Wang Qian, Shi Rong, Dai Yan, Li Yuanyuan, Wang Tianming, Ma Yueming, Cheng Nengneng
Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine Shanghai 201203 People's Republic of China
School of Pharmacy, Anhui University of Chinese Medicine, Anhui Academy of Chinese Medicine Hefei 230012 China.
RSC Adv. 2018 Jan 16;8(7):3364-3373. doi: 10.1039/c7ra08270c.
Wogonin (WO) and its glucuronide, wogonoside (WG) exhibit various beneficial bioactivities that may have potential for the development of novel drugs. In this study, we determined their pharmacokinetic characteristics in rats after intragastric administration of WO and intraportal vein injection of WG. WG was the predominant form in the portal vein and body plasma, and in bile; WO was detected only in the small intestine and liver. WG is a substrate of the multidrug resistance-associated protein (MRP) 1, 2, 3, and 4, and organic anion-transporting polypeptide (OATP) 2B1 and OATP1B3. Metabolism studies indicated that WG formation and WO decrease had similar CL values in rat intestine S9 (RIS9) and rat liver microsome (RLM), and that the hydrolysis rate of WG in RIS9 and rat liver S9 (RLS9) was fast. Thus, WG could be excreted into the intestinal tract by MRP2, and transported into mesenteric blood by MRP1, 3, and 4. OATP2B1 and OATP1B3 mediated the hepatic uptake of WG and MRPs mediated WG efflux to the bile and circulation. The high transport capability of MRPs for WG and the fast hydrolysis in the small intestine and liver may be responsible for the presence of WO in these tissues.
汉黄芩素（WO）及其葡糖醛酸苷汉黄芩苷（WG）具有多种有益的生物活性，可能具有开发新型药物的潜力。在本研究中，我们测定了大鼠经胃内给予WO和经门静脉注射WG后的药代动力学特征。WG是门静脉、体循环血浆和胆汁中的主要形式；仅在小肠和肝脏中检测到WO。WG是多药耐药相关蛋白（MRP）1、2、3和4以及有机阴离子转运多肽（OATP）2B1和OATP1B3的底物。代谢研究表明，在大鼠肠S9（RIS9）和大鼠肝微粒体（RLM）中，WG的形成和WO的减少具有相似的清除率（CL）值，并且WG在RIS9和大鼠肝S9（RLS9）中的水解速率很快。因此，WG可通过MRP2排泄到肠道，并通过MRP1、3和4转运到肠系膜血液中。OATP2B1和OATP1B3介导WG的肝脏摄取，而MRP介导WG向胆汁和循环的外排。MRP对WG的高转运能力以及在小肠和肝脏中的快速水解可能是这些组织中存在WO的原因。
