Using UPLC Q-TOF-MS/MS Combined with Network Pharmacology to Reveal the Potential Mechanism of Aconitum forrestii Stapf in the Treatment of Heart Failure

The genus Aconitum has a long history of treating heart failure (HF), and the group found that Aconitum forrestii Stapf has good anti-HF activity after screening 15 Aconitum species for their medicinal properties. However, there is still a gap in understanding the potential material basis and mechanism of action of A. forrestii against HF. A comprehensive method was established to address the near-gap in the material basis of early A. forrestii efficacy by combining UPLC Q-TOF-MS/MS with network pharmacology. Based on this, molecular docking and in vitro experiments verified the biological activity of three compounds, corydalmine, corydine, and corytuberine, and their possible mechanism of action through the calcium pathway. The components of A. forrestii were determined by UPLC Q-TOF-MS/MS, and 297 potential active ingredients were screened from 597 secondary metabolites, corresponding to 371 HF targets, respectively. Gene enrichment analysis indicated that AKT1, CREBBP, EP300, PTPN11, and STAT3 might be the core factors of anti-HF in A. forrestii . Subsequently, we verified the anti-HF activity of corydalmine, corydine, and corytuberine for the first time. The experimental results show that high concentrations of corydalmine with low concentrations of corytuberine could be well compared with nicorandil for myocardial protection. In this study, UPLC Q-TOF-MS/MS and network pharmacological analysis were used to find for the first time the significant anti-HF efficacy of corydalmine, corydine, and corytuberine, revealing that A. forrestii may exert its pharmacological effects through the Ca ²⁺ Signaling pathway, providing an essential reference for the potential mechanism of HF prevention and treatment.