黄芩素下调TLR4/MyD88/NF-κB信号通路减轻神经炎症发挥治疗血栓性脑卒中作用

doi:10.5246/jcps.2026.01.003

中国药学(英文版) ›› 2026, Vol. 35 ›› Issue (1): 38-53.DOI: 10.5246/jcps.2026.01.003

黄芩素下调TLR4/MyD88/NF-κB信号通路减轻神经炎症发挥治疗血栓性脑卒中作用

尚宇夫, 刘冬妮, 张文芳, 冯琬迪, 冯丹虹, 徐双, 赵闻乐, 杜冠华, 王月华^*()

中国医学科学院北京协和医学院药物研究所脑血管病新药发现及晶型研究北京市重点实验室, 北京 100050

收稿日期:2025-09-04 修回日期:2025-10-20 接受日期:2025-11-05 出版日期:2026-01-31 发布日期:2026-01-31
通讯作者: 王月华

Baicalein attenuates neuroinflammation in thrombotic stroke by downregulating the TLR4/MyD88/NF-κB signaling pathway

Yufu Shang, Dongni Liu, Wenfang Zhang, Wandi Feng, Danhong Feng, Shuang Xu, Wenle Zhao, Guanhua Du, Yuehua Wang^*()

Beijing Key Laboratory of Innovative Drug Discovery and Polymorphic Druggability Research for Cerebrovascular Diseases, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

Received:2025-09-04 Revised:2025-10-20 Accepted:2025-11-05 Online:2026-01-31 Published:2026-01-31
Contact: Yuehua Wang
Supported by:
The Natural Science Foundation of Beijing Municipality (Grant No. 7232299) and the CAMS Innovation Fund for Medical Sciences (CIFMS, 2021-I2M-1-069).

摘要/Abstract

摘要：

黄芩素(baicalein, BAI)对脑缺血具有神经保护作用, 但其对血栓性脑卒中的作用及机制尚未阐明, 本研究采用光化学法诱导血栓性脑卒中小鼠模型探讨其对血栓性脑卒中的作用及机制。发现BAI对血栓性脑卒中小鼠的神经损伤和梗死体积具有显著的保护作用, 进一步研究显示BAI可以降低缺血脑皮质组织中促炎因子和趋化因子的含量, 抑制神经胶质细胞活化, 下调TLR4/MyD88/NF-κB炎症信号通路。研究表明, 黄芩素对血栓性脑卒中具有神经保护作用, 其可能的机制涉及下调TLR4/MyD88/NF-κB通路发挥抗神经炎症作用, 为黄芩素治疗血栓性脑卒中机制提供实验依据。

关键词: 黄芩素, 缺血性卒中, 神经炎症

Abstract:

Baicalein (BAI) has been reported to offer neuroprotection against cerebral ischemia. However, its effects on thrombotic cerebral stroke have yet to be fully elucidated. In the present study, we aimed to explore both the efficacy and underlying mechanisms of BAI in a mouse model of photothrombotic-induced thrombotic cerebral stroke. BAI demonstrated significant protective effects against neuronal injury and reduced the infarct area in mice subjected to thrombotic cerebral stroke. Furthermore, BAI lowered the levels of pro-inflammatory cytokines and chemokines within cortical tissues, suppressed glial cell activation, inhibited neuronal apoptosis, and attenuated apoptotic processes throughout the progression of thrombotic stroke. Importantly, additional investigations revealed that BAI downregulated the TLR4/MyD88/NF-κB signaling pathway. In conclusion, BAI exerted neuroprotective effects during the subacute phase of thrombotic cerebral stroke, likely through its anti-neuroinflammatory action mediated by inhibition of the TLR4/MyD88/NF-κB pathway. These findings offered new insights into the molecular mechanisms by which BAI might contribute to the treatment of thrombotic cerebral stroke.

Key words: Baicalein, Ischemic stroke, Neuroinflammation

Supporting:

尚宇夫, 刘冬妮, 张文芳, 冯琬迪, 冯丹虹, 徐双, 赵闻乐, 杜冠华, 王月华. 黄芩素下调TLR4/MyD88/NF-κB信号通路减轻神经炎症发挥治疗血栓性脑卒中作用[J]. 中国药学(英文版), 2026, 35(1): 38-53.

Yufu Shang, Dongni Liu, Wenfang Zhang, Wandi Feng, Danhong Feng, Shuang Xu, Wenle Zhao, Guanhua Du, Yuehua Wang. Baicalein attenuates neuroinflammation in thrombotic stroke by downregulating the TLR4/MyD88/NF-κB signaling pathway[J]. Journal of Chinese Pharmaceutical Sciences, 2026, 35(1): 38-53.

图/表 6

Figure 1. BAI attenuates neurological function impairments, cerebral infarct volume, and apoptosis in thrombotic cerebral stroke mice. (A) The chemical structure of BAI. BAI reduce mNSS (B) and Longa Score (C) in thrombotic cerebral stroke mice (n = 12). BAI enhances grip strength (D) and reduces left turn rate (E) in thrombotic cerebral stroke mice (n = 12). (F) Effect of BAI on body weight change in thrombotic cerebral stroke mice (n = 12). (G) Representative images of TTC staining. Statistical analysis of infarct volume (n = 6). (H) Representative images of H&E staining in the CA1 field of the hippocampus, ischemic penumbra, and ischemic core. 40× magnification and scale bar = 100 μm (n = 4). (I) Representative images of TUNEL staining (green) in the CA1 field of the hippocampus, ischemic penumbra, and ischemic core and quantitative analysis of immunofluorescent staining (n = 4). The nuclei were stained with DAPI (blue), 75.0× magnification, and scale bar = 100 μm. Values are expressed as mean ± SEM. ##P < 0.01 vs. the Sham group; *P < 0.05, **P < 0.01 vs. the Model group.

Figure 2. GO and PPI analyses of DEGs for BAI against thrombotic cerebral stroke. (A) Top 10 classes of GO enrichment terms of 2630 DEGs for BAI against the thrombotic cerebral stroke in BP; (B) Venn diagram of the 36 inflammatory response-related core DEGs; (C) 36 inflammatory response-related core DEGs in the PPI network. The darker color and the larger volume represent a larger Degree value.

Figure 3. KEGG and GO analyses of inflammatory response-related core DEGs for BAI against thrombotic cerebral stroke. (A) Top 10 classes of GO enrichment terms in BP; (B) Top 10 classes of GO enrichment terms in CC; (C) Top 10 classes of GO enrichment terms in MF; (D) Top 10 classes of KEGG enrichment terms.

Figure 4. Effect of BAI on inflammatory factors, chemokines in the cortex of thrombotic cerebral stroke mice. The levels of IL-6 (A), IL-17 (B), MCP-1 (C), BDNF (D), IL-4 (E), and VEGF (F) were assessed by ELISA (n = 6). Values are expressed as mean ± SEM. ##P < 0.01 vs. the Sham group; *P < 0.05, **P < 0.01 vs. the Model group.

Figure 5. Effect of BAI on glial activation and neuron loss in the thrombotic cerebral stroke mice. Representative fluorescent micrographs of (A) GFAP, (B) Iba-1, and (C) NeuN in the DG field of the hippocampus, ischemic penumbra, and ischemic core. Quantitative analysis of immunofluorescent staining (n = 4). The nuclei were stained with DAPI (blue), 75.0× magnification, and scale bar = 100 μm. Values are expressed as mean ± SEM. ##P < 0.01 vs. the Sham group; *P < 0.05, **P < 0.01 vs. the Model group.

Figure 6. Effect of BAI on TLR4/MyD88/NF-κB signaling pathway in thrombotic cerebral stroke mice. Protein expression levels of TLR4 (A), MyD88 (B), and p-NF-κB/NF-κB (C) in stroke mice (n = 6). Values are expressed as mean ± SEM. ##P < 0.01 vs. the Sham group; *P < 0.05, **P < 0.01 vs. the Model group.

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黄芩素下调TLR4/MyD88/NF-κB信号通路减轻神经炎症发挥治疗血栓性脑卒中作用

Baicalein attenuates neuroinflammation in thrombotic stroke by downregulating the TLR4/MyD88/NF-κB signaling pathway

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