PMID- 33545549 OWN - NLM STAT- MEDLINE DCOM- 20210511 LR - 20240226 IS - 1618-095X (Electronic) IS - 0944-7113 (Linking) VI - 83 DP - 2021 Mar TI - Amelioration of hyperglycaemia and hyperlipidaemia by adjusting the interplay between gut microbiota and bile acid metabolism: Radix Scutellariae as a case. PG - 153477 LID - S0944-7113(21)00019-2 [pii] LID - 10.1016/j.phymed.2021.153477 [doi] AB - BACKGROUND: Our previous clinical research showed that the interaction between gut microbiota and bile acids (BAs) in patients with type 2 diabetes mellitus (T2DM) changed significantly. We hypothesized that T2DM could be improved by adjusting this interaction mediated by farnesoid X receptor (FXR). T2DM belongs to the category of "xiaoke" in traditional Chinese medicine. Radix scutellariae has the effects of clearing away heat and eliminating dampness, curing jaundice and quenching thirst and is widely used alone or in combination with other medicines for the treatment of T2DM in China and throughout Asia. Additionally, the interaction between Radix scutellariae and gut microbiota may influence its efficacy in the treatment of T2DM. PURPOSE: This study chose Radix scutellariae to validate that T2DM could improve by adjusting the interaction between gut microbiota and bile acid metabolism. STUDY DESIGN AND METHODS: Radix scutellariae water extract (WESB) was administered to a T2DM rat model established by a high-fat diet combined with streptozotocin. The body weight and blood glucose and insulin levels were measured. The levels of serum lipids, creatinine, uric acid, albumin and total bile acid were also detected. Changes in the pathology and histology of the pancreas, liver and kidney were observed by haematoxylin-eosin staining. The 16S rRNAs of gut microbiota were sequenced, and the faecal and serum BAs were determined by liquid chromatography tandem mass spectrometry. The expression levels of BA metabolism-associated proteins in the liver and intestine were evaluated by immunoblot analysis. RESULTS: The results showed that WESB improved hyperglycaemia, hyperlipaemia, and liver and kidney damage in T2DM rats. In addition, the abundances of key gut microbiota and the concentrations of certain secondary BAs in faeces and serum were restored. Moreover, there was a significant correlation between the restored gut microbiota and BAs, which might be related to the activation of liver cholesterol 7alpha-hydroxylase (CYP7A1) and the inhibition of FXR expression in the intestine rather than the liver. CONCLUSIONS: This study provided new ideas for the prevention or treatment of clinical diabetes and its complications by adjusting the interaction between gut microbiota and bile acid metabolism. CI - Copyright (c) 2021. Published by Elsevier GmbH. FAU - Zhao, Lijuan AU - Zhao L AD - School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China; Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China. FAU - Ma, Ping AU - Ma P AD - School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. FAU - Peng, Ying AU - Peng Y AD - School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. FAU - Wang, Mengyue AU - Wang M AD - School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. FAU - Peng, Chongsheng AU - Peng C AD - School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. FAU - Zhang, Yulong AU - Zhang Y AD - School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. FAU - Li, Xiaobo AU - Li X AD - School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Electronic address: xbli@sjtu.edu.cn. LA - eng PT - Journal Article DEP - 20210121 PL - Germany TA - Phytomedicine JT - Phytomedicine : international journal of phytotherapy and phytopharmacology JID - 9438794 RN - 0 (Bile Acids and Salts) RN - 0 (Drugs, Chinese Herbal) RN - EC 1.14.14.23 (CYP7A1 protein, rat) RN - EC 1.14.14.23 (Cholesterol 7-alpha-Hydroxylase) SB - IM MH - Animals MH - Bile Acids and Salts/*metabolism MH - Cholesterol 7-alpha-Hydroxylase/metabolism MH - Diabetes Mellitus, Experimental/drug therapy/metabolism MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Drugs, Chinese Herbal/chemistry/pharmacology MH - Gastrointestinal Microbiome/*drug effects/physiology MH - Hyperglycemia/*drug therapy/metabolism/microbiology MH - Hyperlipidemias/*drug therapy/metabolism/microbiology MH - Intestines/drug effects MH - Lipid Metabolism/drug effects MH - Liver/drug effects/metabolism MH - Male MH - Rats, Sprague-Dawley MH - Scutellaria baicalensis/*chemistry MH - Rats OTO - NOTNLM OT - Radix scutellariae OT - bile acid OT - farnesoid X receptor OT - gut microbiota OT - type 2 diabetes mellitus EDAT- 2021/02/06 06:00 MHDA- 2021/05/12 06:00 CRDT- 2021/02/05 20:13 PHST- 2020/06/02 00:00 [received] PHST- 2020/11/06 00:00 [revised] PHST- 2021/01/18 00:00 [accepted] PHST- 2021/02/06 06:00 [pubmed] PHST- 2021/05/12 06:00 [medline] PHST- 2021/02/05 20:13 [entrez] AID - S0944-7113(21)00019-2 [pii] AID - 10.1016/j.phymed.2021.153477 [doi] PST - ppublish SO - Phytomedicine. 2021 Mar;83:153477. doi: 10.1016/j.phymed.2021.153477. Epub 2021 Jan 21.