Fisetin Promotes Functional Recovery after Spinal Cord Injury by Inhibiting Microglia/Macrophage M1 Polarization and JAK2/STAT3 Signaling Pathway.
Rong JiZhizhong HaoHao WangYujing SuWenzhi YangXingfan LiLinyan DuanFangxia GuanShanshan MaPublished in: Journal of agricultural and food chemistry (2024)
Spinal cord injury (SCI) is one of the most serious health problems, with no effective therapy. Recent studies indicate that Fisetin, a natural polyphenolic flavonoid, exhibits multiple functions, such as life-prolonging, antioxidant, antitumor, and neuroprotection. However, the restorative effects of Fisetin on SCI and the underlying mechanism are still unclear. In the present study, we found that Fisetin reduced LPS-induced apoptosis and oxidative damage in PC12 cells and reversed LPS-induced M1 polarization in BV2 cells. Additionally, Fisetin safely and effectively promoted the motor function recovery of SCI mice by attenuating neurological damage and promoting neurogenesis at the lesion. Moreover, Fisetin administration inhibited glial scar formation, modulated microglia/macrophage polarization, and reduced neuroinflammation. Network pharmacology, RNA-seq, and molecular biology revealed that Fisetin inhibited the activation of the JAK2/STAT3 signaling pathway. Notably, Colivelin TFA, an activator of JAK2/STAT3 signaling, attenuated Fis-mediated neuroinflammation inhibition and therapeutic effects on SCI mice. Collectively, Fisetin promotes functional recovery after SCI by inhibiting microglia/macrophage M1 polarization and the JAK2/STAT3 signaling pathway. Thus, Fisetin may be a promising therapeutic drug for the treatment of SCI.
Keyphrases
- spinal cord injury
- induced apoptosis
- signaling pathway
- lps induced
- neuropathic pain
- inflammatory response
- spinal cord
- rna seq
- lipopolysaccharide induced
- endoplasmic reticulum stress
- oxidative stress
- pi k akt
- single cell
- epithelial mesenchymal transition
- mental health
- healthcare
- cerebral ischemia
- toll like receptor
- public health
- adipose tissue
- anti inflammatory
- metabolic syndrome
- high fat diet induced
- subarachnoid hemorrhage
- cell cycle arrest
- climate change
- blood brain barrier
- social media
- cell proliferation