PMID- 32218735 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 11 DP - 2020 TI - Neuroprotective Effect of Danhong Injection on Cerebral Ischemia-Reperfusion Injury in Rats by Activation of the PI3K-Akt Pathway. PG - 298 LID - 10.3389/fphar.2020.00298 [doi] LID - 298 AB - Many traditional Chinese medicines, including Danhong injection (DHI), can be used to treat cerebral ischemia-reperfusion injury and have neuroprotective effects on the brain; however, few studies have explored the mechanism by which this effect is generated. In this study, we investigated the neuroprotective effect of DHI against cerebral ischemia-reperfusion injury mediated via the PI3K-Akt signaling pathway. After establishing the model of middle cerebral artery occlusion (MCAO), 60 male Sprague-Dawley rats were allocated to six groups as follows: sham, MCAO, DHI (MCAO + DHI), LY294002 (MCAO + LY294002 [PI3K-Akt pathway specific inhibitor]), DHI + LY294002 (MCAO + DHI + LY294002), and NMDP + LY294002 (MCAO + NMDP [nimodipine] + LY294002). Hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used to evaluate the pathological changes of brain tissue and the degree of neuronal apoptosis. Real-time quantitative polymerase chain reaction (qRT-PCR), western blot analysis and enzyme-linked immunosorbent assays were used to measure the expression of Bad, Bax, Bcl-2, Bim, P53, MDM2, Akt, PI3K, p-Akt, p-PI3K, and Cyt-C. Compared with the MCAO group, brain tissue cell apoptosis was significantly reduced in the DHI group, and the brain function score was significantly improved. In addition, the expression of pro-apoptotic factors (Bad, Bax, and Bim) was significantly downregulated in the DHI group, while expression of the anti-apoptotic factor Bcl-2 was significantly upregulated, and expression of the apoptotic gene p53 was also significantly attenuated. Moreover, this neuroprotective effect was attenuated by the PI3K-Akt signaling pathway inhibitor (LY294002). Thus, our results confirmed the neuroprotective effects of DHI in rats with ischemia-reperfusion injury and indicate that these effects on the brain are partly generated by activation of the PI3K-Akt signaling pathway. CI - Copyright (c) 2020 Feng, Wan, Zhang, Yu, Shao, He, Wan and Jin. FAU - Feng, Chen AU - Feng C AD - The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Wan, Haofang AU - Wan H AD - Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Zhang, Yangyang AU - Zhang Y AD - College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Yu, Li AU - Yu L AD - College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Shao, Chongyu AU - Shao C AD - College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China. FAU - He, Yu AU - He Y AD - College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Wan, Haitong AU - Wan H AD - College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Jin, Weifeng AU - Jin W AD - College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China. LA - eng PT - Journal Article DEP - 20200311 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC7078680 OTO - NOTNLM OT - Danhong injection OT - PI3K-Akt pathway OT - apoptosis OT - ischemia-reperfusion OT - neuroprotection EDAT- 2020/03/29 06:00 MHDA- 2020/03/29 06:01 PMCR- 2020/03/11 CRDT- 2020/03/29 06:00 PHST- 2019/11/19 00:00 [received] PHST- 2020/02/27 00:00 [accepted] PHST- 2020/03/29 06:00 [entrez] PHST- 2020/03/29 06:00 [pubmed] PHST- 2020/03/29 06:01 [medline] PHST- 2020/03/11 00:00 [pmc-release] AID - 10.3389/fphar.2020.00298 [doi] PST - epublish SO - Front Pharmacol. 2020 Mar 11;11:298. doi: 10.3389/fphar.2020.00298. eCollection 2020.