Multi-Tissue eQTL-MR Investigation of Organ-Specific Action Preference of Salvia miltiorrhiza in the Treatment of Heart Failure Under the Theory of Meridian Tropism
The therapeutic efficacy of Salvia miltiorrhiza against heart failure (HF) is empirically established, yet the organ-directed basis of its meridian tropism remains unquantified. This study integrated multi-tissue expression quantitative trait loci (eQTL) from the Genotype-Tissue Expression (GTEx) database with HF genome-wide association study (GWAS) data to evaluate tissue-specific causal effects of S. miltiorrhiza target genes in heart, liver, lung, and kidney. Active components were screened via TCMSP, ETCM, HERB, and literature, yielding predicted targets subjected to two-sample Mendelian randomization (MR). A volume of interest (VOI) index was constructed to quantify organ-oriented genetic contributions. MR analysis revealed that ALDH2, PDHB, and CETP exhibited elevated VOI in heart and liver, whereas PRKCA demonstrated strong pulmonary preference. CASP7 emerged as a cross-organ consistently protective gene, showing a directional effect toward reduced HF risk and significant downregulation in HF transcriptomic data. These findings establish an integrated meridian tropism–organ regulation–disease causality framework, providing quantitative evidence that S. miltiorrhiza acts predominantly on the heart and liver with ancillary pulmonary involvement. CASP7 is identified as a candidate mediator of cross-organ anti-HF effects, offering a tractable target for meridian-guided therapeutic development.