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Hepatoprotective effect of Vitex negundo against carbon tetrachloride-induced liver damage.

Alcoholic extract of the seeds of Vitex negundo Linn. was obtained by cold maceration. A dose of 250 mg/kg (1/6 of LD50) of the extract was selected to study the hepatoprotective action against carbon tetrachloride-induced liver damage. The extract was found to be effective in preventing liver damage which was evident by morphological, biochemical and functional parameters.

Animals↗

Antiandrogenic effects of a flavonoid-rich fraction of Vitex negundo seeds: a histological and biochemical study in dogs.

The ability of the flavonoid-rich fraction (5,7,3'-trihydroxy, 6,8,4'-trimethoxy flavones) of Vitex negundo seeds to antagonize the androgen action of exogenous testosterone propionate on the male reproductive system was studied in castrated prepubertal and intact adult dog. The flavonoid-rich fraction (F) was administered 10 mg/kg i.p. every other day either alone or in combination with testosterone propionate. The duration of treatment was 30 days in castrates and 60 days in intacts. Treatment with F caused disruption of the latter stages of spermatogenesis. The epididymides were devoid of spermatozoa. Protein, sialic acid and RNA contents of the testes and epididymides were reduced significantly while testicular cholesterol and phosphatase activity in testes and epididymides were elevated. Reduced androgen production was reflected in low levels of sialic acid in testes and epididymides. Castration alone brought about reduction in size and weight of the epididymides whereas castration followed by F treatment caused a reduction in the cellular heights of epididymides. Simultaneous administration of testosterone propionate to F-treated intact adult and castrated prepubertal dogs maintained the viability of spermatozoa, kept epididymal physiology relatively normal and significantly increased the cellular heights of epididymides.

Androgen Antagonists↗

Cytotoxic flavonoids from Vitex agnus-castus.

Four new flavonoids, luteolin 6-C-(4"-methyl-6"-O-trans-caffeoylglucoside), luteolin 6-C-(6"-O-trans-caffeoylglucoside), luteolin 6-C-(2"-O-trans-caffeoylglucoside), and luteolin 7-O-(6"-p-benzoylglucoside), together with four known ones 5, 4'-dihydroxy-3,6,7,3'-tetramethoxyflavone, luteolin, artemetin and isorhamnetin, were isolated from the root bark of Vitex agnus-castus. The structures were elucidated by spectroscopic means.

Antineoplastic Agents, Phytogenic↗

Polymethoxyflavonoids from Vitex rotundifolia inhibit proliferation by inducing apoptosis in human myeloid leukemia cells.

Three polymethoxyflavonoids from the fruit of Vitex rotundifolia, namely 2',3',5-trihydroxy-3,6,7-trimethoxyflavone (Vx-1), vitexicarpin (Vx-5) and artemetin (Vx-6), were tested for their antiproliferative activity in human myeloid leukemia HL-60 cells. They showed a dose-dependent decrease in the growth of HL-60 cells. The concentrations required for 50% inhibition of the growth (IC50) after 96 h were 4.03 microM, 0.12 microM and 30.98 microM for Vx-1, Vx-5 and Vx-6, respectively. Treatment of HL-60 cells with the flavonoids induced morphological changes that are characteristic of apoptosis. We judged the induction of apoptosis by the detection of DNA fragmentation in agarose gel electrophoresis and the degree of apoptosis was quantified by a double-antibody sandwich ELISA and by flow cytometric analysis. The C-3 hydroxyl and C-8 methoxyl groups were found not to be essential for the activity, but the C-3' methoxyl instead of hydroxyl group lowered the antiproliferative and apoptosis inducing activity. These results suggest that the polymethoxyflavonoids isolated from V. rotundifolia may be used as potential chemopreventive and chemotherapeutic agents.

Antineoplastic Agents, Phytogenic↗

Effect of Vitex rotundifolia on immediate-type allergic reaction.

We investigated the effect of aqueous extract of Vitex rotundifolia (L.) (Verbenaceae) fruits (VRFE) on the immediate-type allergic reactions in vivo and in vitro. VRFE (10(-4)-1.0 g/kg) dose-dependently inhibited systemic allergic reaction induced by compound 48/80. When VRFE was employed in a systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. VRFE (5x10(-1) and 1.0 g/kg) inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. VRFE (10(-3)-1.0 mg/ml) also dose-dependently inhibited the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80 or anti-DNP IgE. Moreover, VRFE (10(-3) mg/ml) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production from RPMC. These results suggest that VRFE may be beneficial in the regulation of immediate-type allergic reaction.

Animals↗

Phenylnaphthalene compounds from the subterranean part of Vitex rotundifolia and their antibacterial activity against methicillin-resistant Staphylococcus aureus.

A careful investigation of the subterranean part of Vitex rotundifolia has shown that this plant contains five novel lignans having a 1-phenylnaphthalene-type skeleton together with four known lignans. These structures were elucidated on the basis of spectroscopic data. Furthermore, some of the isolated compounds showed antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA).

Anti-Bacterial Agents↗

New diterpenes and norditerpenes from the fruits of Vitex rotundifolia.

A new labdane-type diterpene, vitexifolin A (1), a new clerodane-type diterpene, vitexifolin B (2), a new abeoabietane-type diterpene, vitexifolin C (3), and two new norlabdane-type diterpenes, vitexifolin D (4) and vitexifolin E (5), were isolated from the fruits of Vitex rotundifolia, along with a known halimane-type diterpene, vitetrifolin D (6), two known norlabdane-type diterpenes, trisnor-gamma-lactone (7) and iso-ambreinolide (8), and three known flavonoids, casticin (9), artemetin (10), and 5,3'-dihydroxy-6,7,4'-trimethoxyflavanone (11). Their chemical structures were determined on the basis of spectroscopic data. Casticin (9) exhibited considerable growth inhibitory activity against human lung cancer cells (PC-12) and human colon cancer cells (HCT116) using the MTT assay.

Animals↗

Chemical investigation and anti-inflammatory activity of Vitex negundo seeds.

The CHCl3 extract of the defatted seeds of Vitex negundo exhibited anti-inflammatory activity and yielded four triterpenoids: 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 [5]. This is the first report of the isolation of compounds 2, 3, and 5 from a natural source.

Animals↗

Diterpenes from the fruits of Vitex rotundifolia.

Eight new labdane-type diterpenes (1-8) were isolated from the fruit of Vitex rotundifolia along with two known abietane-type diterpenoids (9, 10), and their structures were characterized on the basis of spectroscopic data and X-ray crystallographic analysis. Among them, the abietane-type diterpenoid ferruginol (9) exhibited a stronger antioxidative activity than the standard antioxidant, 3-tert-butyl-4-hydroxyanisole (BHA), using a ferric thiocyanate method.

Antioxidants↗

Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebo-controlled double-blind study.

In a placebo-controlled, randomized, double-blind study the efficacy of a Vitex agnus castus extract-containing solution (VACS) was investigated in patients suffering from cyclical mastalgia. Patients had mastalgia on at least 5 days in the pre-treatment cycle. During this cycle and during treatment (3 cycles; 2 x 30 drops/day), the intensity of mastalgia was recorded once per cycle using a visual analogue scale (VAS). After one/two treatment cycles, the mean decrease in pain intensity (mm, VAS) was 21.4 mm /33.7 mm in women taking VACS (n=48) and 10.6 mm/20.3 mm with placebo (n=49). The differences of the VAS-values for VACS were significantly greater than those with placebo (p=0.018; p=0.006). After three cycles, the mean VAS-score reduction for women taking VACS was 34.3 mm, a reduction of 'borderline significance' (p=0.064) on statistical testing compared with placebo (25.7 mm). There was no difference in the frequency of adverse events between both groups (VACS: n=5; placebo : n=4). VACS appears effective and was well tolerated and further evaluation of this agent in the treatment of cyclical mastalgia is warranted.

Clinical Trial↗

Parameters influencing the yield and composition of the essential oil from Cretan Vitex agnus-castus fruits.

Mature and immature fruits of a Cretan Vitex agnus-castus L. population were chosen to investigate different parameters such as comminution, maturity, distillation period and extraction method influencing the essential oil yield and composition. The effect of the comminution and the maturity of the plant material showed highly significant differences in yield and composition of the essential oils obtained, as well as the distillation duration from one to five hours and the method applied (hydrodistillation and simultaneous distillation extraction). The variation of 36 essential oil components due to the parameters applied was studied. The results showed that many different essential oil qualities can be obtained from the same plant material according to the parameters employed in its extraction. Entire fruits hydrodistilled for one hour yielded an oil much richer in monoterpene hydrocarbons and oxygenated compounds whereas the best combination to obtain an oil rich in less volatile compounds is by SDE of comminuted fruits for five hours. For mature fruits the main components varied as follows due to the parameters studied: sabinene 16.4-44.1%, 1,8-cineole 8.4-15.2%, beta-caryophyllene 2.1-5.0%, and trans-beta-farnesene 5.0-11.7%.

Oils, Volatile↗

Vitexicarpin, a flavonoid from the fruits of Vitex rotundifolia, inhibits mouse lymphocyte proliferation and growth of cell lines in vitro.

Certain flavonoids having a C-2,3-double bond were reported to show an inhibitory activity against T-lymphocyte proliferation, but not against B-lymphocyte proliferation in vitro. In the course of these studies, vitexicarpin (3',5-dihydroxy-3,4',6,7-tetramethoxyflavone) isolated from the fruits of Vitex rotundifolia was found to show potent inhibition against lymphocyte proliferation. Vitexicarpin inhibited T-lymphocyte proliferation as well as B-lymphocyte proliferation at > 0.1 microM. IC50's were approximately 0.7 microM both for T- and B-cell proliferation. The inhibitory activity of vitexicarpin was reversible. Vitexicarpin also inhibited the growth of certain cancer cell lines, EL-4 and P815.9 (IC50 = 0.25-0.3 microM). These results suggest that vitexicarpin may be a potential therapeutic agent involved in inflammatory/immunoregulatory disorders such as rheumatoid arthritis and lymphomas.

Animals↗

[GC-MS analysis of essential oils from four Vitex species].

The chemical constituents of the essential oils obtained from the leaves of Vitex negundo var. cannabifolia, V. negundo var. heterophylla, V. negundo and V. trifolia were analysed by GC-MS. Forty compounds including alpha-pinene, linalool, terpinyl acetate, beta-caryophyllene and caryophyllene oxide, etc. were identified. Their percentages in oils were given.

Acyclic Monoterpenes↗

General pharmacology of Vitex leucoxylon Linn leaves.

Ethanol extract (ETE) and cold aqueous infusion (CAI) of Vitex leucoxylon leaf were evaluated in a battery of tests to define the activity profile of the plant. CAI depressed SMA, antagonised d-amphetamine stereotypy and oxotremorine tremors, shortened the duration of mice immobility in behavioural 'despair' test and lowered serum total cholesterol level. ETE showed significant inhibition of carrageenin paw oedema and granulation tissue formation in rats. Suppression of acetic acid writhing was observed with both ETE and CAI. LD50 value of ETE was > 3000 mg kg-1 (ip) and that of CAI 1050 (800-1200) mgkg-1.

Analgesics↗

[Chemical constituents of the fruits of Vitex trifolia L].

Five compounds were isolated from the fruits of Vitex trifolia and identified on the basis of spectral data and chemical methods to be rho-hydroxybenzoic acid, beta-sitosterol, beta-sitosterol-3-O-glucoside, casticin and, 3,6,7-trimethylquercetagetin. Except beta-sitosterol all of the compounds were obtained from the fruits of the plant for the first time.

Drugs, Chinese Herbal↗

[Treatment of cyclical mastodynia using an extract of Vitex agnus castus: results of a double-blind comparison with a placebo].

The aim of study presented here was to gather the data about the tolerability and efficacy of Vitex agnus castus (VACS) extract. The study was designed as double-blind, placebo controlled in two parallel groups (each 50 patients). Treatment phase lasted 3 consequent menstrual cycles (2 x 30 drops/day = 1.8 ml of VASC) or placebo. Mastalgia during at least 5 days of the cycle before the treatment was the strict inclusion condition. For assessment of the efficacy visual analogue scale was used. Altogether 97 patients were included into the statistical analysis (VACS: n = 48, placebo: n = 49). Intensity of breast pain diminished quicker with VACS group. The tolerability was satisfactory. We found VACS to be useful in the treatment of cyclical breast pain in women.

Adult↗