Wongtrakul Jeerang, Thongtan Thananya, Kumrapich Benjawan, Saisawang Chonticha, Ketterman Albert J
Research Institute for Health Sciences, Chiang Mai University, 110 Intavaroros Road, Sriphum, Muang District, Chiang Mai, 50200, Thailand.
Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Pathumwan, Bangkok, 10330, Thailand.
Heliyon. 2021 Oct 13;7(10):e08172. doi: 10.1016/j.heliyon.2021.e08172. eCollection 2021 Oct.
Parkinson's disease is the most frequent neurodegenerative motor disorder. The clinical syndrome and pathology involve motor disturbance and the degeneration of dopaminergic neurons in the substantia nigra. Root extracts of , commonly called Ashwagandha, contain several major chemical constituents known as withanolides. Studies have shown that extracts exhibit numerous therapeutic effects including inflammation and oxidative stress reduction, memory and cognitive function improvement. This study aimed to evaluate the protective effects of KSM-66, root extract, on 6-hydroxydopamine (6-OHDA)-induced toxicity in the human neuroblastoma SH-SY5Y cell line, as well as the associated oxidative response protein expression and redox regulation activity focused on S-glutathionylation. SH-SY5Y cells were treated with 6-OHDA preceded or followed by treatment with the KSM-66 extract. Using KSM-66 concentrations ranging from 0.25 to 1 mg/ml before and after treatment of the cells with 6-OHDA has resulted in an increased viability of SH-SY5Y cells. Interestingly, the extract significantly increased glutathione peroxidase activity and thioltransferase activity upon pre- or post- 6-OHDA treatment. KSM-66 also modulated oxidative response proteins: peroxiredoxin-I, VGF and vimentin proteins upon 6-OHDA pre/post treatments. In addition, the extract controlled redox regulation via S-glutathionylation. Pre-treatment of SH-SY5Y cells with KSM-66 decreased protein-glutathionylation levels in the cells treated with 6-OHDA. The rescue of mitochondria with 0.5 mg/ml KSM-66 extract showed an increase in ATP levels. These findings suggest that root extract acts as a neuroprotectant, thereby introducing a potential agent for the treatment or prevention of neurodegenerative diseases.
帕金森病是最常见的神经退行性运动障碍。其临床综合征和病理涉及运动障碍以及黑质中多巴胺能神经元的退化。印度人参(通常称为Ashwagandha)的根提取物含有几种主要化学成分,称为睡茄内酯。研究表明,印度人参提取物具有多种治疗作用,包括减轻炎症和氧化应激、改善记忆和认知功能。本研究旨在评估印度人参根提取物KSM - 66对6 - 羟基多巴胺(6 - OHDA)诱导的人神经母细胞瘤SH - SY5Y细胞系毒性的保护作用,以及相关的氧化反应蛋白表达和以S - 谷胱甘肽化作用为重点的氧化还原调节活性。用6 - OHDA处理SH - SY5Y细胞之前或之后,再用KSM - 66提取物处理。在6 - OHDA处理细胞之前和之后使用浓度范围为0.25至1 mg/ml的KSM - 66,已导致SH - SY5Y细胞活力增加。有趣的是,该提取物在6 - OHDA处理前或处理后显著增加了谷胱甘肽过氧化物酶活性和硫醇转移酶活性。KSM - 66在6 - OHDA预处理/后处理时还调节了氧化反应蛋白:过氧化物还原酶 - I、VGF和波形蛋白。此外,该提取物通过S - 谷胱甘肽化作用控制氧化还原调节。用KSM - 66预处理SH - SY5Y细胞可降低用6 - OHDA处理的细胞中的蛋白质 - 谷胱甘肽化水平。用0.5 mg/ml KSM - 提取物挽救线粒体显示ATP水平增加。这些发现表明,印度人参根提取物可作为一种神经保护剂,从而为神经退行性疾病的治疗或预防引入一种潜在药物。