arrhythmias, drug treatment as compared to the placebo. The effects were
makes TAAqE a promising and relatively safe cardiotonic maintained till 6 months follow-up and showed a further
beneficial to the healthy heart and the treatment for chronic reduction in hyperlipidemia and inflammatory markers with
heart disease. time. An observational study was conducted to find out the
effects of T. arjuna in patients with dilated cardiomyopathy
(Mandal et al., 2013) investigated antioxidative and
(DCMP) of idiopathic and ischemic cause. Ninety three
antimicrobial properties of methanolic extract of T. arjuna
patients with DCMP receiving standard therapy and/ or bark
bark. The antimicrobial activity showed that higher inhibition
extract of T. arjuna 500 mg 8 hourly were enrolled. Three
against Gram negative bacteria than gram positive bacteria and
groups as standard therapy (ST, Group 1), T. arjuna therapy
showed a promising antioxidant activity, as absorption of
(TA, Group 2) and standard therapy with T. arjuna (ST + TA,
DPPH radicals decreased in DPPH free radical scavenging
Group 3) were formed. At the end of the study period, patients
assay. Methanol extract from bark of T. arjuna exhibited
of group 3 showed significant improvement in percentage of
medicinal as well as physiological activities. Methanol,
left ventricular ejection fraction (LVEF%) (7 ± 1.6, P <
ethanol, acetone, aqueous both hot and cold extracts from the
0.00001) compared to group 1 and 2 (P < 0.00001, P <
leaves and bark of T. arjuna were tested for their antimicrobial
0.0001). Reductions in Left ventricular end systolic and
activity against Staphylococcus aureus, Acinetobacter sp.,
diastolic diameters and volumes were most significant in group
Proteus mirabilis, Escherichia coli, Pseudomonas aeruginosa
3 (8.3 ± 4.7, P < 0.0001 and 3.1 ± 5.7, P < 0.001) and (11 ± 26,
and Candida albicans, pathogens causing ear infections. Three
9 ± 21 P < 0.01) respectively in comparison to other groups.
organic solvents evaluated, acetonic leaf extract was found to
Pulmonary artery pressure reduced significantly in group 1 and
be best against S. aureus. Organic bark extract showed almost
3 (P < 0.0001). A similar reduction in diastolic score and
equal inhibition of all tested Gram negative bacteria except P.
mitral regurgitation (P < 0.01 and P < 0.0001) was observed in
aeruginosa. Aqueous extract of T. arjuna bark exhibited good
groups 1 and 3. From the results, dilated cardiomyopathy with
activity against S. aureus.(Aneja et al., 2012)
reduced LVEF due to either idiopathic or ischemic cause
(Devi et al., 2007) evaluated the effect of methanolic extract of receiving standard therapy with T. arjuna showed significant
T. arjuna (100 mg/kg to 50 mg/kg body weight) on diclofenac improvement in left ventricular parameters as well as
sodium (80 mg/kg bodyweight in water, orally) induced gastric functional capacity.(Bhawani et al., 2013)
ulcer in rats. The gastroprotective effect of T. arjuna was
(Bharani et al., 1995) investigated the salutary effect of T.
assessed from volume of gastric juice, pH, free and total
arjuna in patients with severe refractory heart failure. Twelve
acidity, pepsin concentration, acid output in gastric juice, the
patients with refractory chronic congestive heart failure (Class
levels of non-protein sulfhydryls (NP-SH), lipid peroxide
IV NYHA), related to idiopathic dilated cardiomyopathy (10
(LPO), reduced glutathione (GSH), and activities of enzymic
patients); previous myocardial infarction (one patient) and
antioxidants-super oxide dismutase (SOD), catalase (CAT),
peripartum cardiomyopathy (one patient), received T. arjuna,
glutathione peroxidase (GPx), glutathione-Stransferase (GST)
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as bark extract (500 mg 8 hourly) or matching placebo for 2 daily. Lipids and lipid peroxide levels were determined at 30
weeks each, separated by 2 week washout period, in a double days follow-up. No significant changes in total, HDL, LDL
blind crossover design as an adjuvant to maximally tolerable cholesterol and triglycerides levels were seen in Groups I and
conventional therapy (Phase I). On long term evaluation in an II. In Group III, there was a significant decrease in total
open design (Phase II), wherein Phase I participants continued cholesterol (_9.7 ± 12.7%), and LDL cholesterol (_15.8 ±
T. arjuna in fixed dosage (500 mg 8-hourly) in addition to 25.6%) (paired t-test P < 0.01). Lipid peroxide levels
flexible diuretic, vasodilator and digitalis dosage for 20-28 decreased significantly in both the treatment groups (P < 0.01).
months (mean 24 months) on outpatient basis, patients showed This decrease was more in vitamin E group (_36.4 ± 17.7%) as
continued improvement in symptoms, signs, effort tolerance compared to the T. arjuna group (_29.3 ± 18.9%). T. arjuna
and NYHA Class, with improvement in quality of life. tree bark powder has significant antioxidant action that is
comparable to vitamin E and also has a significant
(Dwivedi et al., 2005) were conducted a study to evaluate the
hypocholesterolaemic effect.
role of T. arjuna in ischemic mitral regurgitation (IMR)
following acute myocardial infarction (AMI). 40 patients with A study was conducted by (Bharani et al., 2004) to determine
fresh AMI showing IMR were randomly divided into 2 groups the improvement of endothelial dysfunction in smokers.
of 20 each. Two groups were observed between one and three Eighteen healthy male smokers (age 28.16 ± 9.45 years) and
months therapy with T. arjuna at a dose of 500 mg twice a day an equal number of age-matched, non-smoker controls
and showed significant decreases in IMR, improvement in E/A participated in the study. The smokers were given T. arjuna
ratio and considerable reduction in angina frequency. (500 mg, 8 h) or matching placebo randomly in a double blind
crossover design for two weeks each, followed by repetition of
(Bharani et al., 2002) conducted a study on the efficacy of T.
brachial artery reactivity studies to determine various
arjuna in chronic stable angina. Fifty eight males with chronic
parameters including flow-mediated dilation after each period.
stable angina (NYHA class II-III) with evidence of provocable
The flow-mediated dilation showed significant improvement
ischemia on treadmill exercise test received TA (500 mg 8
from baseline values after T. arjuna therapy.
hourly), isosorbide (40 mg/daily) or a matching placebo for
oneweek each, separated by a washout period of at least three Table 2 Preliminary tests for Phytochemical Analysis of the
days in a randomized, double-blind, crossover design. They Terminalia Arjuna Extract
underwent clinical, biochemical and treadmill exercise Phytoconstituents Test
evaluation at the end of each therapy, which were compared Alkaloides Dragendroff's test
during the three therapy periods. T. arjuna therapy was Carbohydrates Molisch's test
associated with a significant decrease in the frequency of Flavonoids Lead acetate test
Glycosides KellereKilliant test
angina and the need for isosorbide dinitrate. T. arjuna bark Lactones Legal's test
extract, 500mg 8 hourly, given to patients with stable angina Phenolic compounds 5% FeCl3 test
with provocable ischemia on treadmill exercise, led to and tannins
improvement in clinical and treadmill exercise parameters as Proteins Ninhydrin test
Phytosterols Salkowski's test
compared to placebo therapy. These benefits were similar to
Saponins Foam test
those observed with isosorbide mononitrate (40 mg/day) Liebermanne
Triterpenoids
therapy and the extract was well tolerated. Burchard's test

The effect of an Ayurvedic formulation of T. arjuna, known Toxicity and Side Effects
as‘Arjuna Kwatha’ was assessed by (Rao et al., 2001) in 36
T. arjuna has been used in the dose between 1 to 2g per day in
hypertensive patients at stage III with increased LV mass. The
different clinical studies and found that this is an optimum
patients were divided into two groups, one group received
dose in the patients particularly CAD. These doses have lesser
atenolol (50 mg twice daily) and the other group ‘Arjuna
side effect like headache, mild gastritis and constipation. There
Kwatha’ (25ml twice daily) along with atenolol for 6 months.
were no reports in the regards of hematological, hepatic,
A significant decrease was observed in both SBP and DBP (P
metabolic and renal toxicity after more than two years of its
< 0.001) in both the groups. However, LV mass index was
administration.(Bharani et al., 1995)
only significantly reduced in the atenolol-plus-‘Arjuna
Kwatha’ group as compared to atenolol alone (P < 0.001), due Recently (Bhawani et al., 2013) reported that there was no
to negative chronotropic and inotropic effects of the herbal significant variation in the body and organ weights between
preparation. (Khalil., 2005) reported that the administration of the control and the treated group of 93 patients with dilated
T. arjuna bark powder along with statins for 3months to 30 cardiomyopathy (DCMP) of idiopathic and ischemic cause
patientswith coronary artery disease resulted in a 16% in LDL- was observed after 28 days of treatment under the treatment of
cholesterol, 15% decrease in total cholesterol and 11% in T. arjuna capsules (500 mg at 8 h).
triglycerides, confirming its immense potential to correct
Haematological analysis and biochemical parameters revealed
dyslipidemia in conjunction with statins.
no toxic effects of the extract. Pathologically, neither gross
(Gupta et al., 2001) evaluated the antioxidant and abnormalities nor histopathological changes were observed
hypocholesterolaemic effects of T. arjuna tree bark and to and there was no mortality recorded in 28 days.
compare it with a known antioxidant, vitamin E, also
(Yaidikar et al., 2015) reported that pre-treatment with
performed a randomized controlled trial. One hundred and five
arjunolic acid from the T. arjuna bark effectively prevented the
successive patients with coronary heart disease (CHD) were
cerebral I/R induced oxidative damage by virtue of its
recruited and divided into 3 groups of 35 each in this study.
antioxidant potential and supplementation of arjunolic acid
Group I received placebo capsules; Group II vitamin E
may be beneficial in stroke prone population. Arjunolic acid
capsules 400 units/day; and Group III received finely
from T. arjuna attenuated sodium nitrite-induced cardiac
pulverized T. arjuna tree bark-powder (500 mg) in capsules
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damage in rats and restored the normal balance between pro- III andarjunoside IV, two new triterpenoid glycosides.
and anti-inflammatory cytokines. Moreover, arjunolic acid Phytochemistry. 1982;21:2057-2060.
protected cardiac tissues from both extrinsic and intrinsic cell 11. Anjaneyulu ASR, Prasad AVR. Structure of terminic
death pathways.(Al-Gayyar et al., 2014) acid, a dihydroxy-triterpene carboxylic acid from
Terminalia arjuna. Phytochemistry. 1983;22:993-998.
(Parmar et al., 2006) were observed a decrease in serum
12. Aneja KR, Sharma C, Joshi R. Antimicrobial activity of
concentration of thyroid hormones as well as an increase in the
Terminalia arjuna Wight & Arn.: an ethnomedicinal
hepatic LPO with higher doses of T. arjuna. There is a vital
plant against pathogens causing ear infection. Braz J
need for well controlled multicentric clinical trials in a larger
Otorhinolaryngol. 2012;78:68-74.
setup of subjects with a standardized product for exploring the
13. Bachaya HA, Iqbal Z, Khan MN, Jabbar A, Gilani AH,
true therapeutic potential of T. arjuna.
Din IU. In vitro and in vivo anthelmintic activity of
CONCLUSION Terminalia arjuna bark. Int J Agric Biol. 2009;11: 273-
278.
On the basis of the available literature evidences, T. arjuna is 14. Bajpai M, Pande A, Tewari SK, Prakash D. Phenolic
widely used for treatment of cardiovascular diseases, including contents and antioxidant activity of some food and
heart diseases and related chest pain, high blood pressure and medicinal plants. Int J Food Sci Nutr. 2005;56: 287-291.
high cholesterol. It is also used for earaches and diseases of the 15. Bharani A, Ahirwal K, Jain N. Terminalia arjuna
urinary tract. The effectiveness of T. arjuna as an anti-ischemic reverses impaired endothelial function in chronic
agent and as a potent antioxidant preventing LDL, reperfusion smokers. Indian Heart J. 2004;56:123-128.
ischemic injury to the heart and its potential to reduce 16. Bhawani G, Kumar A, Murthy KSN, Kumari N,
atherogenic lipid levels have been sufficiently demonstrated in Ganapati Swami Ch. A retrospective study of effect of
different experimental and clinical studies. However, Terminalia arjuna and evidence based standard therapy
continuous research progress of using T. arjuna is very much on echocardiographic parameters in patients of dilated
needed in regards to exact molecular mechanism, drug cardiomyopathy. J Pharm Res. 2013;6:493-498.
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studies. Terminalia arjuna in patients with severe refractory
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Terminalia arjuna extracts exhibit significant antimicrobial properties, particularly effective against Gram-negative bacteria. The methanolic extract showed inhibition against various pathogens like Staphylococcus aureus and Escherichia coli. These properties are attributed to its high phenolic and flavonoid content, which disrupt bacterial cell structures or functions. Clinically, these antimicrobial effects support T. arjuna's use in treating infections and could enhance its applicability in preventing bacterial colonization and disease progression when used medicinally .

Evidence supporting Terminalia arjuna as a cardioprotective agent comes from studies showing its effects in reducing oxidative stress and cardiac tissue damage in ischemic-reperfusion injury models. The administration of T. arjuna augmented antioxidants and induced heat shock proteins in treated rabbit hearts, preventing tissue injury and hemodynamic changes associated with ischemic conditions. These findings endorse its potential use in cardiac ischemic conditions, enhancing survival and recovery post-injury .

Terminalia arjuna has shown efficacy in enhancing myocardial function in the context of diabetic cardiomyopathy. Studies report an improvement in myocardial performance, alongside increased baroreflex sensitivity due to reduced oxidative stress and enhanced antioxidant enzyme activity. These effects collectively translate to improved cardiac function and protection against diabetes-induced cardiac dysfunction, highlighting its potential as a therapeutic agent in managing diabetes-related cardiac conditions .

Terminalia arjuna extracts hold potential for various non-cardiac therapeutic applications due to their antioxidant, antimicrobial, and cytoprotective properties. They have shown promise in reducing gastric ulcer lesions, increasing pH, and antioxidant enzyme levels in gastrointestinal applications. Additionally, T. arjuna's antimicrobial activity could aid in treating infections, particularly in settings where preventing or controlling bacterial growth is crucial. These diverse applications underscore its utility beyond cardiac health, in areas like gastroprotection and infection management .

Terminalia arjuna extract has been shown to significantly prevent the increase in oxidative stress and the decline in endogenous antioxidant levels. Studies reported that treatment with T. arjuna extract mitigates oxidative stress and fibrosis induced by agents like isoprenaline. The augmentation of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) have been observed, particularly highlighting its potential in preventing cardiac tissue damage and hemodynamic effects associated with oxidative stress .

The cardioprotective effects of Terminalia arjuna are suggested to arise from its potent antioxidant activities and its role in enhancing myocardial function. Studies indicate that T. arjuna treatment results in a significant decrease in markers of oxidative stress and inflammation, such as IL-6 and TNF-α. Additionally, it has been noted to improve baroreflex sensitivity and myocardial function, which supports its use in enhancing cardiac health and managing heart failure conditions .

The potent antioxidant activity of Terminalia arjuna extract, characterized by its ability to scavenge free radicals and inhibit lipid peroxidation, plays a crucial role in its therapeutic potential. By reducing oxidative stress, T. arjuna extracts help mitigate cellular damage and support the body's defense systems against degenerative diseases. This activity is crucial in conditions like cardiovascular disorders, where oxidative damage is a significant pathological contributor, thereby enhancing its efficacy in both protective and therapeutic settings .

Terminalia arjuna significantly modulates inflammatory markers in coronary artery disease (CAD). Clinical studies revealed a marked decrease in inflammatory cytokines such as hsCRP, IL-18, IL-6, and TNF-α in patients treated with T. arjuna. This modulation suggests its potential in reducing systemic inflammation, which is a critical component in the pathogenesis of CAD, thereby contributing to improved cardiovascular health and reducing disease progression .

Terminalia arjuna has demonstrated significant gastroprotective effects. Treatment with its methanolic extract resulted in reduced lesion index in rats with diclofenac-induced gastric ulcers. This effect is primarily attributed to increased pH levels, heightened levels of non-protein sulfhydryls and reduced glutathione, and enhanced enzymic antioxidants. The reduction in acidity and increase in mucus content are also noted, indicating its potential cytoprotective and free radical scavenging capabilities .

T. arjuna extracts significantly inhibit the activity of CYP3A4, CYP2D6, and CYP2C9 enzymes. This inhibition suggests potential interactions with drugs metabolized by these pathways. Such interactions could either potentiate or inhibit the effects of concurrently administered medications, warranting careful consideration in pharmacotherapy involving T. arjuna, specifically concerning drugs with narrow therapeutic indices or those highly dependent on these cytochromes for metabolism .

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