ABSTRACT
Herein, we investigated the effects of B. diffusa (BDE), a well-known cardiotonic edible medicinal plant against apoptosis in Angiotensin II (Ang II)-stimulated hypertrophic cardiac cells (H9c2). The cells were analyzed for viability, markers of hypertrophy, apoptosis, and the expression of various proteins related to apoptosis. Ang II (100 nM for 48 h)-exposed H9c2 cells treated with BDE (75 µg/ml) showed a significant reduction in apoptosis (58.60%↓) compared to Ang II-alone treated cells. BDE treatment significantly reduced the up-regulation of Bax and cytosolic cytochrome-C caused by Ang II as well as reduced the degree of Ang II- induced down-regulation of Bcl-2. A reduction in caspase-3 activity (33.77%↓) and down-regulation of TNF-α was also observed in BDE treated cells stimulated with Ang II. Furthermore, the up-regulation of phospho-p38 MAPK was attenuated by BDE treatment. Bioactive components in the extract were identified as boeravinone B, quercetin, kaempferol, and caffeic acid as evident from high-performance liquid chromatography (HPLC). Overall, our study shows that B. diffusa is effective in attenuating apoptosis in cardiac cells, which is a major contributor to sudden cardiac death in addition to its nutraceutical properties.
Subject(s)
Apoptosis/drug effects , Cardiomegaly/pathology , Nyctaginaceae/chemistry , Phenols/pharmacology , Plant Extracts/pharmacology , Angiotensin II , Animals , Biomarkers/metabolism , Cardiomegaly/metabolism , Caspases/metabolism , Cell Survival/drug effects , Cytochromes c/metabolism , Interleukin-10/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Staining and Labeling , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , bcl-2-Associated X Protein/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Boerhavia diffusa is a renowned edible medicinal plant extensively used against different ailments including heart diseases in the traditional system of medicine in several countries. The present study aims to evaluate the therapeutic efficacy of ethanolic extract of Boerhavia diffusa (BDE) on cardiac hypertrophy and fibrosis induced by angiotensin II (Ang II) in male wistar rats and to identify the active components present in it. A substantial increase of hypertrophy markers such as cardiac mass index, concentration of ANP and BNP, cardiac injury markers like CK-MB, LDH and SGOT, has been observed in hypertrophied groups whereas BDE treatment attenuated these changes when compared to hypertrophied rats. Moreover, Ang II induced myocardial oxidative stress was reduced by BDE which was apparent from diminished level of lipid and protein oxidation products, increased activities of membrane bound ATPases and endogenous antioxidant enzymes along with enhanced translocation of Nrf2 from the cytosol to nucleus. It appears that BDE evokes its antioxidant effects by attenuating lipid peroxidation, enhancing the translocation of Nrf2 from the cytoplasm to nucleus as well as by regulating the metabolism of glutathione. The extent of fibrosis during cardiac hypertrophy was determined by histopathology analysis and the results revealed that BDE treatment considerably reduced the fibrosis in the heart. HPLC analysis of BDE leads to the identification of four compounds viz., quercetin, kaempferol, boeravinone B and caffeic acid. The study substantiate the effect of B. diffusa in protecting the heart from pathological hypertrophy and the attenuation of cardiac abnormalities may be partly attributed through the reduction of oxidative stress and cardiac fibrosis. Since the plant is widely used as a green leafy vegetable, incorporation of this plant in diet may be an alternative way for the prevention and better management of heart diseases and associated complications.
