Systematic Study of Crucial Transcription Factors of Coptidis rhizoma Alkaloids against Cerebral Ischemia-Reperfusion Injury.

Abstract

Coptidis rhizoma alkaloids (CRAs), extracted from Coptidis rhizoma, have been indicated to play important neuroprotective roles, but the mechanism underlying has not been determined, especially from the perspective of transcription factors (TFs). In this study, crucial TFs involved in the protective activity of CRA were revealed based on RNA-Seq technology, proteomics, and network pharmacological analysis of the effects of CRA on middle cerebral artery occlusion-mediated cerebral ischemia-reperfusion (I/R) injury. Importantly, CRA significantly reduced the infarction rate and neurological deficiency score. Moreover, CRA significantly decreased the levels of TNF-α, MCP-1, and IL-1β. In addition, seven TFs, including Ncor1, Smad1, Bhlhe41, Stat3, Sp100, Satb2, and Lrpprc, were found to be crucial TFs, and five of these TFs were associated with inflammation. Furthermore, eight compounds in CRA were associated with the identified TFs through network pharmacological analysis. The alteration of Lrpprc and Sabt2 was further confirmed by measuring their downstream genes, including Pigg, Hhatl, Wdr77, Mpped1, Arpp21, Ppfia3, Rims1, and Cacna2d1 by reverse transcriptase polymerase chain reaction. Thus, these seven TFs may be important targets in CRA-mediated protection against I/R injury. This research provides a new view of the protective effect of CRA against cerebral I/R injury and reveals new therapeutic targets for treating cerebral ischemia.