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WHO monographs on selected medicinal plants - travolekar.ru

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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 />

creti<strong>on</strong> of sodium and chloride <strong>on</strong> the seventh day and of potassium <strong>on</strong><br />

the sixth day (p < 0.05). No change was observed in plasma electrolytes<br />

and urea in any group, except for a decrease in sodium and chloride c<strong>on</strong>centrati<strong>on</strong><br />

in the group treated with the 16% extract of the c<strong>ru</strong>de d<strong>ru</strong>g. A<br />

decrease in creatinine clearance was observed after treatment with a daily<br />

dose of the 8% extract (33).<br />

Enzyme inducti<strong>on</strong><br />

The effects of an aqueous extract of the leaves and of rosmarinic acid were<br />

investigated <strong>on</strong> xenobiotic metabolizing enzymes in rat liver after dietary<br />

administrati<strong>on</strong> (0.5% daily rati<strong>on</strong>s) for 2 weeks. The modulati<strong>on</strong> of phase<br />

I enzymes such as cytochrome P450 1A, 2B, 2E1, 3A and phase II enzymes<br />

such as glutathi<strong>on</strong>e S-transferase, quin<strong>on</strong>e reductase and uridine<br />

diphosphate (UDP)-glucur<strong>on</strong>osyltransferase was evaluated by measuring<br />

enzyme activities with specific substrates. The aqueous extract enhanced<br />

cytochrome P450 1A1, 2B1/2, 2E1 and glutathi<strong>on</strong>e S-transferase (especially<br />

recombinant glutathi<strong>on</strong>e S-transferase A3/A5, M1 and M2), quin<strong>on</strong>e<br />

reductase and UDP-glucur<strong>on</strong>osyltransferase. No modificati<strong>on</strong> of<br />

xenobiotic metabolizing enzymes was observed in resp<strong>on</strong>se to treatment<br />

with rosmarinic acid, indicating that other c<strong>on</strong>stituents of the leaves are<br />

resp<strong>on</strong>sible for this activity (34).<br />

The ability of the leaves to modulate cytochrome P450 and detoxificati<strong>on</strong><br />

enzymes in rat liver was evaluated by comparing the effects of dried<br />

leaves and leaf extracts with those of the essential oil. Rats received the<br />

powdered leaves or extracts of the leaves in their diet at 0.5% (w/w) for<br />

2 weeks. The effects of such treatments were evaluated for cytochrome<br />

P450 isozymes 1A, 2B, 2E1, glutathi<strong>on</strong>e S-transferase, NAD(P)H, quin<strong>on</strong>e<br />

reductase and UDP-glucur<strong>on</strong>osyltransferase activities and <strong>on</strong> protein<br />

levels (immunoblot analyses). The results dem<strong>on</strong>strated that essential<br />

oil selectively induced cytochrome P450, particularly cytochrome<br />

P450 2B. The leaf extract enhanced both cytochrome P450 and detoxificati<strong>on</strong><br />

enzymes. A dichloromethane extract of the leaves acted as a m<strong>on</strong>ofuncti<strong>on</strong>al<br />

inducer, inducing glutathi<strong>on</strong>e S-transferase, quin<strong>on</strong>e reductase<br />

and UDP-glucur<strong>on</strong>osyltransferase, in particular UDP-glucur<strong>on</strong>osyltransferase<br />

1A6 (35).<br />

An extract of the c<strong>ru</strong>de d<strong>ru</strong>g was fed to female mice at c<strong>on</strong>centrati<strong>on</strong>s<br />

of 0.3% and 0.6% (by weight) for 4 weeks prior to determinati<strong>on</strong> of the<br />

activities of the detoxificati<strong>on</strong> enzymes glutathi<strong>on</strong>e-S-transferase and<br />

NAD(P)H, and quin<strong>on</strong>e reductase in lung, liver and stomach. Liver activities<br />

of glutathi<strong>on</strong>e S-transferase and quin<strong>on</strong>e reductase, and stomach<br />

glutathi<strong>on</strong>e S-transferase activity, were significantly increased in animals<br />

fed diets c<strong>on</strong>taining the extract. However, diets supplemented with the<br />

302

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