Abstract
Objectives: Radix Polygoni Multiflori Praeparata (RPMP) and Dioscorea Bulbifera Rhizomes (DBR) are used in Chinese herbal medicine and have been frequently reported for adverse reactions on liver. In this research, we aimed to evaluate in vivo effects of RPMP and DBR on rat cytochrome P450 enzymes (CYP1A2, CYP2E1 and CYP3A2) with their respective substrates as probes. Methods: Rats were orally administered RPMP, DBR and RPMP/DBR combination at 12, 10 and (12 + 10) g/kg, respectively, or saline as a control, once daily for 7 days. Thereafter, a cocktail containing 10 mg/kg caffeine, 20 mg/kg chlorzoxazone and 10 mg/kg dapsone was tail vein injected to rats. At defined time points, plasma drug concentrations were simultaneously evaluated by HPLC. Pharmacokinetic parameters simulated by DAS software were used to assess RPMP and/or DBR effects on cytochrome P450 enzymes activity. ANOVA and Dunnett’s test were used for data analysis. Results: Caffeine metabolism was enhanced in RPMP animals and reduced after pretreatment with DBR, but no effect was observed in RPMP/DBR combination group. Chlorzoxazone and dapsone metabolism was enhanced in both RPMP and DBR groups and consequently in combination group. The data suggested that RPMP independently induces rat CYP1A2, CYP2E1 and CYP3A2 activity, while DBR independently inhibits activity of rat CYP1A2 and induces that of CYP2E1 and CYP3A2. RPMP/DBR combination showed no significant benefit compared with the two drugs alone and even showed a neutralized effect in CYP1A2 activity. Conclusions: Caution is needed when RPMP and/or DBR are co-administered with drugs metabolized by human CYP1A2, CYP2E1 and CYP3A4.
Highlights
Plant products are increasingly popular as alternative medicines in the western world, and it is estimated that herbal medicines are used by approximately 20% of the US population [1]
Still for caffeine, MRT(0 − t) and t1/2 were decreased by 27.2% and 41.0%, respectively, (P < 0.05), while CL increased significantly by 66.7% (P < 0.01). These data demonstrate that Radix Polygoni Multiflori Praeparata (RPMP) increased CYP1A2 metabolism of caffeine
After pretreatment with MIX, which represents the combination of RPMP and Dioscorea Bulbifera Rhizomes (DBR), no apparent effects were observed. These results indicated that RPMP and DBR had contrary effect on CYP1A2 activity in vivo and the effects of the two herbs would be neutralized in a mix recipe
Summary
Plant products are increasingly popular as alternative medicines in the western world, and it is estimated that herbal medicines are used by approximately 20% of the US population [1]. Radix Polygoni Multiflori (RPM, Heshouwu in Chinese) and Radix Polygoni Multiflori Praeparata (RPMP, Zhiheshouwu in Chinese) are root extracts of Polygonum multiflorum Thunb (Polygonaceae) used in oriental counties for centuries. RPMP, primarily used to tonify kidney and liver, has been utilized in the treatment of premature hair graying, vitiligo and hyperlipemia. Dioscorea Bulbifera Rhizomes (DBR) constitutes a Chinese traditional medicine first described in “Qianjin Yueling” written in Tang dynasty [3]. DBR has been clinically used to treat struma and many tumor types in China for several decades [13] [14]. RPMP and DBR were first used in combination in Bai-Shi Pill, an ancient traditional Chinese medicine described in “Synopsis of the Golden Chamber” in the beginning of the third century. The Bai-Shi Pill has gained prestige for treating vitiligo for many years
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