title: Proteomic analysis of the protective effects of aqueous bark extract of Terminalia arjuna (Roxb.) on isoproterenol-induced cardiac hypertrophy in rats.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To test the efficacy of TA extract in ameliorating cardiac hypertrophy induced by ISO in rats.
  
  
  METHODS
  Cardiac hypertrophy was induced by ISO (5mg/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.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Mehrauli Road, New Delhi 110067, India. Electronic address: santoshszu1517@outlook.com.
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Mehrauli Road, New Delhi 110067, India. Electronic address: md32_sls@jnu.ac.in.
authors.forename: Md
authors.initials: M
authors.lastname: Jahangir Alam
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences (A.I.I.M.S.), Ansari Nagar, 110029, New Delhi, India. Electronic address: pprabhakaraiims@gmail.com.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Prabhakar
authors.affiliation: Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India. Electronic address: sahmad_jh@yahoo.co.in.
authors.forename: Sayeed
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences (A.I.I.M.S.), Ansari Nagar, 110029, New Delhi, India. Electronic address: skmaulik@aiims.ac.in.
authors.forename: Subir K
authors.initials: SK
authors.lastname: Maulik
authors.affiliation: Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization, Lucknow Road, Timarpur, Delhi 110054, India. Electronic address: manishks77@gmail.com.
authors.forename: Manish
authors.initials: M
authors.lastname: Sharma
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Mehrauli Road, New Delhi 110067, India. Electronic address: skgoswami@mail.jnu.ac.in.
authors.forename: Shyamal K
authors.initials: SK
authors.lastname: Goswami
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000627:therapeutic use*; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D029766:Terminalia
chemical_list: D010936:Plant Extracts; D007545:Isoproterenol
keywords: Adrenergic stress; Cardiac hypertrophy; Cardio-protection; Heart failure; Proteomics; Terminalia arjuna