Oligomeric proanthocyanidins mitigate cholesterol and cholic acid diet-induced hepatic dysfunction in male Sprague Dawley rats.

Dysregulated synthesis of hepatic cholesterol is a critical determinant of atherosclerosis. The combination of cholesterol and cholic acid (CC) diet supplementation to animal models is associated with hepatic dysfunction-mediated atherosclerosis. The current study was designed to investigate the hepatic cholesterol-lowering effects of oligomeric proanthocyanidins (OPC) in CC diet fed rats. CC diet-induced group exhibited significant increase in the hepatic lipid profile, activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR), PON-1, LCAT, LPL, and LPO levels, and messenger RNA expression of HMGR, low-density lipoprotein receptor (LDLr), and HNF-4α. Administration of OPC (100 mg/kg/bwt) resulted in the significant reduction of lipid profile and HMGR levels, with concomitant increase in the levels of cholesterol-regulating enzymes and upregulated expression of LDLr and HNF-4α, which was similar to atorvastatin. Molecular docking studies also revealed that proanthocyanidins had a strong binding affinity to HMGR, similar to atorvastatin. Our findings suggest that OPC regulate the impaired cholesterol metabolism-associated atherosclerosis through hepatic cholesterol-lowering effect.

Oligomeric proanthocyanidins protect myocardium by mitigating left ventricular remodeling in isoproterenol-induced postmyocardial infarction.

Extracellular matrix (ECM) remodeling is a major pathophysiological process during post-myocardial infarction (MI). The activation, differentiation, and proliferation of cardiac fibroblasts to myofibroblasts regulate the expression of ECM proteins. The signaling by bone morphogenetic protein (BMP-4), an extracellular ligand of the TGF-ß family, has recently been identified as an essential pathway in regulating cardiovascular dysfunctions including myocardial fibrosis. Oligomeric proanthocyanidins (OPC) are well known for their cardioprotective activity. The primary aim of the study was to investigate BMP-4-mediated ECM turnover in cardiac fibrosis during isoproterenol-induced post-MI and its downregulation by OPC. Myocardial injury was evaluated by assaying serum markers LDH and CK. Oxidative stress and the enzymatic and nonenzymatic antioxidant levels were assessed to support the cardioprotective nature of OPC. The total collagen level was analyzed by measuring hydroxyproline levels. The ISO-induced group showed a significant decrease in the levels of antioxidants due to severe oxidative stress and increased expression of BMP-4 which reflects the increased expression of MMP 2 and 9 with a concomitant increase and deposition of fibrillary collagens type I and III responsible for the fibrotic scar formation as evidenced in the histological analysis.BMP-4 activation, thus, is strongly associated with cardiac fibrosis which was downregulated upon OPC supplementation. This study provides an evidence supporting the antifibrotic effect of OPC via regulation of BMP-4-mediated ECM turnover and also substantiates the remarkable antioxidant efficacy of OPC against isoproterenol induced severe oxidative stress and subsequent post-MI cardiac fibrosis.

In silico approach to study the metabolism and biological activities of oligomeric proanthocyanidin complexes.

OBJECTIVES: Over the past three decades, numerous studies have focused on the biological activities of oligomeric proanthocyanidins (OPCs) in the prevention of many diseases such as neurodegeneration, atherosclerosis, tumorigenesis, and microbial infections. OPC has redox-active metabolites which could modulate the intracellular redox equilibrium to maintain the antioxidant homeostasis. This redox-modulating efficiency of OPC could provide new insights into therapeutic approaches that could reduce the burden of cardiovascular diseases. The main objective of this study was to explore the biological and metabolic activities of OPC using in silico approaches. METHODS: To validate the above objective, chemoinformatic tools were used to predict the metabolism of OPC after ingestion, based on both the ligand and structure of the constituent compounds. RESULTS: OPC showed possible sites for Phase I metabolism by cytochrome P450, and the metabolites obtained thereafter may be responsible for its biological activities. Absorption, distribution, metabolism, elimination, and toxicity properties showed efficient absorption, distribution, and metabolism of OPC, without toxicity. CONCLUSION: Thus, from the results obtained, OPC could be strongly recommended as a cardioprotective drug.