Dihydromyricetin inhibits oxidative stress and apoptosis in oxygen and glucose deprivation/reoxygenation‑induced HT22 cells by activating the Nrf2/HO‑1 pathway

Zhang,Qian; Wang,Jia; Zhang,Huili; Zeng,Tao

doi:10.3892/mmr.2021.12036

Dihydromyricetin inhibits oxidative stress and apoptosis in oxygen and glucose deprivation/reoxygenation‑induced HT22 cells by activating the Nrf2/HO‑1 pathway

Authors:
- Qian Zhang
- Jia Wang
- Huili Zhang
- Tao Zeng
View Affiliations

Affiliations: Department of Encephalopathy, Gansu Provincial Hospital of TCM, Lanzhou, Gansu 730050, P.R. China, Department of Rheumatic Osteopathy, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu 730000, P.R. China, Department of Neurology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China
Published online on: March 25, 2021 https://doi.org/10.3892/mmr.2021.12036
Article Number: 397

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cerebral ischemia‑reperfusion injury (CIRI) refers to the phenomenon that ischemic injury of the brain leads to the injury of brain cells, which is further aggravated after the recovery of blood reperfusion. Dihydromyricetin (DHM) has an effective therapeutic effect on vascular diseases; however, its role in CIRI has not been investigated. The oxygen and glucose deprivation/reoxygenation (OGD/R) cell model was used on HT22 hippocampal neurons in mice, by oxygen and sugar deprivation. DHM was found to increase the cell viability of HT22 cells following OGD/R induction. The levels of malondialdehyde (MDA) decreased, superoxide dismutase (SOD) and glutathione (GSH) in the OGD/R‑induced HT22 cells increased following DHM treatment, accompanied by the decreased protein expression levels of NOX2 and NOX4. DHM also inhibited cell apoptosis induced by OGD/R, and decreased the protein expression levels of Bax and caspase‑3, and increased the expression levels of Bcl‑2. Moreover, the expression levels of the NF‑E2‑related factor 2 (Nrf2)/heme oxygenase (HO‑1) signaling pathway‑associated proteins in OGD/R‑induced HT22 were increased following DHM treatment, and the effect of DHM on oxidative stress and apoptosis was reversed after the addition of the Nrf2/HO‑1 pathway inhibitor, brusatol. In conclusion, DHM inhibited oxidative stress and apoptosis in OGD/R‑induced HT22 cells by activating the Nrf2/HO‑1 signaling pathway.

View Figures

View References

1	Fisher M: Introducing focused updates in cerebrovascular disease. Stroke. 48:26532017. View Article : Google Scholar : PubMed/NCBI
2	Yanez N, Useche JN, Bayona H, Porras A and Carrasquilla G: Analyses of mortality and prevalence of cerebrovascular disease in colombia, south america (2014–2016): A Cross-sectional and ecological study. J Stroke Cerebrovasc Dis. 29:1046992020. View Article : Google Scholar : PubMed/NCBI
3	Soares ROS, Losada DM, Jordani MC, Évora P and Castro-E-Silva O: Ischemia/reperfusion injury revisited: An overview of the latest pharmacological strategies. Int J Mol Sci. 20:50342019. View Article : Google Scholar
4	Wang M, Liu JX, Yao MJ and Ren JG: Advances in research on pharmacological and neuroprotective effects of traditional Chinese medicine after cerebral ischemia. Zhongguo Zhong Yao Za Zhi. 45:513–517. 2020.(In Chinese). PubMed/NCBI
5	Xu Y, Wang S, Chan HF, Lu H, Lin Z, He C and Chen M: Dihydromyricetin induces apoptosis and reverses drug resistance in ovarian cancer cells by p53-mediated downregulation of survivin. Sci Rep. 7:460602017. View Article : Google Scholar : PubMed/NCBI
6	Le L, Jiang B, Wan W, Zhai W, Xu L, Hu K and Xiao P: Metabolomics reveals the protective of Dihydromyricetin on glucose homeostasis by enhancing insulin sensitivity. Sci Rep. 6:361842016. View Article : Google Scholar : PubMed/NCBI
7	Wang J, Wang K, Huang C, Lin D, Zhou Y, Wu Y, Tian N, Fan P, Pan X, Xu D, et al: SIRT3 activation by dihydromyricetin suppresses chondrocytes degeneration via maintaining mitochondrial homeostasis. Int J Biol Sci. 14:1873–1882. 2018. View Article : Google Scholar : PubMed/NCBI
8	Ren W, Liao J, Chen J, Li Z and Huang L: The effect of Chinese herbal medicine combined with western medicine on vascular endothelial function for patients with hypertension: Protocol for a systematic review and Meta-analysis. Medicine (Baltimore). 98:e181342019. View Article : Google Scholar : PubMed/NCBI
9	Wei L, Sun X, Qi X, Zhang Y, Li Y and Xu Y: dihydromyricetin ameliorates cardiac Ischemia/reperfusion injury through Sirt3 activation. Biomed Res Int. 2019:68039432019. View Article : Google Scholar : PubMed/NCBI
10	Chen Y, Lv L, Pi H, Qin W, Chen J, Guo D, Lin J, Chi X, Jiang Z, Yang H and Jiang Y: Dihydromyricetin protects against liver ischemia/reperfusion induced apoptosis via activation of FOXO3a-mediated autophagy. Oncotarget. 7:76508–76522. 2016. View Article : Google Scholar : PubMed/NCBI
11	Feng J, Wang JX, Du YH, Liu Y, Zhang W, Chen JF, Liu YJ, Zheng M, Wang KJ and He GQ: Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice. CNS Neurosci Ther. 24:1207–1218. 2018. View Article : Google Scholar : PubMed/NCBI
12	Zhang R, Xu M, Wang Y, Xie F, Zhang G and Qin X: Nrf2-a promising therapeutic target for defensing against oxidative stress in stroke. Mol Neurobiol. 54:6006–6017. 2017. View Article : Google Scholar : PubMed/NCBI
13	Li F, Liang J, Tong H, Zhu S and Tang D: Inhibition of microRNA-199a-5p ameliorates oxygen-glucose Deprivation/Reoxygenation-induced apoptosis and oxidative stress in HT22 neurons by targeting Brg1 to activate Nrf2/HO-1 signalling. Clin Exp Pharmacol Physiol. 47:1020–1029. 2020. View Article : Google Scholar : PubMed/NCBI
14	Zhao Z, Tang Z, Zhang W, Liu J, Li B and Ding S: Inactivated Pseudomonas aeruginosa protects against myocardial ischemia reperfusion injury via Nrf2 and HO-1. Exp Ther Med. 19:3362–3368. 2020.PubMed/NCBI
15	Han M, Hu L and Chen Y: Rutaecarpine may improve neuronal injury, inhibits apoptosis, inflammation and oxidative stress by regulating the expression of ERK1/2 and Nrf2/HO-1 pathway in rats with cerebral ischemia-reperfusion injury. Drug Des Devel Ther. 13:2923–2931. 2019. View Article : Google Scholar : PubMed/NCBI
16	Luo Y, Lu S, Dong X, Xu L, Sun G and Sun X: Dihydromyricetin protects human umbilical vein endothelial cells from injury through ERK and Akt mediated Nrf2/HO-1 signaling pathway. Apoptosis. 22:1013–1024. 2017. View Article : Google Scholar : PubMed/NCBI
17	Zhang X, Li X, Fang J, Hou X, Fang H, Guo F, Li F, Chen A and Huang S: (2R,3R)Dihydromyricetin inhibits osteoclastogenesis and bone loss through scavenging LPS-induced oxidative stress and NF-κB and MAPKs pathways activating. J Cell Biochem. 119:8981–8995. 2018. View Article : Google Scholar : PubMed/NCBI
18	Hu Q, Zhang T, Yi L, Zhou X and Mi M: Dihydromyricetin inhibits NLRP3 Inflammasome-dependent pyroptosis by activating the Nrf2 signaling pathway in vascular endothelial cells. Biofactors. 44:123–136. 2018. View Article : Google Scholar : PubMed/NCBI
19	Zhang X, Wang L, Peng L, Tian X, Qiu X, Cao H, Yang Q, Liao R and Yan F: Dihydromyricetin protects HUVECs of oxidative damage induced by sodium nitroprusside through activating PI3K/Akt/FoxO3a signalling pathway. J Cell Mol Med. 23:4829–4838. 2019. View Article : Google Scholar : PubMed/NCBI
20	Wang L, Li BR, Xiao ZY, Zhao JL and Yu XD: Dihydromyricetin ameliorates chronic social defeat stress induced cognitive and affective disorder in mice. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 35:496–500. 2019.(In Chinese). PubMed/NCBI
21	Zeng Y, Hua YQ, Wang W, Zhang H and Xu XL: Modulation of SIRT1-mediated signaling cascades in the liver contributes to the amelioration of nonalcoholic steatohepatitis in high fat fed Middle-aged LDL receptor knockout mice by dihydromyricetin. Biochem Pharmacol. 175:1139272020. View Article : Google Scholar : PubMed/NCBI
22	Wang D, Zhang X, Qu D, Han J, Meng F, Xu M and Zheng Q: Astragalin and dihydromyricetin as adjuncts to histidine-tryptophan-ketoglutarate cardioplegia enhances protection during cardioplegic arrest. Mol Med Rep. 18:2929–2936. 2018.PubMed/NCBI
23	Dirnagl U, Iadecola C and Moskowitz MA: Pathobiology of ischaemic stroke: An integrated view. Trends Neurosci. 22:391–397. 1999. View Article : Google Scholar : PubMed/NCBI
24	Kou X, Shen K, An Y, Qi S, Dai WX and Yin Z: Ampelopsin inhibits H₂O₂-induced apoptosis by ERK and Akt signaling pathways and up-regulation of heme oxygenase-1. Phytother Res. 26:988–994. 2012. View Article : Google Scholar : PubMed/NCBI
25	Li F, Liang J and Tang D: Brahma-related gene 1 ameliorates the neuronal apoptosis and oxidative stress induced by oxygen-glucose deprivation/reoxygenation through activation of Nrf2/HO-1 signaling. Biomed Pharmacother. 108:1216–1224. 2018. View Article : Google Scholar : PubMed/NCBI
26	Ji Q, Gao J, Zheng Y, Liu X, Zhou Q, Shi C, Yao M and Chen X: Inhibition of microRNA-153 protects neurons against ischemia/reperfusion injury in an Oxygen-glucose deprivation and reoxygenation cellular model by regulating Nrf2/HO-1 signaling. J Biochem Mol Toxicol. Jul 31–2017.(Epub ahead of print). doi: 10.1002/jbt.21905. View Article : Google Scholar : PubMed/NCBI
27	Liu L, Zhao Z, Yin Q and Zhang X: TTB protects astrocytes against oxygen-glucose deprivation/reoxygenation-induced injury via activation of Nrf2/HO-1 signaling pathway. Front Pharmacol. 10:7922019. View Article : Google Scholar : PubMed/NCBI
28	He F, Zhang Y, Chen S, Ye B, Chen J and Li C: Effect of EGCG on oxidative stress and Nrf2/HO-1 pathway in neurons exposed to oxygen-glucose deprivation/reperfusion. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 43:1041–1047. 2018.(In Chinese). PubMed/NCBI