Corynoline protects ang II-induced hypertensive heart failure by increasing PPARα and Inhibiting NF-κB pathway

• Published in: Biomedicine & pharmacotherapy Vol. 150; p. 113075
• Main Authors: Wang, Mengyang, Luo, Wu, Yu, Tianxiang, Liang, Shiqi, Sun, Jinfeng, Zhang, Yi, Han, Xue, Long, Xiaohong, Liang, Guang, Li, Gao
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.06.2022; Elsevier
• Subjects: Angiotensin II; Corynoline; Hypertensive heart failure; Inflammation; NF-κB; PPARα; Col-1; β-MyHC; COR; Corynoline; LV; Inflammation; IL-1β; MTT; PPARα; Hypertensive heart failure; Ang II; IL-6; IκBα; WGA; NF-κB; FITC; TNF-α; CMC-Na; TGF-β; Angiotensin II; GAPDH
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113075

Heart failure is a fairly common outcome of hypertension. Recent studies have highlighted the key role of the non-hemodynamic activity of angiotensin II (Ang II) in hypertensive heart failure via inducing cardiac inflammation. Drugs that disrupt Ang II-induced cardiac inflammation may have clinical utility in the treatment of hypertensive heart failure. A naturally occurring compound, corynoline, exhibit anti-inflammatory activities in other systems. C57BL/6 mice were injected with Ang II via a micro-osmotic pump for four weeks to develop hypertensive heart failure. The mice were treated with corynoline by gavage for two weeks. RNA-sequencing analysis was performed to explore the potential mechanism of corynoline. We found that corynoline could inhibit inflammation, myocardial fibrosis, and hypertrophy to prevent heart dysfunction, without the alteration of blood pressure. RNA-sequencing analysis indicates that the PPARα pathway is involved Ang II-induced cardiac fibrosis and cardiac remodeling. Corynoline reversed Ang II-induced PPARα inhibition both in vitro and in vivo. We further found that corynoline increases the interaction between PPARα and P65 to inhibit the NF-κB pro-inflammatory pathway in H9c2 cells. Our studies show that corynoline relieves Ang II-induced hypertensive heart failure by increasing the interaction between PPARα and P65 to inhibit the NF-κB pathway. [Display omitted] •Hypertensive heart failure remains a health challenge worldwide, associated with high rates of hospitalization, morbidity, and mortality especially in the elderly. Recently, it has been shown that Corynoline has anti-inflammatory effects in mastitis, rheumatoid arthritis, liver injury and acute lung injury.•However, there remains an unknown on the molecular mechanism of Corynoline in inhibiting inflammation.•This is the first time to show that Corynoline alleviates Ang II-induced cardiac inflammation and remodeling by increasing PPARα and inhibiting the NF-κB pathway both in vitro and in vivo.