Analysis on Mechanism of Adenine-induced Kidney-Yang Deficiency Rats Treated with Different Processed Products of Curculiginis Rhizoma / 中国实验方剂学杂志

Objective:To study on the mechanism of invigorating kidney and strengthening Yang of different processed products of Curculiginis Rhizoma aqueous extracts in rats with kidney-Yang deficiency induced by adenine. Method:Taking Guifu Dihuang pills as the positive drug group (the dosage of 2.466 g·kg-1), after intragastric administration for 4 weeks, enzyme-linked immunosorbent assay (ELISA) was used to compare the effects of different processed products of Curculiginis Rhizoma aqueous extracts (the dosage of 2.742 g·kg-1) on the levels of thyroid stimulating hormone (TSH), 17-hydroxycorticosteroids (17-OHCS), estradiol (E2), testosterone (T), triiodothyronine (T3), thyroxine (T4) and cortisol (COR) in serum of rats with kidney-Yang deficiency induced by adenine. The activity of cytochrome P450 3A (CYP3A) in rat liver and kidney microsomes was determined by Nash colorimetry. Result:All the processed products aqueous extracts could improve the function of hypothalamus-pituitary-target gland axis in rats with kidney-Yang deficiency induced by adenine, and the total score was in the order of Euodiae Fructus juice-processed products (29 points)>salt-processed products (25 points)>rice wine-processed products (23 points)>raw products (17 points)>Zingiberis Rhizoma juice-processed products (11 points). And the different processed products of Curculiginis Rhizoma could increase CYP3A activity of liver and kidney microsomes of kidney-Yang deficiency rats, especially the Euodiae Fructus juice-processed products and salt-processed products. Conclusion:All the processed products of Curculiginis Rhizoma can effectively treat the syndrome of kidney-Yang deficiency in rats, among them, Euodiae Fructus juice-processed products and salt-processed products have more significant effect on invigorating kidney and strengthening Yang.

Inhibition of cytochrome P450 3A enzyme by Millettia aboensis: its effect on the pharmacokinetic properties of efavirenz and nevirapine

ABSTRACT The chronic and comorbid nature of HIV infection necessitate the use of multiple drugs including herbs to relieve symptoms with a possible increase in herb–drug interaction cases. This study was designed to evaluate the effect of Millettia aboensis (Hook. f.) Baker, Fabaceae, on cytochrome P450 3A isoenzyme and the influence of this effect on the bioavailability of two antiretroviral agents. In vitro effect of ethanol extract of M. aboensis on intestinal and liver microsomes extracted from female rats was assessed using erythromycin-N-demethylation assay method while in vivo effects were determined by estimating simvastatin plasma concentrations in rats. The effect of the extract on pharmacokinetic parameters of orally administered efavirenz (25 mg/kg) and nevirapine (20 mg/kg) was determined in rats divided into groups (n = 5). Plasma drug concentrations were assayed using HPLC and pharmacokinetic parameters determined through a non-compartmental analysis as implemented in WinNonlin pharmacokinetic program. The extract inhibited both intestinal and liver microsomal cytochrome P450 3A isoenzyme activities in vitro and enhanced simvastatin absorption in vivo with possible inhibition of metabolizing enzymes as indicated by significant (p < 0.05) increase in maximal concentration, area under curve and mean resident time of the drug. However, further in vivo interaction studies in animal model did not produce significant (p > 0.05) changes in the pharmacokinetic parameters of efavirenz and nevirapine. HPLC fingerprinting indicated the presence of quercetin and kaempferol in the extract. These findings revealed M. aboensis as an inhibitor of cytochrome P450 3A enzyme but, with no significant effect on the bioavailability of orally administered nevirapine and efavirenz.