Network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischemia and experimental verification of JAK2/STAT3 signaling pathway

Abstract

Objective This study elucidated the neuroprotective mechanisms of scutellarin in microglia and astrocytes during the progression of neuropathology in cerebral ischemia. Methods Network pharmacology was first used to filtrate the core targets and pathways. Arising from this, JAK2/STAT3 signaling pathway was specifically identified and experimentally verified. Expression of JAK2/STAT3 signaling related proteins in TNC-1 astrocytes subjected to different treatments with BV-2 microglia conditioned medium (CM) was then analyzed by western blot and immunofluorescence staining. Along with the above, expression of the various biomarkers was also evaluated in astrocytes given pretreatment with AG490, the JAK2/STAT3 signaling inhibitor. In tandem, middle cerebral artery occlusion (MCAO) in rats was performed in different experimental groups to detect the expression of the above biomarkers in the cerebral astrocytes. Results Network pharmacology suggests that JAK2/STAT3 signaling pathway is one of the mechanisms by which scutellarin can mitigate the cerebral ischemia damage. In TNC-1 astrocytes, p-JAK2 and p-STAT3 expression was significantly up-regulated in microglia CM group. Scutellarin promoted the up-regulation of various markers, and of note, AG490 neutralized the effect of scutellarin. In vivo at 1, 3, and 7d after MCAO, p-JAK2 and p-STAT3 expression was significantly increased. Consistent with in vitro results, the rise in expression was augmented by scutellarin. Conclusion It is concluded from this study that scutellarin exerts its neuroprotective effects via activated microglia by activating the astrocyte JAK2/STAT3 signaling pathway. This has given the herbal compound a firm experimental basis for its clinical application.

Current advances on the therapeutic potential of scutellarin: an updated review

“…MENG et al found that scutellarin can treat cerebral ischemia by regulating MARK, phosphatidylinositol 3 kinase (PI3K), hypoxia-inducible factor-1 (HIF-1), and other pathways, thus exerting vasorelaxation, anti-inflammatory and antioxidant effects [ 31 ]. Jia et al [ 32 ] found through network pharmacology and experimental validation that Scutellarin exerts therapeutic effects on cerebral ischemia by activating astrocyte JAK2/STAT3 signaling, which provides a solid experimental basis for its clinical application. Xie et al [ 33 ] found that Scutellarin exhibited antioxidant, anti-inflammatory, and neuroprotective effects in cerebral ischemia/reperfusion injury (CIRI) through PI3K/Akt pathway-mediated Nrf2 activation.…”