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Published on:JANUARY 2018
Indian Journal of Pharmaceutical Education and Research, 2018; 52(1):101-109
Original Article | doi:10.5530/ijper.52.1.12

Protective Effect of A2B Receptor Antagonist (TRP 1) on Acetic Acid Induced Ulcerative Colitis in Rats: in vitro, in vivo and in silico Methods


Authors and affiliation (s):

Praveen Kumar Pasala*1, Ramesh Alluri2, Sri Chandana Mavulati3, Raghu Prasad Mailavaram4, Khasim Shaik5, Prasad Konduri6

1Deparment of Pharmacology, Shri Vishnu College of Pharmacy, Bhimavaram, Andhra Pradesh, INDIA.

2Vishnu Institute of Pharmaceutical Education and Research, BVRIT, Narsapur, Medak, Andhra Pradesh, INDIA.

3Department of Pharmacology, Shri Vishnu College of Pharmacy, Bhimavaram, Andhra Pradesh, INDIA.

4Departmeent of Pharmaceutical Chemistry, Shri Vishnu College of Pharmacy, Bhimavaram, Andhra Pradesh, INDIA.

5Department of Pharmaceutical Chemistry, Shri Vishnu College of Pharmacy, Bhimavaram, Andhra Pradesh, INDIA.

6Department of Pharmacology, Shri Vishnu College of Pharmacy, Bhimavaram, Andhra Pradesh, INDIA.

Abstract:

Aim: Present study was elucidate the protective effect of pyridinone derivatives such as 7-amino-5-oxo-2- Phenyl-5H, 8H-dihydro-[1, 2, 4] triazolo [1, 5-α] pyridine - 6- carbonitril (TRP 1) by in vitro, in vivo and in silico. Methods: Radioligand binding assay was performed on human adenosine receptors (A2B) and assess A2B antagonist effect by adenylyl cyclase activity. In vitro study was carried out to determine the neutralize capacity against DPPH*, NO*, SO*, LPO* free radicals. TRP 1 at the doses 1 mg/ kg bd.wt. and 10 mg/kg bd.wt p.o, was administered consecutively for 14 days in albino rats. Ulcerative colitis was induced with single dose of 2 ml of 3% acetic acid intrarectal on 14th day in treated rats. At the end of treatment, colonic tissue was collected and subjected for estimation of macroscopic score, glutathione, catalase, MPO and inflammatory parameters such as IL 1β, TNF α and IL 6. In silico study was carried out to evaluate the binding energy and IC50 toward IL 1β, TNF α and IL 6. Results: TRP 1 was antagonized the A2B receptors at the concentration of 30000 nM. In vitro study was revealed that TRP1 (1 mg/ml) was significantly neutralizes the free radicals of DPPH*, SO*, NO*and LPO*. In in vivo studies, intrarectal administration of acetic acid caused significantly (***P<0.001) increased macroscopic score, colon weight, colonic MPO, IL 6, IL 1β and TNF-α (*P<0.05), while TRP 1 treated colitis rats antioxidants system such as GSH (**P<0.01), catalase (*P<0.05) activity was significantly improved, decreases inflammatory mediators such TNF α (*P<0.05), IL 1β (**P<0.01) , IL 6 (**P< 0.01) and also suppresses the MPO activity (*P<0.05). In silico study was reported that the IC50 of TPR 1 against IL 1β, IL 6 and TNF-α was 7.5 mM, 28.65 mM and 45.87 mM respectively. Conclusion: Our data demonstrated that the TRP 1 treatment improved clinical score in acetic acid induced colitis in rats. It also inhibited the proinflammatory cytokine IL-6, IL 1β and TNF α and improvements of antioxidant in colitis rats through A2B receptor antagonist property.

Key words: 7-amino-5-oxo-2- phenyl)-5H, 8H-dihydro-[1,2,4] triazolo [1,5-α] pyridine - 6- carbonitril (TRP 1), Ulcerative colitis, Acetic acid, Myeloperoxydase (MPO), Glutathione (GSH), Catalase, TNF α, IL 1β and IL 6.

 

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The Official Journal of Association of Pharmaceutical Teachers of India (APTI)
(Registered under Registration of Societies Act XXI of 1860 No. 122 of 1966-1967, Lucknow)

Indian Journal of Pharmaceutical Education and Research (IJPER) [ISSN-0019-5464] is the official journal of Association of Pharmaceutical Teachers of India (APTI) and is being published since 1967.

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IJPER uses reference linking service using Digital Object Identifiers (DOI) by Crossref. Articles from the year 2013 are being assigned DOIs for its permanent URLs