Neuroprotective Effects of Palmatine via the Enhancement of Antioxidant Defense and Small Heat Shock Protein Expression in Aβ-Transgenic Caenorhabditis elegans

作者：Jia, Weizhang; Su, Qina; Cheng, Qiong; Peng, Qiong; Qiao, Aimin; Luo, Xiongming; Zhang, Jing; Wang, Ying^*

来源：Oxidative Medicine and Cellular Longevity, 2021, 2021: 9966223.

DOI：10.1155/2021/9966223

• AMYLOID-BETA
• OXIDATIVE STRESS
• DISEASE
• ALZHEIMER
• PATHOGENESIS
• AGGREGATION
• INHIBITION
• TARGET
• ROLES

Palmatine is a naturally occurring isoquinoline alkaloid that has been reported to display neuroprotective effects against amyloid-beta- (A beta-) induced neurotoxicity. However, the mechanisms underlying the neuroprotective activities of palmatine remain poorly characterized in vivo. We employed transgenic Caenorhabditis elegans models containing human A beta(1-42) to investigate the effects and possible mechanisms of palmatine-mediated neuroprotection. Treatment with palmatine significantly delayed the paralytic process and reduced the elevated reactive oxygen species levels in A beta-transgenic C. elegans. In addition, it increased oxidative stress resistance without affecting the lifespan of wild-type C. elegans. Pathway analysis suggested that the differentially expressed genes were related mainly to aging, detoxification, and lipid metabolism. Real-time PCR indicated that resistance-related genes such as sod-3 and shsp were significantly upregulated, while the lipid metabolism-related gene fat-5 was downregulated. Further studies demonstrated that the inhibitory effects of palmatine on A beta toxicity were attributable to the free radical-scavenging capacity and that the upregulated expression of resistance-related genes, especially shsp, whose expression was regulated by HSF-1, played crucial roles in protecting cells from A beta-induced toxicity. The research showed that there were significantly fewer A beta deposits in transgenic CL2006 nematodes treated with palmatine than in control nematodes. In addition, our study found that A beta-induced toxicity was accompanied by dysregulation of lipid metabolism, leading to excessive fat accumulation in A beta-transgenic CL4176 nematodes. The alleviation of lipid disorder by palmatine should be attributed not only to the reduction in fat synthesis but also to the inhibition of A beta aggregation and toxicity, which jointly maintained metabolic homeostasis. This study provides new insights into the in vivo neuroprotective effects of palmatine against A beta aggregation and toxicity and provides valuable targets for the prevention and treatment of AD.

• 单位
  y; 广东药学院