PMID- 36394728 OWN - NLM STAT- MEDLINE DCOM- 20221122 LR - 20221216 IS - 2284-0729 (Electronic) IS - 1128-3602 (Linking) VI - 26 IP - 21 DP - 2022 Nov TI - Anti-obesity effect of escin: a study on high-fat diet-induced obese mice. PG - 7797-7812 LID - 30129 [pii] LID - 10.26355/eurrev_202211_30129 [doi] AB - OBJECTIVE: Obesity is characterized by excess fat accumulation and closely associated with insulin resistance and type 2 diabetes. We aimed at exploring the potential effect and mechanism of escin for the treatment of obesity using network pharmacology, and to verify the effect of escin on obese mice. MATERIALS AND METHODS: Escin targets were predicted by DrugBank and SwissTarget database. Potential targets for the treatment of obesity were identified based on the DisGeNET database. Comparative analysis was used to investigate the overlapping genes between escin targets and obesity treatment-related targets. Using STRING database and Cytoscape to analyze interactions among overlapping genes, hub genes were identified. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted in DAVID. High-fat diet (HFD) -induced obese mice were used to observe the anti-obesity effects of escin. The body weight, relevant biochemical markers and HE staining of fat and liver tissues were determined after escin was administered for 18 weeks. RESULTS: We screened 53 overlapping genes for escin and obesity. The mechanism of intervention of escin in treating obesity may involve 10 hub targets (STAT3, MTOR, NR3C1, IKBKB, PTGS2, MMP9, PRKCA, PRKCD, AR, CYP3A4). The screening and enrichment analysis revealed that the treatment of obesity using escin primarily involved 10 GO enriched terms and 13 related pathways. In vivo, escin can reduce the body weight of obese mice induced by HFD and improve lipid metabolism through lowering triglycerides (TG), total cholesterol (TC), and density lipoprotein (LDL) levels and increasing high density lipoprotein (HDL) levels and decreasing leptin level and increasing adiponectin (ADPN) level. Escin can regulate glucose metabolism caused by obesity through decreasing fasting glucose, postprandial blood glucose and regulating the level of insulin. These obese mice induced by HFD displayed the increased insulin resistance that was associated with the increased inflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and monocyte chemoattractant protein-1 (MCP-1). Escin may antagonize the increase of MCP-1 and partially antagonize the low-grade inflammation caused by obesity. From the morphological changes of fat and liver tissues stained by HE stain, escin could decrease the size of adipocytes and improve liver necrosis and fatty degeneration in obese mice fed by HFD. CONCLUSIONS: The network pharmacology of escin in treating obesity may involve 10 hub targets (STAT3, MTOR, NR3C1, IKBKB, PTGS2, MMP9, PRKCA, PRKCD, AR, CYP3A4), 10 GO enriched terms and 13 related pathways. In vivo, escin can be potentially used to prevent or treat obesity through reducing the weight, improving glucose and lipid metabolism, partially antagonizing the low-grade inflammation, and improved insulin resistance. FAU - Zhang, Q-H AU - Zhang QH AD - College of Integrated Traditional Chinese Medicine and Western Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, PR China. 1051374105@qq.com. FAU - Cui, X-Y AU - Cui XY FAU - Wang, D AU - Wang D FAU - Jin, Y AU - Jin Y FAU - Guan, Y-X AU - Guan YX LA - eng PT - Journal Article PL - Italy TA - Eur Rev Med Pharmacol Sci JT - European review for medical and pharmacological sciences JID - 9717360 RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.14.1 (Cytochrome P-450 CYP3A) RN - 6805-41-0 (Escin) RN - IY9XDZ35W2 (Glucose) RN - EC 2.7.11.10 (I-kappa B Kinase) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Mice MH - Cyclooxygenase 2 MH - Cytochrome P-450 CYP3A/therapeutic use MH - *Diabetes Mellitus, Type 2/complications MH - Diet, High-Fat MH - Escin/therapeutic use MH - Glucose/metabolism MH - I-kappa B Kinase MH - Inflammation/metabolism MH - *Insulin Resistance MH - Matrix Metalloproteinase 9 MH - Mice, Obese MH - Obesity MH - TOR Serine-Threonine Kinases EDAT- 2022/11/18 06:00 MHDA- 2022/11/22 06:00 CRDT- 2022/11/17 13:58 PHST- 2022/11/17 13:58 [entrez] PHST- 2022/11/18 06:00 [pubmed] PHST- 2022/11/22 06:00 [medline] AID - 30129 [pii] AID - 10.26355/eurrev_202211_30129 [doi] PST - ppublish SO - Eur Rev Med Pharmacol Sci. 2022 Nov;26(21):7797-7812. doi: 10.26355/eurrev_202211_30129.