Identification of serum predictors of n-acetyl-l-cysteine and isoproterenol induced remodelling in cardiac hypertrophy.

Cardiac hypertrophy (CH), leading to cardiac failure is due to chronic metabolic alterations occurring during cellular stress. Besides the already known relationship between oxidative stress and CH, there are implications of reductive stress leading to CH. This study attempted to develop reductive stress-based CH rat model using n-acetyl-L-cysteine (NAC), a glutathione agonist that was compared with typical isoproterenol (ISO) induced CH model. The main objective was to identify serum metabolites that can serve as potent predictors for seven routine clinical and diagnostic parameters in CH: 3-hydroxybutyrate (3-HB), lactic acid (LA), urea, and ECG-CH parameters (QRS complex, R-amplitude, R-R interval, heart rate) that were hypothesized to underlie metabolic remodelling in this study. CH was assessed using electrocardiography, hypertrophic index and histopathological analysis (H&E stain) in both ventricles after 2 weeks. Gas chromatography mass spectroscopy analysis (GC-MS) identified unique metabolite finger-prints. Correlation and pattern analysis revealed strong relationships between specific metabolites and parameters (Pearson's score > 0.7) of this study. Multiple regression analysis (MRA) for the strongly related metabolites (independent variables) with each of the seven parameters (dependent variables) identified significant predictors for the latter namely fructose, valine, butanoic acid in NAC and cholesterol, erythrose, isoleucine in ISO models, with proline and succinic acid as common for both models. Metabolite set enrichment analysis (MSEA) of those significant predictors (p < 0.05) mapped butyrate metabolism as highly influential pathway in NAC, with arginine-proline metabolism and branched chain amino acid (BCAA) degradation as common pathways in both models, thus providing new insights towards initial metabolic remodeling in the pathogenesis of CH.

Evaluation of Anti-hypertrophic Potential of Enicostemma littorale Blume on Isoproterenol Induced Cardiac Hypertrophy.

The main objective of this study is to evaluate the anti-hypertrophic potential of the aqueous extract of Enicostemma littorale (E. littorale) against isoproterenol induced cardiac hypertrophic rat models (male albino Wistar rats) through biochemical investigations. Aqueous extract of E. littorale known for various beneficial properties was administered (100 mg/kg, 12 days, oral) to isoproterenol (ISO) induced cardiac hypertrophic rats (low ISO-60 mg/kg, 12 days and high ISO-100 mg/kg, 12 days, subcutaneous) and were compared with group that was treated with the reference drug, Losartan (10 mg kg, administered for 12 days, oral). The anti-hypertrophic effect of E. littorale was evaluated by analysing the morphometric indices of the heart, ECG tracings, changes in blood biochemical parameters viz., serum glucose, serum total protein, serum albumin, lipid profile, cardiac specific enzymes (SGOT, SGPT and LDH) and histopathological examination of the heart tissue. The results fundamentally revealed that the plant extract efficiently ameliorated cardiac hypertrophy induced by ISO injected in experimental rats. The outcomes of biochemical investigations of this study highlighted the association between the hypertrophic ß-adrenergic receptor signalling (ß-AR) and the 5' AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) axis in the metabolism of cardiac fibrosis and hypertrophy. This ß-AR/AMPK-PGC1α signalling stem can serve as a key target in ameliorating cardiac hypertrophy through focus on its principal regulators. To add, we also propose that the glycoside, swertiamarin present in this plant with the reported anti-fibrotic potential in liver can be further isolated and evaluated for its anti-hypertrophic potential to treat cardiac hypertrophy.

Antidepressant Activity of Enicostemma littorale Blume in Shp2 (Protein Tyrosine Phosphatase)-inhibited Animal Model of Depression.

BACKGROUND: The objective of this study is to develop a new animal model based on signaling pathways to understand the pathophysiology, therapy of depression, and to investigate the antidepressant activity of Enicostemma littorale which is not yet established. METHODS: Animal models of depression were raised by physical methods and administration of methyl isobutyl ketone (100 mg/kg b.w., i.p.,) and a protein tyrosine phosphatase inhibitor, sodium orthovanadate (30 mg/kg b.w., i.p.,) to young Wistar rats. E. littorale aqueous extract (100 mg/kg b.w., oral) was administered. Forced swimming test (FST), biochemical, and histopathological parameters were performed with reference to fluoxetine (20 mg/kg b.w., oral) treatment. RESULTS: High-performance thin-layer chromatography confirmed the presence of swertiamarin, a unique glycoside present in the Gentianaceae family. FST indicated high rates of immobility in depressed groups and low rates in plant extract-administered group with reference to fluoxetine. Biochemical assays indicated significantly (P < 0.05) increased levels of total protein, superoxide dismutase, triglycerides, and total serum cholesterol, whereas significant reduction (P < 0.05) of glutathione peroxidase, catalase, and lipid peroxidation in plant extract-administered groups in comparison to the depressed groups. Histopathological analysis indicated disorganized neuronal architecture during depression whereas rejuvenation of neuronal patterns was observed during treatment with plant extract and fluoxetine. CONCLUSIONS: This study shows that sodium orthovanadate induces depression in animals and also establishes the antidepressant activity of E. littorale.