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Neuroprotective Effects of Withania somnifera on 4-Hydroxynonenal Induced Cell Death in Human Neuroblastoma SH-SY5Y Cells Through ROS Inhibition and Apoptotic Mitochondrial Pathway

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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 concentration-dependent 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.

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Acknowledgements

The authors are grateful to the Deanship of Scientific Research, King Saud University for funding through Vice Deanship of Scientific Research Chairs. The authors thank the Deanship of Scientific Research and RSSU at King Saud University for their technical support.

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Authors and Affiliations

  1. DNA Research Chair, Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Maqsood A. Siddiqui

  2. Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Maqsood A. Siddiqui & Abdulaziz A. Al-Khedhairy

  3. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

    Nida N. Farshori & Mai M. Al-Oqail

  4. System Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Uttar Pradesh, M.G. Marg, Lucknow, 226001, India

    Aditya B. Pant

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MAS and ABP conceived and designed the research. MAS, NNF and MMA conducted the experimental work. ABP and AAA provided reagents and tools in the laboratory. MAS, ABP and AAA analyzed the data. MAS and NNF wrote the manuscript. All authors have read and approved the manuscript.

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Correspondence to Maqsood A. Siddiqui.

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Siddiqui, M.A., Farshori, N.N., Al-Oqail, M.M. et al. Neuroprotective Effects of Withania somnifera on 4-Hydroxynonenal Induced Cell Death in Human Neuroblastoma SH-SY5Y Cells Through ROS Inhibition and Apoptotic Mitochondrial Pathway. Neurochem Res 46, 171–182 (2021). https://doi.org/10.1007/s11064-020-03146-4

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