Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Ruscogenin regulates endogenous antioxidation in dopamine neurons by activating Keap1/Nrf2/HO-1 pathway

Kai Shi, Bing Wang

Department of Neurology, Huai'an Hospital of Traditional Chinese Medicine, Huai 'an City, Jiangsu Province 223001, China;

For correspondence:- Bing Wang Email: wangbing28028@163.com Tel:+8613813347793

Accepted: 26 August 2023 Published: 30 September 2023

Citation: Shi K, Wang B. Ruscogenin regulates endogenous antioxidation in dopamine neurons by activating Keap1/Nrf2/HO-1 pathway. Trop J Pharm Res 2023; 22(9):1779-1784 doi: 10.4314/tjpr.v22i9.3

© 2023 The authors.
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Abstract

Purpose: To investigate the effect of ruscogenin (RUS) on cell viability, lipid peroxidation and mitochondrial dysfunction in a Parkinson’s disease (PD) model.

Methods: The neuroblastoma cell line SH-SY5Y was modified with 1-methyl-4-phenylpyridine (MPP+) to establish a PD model. RUS (1 or 10 μM) was used to treat MPP+ induced SH-SY5Y cells. Cell viability was assessed using CCK-8 assay. The concentrations of lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) were determined by enzyme-linked immunosorbent assay (ELISA). ATP production, Ca²⁺ concentration and JC-1 were quantified using commercial kits. The expression levels of tyrosine hydroxylase (TH), Keap1, Nrf2 and HO-1 were evaluated by western blot analysis.

Results: RUS protected cell viability, reduced LDH production, and elevated TH expression in MPP⁺-modified SH-SY5Y cells. RUS promoted the release of SOD, CAT and GPx, but suppressed MDA production. Furthermore, RUS enhanced ATP metabolism, decreased Ca²⁺ leakage and maintained mitochondrial function. RUS also repressed Keap1 expression but increased Nrf2 and HO-1 levels.

Conclusion: RUS enhances cell viability while alleviating cytotoxicity, lipid peroxidation and mitochondrial dysfunction in dopamine neurons through the activation of Keap1/Nrf2/HO-1 signaling pathway. Thus, RUS is a promising therapeutic candidate for PD treatment.

Keywords: Antioxidant stress, Dopamine neurons, Parkinson’s disease, Ruscogenin, Keap1/Nrf2/HO-1