title: Insulin sensitizing and cardioprotective effects of Esculetin and Telmisartan combination by attenuating Ang II mediated vascular reactivity and cardiac fibrosis.
abstract: The combination of the angiotensin receptor blockers (ARBs) with other synthetic and natural molecules has been reported to have better safety profile and therapeutic efficacy in prevention of diabetes and its associated complications than their monotherapy. Driven by the aforementioned facts, this study was conceived to evaluate the potential additive effect of combination of Telmisartan and Esculetin in prevention of insulin resistance and associated cardiac fibrosis. Recently, we have reported that Esculetin prevented cardiovascular dysfunction associated with insulin resistance (IR) and type 2 diabetes. Insulin resistance was developed by high fat diet (HFD) feeding to Wistar rats. Telmisartan and Esculetin were administered at 10 mg/kg/day and 50 mg/kg/day doses (P.O, 2 weeks), respectively either alone or in combination. Plasma biochemical analyses, vascular reactivity and immunohistochemical experiments were performed to assess the beneficial effect of Telmisartan, Esculetin and their combination on insulin resistance and associated cardiac fibrosis. The study results showed that, co-administered Telmisartan and Esculetin ameliorated the pathological features like metabolic perturbation, morphometric alterations, vascular hyper responsiveness, extracellular matrix accumulation and the expression of fibronectin and TGF-β more effectively than monotherapy in HFD fed rats. Hence, the study urges us to conclude that the solution to IR and associated cardiovascular dysfunction may lie in the Telmisartan and Esculetin combination therapy.
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India.
authors.forename: Almesh
authors.initials: A
authors.lastname: Kadakol
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Goru
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India.
authors.forename: Vajir
authors.initials: V
authors.lastname: Malek
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India. Electronic address: anil.gaikwad@pilani.bits-pilani.ac.in.
authors.forename: Anil Bhanudas
authors.initials: AB
authors.lastname: Gaikwad
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage*; D001565:Benzoates / Q000008:administration & dosage*; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005355:Fibrosis; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000077333:Telmisartan; D016896:Treatment Outcome; D014468:Umbelliferones / Q000008:administration & dosage*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D002316:Cardiotonic Agents; D014468:Umbelliferones; D000804:Angiotensin II; C007628:esculetin; D000077333:Telmisartan
keywords: Ang II; Cardiac fibrosis; Esculetin; Insulin resistance; TGF-β; Telmisartan