School of Biosciences & Biopharmaceutics, and Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou, 510006, China; Institutes for Life Sciences and School of Medicine, South China University of Technology, Guangzhou, 510641, China.
School of Biosciences & Biopharmaceutics, and Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Eur J Pharmacol. 2022 Feb 15;917:174755. doi: 10.1016/j.ejphar.2022.174755. Epub 2022 Jan 10.
Aesculin, a coumarin compound, is one of the major active ingredients of traditional Chinese herbal medicine Qinpi (Cortex Fraxini), which has been reported to exhibit antioxidative, anti-inflammatory and neuroprotective properties against oxidative stress and cellular apoptosis. However, the regulatory mechanisms remain poorly characterized in vivo. This research was performed to explore the underlying molecular mechanisms behind aesculin response conferring oxidative stress resistance, and the protective effects on amyloid-β (Aβ)-mediated neurotoxicity in Caenorhabditis elegans. Study indicated that aesculin plays the protective roles for C. elegans against oxidative stress and Aβ-mediated neurotoxicity and reduces the elevated ROS and MDA contents through enhancement of antioxidant defenses. The KEGG pathway analysis suggested that the differentially expressed genes are mainly involved in longevity regulating pathway, and the nuclear translocation of DAF-16 and the RNAi of daf-16 and hsf-1 indicated that DAF-16 and HSF-1 play critical roles in integrating upstream signals and inducing the expressions of stress resistance-related genes. Furthermore, the up-regulated expressions of their target genes such as sod-3 and hsp-16.2 were confirmed in transgenic GFP reporter strains CF1553 and CL2070, respectively. These results indicated that the regulators DAF-16 and HSF-1 elevate the stress resistance of C. elegans by modulating stress-responsive genes. Further experiments revealed that aesculin is capable of suppressing Aβ-induced oxidative stress and apoptosis and improves chemosensory behavior dysfunction in Aβ-transgenic nematodes. In summary, this study suggested that aesculin offers increased resistance against oxidative stress and protective effects against Aβ-induced neurotoxicity through activation of stress regulators DAF-16 and HSF-1 in nematodes.
秦皮素（Cortex Fraxini）是一种传统的中草药，其主要活性成分之一是七叶苷，已被报道具有抗氧化、抗炎和神经保护作用，可抵抗氧化应激和细胞凋亡。然而，其体内的调节机制仍未得到很好的描述。本研究旨在探讨七叶苷对氧化应激的反应机制以及对秀丽隐杆线虫中淀粉样β（Aβ）介导的神经毒性的保护作用。研究表明，七叶苷在秀丽隐杆线虫中发挥抗氧化和 Aβ介导的神经毒性的保护作用，并通过增强抗氧化防御来降低 ROS 和 MDA 含量的升高。KEGG 途径分析表明，差异表达的基因主要参与长寿调节途径，DAF-16 的核易位和 daf-16 和 hsf-1 的 RNAi 表明 DAF-16 和 HSF-1 在整合上游信号和诱导应激相关基因表达方面发挥关键作用。此外，在转基因 GFP 报告株 CF1553 和 CL2070 中，分别证实了 sod-3 和 hsp-16.2 等靶基因的上调表达。这些结果表明，DAF-16 和 HSF-1 通过调节应激反应基因来提高秀丽隐杆线虫的应激抗性。进一步的实验表明，七叶苷能够抑制 Aβ诱导的氧化应激和细胞凋亡，并改善 Aβ转基因线虫的化学感觉行为功能障碍。总之，本研究表明，七叶苷通过激活线虫中的应激调节因子 DAF-16 和 HSF-1，提供了对氧化应激的增强抗性和对 Aβ诱导的神经毒性的保护作用。
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