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Heart failure (HF) is a grave health concern, with high morbidity and mortality, calling for the urgent need for new and alternative pharmacotherapies. Lingguizhugan decoction (LD) is a classic Chinese formula clinically used to treat HF. However, the underlying mechanisms involved are not fully elucidated. Based on that, this study aims to investigate the effects and underlying mechanisms of LD on HF. After confirming the therapeutic benefits of LD in transverse aortic constriction (TAC)-induced HF mice, network pharmacology and transcr