PMID- 36330410 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221105 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 10 IP - 19 DP - 2022 Oct TI - Bergenin inhibits palmitic acid-induced pancreatic beta-cell inflammatory death via regulating NLRP3 inflammasome activation. PG - 1058 LID - 10.21037/atm-22-3781 [doi] LID - 1058 AB - BACKGROUND: Bergenin, an active constituent of plants of the genus Bergenia, has been reported to have antidiabetic properties. This study investigated whether bergenin is beneficial for treating type 2 diabetes mellitus (T2DM) via regulating NOD-like receptor family-pyrin domain containing 3 (NLRP3) inflammasome. METHODS: Two pancreatic beta-cell lines, INS-1 and MIN6, were treated with 1, 3, or 10 microM bergenin in the absence or presence of palmitic acid (PA). Cell Counting Kit (CCK)-8, flow cytometry, quantitative reverse transcription-polymerase chain reaction, western blotting, and immunofluorescent staining were performed. RESULTS: Bergenin with concentrations of 1, 3, and 10 microM had no cytotoxicity in INS-1 and MIN6 cells. However, bergenin dose-dependently relieved PA-induced pancreatic beta‑cell loss and apoptosis. Bergenin dose-dependently inhibited NLRP3 inflammasome-related inflammation, as observed by the downregulation of NLRP3, apoptosis associated speck like protein (ASC), cleaved caspase-1, and gasdermin-D (GSDMD)-N, as well as the decreased release of cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, IL-1beta, and IL-18. The NOD-like receptor signaling pathway was predicted to be a downstream signaling pathway regulated by bergenin. Autodock Vina software docked bergenin with NLRP3. The binding energy of interaction was -5.101 kcal/mol and the root-mean-square deviation (RMSD) score was 1.5901A. Treating pancreatic beta‑cells with bergenin accelerated the degeneration of NLRP3. Furthermore, restoration of NLRP3 expression using plasmid transfection reversed the protective effects of bergenin on pancreatic beta-cells. CONCLUSIONS: Our data suggests that bergenin is a potential agent for treating T2DM through preventing NLRP3 inflammasome-related inflammation in pancreatic beta-cells. CI - 2022 Annals of Translational Medicine. All rights reserved. FAU - Lei, Donghong AU - Lei D AD - Department of Pediatrics, The First Hospital of Yulin, Yulin, China. FAU - Sun, Yanru AU - Sun Y AD - Department of Pediatrics, The First Hospital of Yulin, Yulin, China. FAU - Liu, Jie AU - Liu J AD - Department of Pediatrics, The First Hospital of Yulin, Yulin, China. FAU - Chi, Jianxiu AU - Chi J AD - Department of Pediatrics, The First Hospital of Yulin, Yulin, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC9622470 OTO - NOTNLM OT - Diabetes mellitus OT - NOD-like receptor family-pyrin domain containing 3 (NLRP3) OT - bergenin OT - palmitic acid OT - pancreatic beta-cell COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3781/coif). The authors have no conflicts of interest to declare. EDAT- 2022/11/05 06:00 MHDA- 2022/11/05 06:01 PMCR- 2022/10/01 CRDT- 2022/11/04 02:35 PHST- 2022/07/11 00:00 [received] PHST- 2022/08/23 00:00 [accepted] PHST- 2022/11/04 02:35 [entrez] PHST- 2022/11/05 06:00 [pubmed] PHST- 2022/11/05 06:01 [medline] PHST- 2022/10/01 00:00 [pmc-release] AID - atm-10-19-1058 [pii] AID - 10.21037/atm-22-3781 [doi] PST - ppublish SO - Ann Transl Med. 2022 Oct;10(19):1058. doi: 10.21037/atm-22-3781.