2. Academic Validation
  3. Baicalin ameliorates neuroinflammation by targeting TLR4/MD2 complex on microglia via PI3K/AKT/NF-κB signaling pathway

Baicalin ameliorates neuroinflammation by targeting TLR4/MD2 complex on microglia via PI3K/AKT/NF-κB signaling pathway

  • Neuropharmacology. 2025 Apr 1:267:110296. doi: 10.1016/j.neuropharm.2025.110296.
Yufang Lu 1,  Ruiying Zhou 1,  Ruyi Zhu 1,  Xue Wu 2,  Jin Liu 1,  Yue Ma 1,  Xin Zhang 1,  Yaling Zhang 1,  Luting Yang 1,  Yanhua Li 3,  Yuan Zhang 1,  Yaping Yan 4,  Qian Zhang 5
Affiliations

Affiliations

  • 1 National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China.
  • 2 College of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an, Xianyang, Shaanxi, 712046, China.
  • 3 Datong Key Laboratory of Smart Medicine and Health Care for Elderly Chronic Diseases, Medical School, Shanxi Datong University, Datong, Shanxi, 037009, China.
  • 4 National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China. Electronic address: yaping.yan@snnu.edu.cn.
  • 5 National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 710119, China. Electronic address: zq-melody@163.com.
PMID: 39798687 DOI: 10.1016/j.neuropharm.2025.110296
Abstract

This study aims to elucidate the target and mechanism of baicalin, a clinically utilized drug, in the treatment of neuroinflammatory diseases. Neuroinflammation, characterized by the activation of glial cells and the release of various pro-inflammatory cytokines, plays a critical role in the pathogenesis of various diseases, including spinal cord injury (SCI). The remission of such diseases is significantly dependent on the improvement of inflammatory microenvironment. Toll-like Receptor 4/myeloid differentiation protein 2 (TLR4/MD2) complex plays an important role in pathogen recognition and innate immune activation. baicalin, a natural flavonoid, is renowned for its potent anti-inflammatory property. In this study, we discovered that baicalin significantly reduced the activation of glial cells and the levels of pro-inflammatory cytokines at the lesion site of SCI mice, thereby mitigating demyelination and neuronal damage. By directly occupying the active pocket of TLR4/MD2 complex on microglia, baicalin inhibited PI3K/Akt/NF-κB pathway, thereby exerting its anti-inflammatory effect. These findings were corroborated in mice induced by lipopolysaccharide, a TLR4 Agonist. Furthermore, baicalin indirectly altered phenotype of astrocytes by reducing secretion of TNF-α, IL-1α, and C1q levels from microglia. Our work demonstrated that baicalin effectively alleviated neuroinflammation by directly targeting microglia and indirectly modulating astrocytes phenotype. As a natural flavonoid, baicalin holds significant potential as a therapeutic candidate for diseases characterized by neuroinflammation.

Keywords

Astrocyte; Baicalin; Microglia; Neuroinflammation; TLR/MD2 protein complex.

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