PMID- 37044004 OWN - NLM STAT- MEDLINE DCOM- 20230505 LR - 20230505 IS - 1873-264X (Electronic) IS - 0731-7085 (Linking) VI - 230 DP - 2023 Jun 15 TI - Lipidomics of the erythrocyte membrane and network pharmacology to explore the mechanism of mangiferin from Anemarrhenae rhizoma in treating type 2 diabetes mellitus rats. PG - 115386 LID - S0731-7085(23)00155-3 [pii] LID - 10.1016/j.jpba.2023.115386 [doi] AB - Mangiferin, a natural C-glucoside xanthone, is one of the major bioactive ingredients derived from the dry rhizome of Anemarrhenae rhizome, which has been reported to exhibit various pharmacological effects, including anti-oxidant, anti-inflammatory, anti-fatty liver, anti-metabolic syndrome, and anti-diabetic. However, the precise molecular mechanisms underlying its impact on phospholipid metabolism in the erythrocyte membrane of type 2 diabetes mellitus (T2DM) remain unclear. The present research aimed to evaluate the effects of mangiferin on glucose and lipid metabolism in T2DM model rats and discuss the relationship between lipid metabolites and potential targets involved in the hypoglycemic effects by integrating lipidomics and network pharmacology method. After 8 consecutive weeks of treatment with mangiferin, the T2DM model rats exhibited significant improvements in several biochemical indices and cytokines, including fasting blood glucose (FBG) levels after 12 h of fasting, fasting insulin level (FINS), total cholesterol (T-CHO), triacylglycerols (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HMOA-IR), TNF-alpha and IL-6. A total of 22 differential lipid metabolites were selected from erythrocyte membrane phospholipids, which were closely associated with the processes of T2DM. These metabolites mainly belonged to glycerophospholipid metabolism and sphingolipid metabolism. Based on network pharmacology analysis, 22 genes were recognized as the potential targets of mangiferin against diabetes. Moreover, molecular docking analysis revealed that the targets of TNF, CASP3, PTGS2, MMP9, RELA, PLA2G2A, PPARA, and NOS3 could be involved in the modulation of inflammatory signaling pathways and arachidonic acid (AA) metabolism to improve IR and hyperglycemia. The combination of immunohistochemical staining and PCR showed that mangiferin could treat T2DM by regulating the expression of PPARgamma protein and NF-kappaB mRNA expression to impact glycerophospholipids (GPs) and AA metabolism. The present study showed that mangiferin might alleviate IR and hyperglycemia of T2DM model rats via multiple targets and multiple pathways to adjust their phospholipid metabolism, which may be the underlying mechanism for mangiferin in the treatment of T2DM. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Zhong, Yanmei AU - Zhong Y AD - Centre for Drug Research and Development, Guangdong Pharmaceutical University, 280 Waihuan East Road, Guangzhou 510006, China. FAU - Xu, Yingying AU - Xu Y AD - Department of Pharmacy, the Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang East Road, Guangzhou 510260, China. FAU - Tan, Yongzhen AU - Tan Y AD - Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang East Road, Guangzhou 510260, China. FAU - Zhang, Xuanxuan AU - Zhang X AD - Centre for Drug Research and Development, Guangdong Pharmaceutical University, 280 Waihuan East Road, Guangzhou 510006, China. FAU - Wang, Ruolun AU - Wang R AD - Department of Pharmacy, the Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang East Road, Guangzhou 510260, China. FAU - Chen, Danmin AU - Chen D AD - Institute of Neuroscience, Department of Neurosurgery, the Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang East Road, Guangzhou 510260, China. FAU - Wang, Zhaotao AU - Wang Z AD - Institute of Neuroscience, Department of Neurosurgery, the Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang East Road, Guangzhou 510260, China. Electronic address: wangzhaotao@gzhmu.edu.cn. FAU - Zhong, Xunlong AU - Zhong X AD - Department of Pharmacy, the Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang East Road, Guangzhou 510260, China. Electronic address: gzzxls0923@163.com. LA - eng PT - Journal Article DEP - 20230405 PL - England TA - J Pharm Biomed Anal JT - Journal of pharmaceutical and biomedical analysis JID - 8309336 RN - 0 (Drugs, Chinese Herbal) RN - 1M84LD0UMD (mangiferin) RN - 0 (Xanthones) RN - 0 (Phospholipids) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Rats MH - Animals MH - *Diabetes Mellitus, Type 2/metabolism MH - *Drugs, Chinese Herbal/pharmacology/therapeutic use/chemistry MH - *Anemarrhena MH - Lipidomics MH - Rhizome/chemistry MH - Erythrocyte Membrane/metabolism MH - Molecular Docking Simulation MH - Network Pharmacology MH - *Xanthones/pharmacology/therapeutic use MH - *Hyperglycemia/drug therapy MH - Phospholipids MH - Cholesterol OTO - NOTNLM OT - Erythrocyte membrane OT - Lipidomics OT - Mangiferin OT - Molecular docking OT - Network pharmacology OT - Type 2 diabetes mellitus COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/04/13 06:00 MHDA- 2023/05/05 06:42 CRDT- 2023/04/12 18:07 PHST- 2023/01/20 00:00 [received] PHST- 2023/03/23 00:00 [revised] PHST- 2023/04/03 00:00 [accepted] PHST- 2023/05/05 06:42 [medline] PHST- 2023/04/13 06:00 [pubmed] PHST- 2023/04/12 18:07 [entrez] AID - S0731-7085(23)00155-3 [pii] AID - 10.1016/j.jpba.2023.115386 [doi] PST - ppublish SO - J Pharm Biomed Anal. 2023 Jun 15;230:115386. doi: 10.1016/j.jpba.2023.115386. Epub 2023 Apr 5.