Phillyrin attenuates norepinephrine-induced cardiac hypertrophy and inflammatory response by suppressing p38/ERK1/2 MAPK and AKT/NF-kappaB pathways

Phillyrin, a well-known natural compound from the dried fruits of Forsythia suspensa (Thunb.) Vahl., has shown anti-inflammatory, antioxidant and anti-virus activities as well as renal protective effects on diabetic nephropathy. In this study, we investigated whether phillyrin attenuated cardiac hypertrophy induced by catecholamine in vivo and in vitro, and explored the underlying mechanisms. Cardiac hypertrophy was induced in C57BL/6 mice by subcutaneous injection of norepinephrine (NE, a key catecholamine), and in rat cardiomyoblasts (H9c2) by stimulation with NE in vitro. Our results showed that administration of phillyrin (100 mg/kg, i.p. for 15 days) significantly improved cardiac function, histopathological changes, cardiac hypertrophy and decreased the upregulated hypertrophic markers (ANP, BNP, and β-MHC). Moreover, treatment with phillyrin obviously reduced the infiltration of the CD68 positive macrophages and the mRNA expression of proinflammatory genes (IL-1β, IL-6, and TNF-α) in left ventricular tissue. In addition, treatment with phillyrin markedly inhibited the phosphorylation of p38 MAPK, ERK1/2, AKT, and NF-κB p65 in heart tissues. Furthermore, in NE-treated H9c2 cells, pretreatment with phillyrin clearly attenuated cardiomyocyte hypertrophy, reduced ROS production and inhibited the phosphorylation of p38 MAPK, ERK1/2, AKT, and NF-κB p65 in vitro. Collectively, our results demonstrate that phillyrin effectively alleviates NE-induced cardiac hypertrophy and inflammatory response by suppressing p38 MAPK/ERK1/2 and AKT/NF-κB signaling pathways. [Display omitted] •Phillyrin greatly ameliorates cardiac hypertrophy and improves cardiac function in norepinephrine-induced mice.•Phillyrin significantly inhibits cardiac inflammation induced by norepinephrine in vivo and in vitro.•Phillyrin prominently inhibits p38/ERK1/2 MAPK and AKT/NF-kappaB pathways in vivo and in vitro.