ReferenceID 1953
Machine learning enables discovery of Gentianine targeting TLR4/NF-κB pathway to repair ischemic stroke injury
Pharmacol Res
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 Gentia
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Record Fields
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- Reference Id
- 1953
- Evidence Id
- 18543
- Core Evidence Id
- 18543
- Source Reference Id
- 3919
- Herb2 Reference Id
- HBREF004716
- Subject Paper Key
- HBIN027501_34563661
- Pubmed Id
- 34563661
- Doi
- 10.1016/j.phrs.2021.105913
- Paper Title
- Machine learning enables discovery of Gentianine targeting TLR4/NF-κB pathway to repair ischemic stroke injury
- Paper 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-kappaB 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-kappaB expression, as well as NO production and inflammatory cytokines release. Gentianine co-treatment with TLR4 inhibitor, further decreased TLR4, MyD88 and NF-kappaB 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-kappaB 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.
- Journal
- Pharmacol Res
- Publish Year
- 2021
- Experiment Subject
- mouse; bv-2 cells; lps-injuried microglia bv-2 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Stroke Injury; Tmcao; Ischemic Injury; Middle Cerebral Artery Occlusion
- Paper Title Cn
- Paper Title En
- Machine learning enables discovery of Gentianine targeting TLR4/NF-κB pathway to repair ischemic stroke injury
- Bilingual Status
- semi_complete