PMID- 37013717 OWN - NLM STAT- MEDLINE DCOM- 20230814 LR - 20230814 IS - 1099-1573 (Electronic) IS - 0951-418X (Linking) VI - 37 IP - 8 DP - 2023 Aug TI - Mulberry leaf water extract alleviates type 2 diabetes in mice via modulating gut microbiota-host co-metabolism of branched-chain amino acid. PG - 3195-3210 LID - 10.1002/ptr.7822 [doi] AB - Elevations in circling branched-chain amino acids (BCAAs) levels associated with insulin resistance and type 2 diabetes mellitus (T2DM). Morus alba L. water extracts (MLE) show hypoglycemic function, but the precise mechanism remains obscure. This study is designed to investigate the association of the antidiabetes effect of MLE with the BCAAs co-metabolism modulated by host and gut microbiota. Tissue-specific expressions of BCAA-catabolizing enzymes were detected by RT-PCR and western blot, respectively. The components of the intestinal microflora were analyzed by high-throughput 16S rRNA gene sequencing. The results showed that MLE administration improved blood glucose and insulin level, decreased inflammatory cytokines expression, and lowered serum and feces BCAAs levels. Furthermore, MLE reversed the abundance changes of the bacterial genera correlated with serum and feces BCAAs, such as Anaerovorax, Bilophila, Blautia, Colidextribacter, Dubosiella, Intestinimonas, Lachnoclostridium, Lachnospiraceae_NK4A136, Oscillibacter, and Roseburia. Functionality prediction indicated that MLE potentially inhibited bacterial BCAAs biosynthesis, and promoted the tissue-specific expression of BCAAs catabolic enzyme. More importantly, MLE had obvious impacts on BCAA catabolism in germ-free-mimic T2DM mice. Those results indicated that MLE improving T2DM-related biochemical abnormalities is associated with not only gut microbiota modification but also the tissue-specific expression of BCAAs catabolic enzyme. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Zheng, Xiao-Xiao AU - Zheng XX AD - Department of Pharmacy, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, 221116, China. AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Li, Ding-Xiang AU - Li DX AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Li, Ya-Ting AU - Li YT AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Chen, Yu-Lang AU - Chen YL AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Zhao, Yan-Lin AU - Zhao YL AD - Department of Pharmaceutical Analysis, Xuzhou Medical University, Xuzhou, 221204, China. FAU - Ji, Shuai AU - Ji S AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. AD - Department of Pharmacy, Suining People's Hospital Affiliated to Xuzhou Medical University, Suining, 221202, China. FAU - Guo, Meng-Zhe AU - Guo MZ AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. AD - Department of Pharmacy, Suining People's Hospital Affiliated to Xuzhou Medical University, Suining, 221202, China. FAU - Du, Yan AU - Du Y AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. AD - State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center (ChemBIC), Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, 210093, China. FAU - Tang, Dao-Quan AU - Tang DQ AUID- ORCID: 0000-0002-5443-4619 AD - Department of Pharmacy, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, 221116, China. AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. AD - Department of Pharmaceutical Analysis, Xuzhou Medical University, Xuzhou, 221204, China. AD - Department of Pharmacy, Suining People's Hospital Affiliated to Xuzhou Medical University, Suining, 221202, China. LA - eng GR - 82204708/National Natural Science Foundation of China/ GR - 22KJD360004/Natural Science Foundation of Jiangsu Higher Education Institutions of China/ GR - KC21204/Natural Science Foundation of Xuzhou City of China/ GR - KC22146/Natural Science Foundation of Xuzhou City of China/ GR - YB2020050/Traditional Chinese Medicine Scientific and Technological Development of Jiangsu Province of China/ GR - ZT202212/Traditional Chinese Medicine Scientific and Technological Development of Jiangsu Province of China/ PT - Journal Article DEP - 20230404 PL - England TA - Phytother Res JT - Phytotherapy research : PTR JID - 8904486 RN - 0 (RNA, Ribosomal, 16S) RN - 0 (Amino Acids, Branched-Chain) RN - Morus alba SB - IM MH - Mice MH - Animals MH - *Diabetes Mellitus, Type 2/metabolism MH - *Gastrointestinal Microbiome MH - *Morus/chemistry MH - RNA, Ribosomal, 16S/analysis MH - *Insulin Resistance MH - Amino Acids, Branched-Chain/analysis/metabolism MH - Plant Leaves/chemistry OTO - NOTNLM OT - Morus alba leaf water extract OT - branched-chain amino acid OT - gut microbiota OT - insulin resistance OT - type 2 diabetes mellitus EDAT- 2023/04/05 06:00 MHDA- 2023/08/14 06:41 CRDT- 2023/04/04 04:22 PHST- 2023/03/21 00:00 [revised] PHST- 2023/01/31 00:00 [received] PHST- 2023/03/24 00:00 [accepted] PHST- 2023/08/14 06:41 [medline] PHST- 2023/04/05 06:00 [pubmed] PHST- 2023/04/04 04:22 [entrez] AID - 10.1002/ptr.7822 [doi] PST - ppublish SO - Phytother Res. 2023 Aug;37(8):3195-3210. doi: 10.1002/ptr.7822. Epub 2023 Apr 4.