PMID- 32377518 OWN - NLM STAT- MEDLINE DCOM- 20210216 LR - 20220414 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2020 DP - 2020 TI - Banxia Xiexin Decoction Ameliorates t-BHP-Induced Apoptosis in Pancreatic Beta Cells by Activating the PI3K/AKT/FOXO1 Signaling Pathway. PG - 3695689 LID - 10.1155/2020/3695689 [doi] LID - 3695689 AB - BACKGROUND: Banxia Xiexin Decoction (BXXD) reportedly regulates glycolipid metabolism and inhibits pancreatic beta-cell apoptosis. This study is aimed at investigating the protective effect of BXXD on tert-butyl hydroperoxide- (t-BHP-) induced apoptosis in MIN6 cells and the underlying mechanisms. METHODS: MIN6 cells were preincubated with BXXD or liraglutide (Li) with or without PI3K inhibitor LY294002 (LY) for 12 h, following which t-BHP was added to induce MIN6 cell apoptosis. The protective effects of BXXD on MIN6 cells were evaluated by detecting cell viability and proliferation and glucose-stimulated insulin secretion (GSIS). The antiapoptotic effects were evaluated by Hoechst 33342 staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL). Malondialdehyde and glutathione peroxidase content and superoxide dismutase activity were measured using commercial kits. The expression of PI3K/AKT/FOXO1 signaling pathway-related signal molecules, and that of apoptotic indicators Bax, P27, and Caspase-3, was quantified using western blotting. RESULTS: Preincubation with BXXD significantly improved t-BHP-induced proliferation inhibition and apoptosis and enhanced GSIS. t-BHP induced the generation of reactive oxygen species and inhibited the activities of antioxidant enzymes, which could be neutralized by pretreatment with BXXD. BXXD promoted the phosphorylation of AKT and FOXO1 in t-BHP-induced MIN6 cells. Moreover, BXXD attenuated the expression of related apoptotic indicators Bax, P27, and Caspase-3. LY abolished these effects of BXXD. CONCLUSION: BXXD protected MIN6 cells against t-BHP-induced apoptosis and improved insulin secretory function through modulation of the PI3K/AKT pathway and the downstream FOXO1, thus suggesting a novel therapeutic approach for type 2 diabetes mellitus (T2DM). CI - Copyright (c) 2020 Li-juan Du et al. FAU - Du, Li-Juan AU - Du LJ AD - Department of Endocrinology, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Pang, Bing AU - Pang B AUID- ORCID: 0000-0002-0069-5055 AD - Department of Endocrinology, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Tan, Yu-Meng AU - Tan YM AUID- ORCID: 0000-0002-1714-636X AD - Department of Endocrinology, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Yang, Ya-Nan AU - Yang YN AUID- ORCID: 0000-0003-3218-1566 AD - Department of Endocrinology, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Zhang, Mei-Zhen AU - Zhang MZ AUID- ORCID: 0000-0002-7740-8376 AD - Department of Endocrinology, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Pang, Qing AU - Pang Q AD - Department of Endocrinology, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Sun, Min AU - Sun M AUID- ORCID: 0000-0002-8528-0050 AD - School of Life Sciences, Anhui University, Hefei, China. FAU - Ni, Qing AU - Ni Q AUID- ORCID: 0000-0002-4786-4901 AD - Department of Endocrinology, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. LA - eng PT - Journal Article DEP - 20200417 PL - England TA - J Diabetes Res JT - Journal of diabetes research JID - 101605237 RN - 0 (Drugs, Chinese Herbal) RN - 0 (Forkhead Box Protein O1) RN - 0 (Reactive Oxygen Species) RN - 0 (banxia xiexin decoction) RN - 4Y8F71G49Q (Malondialdehyde) RN - 955VYL842B (tert-Butylhydroperoxide) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Caspase 3/metabolism MH - Cell Line MH - Drugs, Chinese Herbal/*pharmacology MH - Forkhead Box Protein O1/metabolism MH - Glutathione Peroxidase/metabolism MH - Insulin-Secreting Cells/*drug effects/metabolism MH - Malondialdehyde/metabolism MH - Mice MH - Oxidative Stress/drug effects MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphorylation/drug effects MH - Proto-Oncogene Proteins c-akt/metabolism MH - Reactive Oxygen Species/metabolism MH - Signal Transduction/*drug effects MH - Superoxide Dismutase/metabolism MH - tert-Butylhydroperoxide/*pharmacology PMC - PMC7191444 COIS- No competing financial interests existed. EDAT- 2020/05/08 06:00 MHDA- 2021/02/17 06:00 PMCR- 2020/04/17 CRDT- 2020/05/08 06:00 PHST- 2019/12/27 00:00 [received] PHST- 2020/03/20 00:00 [revised] PHST- 2020/03/31 00:00 [accepted] PHST- 2020/05/08 06:00 [entrez] PHST- 2020/05/08 06:00 [pubmed] PHST- 2021/02/17 06:00 [medline] PHST- 2020/04/17 00:00 [pmc-release] AID - 10.1155/2020/3695689 [doi] PST - epublish SO - J Diabetes Res. 2020 Apr 17;2020:3695689. doi: 10.1155/2020/3695689. eCollection 2020.