PMID- 31551787 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 10 DP - 2019 TI - Erxian Decoction Attenuates TNF-alpha Induced Osteoblast Apoptosis by Modulating the Akt/Nrf2/HO-1 Signaling Pathway. PG - 988 LID - 10.3389/fphar.2019.00988 [doi] LID - 988 AB - Erxian decoction (EXD), a traditional Chinese medicine formula, has been used for treatment of osteoporosis for many years. The purpose of this study was to investigate the pharmacological effect of EXD in preventing osteoblast apoptosis and the underlying mechanism of prevention. Putative targets of EXD were predicted by network pharmacology, and functional and pathway enrichment analyses were also performed. Evaluations of bone mineral density, serum estradiol level, trabecular area fraction, serum calcium levels, and tumor necrosis factor (TNF)-alpha levels in ovariectomized rats, as well as cell proliferation assays, apoptosis assays, and western blotting in MC3T3-E1 osteoblasts were performed for further experimental validation. Ninety-three active ingredients in the EXD formula and 259 potential targets were identified. Functional and pathway enrichment analyses indicated that EXD significantly influenced the PI3K-Akt signaling pathway. In vivo experiments indicated that EXD treatment attenuated bone loss and decreased TNF-alpha levels in rats with osteoporosis. In vitro experiments showed that EXD treatment increased cell viability markedly and decreased levels of caspase-3 and the rate of apoptosis. It also promoted phosphorylation of Akt, nuclear translocation of transcription factor NF-erythroid 2-related factor (Nrf2), and hemeoxygenase-1 (HO-1) expression in TNF-alpha-induced MC3T3-E1 cells. Our results suggest that EXD exerted profound anti-osteoporosis effects, at least partially by reducing production of TNF-alpha and attenuating osteoblast apoptosis via Akt/Nrf2/HO-1 signaling pathway. FAU - Wang, Nani AU - Wang N AD - Department of Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China. AD - School of Pharmacy, Zhejiang Chinese Medical University, China. FAU - Xin, Hailiang AU - Xin H AD - School of Pharmacy, Second Military Medical University, China. FAU - Xu, Pingcui AU - Xu P AD - Department of Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China. AD - School of Pharmacy, Zhejiang Chinese Medical University, China. FAU - Yu, Zhongming AU - Yu Z AD - Department of Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China. FAU - Shou, Dan AU - Shou D AD - Department of Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China. LA - eng PT - Journal Article DEP - 20190910 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC6748068 OTO - NOTNLM OT - Akt OT - Erxian decoction OT - network pharmacology OT - osteoporosis OT - tumor necrosis factor EDAT- 2019/09/26 06:00 MHDA- 2019/09/26 06:01 PMCR- 2019/09/10 CRDT- 2019/09/26 06:00 PHST- 2018/10/05 00:00 [received] PHST- 2019/07/31 00:00 [accepted] PHST- 2019/09/26 06:00 [entrez] PHST- 2019/09/26 06:00 [pubmed] PHST- 2019/09/26 06:01 [medline] PHST- 2019/09/10 00:00 [pmc-release] AID - 10.3389/fphar.2019.00988 [doi] PST - epublish SO - Front Pharmacol. 2019 Sep 10;10:988. doi: 10.3389/fphar.2019.00988. eCollection 2019.