State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian road, Nanjing, China.
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian road, Nanjing, China.
Phytomedicine. 2022 Sep;104:154264. doi: 10.1016/j.phymed.2022.154264. Epub 2022 Jun 13.
Gut microbiota coupled with their metabolites (bile acids, BAs) get involved in diabetic pathogenesis. Simiao Wan is a famous traditional Chinese formula consisting on Phellodendron chinense C.K.Schneid. (Rutaceae), Atractylodes lancea (Thunb.) DC. (Asteraceae), Achyranthes bidentata Blume (Amaranthaceae) and Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf (Poaceae), and used to treat gouty arthritis and hyperuricemia for thousands of years. However, the mechanisms underlying its beneficial efficacy on diabetes still needs to be explored.
Our study was performed to reveal the effects of the 75% ethanol extraction of Simiao Wan (SMW) on diabetes, gut microbiota and bile acids (BAs) in diabetic mice.
The effects of SMW on diabetes were evaluated in mice treated by high-fat diet (HFD)/streptozotocin (STZ). The 16S rDNA sequencing and BAs metabolomics were performed to assess the changes of BAs profiles and gut microbiota induced by SMW. Western blot and real-time quantitative PCR were conducted to evaluate the possible mechanism of SMW.
SMW significantly improved insulin resistance and hepatic lipid accumulation in HFD/STZ mice. It remarkably enriched in the bacteria Allobaculum, Clostridium, Akkermansia, Lactobacilus and Bilophila whereas decreased Coprococcus and Halomonas in diabetic mice. Furthermore, the profiles of BAs were also modulated by SMW, indicated by the reduction of conjugated BAs and 12α-OH/non-12α-OH BAs ratio in liver as well as the increase of primary BAs in feces. SMW also activated farnesoid X receptor and inhibited sterol regulatory element-binding protein-1 expression, contributing to its beneficial actions on lipid accumulation in liver.
Our results showed that SMW exerted its beneficial effects on insulin resistance and hepatic lipid accumulation indirectly through regulating profiles of gut microbe and BAs.
肠道微生物群及其代谢产物（胆汁酸，BAs）参与糖尿病的发病机制。四妙丸是一种由黄柏（芸香科）、白术（菊科）、牛膝（苋科）和薏苡仁（禾本科）组成的著名中药方剂，千百年来一直用于治疗痛风性关节炎和高尿酸血症。然而，其对糖尿病有益疗效的机制仍有待探索。
本研究旨在揭示四妙丸（SMW）的 75%乙醇提取物对糖尿病小鼠的糖尿病、肠道微生物群和胆汁酸（BAs）的影响。
采用高脂饮食（HFD）/链脲佐菌素（STZ）处理的小鼠评价 SMW 对糖尿病的作用。采用 16S rDNA 测序和 BAs 代谢组学方法评估 SMW 诱导的 BAs 谱和肠道微生物群的变化。采用 Western blot 和实时定量 PCR 检测 SMW 的可能作用机制。
SMW 显著改善 HFD/STZ 小鼠的胰岛素抵抗和肝脂质堆积。它显著富集了 Allobaculum、Clostridium、Akkermansia、Lactobacillus 和 Bilophila 等细菌，而降低了糖尿病小鼠中的 Coprococcus 和 Halomonas。此外，SMW 还调节了 BAs 的谱，表现为肝内结合型 BAs 和 12α-OH/非 12α-OH BAs 比值降低，粪便中初级 BAs 增加。SMW 还激活法尼醇 X 受体并抑制固醇调节元件结合蛋白-1 的表达，有助于其对肝脂质堆积的有益作用。
我们的结果表明，SMW 通过调节肠道微生物群和 BAs 的谱间接发挥其对胰岛素抵抗和肝脂质堆积的有益作用。
