Research Articles

2021  |  Vol: 6(1)  |  Issue: 1(January-February) | https://doi.org/10.31024/apj.2021.6.1.3
Repurposing dihydroartemisinin-piperaquine-doxycycline as an antimalarial drug: A study in Plasmodium berghei infected mice

Udeme Owunari Georgewill1*, Elias Adikwu2

1Department of Pharmacology, Faculty of Basic Clinical Sciences, University of Port Harcourt, Rivers State, Nigeria

2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Bayelsa State, Nigeria

*Address for Corresponding Author

Dr. Udeme O. Georgewill

Department of Pharmacology, Faculty of Basic Clinical Sciences, University of Port Harcourt, Rivers State, Nigeria

 

Abstract

Objective: Artemisinin-based combination (ACT) therapy is the mainstay for malaria treatment. However, parasites with decreased susceptibility to ACT have emerged. Hence, it is imperative to discover new drugs or explore new drug combinations that can decrease Plasmodium parasite resistance. This study assessed the antiplasmodial activity of dihydroartemisinin-piperaquine - doxycyline (D-P-DX) on mice infected with Plasmodium berghei (P. berghei). Materials and Methods: Swiss albino mice (25-30g) of both sexes, inoculated with 1x107P. berghei intraperitoneally were used. The mice were randomly grouped and orally treated with DX (2.2 mg/kg), D-P (1.71/13.7 mg/kg) and D-P-DX daily in curative, suppressive and prophylactic studies. The negative control and the positive control were treated with normal saline and chloroquine (CQ) (10mg/kg) daily for 4 days, respectively. After treatment, blood samples were assessed for percentage parasitemia, hematological and lipid profile. The mice were also observed for mean survival time. Results and Conclusion: DX, D-P and D-P-DX produced significant decreases in percentage parasitemia at p<0.05, p<0.01, and p<0.001, respectively when compared to negative control.  In the curative study, DX, D-P and D-P-DX produced 64.9%, 71.1%, and 93.6% parasitemia inhibitions when compared to 75.0%produced by CQ.  P. berghei-induced alterations in packed cell volume, white blood cells, red blood cells, hemoglobin, high-density lipoprotein cholesterol, total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were significantly restored by  DX (p<0.05) and D-P (p<0.01) and D-P-DX (p<0.001) when compared to negative control. Conclusion: D-P-DX showed antiplasmodial activity against P. berghei infected mice. It may be clinically useful for the treatment of malaria.

Keywords: Antiplasmodial, doxycycline, artemisinins, Plasmodium berghei, chloroquine, dihydroartemisinin

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