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Phytopharmacological overview of Terminalia chebula Retz

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Phytotherapy is the traditional method used to cure many diseases. Various medicinal plants found in many parts of India are well known for their various medicinal values. The Terminalia chebula Retz. a native plant of Asia is found to have various properties like anti-oxidant and free radical scavenging activity, anti-carcinogenic activity, ant-imutagenic activity, anti-bacterial activity, anti-fungal activity, anti-viral activity, anti-diabetic, renoprotective activity, cardio-protective activity, anti-inflammatory and anti-arthritic activity. These properties of T. chebula discussed in this review are mainly due to the presence of various types of phytoconstituents.
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Review Article
Pharmacognosy Journal, Vol 8, Issue 4, Jul-Aug, 2016 307
Phytopharmacological overview of Terminalia chebula Retz.
Agaath Hedina1, Punniya Kotti2, Juveriyah Kausar1, Sivasamy1, Vijaya Anand1*
1Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, Tamil Nadu, INDIA.
2Department of Biochemistry, Kanchi Shri Krishna College of Arts and Science, Kancheepuram, Tamil Nadu, INDIA.
ABSTRACT
Phytotherapy is the traditional method used to cure many diseases. Various
medicinal plants found in many parts of India are well known for their vari-
ous medicinal values. The Terminalia chebula Retz. a native plant of Asia is
found to have various properties like anti-oxidant and free radical scavenging
activity, anti-carcinogenic activity, ant-imutagenic activity, anti-bacterial activity,
anti-fungal activity, anti-viral activity, anti-diabetic, renoprotective activity,
cardio-protective activity, anti-inammatory and anti-arthritic activity. These
properties of T. chebula discussed in this review are mainly due to the pres-
ence of various types of phytoconstituents.
Key words: Terminalia chebula, Anti-oxidant, Phytoconstituents, Free radical,
Anti-fungal, Anti-carcinogenic, Renoprotective, Anti-arthritic, Anti-inammatory.
Corresponding author: Dr. A. Vijaya Anand, Associate Professor and Head,
Department of Human Genetics and Molecular Biology, Bharathiar University,
Coimbatore-641 046, Tamil Nadu, INDIA.
Phone no: +91 9842525830
Email: avamiet@yahoo.com
DOI : 10.5530/pj.2016.4.1
INTRODUCTION
e Siddha and Ayurveda treatments use plants to cure various diseas-
es;1 they are the traditional method adopted in India before 5000 years.
e use of plants in various treatments has drawn attention in recent
years due to their accuracy in treatment and their reduced or absence
of side eects. Treatments involving the use of chemically synthesized
compounds have more severe side eects to patients other than cur-
ing the disease eectively. Terminalia chebula Retz. is one of the many
traditional medicinal trees used to treat many diseased conditions. T.
chebula under the family Combretaceae, a native plant in India and
Southeast Asia, is widely cultivated in Taiwan. Its dried ripe fruit, also
called as medicinal Terminalia fruit, has traditionally been used as a
way to treat various ailments in Asia.2 T. ch e b ula possesses a large num-
ber of dierent types of phytoconstituents which exhibits a number of
medicinal activities. e fruit of the tree provides diverse health benets
and is a traditional medicine for household remedy against various
human ailments over decades.3 T. chebula has been widely used in
Ayurveda, Unani and Homoeopathic medicine and has become an
important part of modern medicine. e presence of the various phyto-
chemicals like polyphenols, terpenes, anthocyanins, avonoids, alka-
loids and glycosides makes them a potent anti-oxidant, anti-fungal, anti-
bacterial, anti-viral agents.
BOTANICAL DESCRIPTION
T. chebula is a native plant of Asia, found predominantly in Srilanka,
Bangladesh, Egypt, Turkey, Tibet, Pakistan and various parts of India.
is is a deciduous tree that grows up to 30 m in height with a crown
shaped like a broad disk.4 is tree grows at the height of 1500-2000 m.
ey have sub-opposite or alternate leaves elliptic blades of 7-18×4.4-10
cm. ey have veins which are lateral and they occur as 6-12 pairs.
T. ch e bula have monoecious owers with unpleasant smell and are pale
yellow in color. e unripen fruit is green in color and the ripe fruit is
yellowish grey in color with the size of 1-2 inches. May to June is the time
the owers appear and July to December the fruits appear.
ANTI-OXIDANT AND FREE RADICAL
SCAVENGING ACTIVITY
Compounds that can scavenge excessive free radicals in the body
can hinder the process of carcinogenesis. e leaves, bark and fruit of
T. chebula possessed high anti-oxidant activity due to the presence of
phenolics which is responsible for this activity.5 Aqueous form of the
extract of T. chebula inhibited xanthine/xanthine oxidase activity and
was also a scavenger of DPPH radicals.5 e poly-herbal formulation of
T. ch ebu la (Aller-7/ NR-A2) is found to inhibit the hemolysis and makes
the lipopolysaccharide to release nitric oxide in an inhibited form.6
Acetone extract has stronger anti-oxidant activity than alpha-tocopherol
and HPLC analysis with diode array detection indicated the presence of
phenolic compounds such as hydroxybenzoic acid derivatives, hydroxyl
cinnamic acid derivatives, avonol aglycones and their glycosides.7
ANTI-CARCINOGENIC ACTIVITY
A group of researchers have reported the phenolics of T. chebu l a fruit
have inhibitory action on cancer cell growth and found that tannic acid,
ellagic acid and chebulinic were the growth inhibitory phenolics of
T. chebula.8 Ethanol extract of T. chebula fruit inhibited cell proliferation
and induce the death of the cell in a dose dependent manner in many
malignant cell lines including breast cancer cell line of mouse (S115)
and human (MCF-7), human osteosarcoma cell line (HOS-1), a non-tu-
morigenic immortalized human prostate cell line (PNT1A) and human
prostate cancer cell (PC-3).9 Besides, acetone extract of bark and fruit
powder of T. chebula have constituents with promising anti-carcinogenic
activity.9
ANTI-MUTAGENIC ACTIVITY
Anti-mutagenic activity of aqueous extract and hydrolyzable tannins
from T. chebula in Salmonella typhimurium has been well documented.10
e aqueous extract of T. c h ebula inhibits gamma radiation induced
strand breaks formation in plasmid PBR322 DNA.11 e administration
of aqueous extract of T. chebula prior to whole body irradiation of mice
resulted in a reduction of peroxidation of membrane lipids in the mice
liver and a decrease in radiation induced errors to DNA. It also protected
the human lymphocytes from the harmful gamma radiation-induced
damage to DNA exposed in vitro.12 T. chebula showed chemo preventive
eects on toxicity, nickel chloride -induced renal oxidative stress, and
cell proliferation response in male Wistar rat.
ANTI-BACTERIAL ACTIVITY
T. chebula showed anti-bacterial activity against both Gram-positive and
Gram-negative human pathogenic bacteria.13,14 Ethanedioic acid and
Anand et al.: T. cheb u l a
308 Pharmacognosy Journal, Vol 8, Issue 4, Jul-Aug, 2016
ellagic acid isolated from T. Chebula fruit extract had strong anti-bacterial
activity against intestinal bacteria, Clostridium perngens and Esch-
erichia coli.15 It is eective against Helicobactor pyroli by inhibiting the
urease activity, and ubiquitous bacterium which cause stomach cancer,
ulcers and gastritis.14 e methicillin-resistant Staphylococcus au-
reus when treated with the extract of T. cheb u l a showed decreased
growth and activity thereby conrming the anti-bacterial activity. e
ripe seeds of T. chebula also have strong anti-bacterial activity against
S. aureus. e aqueous extract of T. chebula strongly inhibited the growth
of Streptococcus mutants, salivary bacteria.16
ANTI-FUNGAL ACTIVITY
An aqueous extract of T. chebula showed anti-fungal activity against a
number of dermatophytes and yeasts. It’s activity is eective against the
pathogenic yeast Candida albicans and dermatophytes Epidermophyton
occosum, Microsporumgy pseum and Trichophyton rubrum.17 Methanol
extract of T. chebula have anti-candidal activity which acts against
clotrimazole resistant Candida albicans. Anti-fungal activity against
Trichophyton glabrata exhibited by seed extracts.18
ANTI-VIRAL ACTIVITY
T. chebula fruits used for four immunodeciency virus HIV-1 (type 1)
integrase inhibitors, GA (I) and three galloyl glucoses (II-IV). eir
galloyl moiety plays an important role for inhibition of 3’-processing
of HIV-1 integrase of the compounds.19 T. chebula also exhibit retroviral
reverse transcriptase inhibitory activity.20 It protects epithelial cells
against inuenza a virus; supporting its use for aiding in treatment of
acute respiratory infections.21 It also showed the therapeutic activity
against herpes simplex virus both in vitro and in vivo tests.22 ese nd-
ings encouraged a team of Japanese researchers to investigate T. chebula
eect on human cytomegalovirus (CMV). e replication of human
cyto-magalo virus in AIDS is found to be inhibited by the extract of
T. ch ebu la and also in preventing CMV disease.
ANTI-DIABETIC AND RENOPROTECTIVE ACTIVITY
In streptozotocin induced diabetic rats T. chebula fruit and seeds showed
dose dependent reduction in blood glucose both in short term and long
term study and also had renoprotective activity. e high blood sugar
level is reduced to normal by using the extract of T. chebula.23,24
CARDIOPROTECTIVE ACTIVITY
Pretreatment with the extract of T. chebula was found to ameliorate the
consequence of isoproterenol on the formation of lipid peroxide and
also retained the activities of the diagnostic marker enzymes in iso-
proterenol induced myocardial damage in rats.25 Its pericap has been
reported to have cardioprotective activity which is showed in isolated
frog heart model.
ANTI-INFLAMMATORY AND ANTI-ARTHRITIC
ACTIVITY
Aqueous extract of dried fruit of T. chebula demonstrated inhibition of
inducible nitric oxide synthesis which shows anti-inammatory activity.26
Chebulagic acid obtained from immature seeds of T. chebula signicantly
suppressed the onset and progression of collagen induced arthritis in
mice.27 Polyherbal formulation (Aller-7) containing T. chebula exhibited
a dose dependent anti-inammatory activity against Freund’s adjuvant
induced arthritis in rats.28
CONCLUSION
Among all the rapidly healing chemical medicines available, a large number
of populations in the whole world are still using plants to cure disease.
e T. cheb u l a with its numerous pharmacological activities found its
rightful place in traditional medicine. More biochemical tests are yet to
be conducted to nd more uses and potential value of T. chebula. is
can lead to a rapid emergence of the use of plant extracts to cure many
diseases without causing any harm to the patient thereby leading to a
healthy environment.
ACKNOWLEDGEMENT
None.
CONFLICT OF INTEREST
No funding source and there is no conict of interest.
ABBREVIATION USED
DPPH: 1,1-Diphenyl-2-picryl-hydrazyl; HPLC: High Performance Liq-
uid Chromatography; AIDS: Acquired Immune Deciency Syndrome.
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PICTORIAL ABSTRACT
This review conrmed the ability of Terminalia chebula Retz.
Terminalia chebula exhibit anti-microbial, anti-diabetic, cardio-protective,
anti-oxidant and anti-cancer activities.
Its support the traditional uses Terminalia chebula.
ABOUT AUTHOR
Dr. A. Vijaya Anand: Associate Professor and Head, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore,
Tamil Nadu, India. He has published multiple scientic articles in international journals. He is currently engaged in the eld of phytopharmacology,
neurogenetics, medical genetics and clinical biochemistry.
SUMMARY
... The presence of phenolics in the leaves, bark, and fruit of T. chebula has resulted in high antioxidant activity. The aqueous extract of T. chebula inhibited xanthine/xanthine oxidase activity and scavenged DPPH radicals [36]. Acetone extract pointed to hydroxybenzoic acid derivatives, hydroxycinnamic acid derivatives, flavonols, aglycon, and glycosides responsible for their antioxidative properties [17]. ...
... The potential anti-bacterial activity of T. chebula has been investigated in several studies. Antibacterial activity was found in T. chebula against both gram-positive and gram-negative human pathogenic microorganisms [36]. Leaf extract is bactericidal against Escherichia coli, Shigella sp, Vibrio cholerae and Salmonella sp [151]. ...
... The ripe seeds have shown potent anti-bacterial properties that are particularly effective against S. aureus. Salivary bacteria called Streptococcus mutants were severely constrained in their growth by the aqueous extract of T. chebula [36]. ...
Article
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Terminalia chebula Retz, commonly known as 'Haritaki/Myrobalan,' has been utilised as a traditional medicine for a long time. It has been extensively exercised in various indigenous medicine practices like Unani, Tibb, Ayur-veda, and Siddha to remedy human ailments such as bleeding, carminative, dysentery, liver tonic, digestive, antidiarrheal, analgesic, anthelmintic, antibacterial and helpful in skin disorders. Studies on the pharmacological effects of T. chebula and its phytoconstituents documented between January, 1996 and December, 2021 were explored using various electronic databases. During the time mentioned above, several laboratory approaches revealed the biological properties of T. chebula, including antioxidative, antiproliferative, anti-microbial, proap-optotic, anti-diabetic, anti-ageing, hepatoprotective, anti-inflammatory, and antiepileptic. It is also beneficial in glucose and lipid metabolism and prevents atherogenesis and endothelial dysfunction. Different parts of T. chebula such as fruits, seeds, galls, barks extracted with various solvent systems (aqueous, ethanol, methanol, chloroform, ethyl-acetate) revealed major bioactive compounds like chebulic acid, chebulinic acid, and chebulaginic acid, which in turn proved to have valuable pharmacological properties through broad scientific investigations. There is a common link between chebulagic acid and chebulanin with its antioxidant property, antiaging activity, antiinflammatory, antidiabetic activity, and cardioprotective activity. The actions may be through neutralizing the free radicals responsible for producing tissue damage alongside interconnecting many other diseases. The current review summarises the scientifically documented literature on pharmacological potentials and chemical compositions of T. chebula, which is expected to investigate further studies on this subject.
... The presence of phenolics in the leaves, bark, and fruit of T. chebula has resulted in high antioxidant activity. The aqueous extract of T. chebula inhibited xanthine/xanthine oxidase activity and scavenged DPPH radicals [36]. Acetone extract pointed to hydroxybenzoic acid derivatives, hydroxycinnamic acid derivatives, flavonols, aglycon, and glycosides responsible for their antioxidative properties [17]. ...
... The potential anti-bacterial activity of T. chebula has been investigated in several studies. Antibacterial activity was found in T. chebula against both gram-positive and gram-negative human pathogenic microorganisms [36]. Leaf extract is bactericidal against Escherichia coli, Shigella sp, Vibrio cholerae and Salmonella sp [151]. ...
... The ripe seeds have shown potent anti-bacterial properties that are particularly effective against S. aureus. Salivary bacteria called Streptococcus mutants were severely constrained in their growth by the aqueous extract of T. chebula [36]. ...
Article
Full-text available
Terminalia chebula Retz, commonly known as ‘Haritaki/Myrobalan,’ has been utilised as a traditional medicine for a long time. It has been extensively exercised in various indigenous medicine practices like Unani, Tibb, Ayurveda, and Siddha to remedy human ailments such as bleeding, carminative, dysentery, liver tonic, digestive, antidiarrheal, analgesic, anthelmintic, antibacterial and helpful in skin disorders. Studies on the pharmacological effects of T. chebula and its phytoconstituents documented between January, 1996 and December, 2021 were explored using various electronic databases. During the time mentioned above, several laboratory approaches revealed the biological properties of T. chebula, including antioxidative, antiproliferative, anti-microbial, proapoptotic, anti-diabetic, anti-ageing, hepatoprotective, anti-inflammatory, and antiepileptic. It is also beneficial in glucose and lipid metabolism and prevents atherogenesis and endothelial dysfunction. Different parts of T. chebula such as fruits, seeds, galls, barks extracted with various solvent systems (aqueous, ethanol, methanol, chloroform, ethyl-acetate) revealed major bioactive compounds like chebulic acid, chebulinic acid, and chebulaginic acid, which in turn proved to have valuable pharmacological properties through broad scientific investigations. There is a common link between chebulagic acid and chebulanin with its antioxidant property, antiaging activity, antiinflammatory, antidiabetic activity, and cardioprotective activity. The actions may be through neutralizing the free radicals responsible for producing tissue damage alongside interconnecting many other diseases. The current review summarises the scientifically documented literature on pharmacological potentials and chemical compositions of T. chebula, which is expected to investigate further studies on this subject.
... This plant have many biological activities such as antioxidant, anti-carcinogenic, anti-imutagenic, antibacterial, anti-fungal, anti-viral, anti-diabetic, renoprotective, cardioprotective, anti-inflammatory, and anti-arthritic actions. Polyphenols, terpenes, anthocyanins, flavonoids, alkaloids glycosides, coumarin, and tannins are among the phytochemicals that responsible to above health benefits [72][73][74]. It has shown therapeutic effectiveness against Herpes simplex virus (HSV) in vitro and in vivo by suppression of retroviral reverse transcriptase activity in virus [73,75]. ...
... Polyphenols, terpenes, anthocyanins, flavonoids, alkaloids glycosides, coumarin, and tannins are among the phytochemicals that responsible to above health benefits [72][73][74]. It has shown therapeutic effectiveness against Herpes simplex virus (HSV) in vitro and in vivo by suppression of retroviral reverse transcriptase activity in virus [73,75]. 84 Kurokawa et al. [76] discovered that combining acyclovir with the herbal extract terminalia chebula Retz had tough combined beneficial anti-HSV-1 activity in mice, with no toxicity and reduced the development of skin lesions in infected mice and/or extended their average survival periods when compared to using both acyclovir and the herbal extract separately. ...
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Herpes are a group of similar viruses that are responsible for a number of infecting diseases, the most important of which are herpes simplex, herpes zoster and pseudopox. Resistance to traditional antiviral medications is becoming increasingly common, making treatment of such infections even more difficult. For example, the usage of nucleoside analogues like acyclovir to target the DNA-polymerase of the virus on a regular and long-term basis promotes the generation of resistant viruses. As a result, a different treatment is required. Natural products, such as herbal remedies, have been shown to have in vitro and in vivo activity against herpes viruses, and have shown to be a valuable source for new antivirals development and separation. The goal of this review is to highlight the most promising extracts and pure chemicals obtained from plants and marine species that have in vivo anti-herpes simplex virus (HSV-1 and HSV-2) action. Natural products as new anti-HSV medications offer a number of benefits, including fewer side effects, minimal toxicity, and lowered resistance, and a variety ways of deed.
... It also contains phenolic compounds, viz., galloylglucose, corilagin, terflavin A, punicalagin, triterpene maslinic acid, and so on [33]. This plant is known to possess broadspectrum activities, viz., antiviral, antiprotozoal, antibacterial, antifungal, etc., and has anticancer [34], antidiabetic [35], hepatoprotective [36,37], immunomodulatory [38], antiinflammatory [30], wound healing [39,40], cardio-protective [41,42], anti-caries [43], etc., activities. Hydrolyzable tannins from T. chebula are well documented for antiviral activities [44], viz., anti-HCV [45,46], anti-HSV-1 [47], anti-HSV-2 (HSV, herpes simplex virus) [48] activity via inhibiting entry and multiple viral targets. ...
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Terminalia chebula Retz. forms a key component of traditional folk medicine and is also reported to possess antihepatitis C virus (HCV) and immunomodulatory activities. However, information on the intermolecular interactions of phytochemicals from this plant with HCV and human proteins are yet to be established. Thus, by this current study, we investigated the HCV NS3/4A inhibitory and host immune-modulatory activity of phytocompounds from T. chebula through in silico strategies involving network pharmacology and structural bioinformatics techniques. To start with, the phytochemical dataset of T. chebula was curated from biological databases and the published literature. Further, the target ability of the phytocompounds was predicted using BindingDB for both HCV NS3/4A and other probable host targets involved in the immune system. Further, the identified targets were docked to the phytochemical dataset using AutoDock Vina executed through the POAP pipeline. The resultant docked complexes with significant binding energy were subjected to 50 ns molecular dynamics (MD) simulation in order to infer the stability of complex formation. During network pharmacology analysis, the gene set pathway enrichment of host targets was performed using the STRING and Reactome pathway databases. Further, the biological network among compounds, proteins, and pathways was constructed using Cytoscape 3.6.1. Furthermore, the druglikeness, side effects, and toxicity of the phytocompounds were also predicted using the MolSoft, ADVERpred, and PreADMET methods, respectively. Out of 41 selected compounds, 10 were predicted to target HCV NS3/4A and also to possess druglike and nontoxic properties. Among these 10 molecules, Chebulagic acid and 1,2,3,4,6-Pentagalloyl glucose exhibited potent HCV NS3/4A inhibitory activity, as these scored a lowest binding energy (BE) of −8.6 kcal/mol and −7.7 kcal/mol with 11 and 20 intermolecular interactions with active site residues, respectively. These findings are highly comparable with Asunaprevir (known inhibitor of HCV NS3/4A), which scored a BE of −7.4 kcal/mol with 20 key intermolecular interactions. MD studies also strongly suggest that chebulagic acid and 1,2,3,4,6-Pentagalloyl glucose as promising leads, as these molecules showed stable binding during 50 ns of production run. Further, the gene set enrichment and network analysis of 18 protein targets prioritized 10 compounds and were predicted to potentially modulate the host immune system, hemostasis, cytokine levels, interleukins signaling pathways, and platelet aggregation. On overall analysis, this present study predicts that tannins from T. chebula have a potential HCV NS3/4A inhibitory and host immune-modulatory activity. However, further experimental studies are required to confirm the efficacies.
... Some Chinese patented drugs, such as "Zhachong shisanwei pill" and "fengshi zhitong pill", contain the fruit of TC as their primary active ingredient and are widely used in clinical practice. The extracts isolated from the fruit of TC are reported to exhibit anti-oxidative, anti-tumor, anti-virus, anti-inflammatory, and anti-arthritic activities [18][19][20]. ...
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Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and progressive joint destruction. Chebulanin is a natural polyphenol acid isolated from the traditional Tibetan medicine Terminalia chebula Retz that has previously been reported to possess anti-inflammatory properties. The present study aimed to investigate the anti-inflammatory and anti-arthritic effects of chebulanin and explore its underlying mechanisms in vivo and in vitro using a collagen-induced arthritis (CIA) mouse model and lipopolysaccharide (LPS) stimulated RAW264.7 cell inflammation model. Arthritis severity scores were assessed twice weekly; the levels of cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum were detected using enzyme-linked immunosorbent assay kits; histopathological assessment was performed using micro computed tomography and hematoxylin and eosin staining. Activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were assessed using western blotting. The inhibition of translocation of cytosolic p38 and p65 into the nucleus was observed using immunofluorescence staining and western blotting in vitro. Chebulanin significantly suppressed the progression and development of RA in CIA mice by decreasing the arthritis severity scores, attenuating paw swelling and joint destruction, and reducing the levels of IL-6 and TNF-α significantly (p < 0.05). Furthermore, chebulanin reduced the levels of excised phosphorylated (p)-p38, phosphorylated-c-JUN N-terminal kinase (p-JNK), p-p65 and phosphorylated NF-κB inhibitor alpha (p-IκBα) in CIA mice, but did not affect the level of phosphorylated extracellular-signal-regulated kinase (ERK). In addition, chebulanin could inhibit the nuclear translocation of p38 and p65 in LPS-stimulated macrophages in dose-dependent manner. In conclusion, this study demonstrated that chebulanin exerts anti-inflammatory and anti-arthritic effects by inhibiting the activation of NF-κB and MAPK signaling pathways.
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Plants from Africa and Mauritius with a history of use in traditional medicine have been investigated for their antiviral activities. Extracts were tested against poliovirus, herpes simplex virus and rhinovirus in plaque reduction assays. Their general toxicity and effects on interferon production were also studied.