Vitex negundo L.

Last updated: 15 Aug 2016

Scientific Name

Vitex negundo L.   

Synonyms

Agnus-castus incisa (Lam.) Carrière, Agnus-castus negundo (L.) Carrière, Vitex arborea Desf., Vitex chinensis Mill., Vitex elmeri Moldenke, Vitex gracilis Salisb., Vitex incisa Lam., Vitex laciniata Schauer, Vitex leucoxylon Blanco [Illegitimate], Vitex simplicifolia B.N.Lin & S.W.Wang [Illegitimate], Vitex sinuata Medik., Vitex spicata Lour. [1]

Vernacular Name

Malaysia Lagundi, lemuning, lenggundi, peninchang [2]
English Chinese chaste tree, horse shoe vitex, negundo chaste tree [2], Indian privet [3], five-leaved chaste tree [2][3]
China Huang ching, huang jing [2]
India Sambhalu, sanduvar (Hindi); nallavavili, nirkkundi, nochi, vellainochi, vennochi (Tamil); nochi, vellanochi, vennochi (Malayalam); indrani, nirgundi, nilanirgundi, surasa, svetasurasa, shephali, sinduvara (Sanskrit) [3]
Indonesia Ai tuban, lagundi laut laki-laki [2]
Thailand Khon thee khamoa, ku-no-kaa-mo, kuuning [2]
Philippines Dangla, lagundi [2]
Cambodia Trasiet [2]
Vietnam Thuoc on rung [3]
Nepal Simali, sinyal [2]
Pakistan Gwanak [2].

Geographical Distributions

Vitex negundo is often found gregariously in humid places or along watercourses, in waste places, thickets and mixed open forest, up to 1700 m altitude. [4]

Botanical Description

V. negundo is a member of the Verbenaceae family. It is very variable and many varieties and formae have been distinguished. It is a deciduous shrub or small tree up to 8 m tall. The bark surface is slightly rough, peeling off in papery flakes, and pale reddish-brown. [4]

There are 3-5 leaflets, narrowly elliptical to ovate-lanceolate, minutely puberulous or glabrous above, densely tomentose or puberulent below, median leaflet 5-15 cm x 1-4 cm, with 2-12(-18) pairs of lateral veins, median leaflet on a 1-2.5 cm long petiolule, lateral ones sometimes subsessile. [4]

The cymes are arranged in panicles which are terminal and axillary in the upper leaf axils. The calyx is 1-2 mm long, shortly 5-toothed, corolla blue-violet, and villous inside. [4]

The fruit is globose to broadly ovoid, 3-6 mm long, purple or black when mature. [4]

Cultivation

No documentation.

Chemical Constituent

Vitex negundo has been reported to contain 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-β-d-glucoside 6, (+)-(-)-pinoresinol 7, and (+)-diasyringaresinol 8. [5]

CHCl3 extract of the V. negundo defatted seeds has been reported to contain triterpenoids (e.g. 3β-acetoxyolean-12-en-27-oic acid, 2α,3α-dihydroxyoleana-5,12-dien-28-oic acid, 2β,3α-diacetoxyoleana-5,12-dien-28-oic acid, and 2α,3β-diacetoxy-18-hydroxyoleana-5,12-dien-28-oic acid). [6]

Plant Part Used

Whole plant, leaves, roots, flowers [4]

Traditional Use

V. negundo  is being used to treat dysmenorrhoea, gastrointestinal disoders and to increase production of milk. [7]

V. negundo leaves were used in traditional medicine to treat dispersing swellings of the joint joints from acute rheumatism and of the testes from suppressed gonorrhea. Extract of the leaves advocates the properties of antibacteria, antitumour, astringent, febrifuge, sedative, tonic and vermifuge [8][9]. Ayurvedic uses V. negundo leaves by crushing them into poultice and is applied to cure headaches, neck gland sores, tubercular neck swellings and sinusitis [9]. In India, a decoction of V. negundo aromatic leaves make up a warm post-partum bath which is suppose to not only help in cleansing the birth canal but also helps in revitalizing the body [10]. The bruised leaves alone are applied to the temple to relieve headache [10] while in Malaysia the leaves are stuffed into pillows and taken to sleep for the same purpose [7]

For the treatment of rheumatic pains some use the a decoction of the leaves and root. [7]

The fresh berries are pound to pulp and used in the form of tincture for the relief of paralysis, pains in the limbs and weakness. [9]

Preclinical 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 250 mg/kg and 500 mg/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]

Hepatoprotective effect of V. negundo against carbon tetrachloride-induced liver damage. [11]

Hepatoprotective activity of V. negundo leaf extract against anti-tubercular drugs induced hepatotoxicity. [12]

Negundoside, an irridiod glycoside from leaves of V. negundo, protects human liver cells against calcium-mediated toxicity induced by carbon tetrachloride. [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]

Another 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 (>/= 15 mg/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

Lignans and their derivatives (e.g. vitexdoin A, vitedoamine B, vitexdions B – E, vitedoin A, vitedoamine A, vitedoin B, negundins A & B, (+)-diasyrinaresinol, (+)-lyoniresinol, vitrofolal E, and vitrofolal F) found in the V. negundo seeds showed high antioxidant activities. [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]

Central nervous system (CNS) activity

Methanol extract of the V. negundo leaves 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 μg/mL. It showed a significant decrease in serum urate level very much similar to those of allopurinol. [23]

Estrogen-like activity

It has been detected that V. negundo extract exhibited estrogen-like acitivities and be the highest amongst the number of Vitex species studied. Such activity could be useful in hormone replacement terapy. [24]

Tyrosinase inhibitory activity

Five out of eight lignans compounds isolated from the V. negundo leaves showed tyrosinase inhibitory potency. 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. [5]

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. [25]

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 200 μg/mL concentration. [26]

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. [27]

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[28]

Crude ethanol extract of V. negundo dried fruits (seeds) showed excellent antifungal activity against Fusarium solani (90%) in agar dilution method which is almost equivalent to the Miconazole and Amphotericin B reference drug while moderate activity was found against Microsporum canis (60%). [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 82 ng/mL. In another study they found that the leaves does not contain the neccessary bioactive compounds. [30][31]

Antinociceptive and anti-inflammatory activities.

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. Dharmasiri et.al studied aqueous extracts of fresh mature leaves and found this to be effective ias an analgesia and anti-inflammatory. [6][35]

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 V 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. [36][37]

Toxicity

No documentation.

Clinical Data

Clinical findings

No documentation.

Precautions

No documentation.

Interaction & Depletion

No documentation.

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. [38]

Case Report

No documentation.

Dosage

No documentation.

Poisonous Management

No documentation.

Line drawing

No documentation.

References

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  12. Tandon VR, Khajuria V, Kapoor B, Kour D, Gupta S. Hepatoprotective activity of Vitex negundo leaf extract against anti-tubercular drugs induced hepatotoxicity. Fitoterapia. 2008;79(7-8):533-538.
  13. Tasduq SA, Kaiser PJ, Gupta BD, Gupta VK, Johri RK. Negundoside, an irridiod glycoside from leaves of Vitex negundo, protects human liver cells against calcium-mediated toxicity induced by carbon tetrachloride. World J Gastroenterol. 2008;14(23):3693-3709.
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  26. Woradulayapinij W, Soonthornchareonnon N, Wiwat C. In vitro HIV type 1 reverse transcriptase inhibitory activities of Thai medicinal plants and Canna indica L. rhizomes. J Ethnopharmacol. 2005;101(1-3):84-89.
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  36. Díaz F, Chávez D, Lee D, et al. Cytotoxic flavone analogues of vitexicarpin, a constituent of the leaves of Vitex negundo. J Nat Prod. 2003;66(6):865-867.
  37. Zhou Y1, Liu YE, Cao J, et al. Vitexins, nature-derived lignan compounds, induce apoptosis and suppress tumor growth. Clin Cancer Res. 2009;15(16):5161-5169.
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