2. Academic Validation
  3. Qingda granules alleviate cerebral ischemia/reperfusion injury by inhibiting TLR4/NF-κB/NLRP3 signaling in microglia

Qingda granules alleviate cerebral ischemia/reperfusion injury by inhibiting TLR4/NF-κB/NLRP3 signaling in microglia

  • J Ethnopharmacol. 2024 Jan 4:117712. doi: 10.1016/j.jep.2024.117712.
Qiaoyan Cai 1,  Chunyu Zhao 2,  Yaoyao Xu 3,  Haowei Lin 4,  Beibei Jia 5,  Bin Huang 6,  Shan Lin 7,  Daxin Chen 8,  PeiZhi Jia 9,  Meiling Wang 10,  Wei Lin 11,  Ling Zhang 12,  Jianfeng Chu 13,  Jun Peng 14
Affiliations

Affiliations

  • 1 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian 350122, China. Electronic address: cqy2005899@163.com.
  • 2 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address: 1094183617@qq.com.
  • 3 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address: 2970230336@qq.com.
  • 4 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address: 1437439469@qq.com.
  • 5 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address: 7872s92381@qq.com.
  • 6 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address: 1196096001@qq.com.
  • 7 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address: lisa3350@163.com.
  • 8 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address: cdx1125@126.com.
  • 9 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address: 986835468@qq.com.
  • 10 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address: 1974248023@qq.com.
  • 11 Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China. Electronic address: 1905617801@qq.com.
  • 12 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian 350122, China. Electronic address: remona1986@126.com.
  • 13 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian 350122, China. Electronic address: jianfengchu@126.com.
  • 14 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian 350122, China. Electronic address: pjunlab@hotmail.com.
PMID: 38184025 DOI: 10.1016/j.jep.2024.117712
Abstract

Ethnopharmacological relevance: Qingda granules (QDG) are effective for treating hypertension and neuronal damage after cerebral ischemia-reperfusion. However, the anti-neuroinflammatory effect of QDG on injury due to cerebral ischemia/reperfusion is unclear.

Aim of the study: The objective was to evaluate the effectiveness and action of QDG in treating neuroinflammation resulting from cerebral ischemia/reperfusion-induced injury.

Materials and methods: Network pharmacology was used to predict targets and pathways of QDG. An in vivo rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) as well as an in vitro model of LPS-stimulated BV-2 cells were established. MRI was used to quantify the area of cerebral infarction, with morphological changes in the brain being assessed by histology. Immunohistochemistry (IHC) was used to assess levels of the microglial marker IBA-1 in brain tissue. Bioplex analysis was used to measure TNF-α, IL-1β, IL-6, and MCP-1 in sera and in BV-2 Cell Culture supernatants. Simultaneously, mRNA level of these factors were examined using RT-qPCR. Proteins of the TLR4/NF-κB/NLRP3 axis was examined using IHC in vivo and Western blot in vitro, respectively. While NF-κB translocation was assessed using immunofluorescence.

Results: The core targets of QDG included TNF, NFKB1, MAPK1, MAPK3, JNK, and TLR4. QDG suppressed inflammation via modulation of TLR4/NF-κB signaling. In addition, our in vivo experiments using MCAO/R rats demonstrated the therapeutic effect of QDG in reducing brain tissue infarction, improving neurological function, and ameliorating cerebral histopathological damage. Furthermore, QDG reduced the levels of TNF-α, IL-1β, IL-6, and MCP-1 in both sera and brain tissues, along with a reduction in the expression of the microglia biomarker IBA-1, as well as that of TLR4, MyD88, p-IKK, p-IκBα, p-P65, and NLRP3 in MCAO/R rats. In LPS-treated BV-2 cells, QDG down-regulated the expression of proinflammatory factors and TLR4/NF-κB/NLRP3 signaling-related proteins. Additionally, QDG reduced translocation of NF-κB to the nucleus in both rat brains and cells. Moreover, the combined treatment of the TLR4 Inhibitor TAK242 and QDG significantly reduced the levels of p-P65, NLRP3, and IL-6.

Conclusions: QDG significantly suppressed neuroinflammation by inhibiting the TLR4/NF-κB/NLRP3 axis in microglia. This suggests potential for QDG in treating ischemia stroke.

Keywords

Ischemia stroke; Microglia; NLRP3; Network pharmacology; Qingda granules; TLR4/NF-κB.

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