Neuroprotective Effects of Withania somnifera on 4-Hydroxynonenal Induced Cell Death in Human Neuroblastoma SH-SY5Y Cell
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ORIGINAL PAPER
Neuroprotective Effects of Withania somnifera on 4‑Hydroxynonenal Induced Cell Death in Human Neuroblastoma SH‑SY5Y Cells Through ROS Inhibition and Apoptotic Mitochondrial Pathway Maqsood A. Siddiqui1,2 · Nida N. Farshori3 · Mai M. Al‑Oqail3 · Aditya B. Pant4 · Abdulaziz A. Al‑Khedhairy2 Received: 27 June 2020 / Revised: 4 October 2020 / Accepted: 7 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The antioxidant, anti-inflammatory, and anticancer activities of Withania somnifera (WS) are known for a long time. This study was aimed to examine whether WS also diminishes 4-hydroxy-trans-2-nonenal (HNE)-induced neurotoxicity in human neuroblastoma (SH-SY5Y) cell line. The cytotoxic response of HNE (0.1–50 μM) and WS (6.25–200 μg/ml) was measured by MTT assay after exposing SH-SY5Y cells for 24 h. Then neuroprotective potential was assessed by exposing the cells to biologically safe concentrations of WS (12.5, 25, and 50 μg/ml) then HNE (50 μM). Results showed a concentrationdependent protective effect of WS at 12.5, 25, and 50 μg/ml against HNE (50 μM) induced cytotoxicity and cell inhibition. Pre-exposure to WS resulted in a strong inhibition of 24, 55 and 83% in malondialdehyde (MDA) level; 5, 27 and 60% in glutathione (GSH) level; 12, 36 and 68% in catalase activity; 11, 33 and 67% in LDH leakage; and 40, 80 and 120% in cellular LDH activity at 12.5, 25, and 50 μg/ml, respectively, induced by 50 μM HNE in SH-SY5Y cells. The HNE-mediated cellular changes (cell shrinkage, rounded bodies, and inhibition of outgrowth) and increased caspase-3 activity were also prevented by WS. The HNE-induced upregulation of proapoptotic markers (p53, caspase-3, and -9, and Bax) and downregulation of antiapoptotic marker Bcl-2 genes were also blocked by pretreatment with WS. Altogether, our findings indicate that WS possesses a protective potential against HNE-induced neurotoxicity. Keywords Withania somnifera · 4-hydroxy-trans-2-nonenal · SH-SY5Y · Cytotoxicity · Oxidative stress · Apoptosis
Introduction Among the harmful by-products of lipid peroxidation (LP), 4-hydroxy-trans-2-nonenal (HNE) is a potentially dangerous product [1]. It remains stable in the lipid bilayer and subsequently diffuses through the membrane into the cytosol [2]. Studies have confirmed that aldehydes generated * Maqsood A. Siddiqui [email protected] 1
DNA Research Chair, Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
2
Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
3
Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
4
System Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Uttar Pradesh, M.G. Marg, Lucknow 226001, India
endogenously through the process of LP are informally involved in the etiology of numerous neurodegenerative ailments [3, 4]. HNE, a long-chain alpha, beta
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