Qishen paste improves cardiac conduction in heart failure by regulating cardiac resident macrophage Connexin43

Ethnopharmacological relevance: Heart failure (HF) is a complex clinical syndrome characterized by significant cardiac electrical conduction disturbances. Qishen paste (QSP), a modern herbal formulation consisting of the dried root of Astragalus membranaceus (Fisch.) Bge. (Fabaceae), the dried root and rhizome of Salvia miltiorrhiza Bunge (Lamiaceae), the processed lateral root of Aconitum carmichaelii Debeaux (Ranunculaceae), the dried root of Scrophularia ningpoensis Hemsl. (Scrophulariaceae), the dried flower bud of Lonicera japonica Thunb. (Caprifoliaceae), and the dried root and rhizome of Glycyrrhiza uralensis Fisch. ex DC. (Fabaceae), has shown therapeutic efficacy in HF, but its mechanisms in regulating immune homeostasis and electrical conduction remain unclear.

Aim of the study: This study aims to evaluate the therapeutic effect of QSP on HF from the perspective of immune homeostasis and electrical conduction.

Materials and methods: HF was induced in mice by left anterior descending coronary artery (LAD) ligation. After treatment with QSP, cardiac structure and function were assessed in each group. Electrical conduction was monitored by electrocardiography, a multi-channel electrical mapping system, and microelectrode arrays. Network pharmacology and RNA-seq were used to predict potential mechanisms. Flow cytometry, Western blot, quantitative Real-Time PCR, and immunofluorescence were employed to detect the proportion of cardiac resident macrophages (RCMs) and the expression of connexin43 (Cx43) in HF mice.

Results: QSP improved cardiac function, inflammation and fibrosis, and electrophysiological abnormalities in HF mice. In macrophage-cardiomyocyte (CM) co-cultures, it improved repolarization parameters, with Cx43 as a key target. In vivo experiments confirmed that QSP upregulated Cx43 expression in RCMs.

Conclusions: QSP ameliorates HF by enhancing cardiac conduction through modulating Cx43 in RCMs, highlighting the therapeutic promise of targeting RCM-CM electrical coupling. However, future validation using multiple batches of QSP is required to confirm the reproducibility of these results.