肠道菌群紊乱对泻心汤药效成分大黄素药动学的影响

Effect of intestinal flora disorder on pharmacokinetics of emodin in Xiexin Decoction

目的通过比较大黄素以及配伍泻心汤药效成分(盐酸小檗碱、黄芩苷)前后在正常和抗生素致菌群紊乱大鼠中的药动学差异,揭示肠道菌群对泻心汤药效成分大黄素药动学的影响。方法通过ig混合抗生素建立菌群紊乱大鼠模型,经高通量16S rDNA测序技术进行模型评价。采用β-葡萄糖醛酸酶水解法处理血液样品,通过血液中总大黄素质量浓度表征大黄素的体内药动学特征。通过比较正常和抗生素致菌群紊乱大鼠中大黄素及其配伍盐酸小檗碱和黄芩苷前后的药动学差异特征评价肠道菌群对泻心汤药效成分大黄素药动学的影响。结果与正常大鼠相比,单独ig大黄素,菌群紊乱大鼠中大黄素在0~12 h内基本无吸收,即在0~12 h内生物利用度极显著降低;大黄素配伍盐酸小檗碱和黄芩苷后,菌群紊乱大鼠中大黄素在0~12 h内生物利用度仍然显著降低。与单独ig大黄素相比,大黄素配伍盐酸小檗碱和黄芩苷后,菌群紊乱大鼠模型中大黄素在0~12 h内的体内生物利用度显著升高;然而,正常大鼠中大黄素在0~12 h内的体内生物利用度显著降低。结论大黄素单独给药或配伍泻心汤药效成分后在菌群紊乱大鼠模型中药动学均显著改变,表明肠道菌群能够显著影响泻心汤药效成分大黄素的药动学特征。

Objective To reveal the effect of intestinal flora on pharmacokinetics of emodin,active ingredient(berberine hydrochloride,baicalin)in Xiexin Decoction(泻心汤)by comparing the pharmacokinetic differences between emodin and active ingredients of Xiexin Decoction in normal and antibiotic-induced flora disorder rats.Methods Rats model of bacterial flora disorder was established by ig mixed antibiotic,and model was evaluated by high-throughput 16S rDNA sequencing technology.Blood samples were treated byβ-glucuronidase hydrolysis method,and in vivo pharmacokinetic characteristics of emodin were characterized by concentration of total emodin in blood.Effect of intestinal flora on pharmacokinetics of emodin of Xiexin Decoction was evaluated through comparing the pharmacokinetic characteristics of emodin and its compatibility with berberine hydrochloride and baicalin in normal rats and flora disorder rats that modeled by antibiotics.Results Compared with normal rats,rats with disordered flora basically which ig emodin alone had no absorb emodin within 0—12 h,that was the bioavailability decreased significantly within 0—12 h;After berberine and baicalin were added,bioavailability of emodin was still significantly reduced in 0—12 h in rats with dysbacteriosis.Compared with ig emodin alone,emodin combined with berberine hydrochloride and baicalin significantly increased in vivo bioavailability of emodin within 0—12 h in rats model of dysbiosis;However,bioavailability of emodin in vivo in normal rats was significantly decreased within 0—12 h.Conclusion Pharmacokinetics of emodin in rats model of dysbacteriosis are significantly changed after administration of emodin alone or in combination with active ingredients of Xiexin Decoction,indicating that intestinal flora significantly affects the pharmacokinetic characteristics of emodin,active ingredient in Xiexin Decoction.