Nobiletin ameliorates cardiac impairment and alleviates cardiac remodeling after acute myocardial infarction in rats via JNK regulation

Abstract

Nobiletin was found to protect against acute myocardial infarction (AMI)‐induced cardiac function decline and myocardial remodeling, although the dose–effect relationship and underlying pathways remained unclear. In the current research, different doses of Nobiletin (7.5, 15 and 30 mg/kg/day) were administered to AMI rat model for 21 days. Survival rate, echocardiography, and histological analysis were assessed in vivo. In addition, MTT assay, flow cytometry, and Western blotting were conducted to explore Nobiletin's cytotoxicity and antiapoptotic effect on H9C2 cells. Mechanistically, the activation of MAPK effectors and p38 in vivo was studied. The results showed medium‐ and high‐dose Nobiletin could significantly improve survival rate and cardiac function and reduce the area of infarction and cardiac fibrosis. Medium dose showed the best protection on cardiac functions, whereas high dose showed the best protective effect on cellular apoptosis and histological changes. JNK activation was significantly inhibited by Nobiletin in vivo, which could help to explain the partial contribution of autophagy to AMI‐induced apoptosis and the discrepancy on dose–effect relationships. Together, our study suggested that JNK inhibition plays an important role in Nobiletin‐induced antiapoptotic effect in myocardial infarction, and medium‐dose Nobiletin demonstrated the strongest effect in vivo.

Echinacoside inhibited cardiomyocyte pyroptosis and improved heart function of HF rats induced by isoproterenol via suppressing NADPH/ROS/ER stress

“…Presumably, ECH protected against HF also via regulating NF‐kappa B, FOXO1 and Akt/ERK signalling pathways. In the present study, we found that ECH down‐regulated phosphorylation levels of SAPK/JNK, the activation of JNK mediated cardiac hypertrophy, apoptosis, interstitial fibrosis, remodelling and dysfunction and inhibited the activation of JNK can protect against cardiac remodelling 30–34 . So, JNK inhibition was involved in the mechanism of ECH actions.…”

Nobiletin Alleviates Ferroptosis-Associated Renal Injury, Inflammation, and Fibrosis in a Unilateral Ureteral Obstruction Mouse Model

“…Nob, a unique dietary class of flavonoids in the peel of citrus fruits [15], displays lowtoxicity and multiple pharmacological properties, including anti-inflammatory, inhibition of oxidative stress, immunomodulatory, anti-cancer, neuroprotective, antiatherosclerosis, and antidiabetic effects [16,17]. More recently, Liu et al demonstrated the antiapoptotic effects of Nob treatment in myocardial infarction and fibrosis in a rat model via JNK regulation [18]. Li et al demonstrated that Nob treatment mitigates inflammation and apoptotic death in a murine model [19].…”

Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

“…NOB has been reported to possess anti-inflammatory [ 11 ], antiapoptotic [ 12 ], and antineurotoxic [ 13 ] functions. In the cardiovascular system, NOB has been reported to attenuate adverse cardiac remodeling in rats following MI by restoring autophagy flux [ 14 ] and regulating c-Jun N-terminal kinase (JNK) [ 15 ]. However, both the researches mainly focused on rats and the underlying mechanisms through which NOB protects against pathological cardiac remodeling after MI have not been fully explored.…”