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

Abstract

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.

• Authors: Kecheng Tang, Bin Zhong, Qingman Luo, Qiao Liu, Xin Chen, Dayan Cao, Xiaohui Li, Shengqian Yang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 927 Pg. 175022 (Jul 15 2022) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 35569549 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier B.V.

Chemical References

• Glucosides
• NF-kappa B
• Proto-Oncogene Proteins c-akt
• p38 Mitogen-Activated Protein Kinases
• phillyrin
• Norepinephrine

Topics

• Animals
• Cardiomegaly (chemically induced, drug therapy)
• Glucosides
• MAP Kinase Signaling System
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Norepinephrine (pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• p38 Mitogen-Activated Protein Kinases (metabolism)