The intervention mechanism of Tanshinone IIA in alleviating neuronal injury induced by HMGB1 or TNF-α-mediated microglial activation.

IF 2.6 3区医学 Q3 TOXICOLOGY Toxicology in Vitro Pub Date : 2024-09-30 DOI:10.1016/j.tiv.2024.105950

Yan-Zhu Quan, Jing-He Wang, Si-Hui Zhang, Guang-Nan Jin, Jing-Mei Lu, Yi-Ming Liu, Hong-Yan Gao, Jin-Yi Zhou, Bing-Zhe Wang, Yan Xin, Yue-Xian Cui, Xiang Xu, Lian-Xun Piao

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Abstract

Tanshinone IIA (Tan IIA), a neuroprotective natural compound extracted from Salvia miltiorrhiza, is used in stroke treatment. However, elucidating Tan IIA's neuroprotective mechanisms remains challenging due to limitations in assessing drug efficacy and biochemical parameters in clinical studies. This study investigated Tan IIA's impact on neuroinflammatory responses and its neuroprotective mechanisms using HMGB1- or TNF-α-stimulated BV2 microglia in a co-culture system with primary neuron cells. The results indicated that Tan IIA significantly reduced microglial activation induced by TNF-α or HMGB1. Concurrently, Tan IIA disrupted the interactions between HMGB1 and toll-like receptor 4 (TLR4), and between TNF-α and TNF receptor 1 (TNFR1), modulating the HMGB1/TLR4/nuclear factor-kappa B (NF-κB) and TNF-α/TNFR1/NF-κB signaling pathways and related protein expressions. Moreover, co-culture experiments showed that neuronal apoptosis induced by microglial activation was reversed by Tan IIA. In conclusion, Tan IIA provides neuroprotection by modulating signaling pathways in microglia, thus preventing neuronal apoptosis. This study offers new insights into therapeutic targets for ischemic stroke.

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丹参酮 IIA 在减轻 HMGB1 或 TNF-α 介导的微神经胶质细胞活化引起的神经元损伤方面的干预机制

丹参酮 IIA（Tan IIA）是从丹参中提取的一种具有神经保护作用的天然化合物，可用于中风治疗。然而，由于临床研究中药物疗效和生化参数评估的局限性，阐明丹参酮 IIA 的神经保护机制仍具有挑战性。本研究使用 HMGB1 或 TNF-α 刺激的 BV2 小胶质细胞与原代神经元细胞共培养系统，研究了 Tan IIA 对神经炎症反应的影响及其神经保护机制。结果表明，Tan IIA 能显著降低 TNF-α 或 HMGB1 诱导的小胶质细胞活化。同时，Tan IIA 还能破坏 HMGB1 与收费样受体 4（TLR4）之间以及 TNF-α 与 TNF 受体 1（TNFR1）之间的相互作用，从而调节 HMGB1/TLR4/ 核因子-卡巴 B（NF-κB）和 TNF-α/TNFR1/NF-κB 信号通路及相关蛋白的表达。此外，共培养实验表明，Tan IIA 能逆转小胶质细胞活化诱导的神经细胞凋亡。总之，Tan IIA 可通过调节小胶质细胞的信号通路提供神经保护，从而防止神经细胞凋亡。这项研究为缺血性中风的治疗靶点提供了新的见解。

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.