Tan I modulates astrocyte inflammatory responses through enhanced NAD+–Sirt1 pathway: Insights from metabolomics studies

IF 4.7 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-03-01 DOI:10.1016/j.intimp.2025.114364

Feng-Lun Zhao , Jia-Rui Zhang , Man-Hua Liu , Hui-Yi Liu , Cheng-Jie Mao , Fen Wang , Ju-Ping Chen , Chun-Feng Liu

{"title":"Tan I modulates astrocyte inflammatory responses through enhanced NAD+–Sirt1 pathway: Insights from metabolomics studies","authors":"Feng-Lun Zhao , Jia-Rui Zhang , Man-Hua Liu , Hui-Yi Liu , Cheng-Jie Mao , Fen Wang , Ju-Ping Chen , Chun-Feng Liu","doi":"10.1016/j.intimp.2025.114364","DOIUrl":null,"url":null,"abstract":"<div><div>Over the past decade, research has increasingly demonstrated that oligomeric α-synuclein (O-αS) plays a pivotal role in the pathogenesis of Parkinson's disease (PD), particularly in mediating dopaminergic neuron injury and neuroinflammation. In this study, we investigated the anti-inflammatory effects of tanshinone I (Tan I), an active component of the traditional Chinese medicine Danshen, on O-αS-induced inflammation in primary mouse astrocytes. Using metabolomics analysis, we identified key pathways regulated by Tan I. Our results showed that Tan I significantly suppressed O-αS-induced mRNA expression of pro-inflammatory cytokines, including interleukin-1β, IL-6, tumor necrosis factor-α and cyclooxygenase-2. Metabolomic profiling revealed that Tan I enhanced NAD<sup>+</sup> metabolism, leading to activation of the NAD<sup>+</sup>-Sirt1 pathway and subsequent inhibition of nuclear factor-κB activity. Together, these findings suggest that Tan I attenuates neuroinflammatory response in astrocytes by modulating NAD<sup>+</sup>-dependent signaling mechanisms.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"151 ","pages":"Article 114364"},"PeriodicalIF":4.7000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1567576925003546","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Over the past decade, research has increasingly demonstrated that oligomeric α-synuclein (O-αS) plays a pivotal role in the pathogenesis of Parkinson's disease (PD), particularly in mediating dopaminergic neuron injury and neuroinflammation. In this study, we investigated the anti-inflammatory effects of tanshinone I (Tan I), an active component of the traditional Chinese medicine Danshen, on O-αS-induced inflammation in primary mouse astrocytes. Using metabolomics analysis, we identified key pathways regulated by Tan I. Our results showed that Tan I significantly suppressed O-αS-induced mRNA expression of pro-inflammatory cytokines, including interleukin-1β, IL-6, tumor necrosis factor-α and cyclooxygenase-2. Metabolomic profiling revealed that Tan I enhanced NAD⁺ metabolism, leading to activation of the NAD⁺-Sirt1 pathway and subsequent inhibition of nuclear factor-κB activity. Together, these findings suggest that Tan I attenuates neuroinflammatory response in astrocytes by modulating NAD⁺-dependent signaling mechanisms.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

Tan I通过增强NAD+ -Sirt1通路调节星形胶质细胞炎症反应：来自代谢组学研究的见解

近十年来，越来越多的研究表明，寡聚α-突触核蛋白（O-αS）在帕金森病（PD）的发病机制中起着关键作用，特别是介导多巴胺能神经元损伤和神经炎症。本研究研究了丹参有效成分丹参酮I （Tan I）对小鼠原代星形胶质细胞O-α s诱导炎症的抗炎作用。结果表明，Tan I可显著抑制O-α s诱导的促炎细胞因子，包括白细胞介素-1β、IL-6、肿瘤坏死因子-α和环氧化酶-2的mRNA表达。代谢组学分析显示，Tan I增强NAD+代谢，导致NAD+-Sirt1通路激活，随后抑制核因子-κB活性。总之，这些发现表明Tan I通过调节NAD+依赖的信号机制减弱星形胶质细胞的神经炎症反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.