Analysis of the mechanism of Buyang Huanwu Decoction against cerebral ischemia-reperfusion by multi-omics

Abstract

Ethnopharmacological relevance: Buyang Huanwu Decoction (BYHW) is a classic representative formula for treating qi deficiency and the blood stasis syndrome of stroke in the Qing Dynasty physician Wang Qingren's Correction on the Errors of Medical Works. However, the research on the mechanism of BYHW in the treatment of stroke is not systematic and comprehensive.

Aim of the study: Combined with multi-omics analysis methods to explore the potential targets of BYHW in the treatment of cerebral ischemia-reperfusion (I/R).

Materials and methods: The rat middle cerebral artery occlusion (MCAO) model was established to study the effect of BYHW on cerebral I/R injury in rats. Then, the potential targets and pathways of BYHW in the treatment of cerebral I/R injury were analyzed by proteomic, transcriptomic, and metabolomic methods. Finally, 4D-PRM was used to validate potential targets.

Results: BYHW effectively improved the neurological function scores of MCAO rats and significantly reduced the rate of cerebral infarction in MCAO rats. Multi-omics analysis had identified 15 potential targets and 4 potential signaling pathways. The results of 4D-PRM targeted proteomics verification showed that Pde1b was reversed up-regulated, and Aprt, Gpd1, Glb1, HEXA, and HEXB were reversed down-regulated.

Conclusion: BYHW may improve cerebral I/R through Aprt, Pde1b, Gpd1, Glb1, HEXA and HEXB targets, and Glycerophospholipid metabolism, Purine metabolism and Glycosphingolipid biosynthesis - globoseries pathway.

Keywords: 4D-parallel reaction monitoring; Buyang Huanwu Decoction; Cerebral ischemia-reperfusion; Multi-omics.