Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

In-vivo antitrypanosomal effect and in-silico prediction of chronic toxicity of N-methylholaphyllamine in rats

Charles O Nnadi , Linda-Mary U Ozioko, Glory C Eneje, Chinwe M Onah, Wilfred O Obonga

Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka, Nigeria;

For correspondence:- Charles Nnadi Email: charles.nnadi@unn.edu.ng Tel:+2348064947734

Accepted: 20 October 2020 Published: 30 November 2020

Citation: Nnadi CO, Ozioko LU, Eneje GC, Onah CM, Obonga WO. In-vivo antitrypanosomal effect and in-silico prediction of chronic toxicity of N-methylholaphyllamine in rats. Trop J Pharm Res 2020; 19(11):2369-2375 doi: 10.4314/tjpr.v19i11.18

© 2020 The authors.
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Abstract

Purpose: To determine the in-vivo anti-trypanosomal effect and sub-chronic toxicity of N-methylholaphyllamine (MHA) isolated from H. africana against Trypanosoma brucei in rats and also to predict its toxicity by an in-silico method.

Methods: Parasitemia was induced in rats with 1.5 x 10⁵/mL trypanosomes and treatment commenced 5 days post-infection for 12 days. The rats were treated with MHA (3.5 μM/rat) for 5 days and with diminazene (3.5 mg/kg) for 2 days and were monitored every other day during and after treatment for the level of parasitemia and PCV. The chronic toxicity study was carried out with a 28-day sub-chronic toxicity cycle protocol while the toxicity was predicted in-silico with ProTox-II which is freely available on a web server.

Results: MHA exhibited anti-trypanosomal effect in infected rats leading to the restoration of PCV to baseline values (≥ 40 %) on the 14th day and consequent disappearance of parasitemia on day 17 post-infection with no relapse. The slight changes in clinical observation, weight, feed consumption, clinical and histopathology of high-dose MHA rats were not significant (p < 0.05) and were not attributed to the treatment. Apart from MHA-induced immunotoxicity observed in in-silico prediction, no other predicted toxicities were significant; however, few undetected toxicities were found to be mediated by amine oxidase A, androgen and/or histamine, H1 receptors toxicophore fit.

Conclusion: The high in-vivo antitrypanosomal effect and non-toxicity of MHA in this study further provide useful empirical data for lead optimization of MHA to combat sleeping sickness.

Keywords: Holaphyllamine, Antitrypanosomal, Trypanosomes, Chronic toxicity, In-silico