Curcumin Suppresses Gelatinase B Mediated Norepinephrine Induced Stress in H9c2 Cardiomyocytes

Abstract

BackgroundExtracellular matrix (ECM) remodeling facilitates biomechanical signals in response to abnormal physiological conditions. This process is witnessed as one of the major effects of the stress imposed by catecholamines, such as epinephrine and norepinephrine (NE), on cardiac muscle cells. Matrix metalloproteinases (MMPs) are the key proteases involved in degradation of the ECM in heart.ObjectivesThe present study focuses on studying the effect of curcumin on Gelatinase B (MMP-9), an ECM remodeling regulatory enzyme, in NE-induced cardiac stress. Curcumin, a bioactive polyphenol found in the spice turmeric, has been studied for its multi-fold beneficial properties. This study focuses on investigating the role of curcumin as a cardio-protectant.MethodsH9c2 cardiomyocytes were subjected to NE and curcumin treatments to study the response in stress conditions. Effect on total collagen content was studied using Picrosirus red staining. Gelatinase B activity was assessed through Gel-Diffusion Assay and Zymographic techniques. RT-PCR, Western Blotting and Immunocytochemistry were performed to study effect on expression of gelatinase B. Further, the effect of curcumin on the localization of NF-κB, known to regulate gelatinase B, was also examined.ResultsCurcumin suppressed the increase in the total collagen content under hypertrophic stress and was found to inhibit the in-gel and in-situ gelatinolytic activity of gelatinase B. Moreover, it was found to suppress the mRNA and protein expression of gelatinase B.ConclusionsThe study provides an evidence for an overall inhibitory effect of curcumin on Gelatinase B in NE-induced hypertrophic stress in H9c2 cardiomyocytes which may contribute in the prevention of ECM remodeling.

Bioactivity, Health Benefits, and Related Molecular Mechanisms of Curcumin: Current Progress, Challenges, and Perspectives

“…Curcumin can protect cardiomyocytes as a cardio-protectant. For instance, curcumin protects against norepinephrine-induced hypertrophic stress and maintains extracellular matrix remodeling by inhibiting the increased collagen content under hypertrophic stress, and suppressing enhanced gelatinase B expression and gelatinolytic activity in H9c2 cardiomyocytes [ 155 ]. It has also been found that curcumin prevents cardiomyocytes from norepinephrine-induced apoptosis and restores their physiological status [ 156 ].…”

Jujuboside A attenuates norepinephrine-induced apoptosis of H9c2 cardiomyocytes by modulating MAPK and AKT signaling pathways

“…The majority of in vitro and in vivo studies have demonstrated that NE-induced cardiotoxicity is a major mediator of the biochemical alterations leading to cardiomyocyte apoptosis and necrosis (14)(15)(16)(17). Our previous study revealed that increased plasma NE and epinephrine levels in stress-induced rats promoted myocardial damage and cardiac dysfunction (6).…”

Cardioprotective potential of curcumin against norepinephrine‐induced cell death: a microscopic study

“…After 16 h, NE was induced in the cells at concentrations of 2.5 and 100 M. Curcumin dose of 8 M was earlier used by our group to reverse the hypertrophic effect of NE (Kohli et al ., ). The cells were incubated for 48 h before observing them under an inverted microscope (Olympus Corporation).…”

“…Curcumin, a well‐known phytoceutical and one of the main curcuminoids of turmeric, is well known for its beneficial effects in varied physiological conditions (Aggarwal & Harikumar, ). The cardio protective potential of curcumin has been investigated and established in our studies conducted earlier (Kohli et al ., ; Ahuja et al ., ) and hence it can be inferred that curcumin may be used to prevent cardiac stress. There are several proposed mechanisms by which curcumin exerts its cardioprotective action, one of them being inhibiting the activity of TNF, a local inflammatory cytokine whose over expression is said to contribute towards heart failure.…”