Ginseng is a popular herbal medicine and known to have protective and therapeutic effects in various diseases. Ginsenosides are active gradients representing the diverse pharmacological efficacy of ginseng. Huntington’s disease (HD) is incurable genetic disorder associated with mutant huntingtin (mHtt) aggregation in the central nervous system. This study was conducted to investigate the effects of ginsenoside Rg3 and Rf on mHtt aggregation, cell viability, mitochondrial function, and apoptotic molecules on HD model. To investigate the effect of ginsenosides on HD, neural stem cells were isolated from the R6/2 mouse brain and used as a cellular model of HD. Nuclear aggregation of mHtt was measured by immunocytochemistry, and expressions of mitochondrial biogenesis and apoptotic molecules were investigated by western blot. As a result, the number of mHtt aggregates positive cells has decreased by ginsenoside Rg3 and Rf treatment in cellular model of HD. Mitochondrial biogenesis-related molecules such as PGC-1α and phosphorylated CREB were increased or showed increased tendency by ginsenoside Rg3 and Rf. Apoptotic molecules, p53, Bax, and cleaved caspase-3, were down-regulated by treatment of ginsenoside Rg3 and Rf. In addition, Lysotracker staining result showed that cellular lysosomal content was reduced by ginsenoside Rg3 and Rf. Given that ginsenoside Rg3 and Rf have the potential to reduce mHtt aggregation and cellular apoptosis, these ginsenosides can be possible therapeutic candidates for treating HD phenotypes.

人参是一种流行的草药，已知对各种疾病具有保护和治疗作用。人参皂苷是代表人参多种药理功效的活性梯度。亨廷顿病 (HD) 是与中枢神经系统中的突变亨廷顿 (mHtt) 聚集相关的无法治愈的遗传疾病。本研究旨在研究人参皂苷 Rg3 和 Rf 对 HD 模型上 mHtt 聚集、细胞活力、线粒体功能和凋亡分子的影响。为了研究人参皂甙对 HD 的影响，从 R6/2 小鼠大脑中分离出神经干细胞并用作 HD 的细胞模型。通过免疫细胞化学测量mHtt的核聚集，并通过蛋白质印迹研究线粒体生物发生和凋亡分子的表达。因此，在 HD 细胞模型中，人参皂苷 Rg3 和 Rf 处理减少了 mHtt 聚集阳性细胞的数量。人参皂苷Rg3和Rf使线粒体生物发生相关分子如PGC-1α和磷酸化CREB增加或呈增加趋势。凋亡分子 p53、Bax 和切割的 caspase-3 被人参皂苷 Rg3 和 Rf 处理下调。此外，Lysotracker 染色结果显示细胞溶酶体含量被人参皂苷 Rg3 和 Rf 降低。鉴于人参皂苷 Rg3 和 Rf 具有减少 mHtt 聚集和细胞凋亡的潜力，这些人参皂苷可能成为治疗 HD 表型的候选药物。人参皂苷Rg3和Rf使线粒体生物发生相关分子如PGC-1α和磷酸化CREB增加或呈增加趋势。凋亡分子 p53、Bax 和切割的 caspase-3 被人参皂苷 Rg3 和 Rf 处理下调。此外，Lysotracker 染色结果显示细胞溶酶体含量被人参皂苷 Rg3 和 Rf 降低。鉴于人参皂苷 Rg3 和 Rf 具有减少 mHtt 聚集和细胞凋亡的潜力，这些人参皂苷可能成为治疗 HD 表型的候选药物。人参皂苷Rg3和Rf使线粒体生物发生相关分子如PGC-1α和磷酸化CREB增加或呈增加趋势。凋亡分子 p53、Bax 和切割的 caspase-3 被人参皂苷 Rg3 和 Rf 处理下调。此外，Lysotracker 染色结果显示细胞溶酶体含量被人参皂苷 Rg3 和 Rf 降低。鉴于人参皂苷 Rg3 和 Rf 具有减少 mHtt 聚集和细胞凋亡的潜力，这些人参皂苷可能成为治疗 HD 表型的候选药物。Lysotracker 染色结果显示细胞溶酶体含量被人参皂苷 Rg3 和 Rf 降低。鉴于人参皂苷 Rg3 和 Rf 具有减少 mHtt 聚集和细胞凋亡的潜力，这些人参皂苷可能成为治疗 HD 表型的候选药物。Lysotracker 染色结果显示细胞溶酶体含量被人参皂苷 Rg3 和 Rf 降低。鉴于人参皂苷 Rg3 和 Rf 具有减少 mHtt 聚集和细胞凋亡的潜力，这些人参皂苷可能成为治疗 HD 表型的候选药物。