2. Academic Validation
  3. Machine learning enables discovery of Gentianine targeting TLR4/NF-κB pathway to repair ischemic stroke injury

Machine learning enables discovery of Gentianine targeting TLR4/NF-κB pathway to repair ischemic stroke injury

  • Pharmacol Res. 2021 Nov;173:105913. doi: 10.1016/j.phrs.2021.105913.
Na Wang 1,  Yao Liu 2,  Caixia Jia 1,  Chengwen Gao 2,  Ting Zheng 3,  Mingxuan Wu 2,  Qian Zhang 2,  Xiangzhong Zhao 2,  Zhiqiang Li 4,  Jianxin Chen 5,  Chuanhong Wu 6
Affiliations

Affiliations

  • 1 School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
  • 2 The Affiliated Hospital of Qingdao University and Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, China.
  • 3 Lanzhou University, Lanzhou, China.
  • 4 The Affiliated Hospital of Qingdao University and Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, China. Electronic address: lizqsjtu@163.com.
  • 5 School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. Electronic address: cjx@bucm.edu.cn.
  • 6 School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; The Affiliated Hospital of Qingdao University and Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, China. Electronic address: chuanhongwu@qdu.edu.cn.
PMID: 34563661 DOI: 10.1016/j.phrs.2021.105913
Abstract

Inflammatory response is believed to accelerate the development of stroke injury. Gentianine, an alkaloid isolated from Gentiana Scabra Bunge, shows effectiveness in anti-inflammation. In this study, the effect of Gentianine on transient middle cerebral artery occlusion (tMCAO) induced mouse model in vivo and further related mechanism in LPS-injuried microglia BV-2 cells in vitro were explored. Effect of Gentianine on tMCAO mouse demonstrated that Gentianine significantly ameliorated tMCAO induced ischemic injury by decreasing brain infarct volume and increasing the neurological score and upper limb muscle strength. Meanwhile, Gentianine significantly decreased the release of serum inflammatory cytokines. Machine learning enables that Gentianine might had anti-ischemic stroke effect through the TLR4/NF-κB signaling pathway. This was verified in vivo and in vitro. Gentianine significantly decrease the TLR4 and Iba-1 expression in vivo. These results also verified in BV-2 cells. Gentianine significantly decreased TLR4, MyD88 and NF-κB expression, as well as NO production and inflammatory cytokines release. Gentianine co-treatment with TLR4 Inhibitor, further decreased TLR4, MyD88 and NF-κB expression, NO production, as well as the inflammatory cytokines. Taken together, Gentianine could be used as a potential anti-ischemic stroke agent by suppressing inflammatory responses via TLR4/NF-κB signaling pathway. This study is expected to provide an integrated traditional Chinese and western medicine solution to find potential anti-ischemic stroke compounds based on machine learning.

Keywords

Gentianine; Inflammation; Ischemic stroke; Machine learning.

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