In conclusion, Isorhamnetin, Quercetin, Calycosin, Formononetin, and Kaempferol might be the primary active ingredients of HQ, dominating its cardioprotective effects against heart failure probably through regulating ESR1 expression, which provided a potential mechanism for the clinical application of HQ to regulate cardiac hypertrophy and heart failure. The gene discussed is ESR1; the disease is heart failure.