Effects of artesunate on oxidative stress in cultured retinal ganglion cells and its protective mechanism

doi:10.12092/j.issn.1009-2501.2019.10.007

Abstract

Abstract:

AIM: To study the effects of artesunate on oxidative stress in cultured retinal ganglion cells (RGC-5) and to investigate its possible mechanism. METHODS: RGC-5 cells were cultured in vitro and were divided into five groups, including control group, H2O2 group, low-, middle-, high-dose artesunate groups. CCK8 assay was used to measure the relative survival rate of RGC-5 cells. Cell apoptotic rate was determined by flow cytometry. Related kits were used to determine the levels of MDA, NO and SOD1. Western bot method was used to analyze the expression levels of HO-1, SOD1, PI3K, p-Akt and Akt. RESULTS:Compared with H2O2 group, the relative survival rates were significantly increased and cell apoptotic rates were greatly decreased in varying concentrations of artesunate groups (P<0.05). The contents of MDA, NO were greatly decreased, while the activity of SOD1 was strongly increased in artesunate groups compared with H2O2 group (P<0.05). The expression levels of HO-1, SOD1, PI3K and p-Akt were greatly increased in artesunate groups compared with H2O2 group (P<0.05). Moreover, PI3K inhibitor decreased the protective effect of artesunate on the injury of RGC-5 cells. CONCLUSION: Artesunate significantly inhibit the oxidative stress injury of RGC-5 cells and its underlying mechanism maybe related with inducing the activation of PI3K/Akt signaling pathway.

Key words: artesunate, oxidative stress, retinal ganglion cells

CLC Number:

QIN Hui, LAI Li. Effects of artesunate on oxidative stress in cultured retinal ganglion cells and its protective mechanism[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(10): 1128-1133.

References

［1］Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review［J］. JAMA, 2014 , 311(18):1901-1911.
［2］Cohen LP, Pasquale LR. Clinical characteristics and current treatment of glaucoma［J］. Cold Spring Harb Perspect Med, 2014, 4(6): 21-28.
［3］Morales J, Al Qahtani M, Khandekar R, et al. Intraocular pressure following phacoemulsification and endoscopic cyclophotocoagulation for advanced glaucoma: 1-year outcomes［J］. J Glaucoma, 2015, 24(6):e157-162.
［4］胡玉贞, 李淼, 张桐桐, 等. 青蒿琥酯脂质体粉雾剂的制备及其治疗大鼠急性肺损伤的作用［J］. 药学学报, 2016, 51(12): 1906-1912.
［5］张洪喜, 吕水清, 王敦敬. 青蒿琥酯对缺氧诱导的BV-2小胶质细胞激活的抑制作用及其可能机制［J］. 中国医疗设备, 2017, 32(S1):84-85.
［6］Li L, Tan J, Miao Y, et al. ROS and autophagy: interactions and molecular regulatory mechanisms［J］. Cell Mol Neurobiol, 2015,35(5):615-621.
［7］Wang R, Peng L, Zhao J, et al. Gardenamide a protects RGC-5 cells from H2O2-induced oxidative stress insults by activating PI3K/Akt/eNOS signaling pathway［J］. Int J Mol Sci, 2015, 16(9):22350-22367.
［8］Lin WJ, Kuang HY. Oxidative stress induces autophagy in response to multiple noxious stimuli in retinal ganglion cells［J］. Autophagy, 2014, 10(10):1692-1701.
［9］Ishisaka R，Utsumi K, Utsumi T. Involvement of lysosomal cysteine proteases in hydrogen peroxide induced apoptosis in HL-60 cells［J］. Biosci Biotechnol Biochem, 2002, 66(9): 1865-1872.
［10］Watcharasit P, Bijur GN, Zmijewski JW, et al. Direct, activating interaction between glycogen synthase kinase-3beta and p53 after DNA damage［J］. Proc Natl Acad Sci USA, 2012, 99(12):7951-7955.
［11］Hambright HG, Meng P, Kumar AP, et al. Inhibition of PI3K/AKT/mTOR axis disrupts oxidative stress-mediated survival of melanoma cells［J］. Oncotarget, 2015, 6(9):7195-7208.
［12］Padiya R, Chowdhury D, Borkar R, et al. Garlic attenuates cardiac oxidative stress via activation of PI3K/AKT/Nrf2-Keap1 pathway in fructose-fed diabetic rat［J］. PLoS One, 2014, 9(5):e94228.
［13］Xu X, Li H, Hou X, et al. Punicalagin induces Nrf2/HO-1 expression via upregulation of PI3K/AKT pathway and inhibits LPS-induced oxidative stress in RAW264.7 macrophages［J］. Mediators Inflamm, 2015, 15:380-388.

[1]	LIAO Mengling, WANG Yan, LUO Jing, WANG Nuoyan, HUA Ling, ZHANG Yu, DENG Fei, YUAN Yue, ZHOU Jun, ZHOU Hong. Molecular mechanism of artesunate attenuates the release of proinflammatory cytokines from macrophages [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(9): 969-978.
[2]	LIU Lijing, QIAN Hong, MENG Qingxin, ZHANG Xiang, HE Bin, HE Jianbin, WEI Yingmin. Sinomenine inhibits oxidative stress and pulmonary fibrosis by activating the Keap1/Nrf2 signaling pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(9): 979-987.
[3]	LI Yating, YUE Hongmei, LIU Miaomiao, XU Jinhui, WU Xingdong, ZHU Haobin. The possibility of phosphodiesterase 4 inhibitors as drug therapy for idiopathic pulmonary fibrosis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(7): 818-823.
[4]	WANG Donghui, JIANG Suwen, HU Airong, ZHU Bo, HE Zheyun, ZHANG Lukan, WANG Jialan, FAN Ying, LIN Ken . Mulberry exerts antioxidant stress effect in rats with nonalcoholic fatty liver disease [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(6): 609-616.
[5]	BAI Jia, YANG Hong, LI Lingling, ZHANG Yangyang, YANG Ying, LV Haihong. Study on the effect of vitamin D on diabetic neuropathy through mitochondrial/autophagy pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(2): 214-219.
[6]	ZHU Haobin, YUE Hongmei, WU Xingdong, LIU Miaomiao, LI Yating, XU Jinhui. Research progress on the role of the Nrf2 signaling pathway in the complications associated with obstructive sleep apnea [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(11): 1283-1291.
[7]	YANG Zhian, ZHAO Yan, HE Yao, LIU Weiying, YU Qin. Pyroptosis mediated renal injury caused by chronic intermittent hypoxia and the intervention effect of edaravone in rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(1): 10-18.
[8]	HUA Haiyan, YAN Jie, QIN Yufen. Experimental study of schisandrin B attenuates acute myocardial ischemia injury in rats by inhibiting cardiomyocyte apoptosis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(8): 848-856.
[9]	WANG Jinhuo, GAO Xinyue, GUO Jianrong. Effect of COX-2 inhibitors on postoperative delirium in elderly patients undergoing orthopedic surgery and its possible mechanism [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(8): 863-869.
[10]	LI Xueheng, LI Long. Research progress on the relationship between melatonin and idiopathic pulmonary fibrosis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(6): 715-720.
[11]	WANG Xinli, XU Xiaqing, FANG Hanbing, GUO Yuzhong. Study of TPA on enhancing the anti-tumor effects of cisplatin and reducing its renal toxicity [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(5): 535-543.
[12]	REN Yixing, LENG Yufang, GUO Mingjun, ZHANG Jianmin, SHI Yajing, CHEN Feng, LIU Xin. Role and mechanism of SIRT3 in attenuation of intestinal ischemia-reperfusion injury by dexmedetomidine in mice [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(3): 253-259.
[13]	HE Liyang, WEI Wenjie, YIN Qin, LIU Lijing, ZHONG Boying, LIU Cungen, ZHOU Meiling, HE Jianbin. Preventive and therapeutic effects of the Kiwi fruit essence (unsaturated fatty acid of actinidia chinesis planch seed oil) on radiation-induced lung injury rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(2): 154-162.
[14]	LIN Naping, WU Yutang, HUANG Defen, XU Chaoxiang. Effects of miR-195-5p on ox-LDL-induced vascular endothelial cell injury through regulating FBXW7 [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(2): 163-170.
[15]	LI Ying, YAO Wei, WANG Meng, YU Zhihong, GONG Yuanqi, LAN Haibing, QI Xiefei. Experimental study of irisin alleviates house dust mite-induced airway epithelial cells inflammation and apoptosis via the NF-κB and JNK signaling pathways [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(10): 1106-1112.