Qishen Yiqi Dripping Pills improved cardiac function and alleviated myocardial fibrotic injury following ischemia-reperfusion by reducing TGF-β, Postn, α-SMA, and COL1A1 expression.
Qishen Yiqi Dripping Pills may alleviate myocardial ischemia-reperfusion-induced fibrotic injury by inhibiting fibroblast activation via the TGF-β/Periostin pathway.
ETHNOPHARMACOLOGICAL RELEVANCE: Qishen Yiqi Dripping Pills (QSYQ), composed of Astragalus membranaceus Fisch. ex Bunge, Salvia miltiorrhiza Bunge, Panax notoginseng (Burkill) F.H.Chen, Dalbergia odorifera T.C.Chen have been included in the Pharmacopoeia of the People's Republic of China and are known to alleviate myocardial ischemia-reperfusion injury. However, whether QSYQ regulates transforming growth factor-beta (TGF-β)/Periostin (Postn) signaling to inhibit fibroblast activation remains unclear. AIM OF THE STUDY: Pathological repair following myocardial ischemia-reperfusion injury (MIRI) is driven by the TGF-β/Postn signaling axis. Targeted modulation of this process may represent a potential pathway for antifibrotic therapy. In this study, we integrated multi-omics analyses with experimental validation to systematically elucidate that QSYQ reverses fibroblast activation by targeting the TGF-β/Postn axis, thereby ameliorating fibrotic remodeling associated with MIRI. Materials and Methods BIOINFORMATICS ANALYSIS: By integrating single-cell and transcriptomic data, along with network pharmacology and Least Absolute Shrinkage and Selection Operator (LASSO), potential targets of QSYQ against MIRI were identified. Molecular dynamics simulations were then employed to predict the binding affinity between QSYQ components and these potential targets. EXPERIMENTS: In vivo, C57BL/6N mice orally received QSYQ before MIRI surgery. Cardiac function was assessed by echocardiography and cTnT, myocardial pathology by Masson staining, the protein levels of TGF-β/Postn and the expression of Alpha smooth muscle actin (α-SMA) and Collagen Type I alpha 1 Chain (COL1A1) were assessed by immunofluorescence or Western blotting. In vitro, HL-1 cells were treated with QSYQ-containing serum; cytotoxicity was measured by Cell Counting Kit-8 (CCK-8), and the effect on SRI-011381 intervention was evaluated. RESULTS: Single-cell sequencing and transcriptomic data indicated that activated fibroblasts were significantly increased after MIRI, and that Postn serves as a potential target driving the transition of fibroblasts toward an activated phenotype. Network pharmacology and molecular dynamics simulations further demonstrated that the circulating components of QSYQ, Calycosin-7-O-β-D-glucoside and Notoginsenoside R2, exhibit favorable binding affinities for both TGF-β and Postn. In vivo and in vitro experiments confirmed that QSYQ improves cardiac function, alleviates pathological myocardial injury, and reduces the protein expression levels of TGF-β, Postn, α-SMA, and COL1A1 following MIRI. CONCLUSION: The alleviation of fibrosis by QSYQ following MIRI may be associated with the regulation of the TGF-β/Postn signaling pathway.
Ge et al. (Mon,) conducted a other in Myocardial ischemia-reperfusion injury. Qishen Yiqi Dripping Pills (QSYQ) was evaluated on Cardiac function, myocardial pathology, and protein levels of TGF-β, Postn, α-SMA, and COL1A1. Qishen Yiqi Dripping Pills improved cardiac function and alleviated myocardial fibrotic injury following ischemia-reperfusion by reducing TGF-β, Postn, α-SMA, and COL1A1 expression.
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