小檗碱的药理活性以及提升其口服生物利用度的策略

Pharmacological activities of berberine and strategies to improve its oral bioavailability

小檗碱(berberine)是一种天然存在的苄基异喹啉类生物碱,具有抗菌、抗癌、降血脂、抗糖尿病和止泻等广泛药理活性,但因其极低的口服生物利用度(<1%),限制了其在临床上的应用,尚无纯小檗碱配方被批准用于任何特定疾病。小檗碱口服生物利用度低主要是由于其在酸性条件下自聚集导致的溶解度差、渗透性低、P-gp(P-glycoprotein)介导的外排和肝肠代谢。提高小檗碱的口服生物利用度可提高小檗碱的药理活性,降低给药剂量进而减少不良反应。本文综述了小檗碱的多种药理活性、代谢过程、药代动力学特征,重点介绍了通过提高溶解度和渗透性、抑制P-gp外排和结构修饰等途径提高小檗碱口服生物利用度的策略,并对小檗碱的研究进行了展望,为其深入研究提供指导。

Berberine is a naturally occurring benzylisoquinoline alkaloid with a wide range of pharmacological activities,such as antibacterial,anticancer,hypolipidemic,antidiabetic and antidiarrheal.Although berberine has a wide range of curative effects,the extremely low bioavailability(<1%)limits its clinical application.Pure berberine preparations have not yet been approved for any specific disease.The low oral bioavailability of berberine is mainly due to poor solubility caused by self-aggregation under acidic conditions,low permeability,P-glycoprotein(P-gp)-mediated efflux,and liver and intestine metabolism.To improve the oral bioavailability of berberine,researchers have adopted a variety of strategies,including the application of various nano-delivery systems,penetration enhancers and P-gp inhibitors,structural modifications,and development of berberine derivatives.Improving the oral bioavailability of berberine can improve the pharmacological activity of berberine,reduce the dosage,and then reduce the toxic and side effects.This review summarized the various pharmacological activities,metabolism progress and pharmacokinetic characteristics of berberine,the newly discovered berberine target intestinal microbiota and focused on the strategies to improve the oral bioavailability of berberine by improving solubility and permeability,inhibiting P-gp efflux,and structural modification.The research on berberine was prospected,which provided guidance for the in-depth study of berberine.