WHO monographs on selected medicinal plants - travolekar.ru
WHO monographs on selected medicinal plants - travolekar.ru WHO monographs on selected medicinal plants - travolekar.ru
Fructus Momordicae and glutathione S-transferase activity was observed in diabetic rats treated with the extract. Chronic feeding of rats with the extract reversed the effect of chronic diabetes on the modulation of both P450-dependent monooxygenase activities and glutathione-dependent oxidative stress-related lipid peroxidase and glutathione S-transferase activities (47). The effect of oral feeding of the fruit juice (10 ml of 100% juice) on the hepatic cytochrome P450 and glutathione S-transferase drug-metabolizing enzymes was investigated in rats with streptozotocin-induced diabetes. Hepatic cytochrome P450 contents, ethoxycoumarin-O-deethylase, ethoxyresorufin-O-deethylase, aniline hydroxylase and aminopyrene N-demethylase activities were measured in control, diabetic and juice-fed animals. Diabetic rats exhibited a 50–100% increase in aniline hydroxylase and ethoxyresorufin-O-deethylase activities, which were reversed after being fed the juice. In addition, a decrease (17–20%) in the activities of N-demethylase and ethoxycoumarin-O-deethylase was observed in the liver of diabetic rats. Feeding the juice to the diabetic animals brought the level of N-demethylase close to that of control animals, while ethoxycoumarin-O-deethylase was further reduced to 60% of the levels in the control animals (48). Toxicology The effect of the fruit on certain key hepatic enzymes was investigated in rats. A fruit juice product was administered by gavage at a daily dose of 10 ml of pure juice/kg bw for 30 days under light ether anaesthesia while the control group received equivalent amounts of distilled water under identical conditions (n = 10 in each group). Serum -glutamyl transferase and alkaline phosphatase concentrations were found to be significantly elevated (p < 0.001 and p < 0.01–0.001, respectively), following oral administration of the fruit juice. No consistent significant histopathological changes in the liver were observed in either treatment group, although the prevalence of dilatation and/or congestion of the central vein sinusoidal system appeared to be twice as high following fruit juice treatment as in the other two groups (49). Feeding of the fruit to normal adult rats at 0.02, 0.1 and 0.5% (dry weight) in a semi-synthetic diet for a period of 8 weeks had no adverse influence on the food intake, growth or organ weights of normal adult rats. The haematological parameters of the experimental rats were also normal. Serum cholesterol levels of the rats receiving 0.5% of the crude drug were significantly lower than those of the control rats (50). Clinical pharmacology Numerous case-reports and clinical studies have found that the juice, fruit, and dried fruit powder have a moderate hypoglycaemic effect. These 201
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<str<strong>on</strong>g>WHO</str<strong>on</strong>g> <str<strong>on</strong>g>m<strong>on</strong>ographs</str<strong>on</strong>g> <strong>on</strong> <strong>selected</strong> <strong>medicinal</strong> <strong>plants</strong><br />
periment 2). Dietary intake of powdered c<strong>ru</strong>de d<strong>ru</strong>g resulted in a c<strong>on</strong>sistent<br />
decrease in se<strong>ru</strong>m glucose levels in rats fed cholesterol-free diets, but<br />
not in those fed cholesterol-enriched diets, although no dose–resp<strong>on</strong>se<br />
was noted. The c<strong>ru</strong>de d<strong>ru</strong>g had no effect <strong>on</strong> se<strong>ru</strong>m lipid parameters, except<br />
for high-density lipoprotein-cholesterol levels, which were elevated,<br />
indicating an anti-atherogenic activity. In additi<strong>on</strong>, the c<strong>ru</strong>de d<strong>ru</strong>g caused<br />
a marked reducti<strong>on</strong> of hepatic total cholesterol and triglyceride levels<br />
both in the presence and absence of dietary cholesterol (44).<br />
Antiviral activity<br />
MAP30 (Momordica anti-HIV protein of 30 kDa), isolated from the plant<br />
material, is capable of inhibiting infecti<strong>on</strong> of HIV type 1 (HIV-1) in<br />
T lymphocytes and m<strong>on</strong>ocytes as well as replicati<strong>on</strong> of the vi<strong>ru</strong>s in infected<br />
cells. An investigati<strong>on</strong> of the effect of MAP30 <strong>on</strong> HIV-1 integrase<br />
suggests that the protein exhibits a dose-dependent inhibiti<strong>on</strong> of HIV-1<br />
integrase. In the presence of 20 ng of viral substrate, 50 ng of target substrate,<br />
and 4 μM integrase, total inhibiti<strong>on</strong> was achieved at equimolar c<strong>on</strong>centrati<strong>on</strong>s<br />
of the integrase and the antiviral proteins, with a median effective<br />
c<strong>on</strong>centrati<strong>on</strong> of 1 μM (45).<br />
A protein (MRK29), isolated from the f<strong>ru</strong>it and seed, inhibited HIV-1<br />
reverse transcriptase by 50% at a c<strong>on</strong>centrati<strong>on</strong> of 18 μg/ml. MRK29, at a<br />
c<strong>on</strong>centrati<strong>on</strong> of 0.175 μg/ml, reduced viral core protein, p24, expressi<strong>on</strong><br />
in HIV-infected cells by 82%. MRK29 also produced a 3-fold increase in<br />
tumour necrosis factor activity (46).<br />
Xenobiotic metabolism<br />
The effects of a f<strong>ru</strong>it juice (10 ml of 100% pure juice) <strong>on</strong> streptozotocininduced<br />
diabetes <strong>on</strong> tissue-specific cytochrome P450 (CYP) and glutathi<strong>on</strong>e-dependent<br />
xenobiotic metabolism was investigated in rats. Results<br />
dem<strong>on</strong>strated that rats with streptozotocin-induced diabetes exhibited an<br />
increase (35–50%) in cytochrome P4504A-dependent lauric acid hydroxylati<strong>on</strong><br />
in liver, kidney and brain. About a twofold increase in cytochrome<br />
P4502E-dependent hepatic aniline hydroxylati<strong>on</strong> and a 90–100% increase<br />
in cytochrome P4501A-dependent ethoxycoumarin-O-deethylase activities<br />
in kidney and brain was also observed. A significant increase (80%,<br />
p < 0.01) in aminopyrene N-demethylase activity was observed <strong>on</strong>ly in the<br />
kidney of rats with streptozotocin-induced diabetes, and a decrease was<br />
observed in the liver and brain of rats with streptozotocin-induced diabetes.<br />
A significant increase (77%) in NADPH-dependent lipid peroxidati<strong>on</strong><br />
(plasma lipid peroxidase) in kidney of diabetic rats was also observed.<br />
A marked decrease (65%) in hepatic glutathi<strong>on</strong>e c<strong>on</strong>tent and glutathi<strong>on</strong>e<br />
S-transferase activity and an increase (about twofold) in brain glutathi<strong>on</strong>e<br />
200