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

IF 4.8 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

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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.

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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.