Proteomic analysis of the protective effects of aqueous bark extract of Terminalia arjuna (Roxb.) on isoproterenol-induced cardiac hypertrophy in rats. (23rd February 2017)

• Record Type: Journal Article
• Authors: Kumar, Santosh; Jahangir Alam, Md.; Prabhakar, Pankaj; Ahmad, Sayeed; Maulik, Subir K.; Sharma, Manish; Goswami, Shyamal K.
• Is Part Of: Journal of ethnopharmacology. Volume 198(2017)
• Page Start: 98
• Page End: 108
• Publication Date: 2017-02-23
• Subjects: ACE Angiotensin converting enzyme -- AP-1 Activator protein 1 -- AT Angiotensin II -- BNP Brain natriuretic peptide -- CH Cardiac hypertrophy -- EF Ejection fraction -- eNOS Endothelial Nitric Oxide Synthase -- ERK Extracellular signal–regulated kinases -- FS Fractional shortening -- GRP78 Glucose regulated protein 78 -- GSK-3β Glycogen synthase kinase 3 beta -- HDAC5 Histone deacetylase 5 -- ISO Isoproterenol -- IVS Interventricular septal -- LVPW Left ventricular posterior wall -- MDH2 Malate Dehydrogenase 2 -- MEF2D Myocyte enhancer factor-2D -- MLC3 Myosin light chain 3 -- NFκB Nuclear factor kappa-light-chain-enhancer of activated B cells -- NPP Natriuretic peptide -- PI3K Phosphoinositide 3-kinase -- P2rX6 P2X purinoceptor 6 -- TA Terminalia arjuna -- TGF-β2 Transforming Growth Factor-β2 -- TPM1 Tropomyosin 1 (Alpha) -- β-AR β-Adrenergic receptors -- β-MHC β-Myosin Heavy Chain; Terminalia arjuna -- Cardiac hypertrophy -- Adrenergic stress -- Heart failure -- Proteomics -- Cardio-protection; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2016.12.050
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Aqueous bark extract of Terminalia arjuna (TA) has been in use as an ethnomedicine for cardiovascular ailments in the Indian subcontinent for centuries. Studies using hemodynamic, ROS scavenging and anti-inflammatory parameters in animal models have shown its anti-atherogenic, hypotensive, inotropic, anti-inflammatory effects. However, details analysis on its effects on established molecular and cell biological markers are a prerequisite for its wider acceptance to the medical community. Aims of the study: To test the efficacy of TA extract in ameliorating cardiac hypertrophy induced by ISO in rats. Methods: Cardiac hypertrophy was induced by ISO (5 mg/kg/day s.c. for 14 days) in rats and a standardized aqueous extract of TA stem bark was orally administered by gavage. Total RNA and protein were isolated from control, ISO, ISO plus TA and TA treated rat hearts and analyzed for the transcripts for the markers of hypertrophy, signaling kinases, transcription factors and total protein profile. Results: TA extract reversed the induction of fetal genes like β-myosin heavy chain, skeletal α-actin and brain natriuretic peptide in hypertrophic rat hearts. While ISO slightly increased the level of phospho-ERK, TA repressed it to about one third of the base line level. Survival kinase Akt, ER stress marker Grp78 and epigenetic regulator HDAC5 were augmented by ISO and TA restored them by various extents. ISO administration moderately increased the transcription factor NFκB binding activity, while coadministration of TA further increased it. AP-1 binding activity was largely unchanged by ISO treatment but it was upregulated when administered along with TA. MEF2D binding activity was increased by ISO and TA restored it to the baseline level. Global proteomic analysis revealed that TA treatment restored a subset of proteins up- and down-regulated in the hypertrophied hearts. Amongst those restored by TA were purinergic receptor X, myosin light chain 3, tropomyosin, and kininogen; suggesting a nodal role of TA in modulating cardiac function. Conclusions: This study for the first time reveals that TA partially or completely restores the marker mRNAs, signaling kinases, transcription factors and total protein profile in rat heart, thereby demonstrating its efficacy in preventing ISO-induced cardiac hypertrophy. Graphical abstract: