Vitex negundo

Synonyms

No documentation

Vernacular Names:

Malaysia:

Lemuni, Langgundi, Lenggundi, Legundi, Lagundi, Lemuning, Muning, Demundi

English:  Indian Privet, Five-leaves Chastetree
India:  Sambhalu, Sanduvar (Hindi); Nallavavili, Nirkkundi, Nochi, Vellainochi, Vennochi (Tamil); Nochi, Vellanochi, Vennochi (Malayalam) Indrani, Nirgundi, Nilanirgundi, Surasa, Svetasurasa, Shephali, Sinduvara (Sanskrit)
Nepal:  Simali
China:  Muen kim
Vietnam:  Thuoc on rung [2]

General Information

Description

Vitex negundo is a member of the Verbenaceae family with wide distribution. There are 5 known vartieties of this species of which only one is found in Malaysia i.e Vitex negundo var. negundo. This is a large shrub or small tree with thin grey bark. The young branchlets are quadrangular and are covered with fine white hairs. The tree can reach up to 3 m in height. The leaves are oppositely arranged with 3 to 5 leaflets. Each leaflet is lanceolate, acute, glabrous above with a white, fine hairs below. The terminal leaflet which measures 1.6 – 3.2 cm wide and 5 – 10 cm. long is the longest leaflet and  sits on a long petiole. The lateral leaflets have very short petioles. Flowers are bluish purple and are borne on axillary or terminal panicles up to 30 cm long. They give rise to black globose drupes with four seeds when ripe. In Malaysia there are two variants of this particular species i.e. the one with purple undersurface (Lemuni hitam) and the one with white undersurface (Lemuni putih). The purple one is more common and also the more preferred one. 

Plant Part Used

Whole plant

Chemical Constituents

2b,3a-diacetoxyoleana-5,12-dien-28-oic acid, 2a,3a-dihydroxyoleana-5,12-dien-28-oic acid, 2a, 3b-diacetoxy- 18-hydroxyoleana-5,12-dien-28-oic acid, protocatechuic acid, 2'-p-hydroxy benzoyl mussaenosidic acid, p-hydroxybenzoic acid, hexadecanoic acid, 3, 4-dihydroxy benzoic acid; 6′-p-hydroxybenzoylmussaenosidic acid.

1,4a,5,7a-tetrahydro-1-beta-D-glucosyl-7-(3',4'-dihydroxybenzoyloxymethyl)-5-ketocyclopenta[c]pyran-4-carboxylic acid, 3 beta-acetoxyolean-12-en-27-oic acid, betulinic acid (3beta-hydroxylup-20-(29)-en-28-oic acid), ursolic acid (2beta-hydroxyurs-12-en-28-oic acid), β-caryophyllene a-selinene, β -selinene a-cedrene, germacrene D, sabinene, d-guaiene squalene; gamma-terpinene, alpha-pinene, globulol, germacren-4-ol,b-sitosterol,(E)-nerolidol, viridiflorol; 4-terpineol,1-oceten-3-ol, (+)-lyoniresinol, (+)-(-)-pinoresinol, (+)-diasyringaresinol, linalool, n-hentriacontanol, beta-sitosterol, (+)-lyoniresinol.

carryophyllene epoxide, caryophyllene oxide, ethyl-hexadecenoate, terpinyl acetate, vitexin, isovitexin, vitedoin B, negundin A, negundin B, isoorientin, 5-hydroxy 3, 6, 7, 3', 4'-pentamethoxy flavone; 5-hydroxy 3, 7, 3', 4'-tetramethoxy flavone; 5, 3'-dihydroxy 7, 8, 4'-trimethoxy flavanone; 5,3′-dihydroxy-7,8,4′-trimethoxyflavanone, 5,3′-dihydroxy-6,7,4′-trimethoxyflavanone, negundoside, luteolin 7-glucoside, agnuside luteolin-7-O-beta-D glucoside, nishindaside, (+)-lyoniresinol-3alpha-O-beta-d-glucoside,  6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydroxymethyl-7-methoxy-3,4-dihydro-2- naphthaldehyde, 6-hydroxy-4-(4-hydroxy-3-methoxy)-3-hydroxymethyl-7-methoxy-3,4-dihydro-2-naphtha ledehyde, vitrofolal E,  vitrofolal F, vitrofolal E, 6-hydroxy-4-(4-hydroxy-3-methoxy)-3-hydroxymethyl-7-methoxy-3,4-dihydro-2-naphtha ledehyde,  vitedoamine A.

Traditional Used:

Gastrointestinal Disorders

The juice expressed from the leaves are used to treat various digestive conditions from dyspepsia to helminthiasis. It has the following properties which justify its use in the treatment of various gastrointestinal disorders i.e. anthelminthic, carminative, digestive and stomachic. The roots had been adovacted for the use in the treatment of dyspepsia, colic, verminosis, flatulance and dysentery. The bark is also used to treat worm infestations while the flowers are useful for diarrhoea and cholera. [1] [2]

Respiratory Disorders

The expectorant and anti-inflammatory effects of the plant had been recognized by traditional practitioners all over and had been taken advantage of by many to treat various respitatory conditions. Amongst the most notable use of this plant is in the treatment of cough, a distressing symptom of respiratory disorder. An Ayurvedic cure for productive cough is the use of the decoction of the roots. [3] Others advocate the use of freshly squeezed juice as an expectorant and to treat bronchitis and asthma. [4]

Analgesic and Anti-inflammatory

The fresh leaves of V. negundo had been used in the treatment of pain of rheumatism, gout, lumbago. They are believed to work both as an antinociceptive and an anti-inflammatory.

In Fiji the leaves are pounded with dried ginger and applied as poultice over the forehead to treat headaches. In india the bruised leaves alone are applied to the temple to relieve headache while in Malaysia the leaves are stuffed into pillows and taken to sleep on for similar condition. [5] [6] [7]

For the treatment of rheumatic pains some use the root bark while others advocate the use of the leaves in a decoction.

Obstetrics and Gynaecological uses

In Malaysia the leaves of V. negundo make up one of the ingredients in the post-partum bath which is suppose to not only help in cleansing the birth canal but also helps in revitalizing the body. The mother is also fed “nasi lemuni” which a prepared by taking the juice of the shoots of V. negundo as one of the principle ingredient. It is also being used to treat dysmenorrhoea, dysfunctional uterine bleeding and also to increase production of milk. [8] [9]

Skin conditions

The anti-inflammatory and antimicrobial properties of V. negundo is being taken advantage of in the treatment of various skin conditions including parasiting and bacterial conditions. It is beings used in the treatment of insect bites and snake bites where inflammatory processes is dominent while at the same time the analgesic properties provide relieve of pain. Fresh juice of the leaves forms part of a concoction for the treatment of alopecia. [10]

Pre-Clinical Data

Pharmacology

 

Hepatoprotective effects

Both alcoholic extracts of seeds and leaves of V. negundo showed significant effects in protecting the liver from liver toxins.  Studies found that the alcoholic extract of seeds provide protection from liver damage due to exposure to carbon tetrachloride. They found the extract was able to effectively prevent liver damage as evidenced from morpholigical, biochemical and functional parameters. Tandon et.al did the study on the ethanol extract of the leaves against the hepatotoxic effects of three anti-tuberculous drugs i.e. isoniazid, rifampicin and pyrazinamide. They found that the hepatoproctective effects were significantly seen in doses of 250mg/kg and 500mg/kg. They observed a significant decrease in TB, AST, ALT and ALP levels as compared to control. Histological sections confirmed the hepatoprotective activity. [11] [12]

Tasduq et.al isolated the compound 2’-p-hydroxybenzoylmussaenosidic acid [negundoside] and evaluated it for a possible hepatoprotective property. They found that negundoside did exert a protective effect on CYP2E1-dependent CCl4 toxicity via inhibition of lipid peroxidation, followed by an improve intracellular calcium homeostasis and inhibition of Ca2+-dependent proteases. [13]

Anti-androgenic activity

V. negundo contains a number of flavonoids(5,7,3'-trihydroxy, 6,8,4'-trimethoxy flavones) in it seeds. Bhargava et.al looked into the activities of these flavinoids especially the androgenic effects. They studied the effects of flavinoid rich fraction of the seeds in castrated pre-pubertal and intact adult dogs. Two test models were used one the extract alone and the other the extract together with exogenous testosterone propionate. Treatment with the extract resulted in disruption of the latter stages of sprematogenesis – epididymides were devoid of spermatozoa; there was a reduction in protein, sialic acid and RNA contents of testes and epididymides; elevation of testicular cholesterol and phosphatase activity in testes and epididymes. Reduced androgen production was reflected in the low levels of sialic acid in testes and epididymides. Castration alone resulted in reduction in size and weight of epididymides while the addition of the extract alone cause a reduction in the cellular heights of epididymides. The addition of testosterone proprionate maintained the viability of spermatozoa, kept epididymal physiology relatively normal and significantly increases the cellular heights of epididymides. [14]

A more recent study of a similar preparation and its effects on the reproductive system of male rats showed a reduction in weight of all major accessory sex organs within 15 days of treatment (>/= 15mg/rat/day). This was also reflected in the disturbed tissue biochemistry i.e. diminution of citric acid in the prostate, frutctose in seminal vesicles and epididymal alpha-glucosidae activity and the indices of accessory sex organ function. Microscopic examination of sperm derived from cauda epididymides of treated animals showed only marginal change in vitality. However, there was a reduction in sperm numbers and slackness of their motility was observed. They did the toxicity studies which showed not distress in any of the vital organs. [15]

Antioxidant activity

In the seeds of V. negundo is found lignans and their derivatives which showed high antioxidant activities. These lignans included vitexdoin A, vitedoamine B, vitexdions B – E, vitedoin A, vitedoamine A, vitedoin B, negundins A & B, (+)-diasyrinaresinol, (+)-lyoniresinol, vitrofolal E, vitrofolal F. [16] [17] [18]

Anticataractogenesis

Cataract is the leading cause of blindness and is associated with oxidative damage to the lens. Among the factors that are active in selenite-induced cataracts included loss of calcium homeostasis, calpain activations and protein insolubilization in the lens. A study on the effects of flavonoids from V. negundo showed that this extract there was mild opacification seen in animals treated with the extract as compared to the non treated group. There were significant increase in activities of superoxide dismutase, catalase, Ca2+ATPase, concentration of reduced glutathione and protein sulphhydryl content, where as the activities of calpains was reduced, as were the concentrations of calcium and thiobarbituric acid reactive substances. Then lens protein profile of water soluble proteins showed normal levels of expression. These indicated good antioxidant and therapeutics potential of the flavonoids from V. negundo in modulating biochemical parameters against selenite-induced cataract. [19] [20]

 

CNS Activity

The Methanol extract of the leaves of V. negundo exhibited significant CNS depressant activity in a dose dependent manner. This is evidenced when it was shown that the extract significantly potentiated the sleeping time induced by pentabarbitone sodium, diazepan and chloropromazine in mice, showed significant protection againszt strychnine and leptazole induce convulsion and its ability to potentiate analgesia induced by morphine and pethidine. [21]

In evaluating the anticonvulsion activity of V. negundo leaves Tandon et.al using ethanolic extract did not find anti-convulsant activity to be equi-effective with standard drugs. However, they found it to be more effective in potentiating anticonvulsant activity of valporic acid and those of duphenylhydrantoin. [22]

Antigout activity

In a screening study on a number of Indian medicinal plants for their Xanthine oxidase inhibitory activity, Umamaheswari et.al found that the methanol extract of V. negundo showed xanthine oxidase inhibitory activity greater than 50% with IC50 values below 100 microg/ml. It showed a significant decrease in serum urate level very much similar to those of allopurinol. [23]

Estrogen-like activity

Hu et al detected estrogen-like acitivities from extract of V. negundo to be the highest amongst the number of Vitex species they studied. Such activity could be useful in hormone replacement terapy. [24]

Hypoglycemic activity

In a screening exercise Villasenor et. al found that leaves of V. negundo showed significant decrease in blood glucose level at 60 minutes at alpha=0.05.

Tyrosinase inhibitory activity

Eight lignans were isolated from the leaves of V. negundo which showed tyrosinase inhibitory potency. [negundin A 1, negundin B 2, 6-hydroxy-4-(4-hydroxy-3-methoxy)-3-hydroxymethyl-7-methoxy-3,4-dihydro-2-naphtha ledehyde 3, vitrofolal E 4, (+)-lyoniresinol 5, (+)-lyoniresinol-3alpha-O-beta-d-glucoside 6, (+)-(-)-pinoresinol 7, and (+)-diasyringaresinol 8.] Of the eight compound 5 showed the most potent activity. It was found that the fuctional groups at C-2 and C-3 positions and the presence of –CH2OH group plays an important role in the potency of the compound. [25]

Antisnake venom acitivity

Methanol extract of root of V. negundo was tested for antisnake venom activity. It was found that this extract could neutralize the effects of Vipera russellii and Naja kaouthia venom both in vitro and in vivo. Vipera russellii venom induce haemorrhage, coagulation, defibrinogenation and inflammation and this was significantly neutralized by this extract. [26]

Antimicrobial activities

Antiviral

The water extract of aerial part of V. negundo showed HIV-1 reverse transcriptase inhibitory activity with an inhibition ratio higher than 90% at a 200microg/ml concentration. [27]

Antibacterial

The study of antibacterial activity of various extracts of fruit, flowers and leaves of V. negundo was carried our by Khokra et.al.They found that the essential oils and extracts had promising antibacterial properties against B. subtilis and E. coli. The ethyl acetate and the ethanol extracts had significant antibacterial activity against all tested strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa bacterial strains). Fruits and leaves oil were more active against E.coli and S. Aureus respectively while the flower oil was active against P. Aeruginosa. [28]

 

Antifungal

Sathiamoorthy et.al through bioactivity guided fractionation of ethanolic extract of leaves of Vitex negundo, were able to isolate new flavones glycoside. This compound was found to have significant antifungal activity against Trichophyuton mentagrophytes and Cryptococcus neoformans. [29]

Antifilarial

In a screen activity to look for effective antifilarial activity in herbal plants proved that the aqueous/methanol extract from the roots of V. negundo does have inhibitory activity against Brugia malayi with IC50 of 82ng/ml. In another study they found that the leaves does not contain the neccessary bioactive compounds. [30] [31]

Antinociceptive and Adjuvant tof standard anti-inflammatory drugs

Ethanol extract of the leaves of V. negundo were evaluated for  it antinociceptive activity. Gupta et.al found that does have an antinociceptive property and this this is both of central and peripheral in nature. The central analgesic activity does not seem to be mediated through opoid receptors. They further evaluated its potential as adjuvant to anti-inflammatory drugs and found that this extract was able to potentiated the anti-inflammatory activites of phenylbutazone and ibuprofen. Zheng et.al isolated a lignan – 6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl0-3-hydroxymethyl-7-methoxy-3,4-dihydro-2-naphthaldehyde – from the seeds of V. negundo which proved to have notable anti-inflammaotry activity together with analgesic activity. [32] [33] [34]

Anti-inflammatory activities

The anti-inflammatory activities of various parts of the plant is evident in its use as treatment of a number of inflammatory conditions by the traditional practitioners. Chawla et.al looked into this potential activity in the seeds and isolated a number of triterpenoids which showed anti-inflammatory activity. They are 3 beta-acetoxyolean-12-en-27-oic acid [1], 2 alpha, 3 alpha-dihydroxyoleana-5,12-dien-28-oic acid [2], 2 beta,3 alpha-diacetoxyoleana-5,12-dien-28-oic acid [3], and 2 alpha,3 beta-diacetoxy-18-hydroxyoleana-5,12-dien-28-oic acid [4]. Dharmasiri et.al studied aqueous extracts of fresh mature leaves and found this to be effective ias an analgesia and anti-inflammatory. [35] [36]

Cytotoxic activities

A flavone vitexicarpan exhibited broad cytotoxicity in a human cancer cell line panel. This compound was isolated from bioassay-guided fractionation of chloroform-soluble extracts of the leaves of Vitex negundo. Vitexin lignan compounds were purified and their cytotoxic and antitumour effects were analyzed in cancer cells and in tumout xenoigraft models. It was found that 6-hydroxy-4-(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-7-methoxy-3,  4-dihydro-2-naphthaldehyde have cytotoxic effect on breast, prostate, and ovarian cancer cells and induces apoptosis with cleavage in poly ADP ribose polymerase protein, up-regulation of Bax, and down-regulation of Bcl-2. This induction of apoptosis seems to be mediated by activation of caspases because inhibition of caspases activity significantly reduced apoptosis. [37] [38]

Toxicities

No documentation.

Clinical Data

Clinical Trials

No documentation.

Adverse Effects in Human:

No documentation.

Used in Certain Conditions

Pregnancy / Breastfeeding

No documentation.

Age Limitations

Neonates / Adolescents

No documentation.

Geriatrics

No documentation.

Chronic Disease Conditions

No documentation.

Interactions

Interactions with drugs

No documentation.

Interactions with Other Herbs / Herbal Constituents

No documentation.

Contraindications

Contraindications

V. negundo should be used with caution with the concurrent use of psychotropic drugs, including analgesics, sedatives, antidepressants, anticonvulsants and anti psychotics. With its similarity botanically to the better studied V.agnus castus, and thus may have a similar range of contraindications, including the concurrent use of progesterogenic drugs and hormone replacement therapies. [39]

Case Reports

No documentation.

References

  1. Available from: M. Shaukat, S. Huma, F. Umbreen, K. Arfa and H.R. Ghazala. Antifungal Activities Of Vitex Negundo Linn. 2009. Pak. J. Bot., 41(4): 1941-1943. http://www.pakbs.org/pjbot/PDFs/41%284%29/PJB41%284%291941.pdf. [Accessed on 27th March 2010].
  2. P. K. Warrier, V. P. K. Nambiar, Indian medicinal plants: a compendium of 500 species.Vol 5. Chennai: Orient Longman Private Limited;2002.387.
  3. C. Todd. Āyurveda: the divine science of life. Philadelphia: Elsevier Health Sciences;2006. 255-256.
  4. A.R. Ivan. Medicinal plants of the world: chemical constituents, traditional and modern medicinal uses. New Jersey:Humana Press;2005.510.
  5. L. John. The vegetable kingdom; or, The structure, classification, and uses of plants. London: Bradbury & Evans; 1853.664.
  6. H.C. Ong. Tumbuhan liar: khasiat ubatan & kegunaan lain. Kuala Lumpur: Utusan Publication & Distributors Sdn Bhd;2008.121.
  7. Y. Avadhoot, A.C.Rana. Hepatoprotective effect of Vitex negundo against carbon tetrachloride-induced liver damage. Arch Pharm Res. Mar1991;14(1):96-98.
  8. V.R. Tandon, V. Khajuria, B. Kapoor, D. Kour, S. Gupta. Hepatoprotective activity of Vitex negundo leaf extract against anti-tubercular drugs induced hepatotoxicity. Fitoterapia. Dec2008;79(7-8):533-538.
  9. S.A. Tasduq, P.J. Kaiser, B.D. Gupta, V.K. Gupta, R.K. Johri. Negundoside, an irridiod glycoside from leaves of Vitex negundo, protects human liver cells against calcium-mediated toxicity induced by carbon tetrachloride. World J Gastroenterol. 21Jun2008;14(23):3693-3709.
  10. S.K. Bhargava. Antiandrogenic effects of a flavonoid-rich fraction of Vitex negundo seeds: a histological and biochemical study in dogs. J Ethnopharmacol. Dec1989;27(3):327-339.
  11. S. Das, S. Parveen, C.P. Kundra, B.M. Pereira. Reproduction in male rats is vulnerable to treatment with the flavonoid-rich seed extracts of Vitex negundo. Phytother Res. Jan2004;18(1):8-13.
  12. C.J. Zheng, B.K. Huang, T. Han, Q.Y. Zhang, H. Zhang, K. Rahman, L.P. Qin. Nitric oxide scavenging lignans from Vitex negundo seeds. J Nat Prod. Sep2009;72(9):1627-1630.
  13. M. Ono, Y. Nishida, C. Masuoka, J.C. Li, M. Okawa, T. Ikeda, T. Nohara. Lignan derivatives and a norditerpene from the seeds of Vitex negundo. J Nat Prod. Dec2004;67(12):2073-2075.
  14. Azhar-Ul-Haq, A. Malik, I. Anis, S.B. Khan, E. Ahmed, Z. Ahmed, S.A. Nawaz, M.I. Choudhary. Enzyme inhibiting lignans from Vitex negundo. Chem Pharm Bull (Tokyo). Nov2004;52(11):1269-1272.
  15. B.N. Rooban, Y. Lija, P.G. Biju, V. Sasikala, V. Sahasranamam, A. Abraham. Vitex negundo attenuates calpain activation and cataractogenesis in selenite models. Exp Eye Res. Mar2009;88(3):575-582.
  16. B.N. Rooban, V. Sasikala, V. Sahasranamam, A. Abraham. Vitex negundo Modulates Selenite-Induced Opacification and Cataractogensis in Rat Pups. Biol Trace Elem Res. 20Feb2010.
  17. M. Gupta, U.K. Mazumder, S.R.Bhawal. CNS activity of Vitex negundo Linn. in mice. Indian J Exp Biol. Feb1999;37(2):143-146.
  18. V.R. Tandon, R.K. Gupta. An experimental evaluation of anticonvulsant activity of Vitex-negundo. Indian J Physiol Pharmacol. Apr2005;49(2):199-205.
  19. M. Umamaheswari, K. Asok Kumar, A. Somasundaram, T. Sivashanmugam, V. Subhadradevi, T.K. Ravi. Xanthine oxidase inhibitory activity of some Indian medical plants. J Ethnopharmacol. 12Feb2007 ;109(3):547-551.
  20. Y. Hu, Q.Y. Zhang, T.T. Hou, H.L. Xin, H.C. Zheng, K. Rahman, L.P. Qin. Estrogen-like activities in Vitex species from China determined by a cell based proliferation assay. Pharmazie. Nov2007;62(11):872-875.
  21. Azhar-Ul-Haq, A. Malik, M.T. Khan, Anwar-Ul-Haq, S.B. Khan, A. Ahmad, M.I. Choudhary. Tyrosinase inhibitory lignans from the methanol extract of the roots of Vitex negundo Linn. and their structure-activity relationship. Phytomedicine. Mar2006;13(4):255-260.
  22. M.I. Alam MI, A. Gomes. Snake venom neutralization by Indian medicinal plants (Vitex negundo and Emblica officinalis) root extracts. J Ethnopharmacol. May2003;86(1):75-80.
  23. W. Woradulayapinij, N. Soonthornchareonnon, C. Wiwat. In vitro HIV type 1 reverse transcriptase inhibitory activities of Thai medicinal plants and Canna indica L. rhizomes. J Ethnopharmacol. 3Oct 2005;101(1-3):84-89.
  24. S.L. Khokra, O. Prakash, S. Jain, K.R. Aneja, Y. Dhingra. Essential Oil Composition and Antibacterial Studies of Vitex negundo Linn. Extracts. Indian J Pharm Sci. Jul-Aug2008;70(4):522-526
  25. B. Sathiamoorthy, P. Gupta, M. Kumar, A.K. Chaturvedi, P.K. Shukla, R. Maurya. New antifungal flavonoid glycoside from Vitex negundo. Bioorg Med Chem Lett. 1Jan2007;17(1):239-242.
  26. K.N. Sahare, V. Anandhraman, V.G. Meshram, S.U. Meshram, M.V. Reddy, P.M. Tumane, K. Goswami. Anti-microfilarial activity of methanolic extract of Vitex negundo and Aegle marmelos and their phytochemical analysis. Indian J Exp Biol. Feb2008;46(2):128-131.
  27. K.N. Sahare, V. Anandharaman, V.G. Meshram, S.U. Meshram, D. Gajalakshmi, K. Goswami, M.V. Reddy. In vitro effect of four herbal plants on the motility of Brugia malayi microfilariae. Indian J Med Res. May2008; 127(5): 467-471.
  28. R.K. Gupta, V.R. Tandon. Antinociceptive activity of Vitex-negundo Linn leaf extract. Indian J Physiol Pharmacol. Apr2005;49(2):163-170.
  29. V.R. Tandon, R.K. Gupta. Vitex negundo Linn (VN) leaf extract as an adjuvant therapy to standard anti-inflammatory drugs. Indian J Med Res. Oct2006;124(4):447-450.
  30. C.J. Zheng, W.Z. Tang, B.K. Huang, T. Han, Q.Y. Zhang, H. Zhang, L.P. Qin. Bioactivity-guided fractionation for analgesic properties and constituents of Vitex negundo L. seeds. Phytomedicine. Jun 2009;16(6-7):560-567.
  31. A.S. Chawla, A.K. Sharma, S.S. Handa, K.L. Dhar. Chemical investigation and anti-inflammatory activity of Vitex negundo seeds. J Nat Prod. Feb1992;55(2):163-167.
  32. M.G. Dharmasiri, J.R. Jayakody, G. Galhena, S.S. Liyanage, W.D. Ratnasooriya. Anti-inflammatory and analgesic activities of mature fresh leaves of Vitex negundo. J Ethnopharmacol. Aug2003;87(2-3):199-206.
  33. F. Díaz, D. Chávez, D. Lee, Q. Mi, H.B. Chai, G.T. Tan, L.B. Kardono, S. Riswan, C.R. Fairchild, R. Wild, N.R. Farnsworth, G.A. Cordell, J.M. Pezzuto, A.D. Kinghorn. Cytotoxic flavone analogues of vitexicarpin, a constituent of the leaves of Vitex negundo. J Nat Prod. Jun2003;66(6):865-867.
  34. Y. Zhou, Y.E. Liu, J. Cao, G. Zeng, C. Shen, Y. Li, M. Zhou, Y. Chen, W. Pu, L. Potters, Y.E. Shi. Vitexins, nature-derived lignan compounds, induce apoptosis and suppress tumor growth. Clin Cancer Res. 15 Aug2009;15(16):5161-5169.
  35. Chawla AS, Sharma AK, Handa SS, Dhar KL. Chemical investigation and anti-inflammatory activity of Vitex negundo seeds. J Nat Prod. Feb1992;55(2):163-167.
  36. Dharmasiri MG, Jayakody JR, Galhena G, Liyanage SS, Ratnasooriya WD. Anti-inflammatory and analgesic activities of mature fresh leaves of Vitex negundo. J Ethnopharmacol. Aug2003;87(2-3):199-206.
  37. Díaz F, Chávez D, Lee D, Mi Q, Chai HB, Tan GT, Kardono LB, Riswan S, Fairchild CR, Wild R, Farnsworth NR, Cordell GA, Pezzuto JM, Kinghorn AD. Cytotoxic flavone analogues of vitexicarpin, a constituent of the leaves of Vitex negundo. J Nat Prod. Jun2003;66(6):865-867.
  38. Zhou Y, Liu YE, Cao J, Zeng G, Shen C, Li Y, Zhou M, Chen Y, Pu W, Potters L, Shi YE. Vitexins, nature-derived lignan compounds, induce apoptosis and suppress tumor growth. Clin Cancer Res. 15 Aug2009;15(16):5161-5169.
  39. Todd Caldecott. Āyurveda: the divine science of life. Philadelphia: Elsevier Health Sciences;2006.  255-256