Oleanonic acid ameliorates pressure overload-induced cardiac hypertrophy in rats: The role of PKCζ-NF-κB pathway

It has been reported that inflammation is closely related with cardiac hypertrophy. Some inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6 directly induce cardiac hypertrophy, which is associated with the activation of nuclear factorkappa B (NF-κB). Thus, NF-κB is an attractive target for cardiac hypertrophy. In the present study, oleanonic acid inhibited the elevation of transcriptional activity of NF-κB and reduced the mRNA expressions of hypertrophic genes such as atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) in a concentration-dependent manner in phenylephrine (PE)-treated cardiomyocytes. Furthermore, we found that oleanonic acid inhibited the phosphorylation of protein kinase C ζ (PKCζ) at Thr410 site and then reduced the activation of NF-κB using gain- and loss-of-function approaches in PE-treated cardiomyocytes. In vivo, similar results were observed in abdominal aortic constriction (AAC) rats that were intragastrically administered with oleanonic acid, and the pathological changes accompanying cardiac hypertrophy were relieved. In conclusion, oleanonic acid can effectively ameliorate cardiac hypertrophy by inhibiting PKCζ-NF-κB signaling pathway.

Cardiac hypertrophy; Nuclear factor-kappa B; Oleanonic acid; Protein kinase C zeta.