文献类型：期刊文献

英文题名：Asiaticoside exerts neuroprotection through targeting NLRP3 inflammasome activation

作者：He, Ziliang[1];Hu, Yeye[1];Zhang, Ying[1];Xie, Jing[2];Niu, Zhiqiang[1];Yang, Guigui[2];Zhang, Ji[2];Zhao, Zixuan[4];Wei, Shuai[3];Wu, Haifeng[4];Hu, Weicheng[1,5]

机构：[1]Yangzhou Univ, Inst Translat Med, Sch Med, Yangzhou 225009, Peoples R China;[2]Huaiyin Normal Univ, Sch Life Sci, Huaian 223300, Peoples R China;[3]Guangdong Ocean Univ, Coll Food Sci & Technol, Guangdong Prov Engn Technol Res Ctr Seafood, Guangdong Prov Engn Technol Res Ctr Prefabricated, Zhanjiang 524088, Peoples R China;[4]Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Plant Dev, Beijing Key Lab New Drug Discovery based Class chi, Key Lab Bioact Subst & Resources Utilizat Chinese, Beijing 100193, Peoples R China;[5]Yangzhou Univ, Jiangsu Key Lab Integrated Tradit Chinese & Wester, Yangzhou 225009, Peoples R China

年份：2024

卷号：127

外文期刊名：PHYTOMEDICINE

收录：SCI-EXPANDED(收录号：WOS:001207497100001)、、WOS

基金：This research was funded by Hainan Province Science and Technology Special Fund (ZDYF2024XDNY177) , CAMS Innovation Fund for Medical Sciences (CIFS 2021-I2M-1-071) , the Foundation of Hunan Double First-rate Discipline Construction Projects of Bioengineering (YYZW2019-36) and the State Scholarship Fund from China Scholarship Council.

语种：英文

外文关键词：Asiaticoside; Parkinson's disease; NLRP3; Network pharmacology

外文摘要：Background: Parkinson's disease (PD), a neurodegenerative disorder, is characterized by motor symptoms due to the progressive loss of dopaminergic neurons in the substantia nigra (SN) and striatum (STR), alongside neuroinflammation. Asiaticoside (AS), a primary active component with anti-inflammatory and neuroprotective properties, is derived from Centella asiatica. However, the precise mechanisms through which AS influences PD associated with inflammation are not yet fully understood. Purpose: This study aimed to explore the protective mechanism of AS in PD. Methods: Targets associated with AS and PD were identified from the Swiss Target Prediction, Similarity Ensemble Approach, PharmMapper, and GeneCards database. A protein -protein interaction (PPI) network was constructed to identify potential therapeutic targets. Concurrently, GO and KEGG analyses were performed to predict potential signaling pathways. To validate these mechanisms, the effects of AS on 1-Methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mice were investigated. Furthermore, neuroinflammation and the activation of the NLRP3 inflammasome were assessed to confirm the anti-inflammatory properties of AS. In vitro experiments in BV2 cells were then performed to investigate the mechanisms of AS in PD. Moreover, CETSA, molecular docking, and molecular dynamics simulations (MDs) were performed for further validation. Results: Network pharmacology analysis identified 17 potential targets affected by AS in PD. GO and KEGG analyses suggested the biological roles of these targets, demonstrating that AS interacts with 149 pathways in PD. Notably, the NOD -like receptor signaling pathway was identified as a key pathway mediating AS's effect on PD. In vivo studies demonstrated that AS alleviated motor dysfunction and reduced the loss of dopaminergic neurons in MPTP-induced PD mice. In vitro experiments demonstrated that AS substantially decreased IL-1 beta release in BV2 cells, attributing this to the modulation of the NLRP3 signaling pathway. CETSA and molecular docking studies indicated that AS forms a stable complex with NLRP3. MDs suggested that ARG578 played an important role in the formation of the complex. Conclusion: In this study, we first predicted that the potential target and pathway of AS's effect on PD could be NLRP3 protein and NOD -like receptor signaling pathway by network pharmacology analysis. Further, we demonstrated that AS could alleviate symptoms of PD induced by MPTP through its interaction with the NLRP3 protein for the first time by in vivo and in vitro experiments. By binding to NLRP3, AS effectively inhibits the assembly and activation of the inflammasome. These findings suggest that AS is a promising inhibitor for PD driven by NLRP3 overactivation.