Integrative transcriptomic and metabolomic analysis explores mechanisms by which Astragalus membranaceus and Salvia miltiorrhiza ameliorates hypertensive renal damage.

To explore the mechanism by which Astragalus membranaceus and Salvia miltiorrhiza (AS) regulates the "metabolic- transcriptional" co-expression network to improve Hypertensive renal damage (HRD). Spontaneously hypertensive rats (SHRs) were used to establish the model of HRD. The structure and function of the kidney were observed following AS intervention. We identified various metabolites in the kidneys using UHPLC-MS/MS and observed renal mRNA expression through RNA sequencing. The "metabolism-transcription" coexpression network was further constructed, and the target metabolites and target genes of AS were ultimately screened and validated. AS significantly reduced blood pressure, improved renal function and alleviated renal pathological damage in SHRs. A total of 596 target mRNAs of AS were identified. Of note, 254 of these mRNAs were expressed in 25 pathways that were closely related to metabolic processes. Additionally, the target metabolites of AS were determined, predominantly enriched in 8 pathways, including linoleic acid metabolism, cholesterol metabolism, choline metabolism in cancer, and the synthesis and degradation of ketone bodies, etc. In addition, the target metabolites and target mRNAs of AS were co-enriched in 3 specific pathways of linoleic acid metabolism, cholesterol metabolism, taurine and hypotaurine metabolism, involving 7 different metabolites and 18 differentially expressed (DE) mRNAs. The 7 metabolites exhibited high AUC prediction values, and the verification and sequencing results of the 4 genes were basically consistent. Conclusion The mechanisms by which AS improves HRD may be closely related to the regulation of linoleic acid metabolism, cholesterol metabolism and taurine and hypotaurine metabolism pathways as well as the relevant target genes.