Bee venom alleviates isoproterenol-induced cardiac hypertrophy via JAK2/NF-κB signaling cascade.

Pathological cardiac hypertrophy (CH) often progresses towards heart failure, which presents a serious threat to global public health security. Fortunately, peptides from animal venoms have emerged as potential drugs for the therapeutic care of cardiovascular diseases. This paper aims to investigate the therapeutic potentials and mechanism of bee venom (BV) using isoproterenol (ISO)-induced CH models in vivo and in vitro. Melittin was identified as the dominant component in air-dried BV using UPLC-Q/TOF-MS, and subsequently it confirmed that BV prevented electrocardiogram and echocardiography abnormalities, and attenuated morphological and histopathological alterations of hypertrophic hearts in mice. Mechanistically, through network pharmacology exploration, angiotensin-converting enzyme (ACE) and renin (REN) were predicted as the key targets of melittin against CH. This was further confirmed by the in vitro experimental results that BV significantly downregulated the protein or mRNA expression levels of CH markers (β-MHC, ANP, BNP), ACE, and IL-1β in ISO-induced hypertrophic cardiomyocytes. Furthermore, it was ascertained that BV inhibited JAK2/NF-κB signaling cascade via decreasing the protein expression ratio of p-JAK2/JAK2 and the protein expression level of NF-κB. This study showed that BV alleviated ISO-induced CH in vivo and in vitro via JAK2/NF-κB signaling cascade, providing a basis for treating CH with BV or melittin.