ZGC Granules improve HFpEF complicated with atrial fibrillation by inhibiting proinflammatory and pro-fibrotic effects

Objective: This study investigated the efficacy and mechanism of Zhigancao Granules (ZGC) in improving outcomes in patients with heart failure with preserved ejection fraction (HFpEF) complicated by atrial fibrillation (AF), focusing on its anti-inflammatory and anti-fibrotic effects.Method: A total of 220 patients with HFpEF and AF were included and received conventional therapy alone (n = 109) or with ZGC Granules (n = 111) for 3 months, followed by 1-year follow-up.In vitro, HL-1 cardiomyocytes were stimulated with LPS plus palmitic acid and treated with ZGC (0.5, 1.0, 2.0 mg/mL).Cell viability was assessed by CCK-8; mRNA and protein expression of inflammatory and fibrotic markers were measured by qRT-PCR, ELISA, and Western blot.Results: The ZGC group showed significantly greater reductions in B-type natriuretic peptide (BNP), C-reactive protein (CRP), Tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), IL-16, and Transforming growth factor-beta 1 (TGF-β1), along with significantly greater improvements in New York Heart Association (NYHA) functional class, 6-minute walk test (6MWT), Atrial Fibrillation Symptom Scale (AFSS), and Traditional Chinese Medicine (TCM) syndrome efficacy (90.99% vs. 78.90%,P < 0.05).At 1 year, the ZGC group had a lower readmission rate (18.02% vs. 28.83%,P < 0.05), while mortality and adverse events were similar between groups.In vitro, ZGC treatment restored cell viability and dose-dependently downregulated LPS/palmitic acid-induced inflammatory and fibrotic responses.Conclusion: ZGC Granules improve cardiac function, exercise capacity, and inflammatory/fibrotic markers in HFpEF patients with AF, reduce readmission rates, and exhibit a favorable safety profile.Mechanistically, ZGC suppresses LPS/palmitic acid-induced inflammatory and fibrotic responses in cardiomyocytes, potentially through inhibition of NLRP3/Caspase-1 inflammasome activation.