Center of Excellence in Molecular Crop, Department of Biochemistry, Faculty of Science, Chulalongkorn University, 254 Phayathai Road, Bangkok, 10330, Thailand.
Preclinical Toxicity and Efficacy Assessment of Medicines and Chemicals Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand.
Sci Rep. 2024 Jul 2;14(1):15153. doi: 10.1038/s41598-024-65219-6.
Durian (Durio zibethinus L.) fruit pulp is a rich source of γ-glutamylcysteine (γ-EC), a direct precursor to the antioxidant glutathione (GSH). This study elucidated the in vitro neuroprotective potential of unripe durian fruit pulp extract (UDE) against HO-induced neurotoxicity in SH-SY5Y cells and neuroinflammation in lipopolysaccharide (LPS)-stimulated BV-2 cells. Treatments with γ-EC, GSH standards, or UDE exhibited no cytotoxicity in SH-SY5Y and BV-2 cells, except at high concentrations. A 4-h pretreatment with 100 µM γ-EC or UDE containing 100 µM γ-EC significantly increased SH-SY5Y cell viability post HO induction. Moreover, a similar pretreatment reduced LPS-stimulated production of proinflammatory cytokines in BV-2 cells. The neuroprotective effect of UDE is primarily attributed to γ-EC provision and the promotion of GSH synthesis, which in turn elevates intracellular GSH levels and reduces proinflammatory cytokines. This study identifies γ-EC in UDE as a potential neuroprotective biomarker boosting intracellular GSH levels, providing insights into UDE's therapeutic potential.
榴莲（Durio zibethinus L.）果肉是γ-谷氨酰半胱氨酸（γ-EC）的丰富来源，γ-EC 是抗氧化剂谷胱甘肽（GSH）的直接前体。本研究阐明了未成熟榴莲果肉提取物（UDE）在 HO 诱导的 SH-SY5Y 细胞神经毒性和 LPS 刺激的 BV-2 细胞神经炎症中的体外神经保护潜力。γ-EC、GSH 标准品或 UDE 处理在 SH-SY5Y 和 BV-2 细胞中均无细胞毒性，除了在高浓度下。用 100 μM γ-EC 预处理 4 小时或包含 100 μM γ-EC 的 UDE 预处理可显著提高 HO 诱导后 SH-SY5Y 细胞的活力。此外，类似的预处理可减少 LPS 刺激的 BV-2 细胞中促炎细胞因子的产生。UDE 的神经保护作用主要归因于 γ-EC 的提供和 GSH 合成的促进，这反过来又提高了细胞内 GSH 水平并减少了促炎细胞因子。本研究确定 UDE 中的 γ-EC 是一种潜在的神经保护生物标志物，可提高细胞内 GSH 水平，为 UDE 的治疗潜力提供了新的见解。
