Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing, 100193, PR China.
Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing, 100193, PR China; Life Sciences and Environmental Sciences Center, Harbin University of Commerce, Harbin, 150076, PR China.
Colloids Surf B Biointerfaces. 2020 Sep;193:111069. doi: 10.1016/j.colsurfb.2020.111069. Epub 2020 Apr 29.
Cajaninstilbene acid (CSA) exerts wide pharmacological activities, such as anti-inflammation, hypoglycaemic activity, analgesic effect and cognition improvement. However, it underwent severe phase II metabolism mediated by UDP-glucuronosyltransferase (UGT) in the gastrointestinal (GI) tract after oral administration, affecting its oral bioavailability. In the present study, we utilize UGT inhibitory excipient containing self-microemulsion (SME) delivery system to reduce the production of glucuronide metabolites and increase its oral bioavailability. The present results showed that although similar properties in physiochemical, cytotoxicity, cellular uptake, absorption and transport across rat everted gut sacs between SME-1 (inhibitory excipient containing SME) and SME-2 (control SME, without inhibitory excipient), an improved absolute bioavailability of 57.3 % was conferred by SME-1, significantly higher than the value of 35.4 % by SME-2 and 34.0 % by free CSA. Noticeably, the significantly lower AUC value of CSA glucuronide was determined in rats treated with SME-1 than those either treated with SME-2 or free CSA. Thus, the ability of SME-1 to enhance oral bioavailability of CSA is mainly attributed to the inhibition of phase II metabolism in the GI tract.
兵豆异戊烯素（CSA）具有广泛的药理活性，如抗炎、降血糖活性、镇痛作用和认知改善。然而，它在口服后会在胃肠道（GI）中经历严重的 II 期代谢，由 UDP-葡糖醛酸基转移酶（UGT）介导，这会影响其口服生物利用度。在本研究中，我们利用含有 UDP-葡糖醛酸基转移酶抑制剂的自微乳（SME）给药系统来减少葡萄糖醛酸化物代谢产物的生成，提高其口服生物利用度。本研究结果表明，尽管 SME-1（含有抑制剂的自微乳）和 SME-2（对照自微乳，不含抑制剂）在物理化学性质、细胞毒性、细胞摄取、在大鼠外翻肠囊中的吸收和转运方面具有相似的性质，但 SME-1 使 CSA 的绝对生物利用度提高了 57.3%，明显高于 SME-2 的 35.4%和游离 CSA 的 34.0%。值得注意的是，与 SME-2 或游离 CSA 相比，用 SME-1 处理的大鼠中 CSA 葡萄糖醛酸化物的 AUC 值显著降低。因此，SME-1 增强 CSA 口服生物利用度的能力主要归因于对 GI 道中 II 期代谢的抑制。
