PMID- 34718103 OWN - NLM STAT- MEDLINE DCOM- 20220225 LR - 20220225 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 284 DP - 2022 Feb 10 TI - Integrating network pharmacology and non-targeted metabolomics to explore the common mechanism of Coptis Categorized Formula improving T2DM zebrafish. PG - 114784 LID - S0378-8741(21)01014-X [pii] LID - 10.1016/j.jep.2021.114784 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Coptis Categorized Formula (CCF) is one of the core prescriptions in Treatise on Febrile Diseases. Its efficacy can be available not only in exogenous diseases but widely in various internal injuries and miscellaneous diseases. CCF (i.e., Huanglian Jiedu Decoction, Huanglian Ejiao Decoction, Dahuang Huanglian Xiexin Decoction, Gegen Qinlian Decoction) is different in composition, but they all play a favorable role in curative effect on type 2 diabetes mellitus (T2DM). Therefore, it is of great significance to reveal the common mechanism of CCF in treating T2DM. AIM OF THE STUDY: Based on network pharmacology and non-targeted metabolomics research strategy, the common mechanism of the CCF treating T2DM was discussed. MATERIALS AND METHODS: Firstly, Ultra-high performance liquid chromatography-quadrupole-time of flight/mass spectrometry was used to identify the chemical constituents of the CCF. Then, the targets of these chemical components were used for network pharmacology analysis associated with therapeutic effect. Finally, the diabetic zebrafish model was constructed to further verify the common mechanism of the CCF in treating T2DM. RESULTS: A total of 160 chemical compositions were identified and 16 of them were common chemical compositions of the four CCF, including berberine, baicalin, coptisine and so forth. Network pharmacology results showed that Dipeptidyl peptidase (DPP)-4, cysteinyl aspartate specific proteinase (CASP)3, nitric oxide synthase (NOS)2, NOS3, and other 37 targets were common targets of CCF, and advanced glycation end products (AGE)-receptor of advanced glycation end products (RAGE) signaling pathway in diabetic complications, mitogen-activated protein kinase (MAPK) signaling pathway and hypoxia inducible factor (HIF)-1 signaling pathway were critical pathways of four CCF in the treatment of T2DM. CCF can lessen the blood glucose of diabetic zebrafish. The contents of 25 differential metabolites in diabetic zebrafish were altered. These metabolites were mainly related to phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, sphingolipid metabolism, and tyrosine metabolism. CONCLUSION: Our research shows that the common mechanism of CCF in improving T2DM is as follows: berberine, baicalin, coptisine and other chemical components can directionally regulate DPP-4, CASP3, NOS2, NOS3 and other targets, which are mediated by AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and HIF-1 signaling pathway. The content of endogenous metabolites such as L-valine and L-sorbitose changes, and further regulates the metabolism of amino acid metabolism, lipid metabolism, purine metabolism, sphingosine metabolism and arachidonic acid metabolism, so as to play a significant role in regulating glycolipid metabolism, improving insulin resistance, inhibiting cell apoptosis, anti-oxidation and anti-inflammation, and finally ameliorating T2DM. CI - Copyright (c) 2021. Published by Elsevier B.V. FAU - He, Tao AU - He T AD - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China. FAU - Wang, Mingshuang AU - Wang M AD - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China; Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, 102488, China. FAU - Kong, Jiao AU - Kong J AD - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China. FAU - Wang, Qiang AU - Wang Q AD - School of Pharmacy China Pharmaceutical University, Nanjing, Jiangsu, 210009, China. FAU - Tian, Yue AU - Tian Y AD - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China. FAU - Li, Chaofeng AU - Li C AD - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China; Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing, 102488, China. FAU - Wang, Qian AU - Wang Q AD - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China. FAU - Liu, Chuanxin AU - Liu C AD - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China; Department of Metabolism and Endocrinology, Endocrine and Metabolic Disease Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology; Medical Key Laboratory of Hereditary Rare Diseases of Henan; Luoyang Sub-center of National Clinical Research Center for Metabolic Diseases, Luoyang, 471003, China. Electronic address: 15222003775@163.com. FAU - Huang, Jianmei AU - Huang J AD - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China. Electronic address: huangjm@bucm.edu.cn. LA - eng PT - Journal Article DEP - 20211027 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Drugs, Chinese Herbal) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Coptis/*chemistry MH - Diabetes Mellitus, Type 2/*drug therapy MH - Drugs, Chinese Herbal/*pharmacology MH - Embryo, Nonmammalian MH - Glucose/metabolism MH - Molecular Docking Simulation MH - *Network Pharmacology MH - *Phytotherapy MH - Zebrafish OTO - NOTNLM OT - Chemical composition OT - Coptis categorized formula OT - Molecular mechanism OT - Type 2 diabetes mellitus OT - Zebrafish EDAT- 2021/11/01 06:00 MHDA- 2022/02/26 06:00 CRDT- 2021/10/31 20:48 PHST- 2021/08/18 00:00 [received] PHST- 2021/10/22 00:00 [revised] PHST- 2021/10/25 00:00 [accepted] PHST- 2021/11/01 06:00 [pubmed] PHST- 2022/02/26 06:00 [medline] PHST- 2021/10/31 20:48 [entrez] AID - S0378-8741(21)01014-X [pii] AID - 10.1016/j.jep.2021.114784 [doi] PST - ppublish SO - J Ethnopharmacol. 2022 Feb 10;284:114784. doi: 10.1016/j.jep.2021.114784. Epub 2021 Oct 27.