Department of HealthCare Administration, Asia University, Taichung, Taiwan.
Department of Psychology, Chung Shan Medical University, Taichung, Taiwan.
Am J Chin Med. 2020;48(2):391-406. doi: 10.1142/S0192415X20500202. Epub 2020 Mar 5.
The purpose of this study was to evaluate the effects of diosgenin on the D-galactose-induced cerebral cortical widely dispersed apoptosis. Male 12-week-old Wistar rats were divided into four groups: Control (1mg/kg/day of saline, i.p.), DD0 (150mg/kg/day of D-galactose, i.p.), DD10, and DD50 (D-galactose or 50mg/kg/day of diosgenin orally). After eight weeks, histopathological analysis, positive TUNEL and Western blotting assays were performed on the excised cerebral cortex from all four groups. The TUNEL-positive apoptotic cells, the components of Fas pathway (Fas, FADD, active caspase-8 and active caspase-3), and mitochondria pathway (t-Bid, Bax, cytochrome , active caspase-9 and active caspase-3) were increased in the DD0 group compared with the control group, whereas they were decreased in the DD50 group. The components of survival pathway (p-Bad, Bcl-2, Bcl-xL, IGF-1, p-PI3K and p-AKT) were increased in the DD50 group compared to the control group, whereas the levels of Bcl-xL, p-PI3K, and p-AKT were also compensatorily increased in the DD0 group compared to the control group. Taken together, diosgenin suppressed D-galactose-induced neuronal Fas-dependent and mitochondria-dependent apoptotic pathways and enhanced the Bcl-2 family associated pro-survival and IGF-1-PI3K-AKT survival pathways, which might provide neuroprotective effects of diosgenin for prevention of the D-galactose-induced aging brain.
本研究旨在评估薯蓣皂素对 D-半乳糖诱导的大脑皮质广泛弥散性凋亡的影响。雄性 12 周龄 Wistar 大鼠分为四组：对照组（1mg/kg/天生理盐水，腹腔注射）、DD0 组（150mg/kg/天 D-半乳糖，腹腔注射）、DD10 组和 DD50 组（D-半乳糖或 50mg/kg/天薯蓣皂素口服）。八周后，对所有四组切除的大脑皮质进行组织病理学分析、阳性 TUNEL 和 Western blot 检测。与对照组相比，DD0 组的 TUNEL 阳性凋亡细胞、Fas 通路（Fas、FADD、活性 caspase-8 和活性 caspase-3）和线粒体通路（t-Bid、Bax、细胞色素 c、活性 caspase-9 和活性 caspase-3）成分增加，而 DD50 组则减少。与对照组相比，DD50 组的存活通路（p-Bad、Bcl-2、Bcl-xL、IGF-1、p-PI3K 和 p-AKT）成分增加，而与对照组相比，DD0 组的 Bcl-xL、p-PI3K 和 p-AKT 水平也代偿性增加。综上所述，薯蓣皂素抑制 D-半乳糖诱导的神经元 Fas 依赖性和线粒体依赖性凋亡途径，并增强 Bcl-2 家族相关的促生存和 IGF-1-PI3K-AKT 生存途径，这可能为薯蓣皂素预防 D-半乳糖诱导的衰老大脑提供神经保护作用。
