Zhao Nan, Wu Menghai, Velu Periyannan, Annamalai Vijayalakshmi, Zhang Jianbin
Internal Medicine-Neurology, Harbin 242 Hospital, Harbin, 150066, China.
Department of Neurology, Jinan People's Hospital Affiliated to Shandong First Medical University, Jinan Shandong, 271199, China.
Comb Chem High Throughput Screen. 2024 Dec 13. doi: 10.2174/0113862073358649241128053921.
Parkinson's disease (PD) is the age-associated, second most advanced neurodegenerative illness. Rotenone is an extensively used pesticide to study PD pathology and inhibits mitochondrial complex I. Reports indicate that rotenone exerts neurotoxicity by its capability to produce reactive oxygen species (ROS), which eventually leads to neuronal apoptosis.
Sanggenol L (SL) is an eminent flavonoid present in the Morus alba root bark, which exhibits neuroprotective, anticancer, and antioxidant properties.
Hence, we assessed the neuroprotective activity of SL (5 and 10 μM/ml) on rotenone-stimulated SK-NSH neuroblastoma cells and elucidated the effect of the P13K/AKT/mTOR signalling.
The anti-PD action of SL on proliferation, oxidative stress (OS), intracellular ROS, apoptosis, Bax, cleaved Caspase-12, -9, -3, and Cyt-c, Bcl-2 and P13K/AKT/mTOR signaling was determined by MTT assay, biochemical analysis, DCFDA, AO/EB staining and western blot. It was found that SL (5 and 10 μM/ml) reduced rotenone-triggered OS, ROS levels, and apoptosis in a concentration-related way. SL alleviates Bax, cleaved caspase-12, -9, -3, and Cytc, while reducing Bcl-2. Furthermore, SL safer mitochondria by increase MMP and suppresses phosphorylation of P13k/AKT/mTOR pathway, thereby regulating apoptotic signalling.
Our findings indicate that SL showed protective effects against rotenone-induced OS, mitochondrial complex-I in neuronal cell damage, which suggests that SL might potentially serve as an anti-PD remedial candidate for PD treatment.
帕金森病（PD）是与年龄相关的第二大常见神经退行性疾病。鱼藤酮是一种广泛用于研究PD病理的农药，可抑制线粒体复合物I。报告表明，鱼藤酮通过产生活性氧（ROS）发挥神经毒性作用，最终导致神经元凋亡。
桑根醇L（SL）是一种存在于桑白皮中的著名黄酮类化合物，具有神经保护、抗癌和抗氧化特性。
因此，我们评估了SL（5和10μM/ml）对鱼藤酮刺激的SK-NSH神经母细胞瘤细胞的神经保护活性，并阐明了PI3K/AKT/mTOR信号通路的作用。
通过MTT法、生化分析、DCFDA、AO/EB染色和蛋白质印迹法测定了SL对增殖、氧化应激（OS）、细胞内ROS、凋亡、Bax、裂解的半胱天冬酶-12、-9、-3和细胞色素c、Bcl-2以及PI3K/AKT/mTOR信号通路的抗PD作用。发现SL（5和10μM/ml）以浓度相关的方式降低了鱼藤酮引发的OS、ROS水平和凋亡。SL减轻了Bax、裂解的半胱天冬酶-12、-9、-3和细胞色素c，同时降低了Bcl-2。此外，SL通过增加线粒体膜电位（MMP）保护线粒体，并抑制PI3K/AKT/mTOR通路的磷酸化，从而调节凋亡信号。
我们的研究结果表明，SL对鱼藤酮诱导的OS、神经元细胞损伤中的线粒体复合物I具有保护作用，这表明SL可能有潜力作为一种抗PD治疗的候选药物。
