The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Neihuan Xilu, Guangzhou Higher Education Mega Center, Guangzhou 510006, China.
School of Pharmacy, Guangdong Pharmaceutical University, Waihuan Donglu, Guangzhou Higher Education Mega Center, Guangzhou 510006, China.
J Pharm Pharmacol. 2022 Nov 4;74(11):1588-1597. doi: 10.1093/jpp/rgac062.
This study aimed to explore whether the liver-targeting enhancing effect of vinegar-baked Radix Bupleuri (VBRB) on rhein was achieved by affecting transporters, metabolism enzymes as well as hepatocyte nuclear factor 1α/4α (HNF1α/HNF4α) in liver injury.
The effect of VBRB on the efficacy of rhein was performed with the LPS-induced acute liver injury rat model. Aspartate aminotransferase (AST), alanine transaminase (ALT) and superoxide dismutase (SOD) levels were determined and histopathological examination was taken. Drug concentrations in tissues were determined by high performance liquid chromatography (HPLC). The protein expressions of drug transporters, metabolic enzymes and hepatic nuclear factors were determined by Western blotting and ELISA assays.
VBRB improved the liver protecting effect of rhein, which was consistent with its promoting effect on targeted enrichment of rhein in the liver. VBRB or in combination with rhein inhibited P-glycoprotein (Pgp) and multi-resistance related protein 2 (MRP2), while increased organic anion transporting polypeptide 2 (OATP2), which might be the reason why VBRB promoted liver-targeting effect of rhein.
VBRB enhances the liver-protecting effect of rhein by down-regulating Pgp, MRP2, and up-regulating OATP2.
本研究旨在探讨醋制柴胡对大黄酸的肝靶向增强作用是否通过影响肝脏中的转运体、代谢酶以及肝核因子 1α/4α（HNF1α/HNF4α）来实现。
采用 LPS 诱导的急性肝损伤大鼠模型，考察醋制柴胡对大黄酸药效的影响。测定天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和超氧化物歧化酶（SOD）水平，并进行组织病理学检查。采用高效液相色谱法（HPLC）测定组织中的药物浓度。采用 Western blot 和 ELISA 法测定药物转运体、代谢酶和肝核因子的蛋白表达。
醋制柴胡可提高大黄酸的肝保护作用，这与其促进大黄酸在肝脏中的靶向富集作用一致。醋制柴胡或与大黄酸合用可抑制 P 糖蛋白（Pgp）和多药耐药相关蛋白 2（MRP2），同时增加有机阴离子转运多肽 2（OATP2），这可能是醋制柴胡促进大黄酸肝靶向作用的原因。
醋制柴胡通过下调 Pgp、MRP2 和上调 OATP2 增强了大黄酸的肝保护作用。
