Understanding aconite's anti-fibrotic effects in cardiac fibrosis

Background: The prevalence of cardiac fibrosis, intricately linked to various cardiovascular diseases, continues to rise. Aconite, a traditional Chinese herb renowned for its cardiovascular benefits, holds promise in treating heart ailments. However, the mechanisms underlying its anti-fibrotic effects, particularly in cardiac fibrosis, remain elusive. Hypothesis/purpose: This study aims to shed light on aconite's potential as an anti-fibrotic agent and elucidate its mechanisms in a rat model of isoproterenol (ISO)-induced cardiac fibrosis. Methods: By inducing cardiac fibrosis through ISO injection, the study investigates the role of decoction of white aconite (DWA) in mitigating fibrotic processes. Techniques including metabolomics, RT-qPCR, western blot, and immunofluorescence were employed to unveil the molecular changes induced by DWA. Results: DWA exhibited a remarkable reduction in echocardiographic parameters, cardiac weight increase, myocardial infarction extent, inflammatory cell infiltration, collagen deposition in heart tissue, and serum CK-MB, cTnT, cTnI levels post ISO injection. Metabolomic analysis unveiled DWA's modulation of 27 metabolites, especially in galactose metabolism, addressing metabolic disturbances in cardiac fibrosis. Additionally, DWA suppressed mRNA expression of fibrosis markers (Collagen I, CTGF, TGF-beta), inhibited protein levels of MMP-9, alpha-SMA, and Galectin-3, while elevating TIMP1 expression. Conclusion: DWA demonstrated potent anti-fibrotic effects by curbing collagen deposition and alleviating metabolic disruptions in cardiac fibrosis via the galactose metabolism pathway, possibly mediated by the Gal-3/TGF-beta/Smad signaling pathway.