PMID- 37667364 OWN - NLM STAT- MEDLINE DCOM- 20230906 LR - 20231120 IS - 2662-7671 (Electronic) IS - 2662-7671 (Linking) VI - 23 IP - 1 DP - 2023 Sep 4 TI - Identifying potential therapeutic targets of mulberry leaf extract for the treatment of type 2 diabetes: a TMT-based quantitative proteomic analysis. PG - 308 LID - 10.1186/s12906-023-04140-3 [doi] LID - 308 AB - BACKGROUND: Mulberry (Morus alba L.) leaf, as a medicinal and food homologous traditional Chinese medicine, has a clear therapeutic effect on type 2 diabetes mellitus (T2DM), yet its underlying mechanisms have not been totally clarified. The study aimed to explore the mechanism of mulberry leaf in the treatment of T2DM through tandem mass tag (TMT)-based quantitative proteomics analysis of skeletal muscle. METHODS: The anti-diabetic activity of mulberry leaf extract (MLE) was evaluated by using streptozotocin-induced diabetic rats at a dose of 4.0 g crude drug /kg p.o. daily for 8 weeks. Fasting blood glucose, body weight, food and water intake were monitored at specific intervals, and oral glucose tolerance test and insulin tolerance test were conducted at the 7th and 8th week respectively. At the end of the experiment, levels of glycated hemoglobin A1c, insulin, free fat acid, leptin, adiponectin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were assessed and the pathological changes of rat skeletal muscle were observed by HE staining. TMT-based quantitative proteomic analysis of skeletal muscle and bioinformatics analysis were performed and differentially expressed proteins (DEPs) were validated by western blot. The interactions between the components of MLE and DEPs were further assessed using molecular docking. RESULTS: After 8 weeks of MLE intervention, the clinical indications of T2DM such as body weight, food and water intake of rats were improved to a certain extent, while insulin sensitivity was increased and glycemic control was improved. Serum lipid profiles were significantly reduced, and the skeletal muscle fiber gap and atrophy were alleviated. Proteomic analysis of skeletal muscle showed that MLE treatment reversed 19 DEPs in T2DM rats, regulated cholesterol metabolism, fat digestion and absorption, vitamin digestion and absorption and ferroptosis signaling pathways. Key differential proteins Apolipoprotein A-1 (ApoA1) and ApoA4 were successfully validated by western blot and exhibited strong binding activity to the MLE's ingredients. CONCLUSIONS: This study first provided skeletal muscle proteomic changes in T2DM rats before and after MLE treatment, which may help us understand the molecular mechanisms, and provide a foundation for developing potential therapeutic targets of anti-T2DM of MLE. CI - (c) 2023. BioMed Central Ltd., part of Springer Nature. FAU - Shi, Lu AU - Shi L AD - Department of Pharmacology of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China. AD - Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, China. FAU - Wang, Jingkang AU - Wang J AD - Department of Pharmacology of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - He, Changhao AU - He C AD - Department of Pharmacology of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Huang, Yan AU - Huang Y AD - College of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Fu, Wanxin AU - Fu W AD - College of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Zhang, Huilin AU - Zhang H AD - Department of Pharmacology of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - An, Yongcheng AU - An Y AD - Department of Pharmacology of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Wang, Menglu AU - Wang M AD - Department of Pharmacology of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Shan, Ziyi AU - Shan Z AD - College of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Li, Huimin AU - Li H AD - Department of Pharmacology of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Lv, Yinglan AU - Lv Y AD - Department of Pharmacology of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Wang, Chen AU - Wang C AD - College of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Cheng, Long AU - Cheng L AD - Department of Pharmacology of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Dai, Hongyu AU - Dai H AD - Department of Pharmacology of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Duan, Yuhui AU - Duan Y AD - Department of Pharmacology of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Zhao, Hongbin AU - Zhao H AD - Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100029, China. FAU - Zhao, Baosheng AU - Zhao B AD - Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China. zhaobs1973@163.com. LA - eng PT - Journal Article DEP - 20230904 PL - England TA - BMC Complement Med Ther JT - BMC complementary medicine and therapies JID - 101761232 RN - 0 (Insulin) RN - 0 (Cholesterol, HDL) RN - 0 (Plant Extracts) RN - Morus alba SB - IM MH - Animals MH - Rats MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Morus MH - *Diabetes Mellitus, Experimental/drug therapy MH - Molecular Docking Simulation MH - Proteomics MH - Insulin MH - Body Weight MH - Cholesterol, HDL MH - Plant Extracts/pharmacology PMC - PMC10476348 OTO - NOTNLM OT - Lipid metabolism OT - Mulberry leaf OT - Proteomics OT - Type 2 diabetes mellitus COIS- The authors declare that they have no competing interests. EDAT- 2023/09/05 00:42 MHDA- 2023/09/06 06:42 PMCR- 2023/09/04 CRDT- 2023/09/04 23:51 PHST- 2022/12/29 00:00 [received] PHST- 2023/08/25 00:00 [accepted] PHST- 2023/09/06 06:42 [medline] PHST- 2023/09/05 00:42 [pubmed] PHST- 2023/09/04 23:51 [entrez] PHST- 2023/09/04 00:00 [pmc-release] AID - 10.1186/s12906-023-04140-3 [pii] AID - 4140 [pii] AID - 10.1186/s12906-023-04140-3 [doi] PST - epublish SO - BMC Complement Med Ther. 2023 Sep 4;23(1):308. doi: 10.1186/s12906-023-04140-3.