Evaluation of the combination of Uvaria chamae (P. Beauv.) and amodiaquine in murine malaria

doi:10.1016/j.jep.2016.07.035

Journal of Ethnopharmacology

Volume 193, 4 December 2016, Pages 30-35

https://doi.org/10.1016/j.jep.2016.07.035 Get rights and content

Abstract

Ethnopharmacological relevance

The leaf and fruit of Uvaria chamae P. Beauv (Annonaceae) are used in antimalarial ethnomedical preparations. Therefore, they were investigated for antimalarial activities as well as possible herb-drug interaction with amodiaquine (AQ).

Materials and methods

The methanol extracts of the leaf (UCL) and fruit (UCF) were administered orally at 100–800 mg/kg/day in mice infected with chloroquine (CQ)-sensitive Plasmodium berghei NK65 using the four-day, curative and prophylactic antimalarial test models. The UCL was further evaluated at 100–800 mg/kg as twice-daily doses and combinations of UCL+AQ using the four-day test. Mice infected with CQ-resistant P. berghei ANKA were treated with UCL at 400 mg/kg and AQ at 10 mg/kg – [UCL400+AQ10] mg/kg – in the four-day and curative test models.

Result

At 800 mg/kg/day, UCL, UCF gave chemosuppression of 42, 28% (four-day test), parasite clearance of 36.3, 49.5% on day 5 (curative test) and 64.3, 82.6% (prophylactic test), respectively. The twice-daily dose of UCL at 800 mg/kg showed activity of 51.50% while the combination of [UCL200+AQ5] mg/kg exhibited chemosuppression of 91.66%, which was not significantly different (p>0.05) from AQ at 10 mg/kg (85.41%). In the CQ-resistant P. berghei experiment, the combination gave a chemosuppression of 45.80%, significantly lower (p<0.05) than AQ (78.40%) while the parasite clearance was not significantly different from AQ (curative test).

Conclusion

The leaf extract showed moderate chemosuppressive activity. The lower-dose combination of the leaf extract and amodiaquine had better antimalarial activity in CQ-sensitive murine malaria. However, the tested combination had no beneficial antimalarial effect in CQ-resistant murine malaria.

Graphical abstract

Introduction

Malaria is a disease caused by protozoan parasites of the genus Plasmodium and is a major cause of mortality and morbidity especially in the tropical and sub-tropical areas of the world (WHO, 2014). The use of different morphological parts of plant is a common practice in antimalarial ethnomedicine in Africa. Scientific evaluation of such parts to verify indigenous claims is important. Uvaria chamae P. Beauv (Annonaceae) is a small tree native to the tropical rain forest of West and Central Africa. Its synonyms include Uvaria cristata, U. echinata, and U. cylindrica. The common name is bush banana while the local (Yoruba, Nigeria) names are Akisan or Oko-aja (Burkill, 1985). The anti-hepatotoxic (Madubunyi, 2012), anti-sickling (Adejumo et al., 2010), anti-viral (Silva et al., 1997, Ogbole et al., 2013), anti-microbial (Hufford and Lasswell, 1978, Oluremi et al., 2010), cytotoxic (Uwaifo et al., 1979), anti-inflammatory and anti-trypanosomal (Adelodun et al., 2013) activities of the plant have been reported. Preliminary screening of the leaf and fruit showed their antimalarial potentials (Adepiti et al., 2013) which supported their ethnomedical use in febrile conditions (Burkill, 1985).

The resistance of Plasmodium parasites to artemisinin and its derivatives as monotherapy as well as resistance to artemisinin-based combination therapy (ACT) has brought about serious concerns in the chemotherapy of malaria (WHO, 2015). Consequently, new drugs and/or new combinations, especially from plants, are evaluated in order to combat this phenomenon (Anagu et al., 2014). Therefore, this study evaluated the antimalarial activities of the leaf and fruit of U. chamae as well as that of the combination of the leaf with amodiaquine in mice.

Section snippets

Drugs, reagents and chemicals

Amodiaquine dihydrochloride dihydrate [PubChem CID: 64646], Pyrimethamine [PubChem CID: 4993] tween 80 [PubChem CID: 443315] (Sigma, Mo, USA), Giemsa stain [PubChem CID: 13735] (Wuhan Chemicals, Wuhan, China) and methanol [PubChem CID 887] (BDH, Poole, UK), Levamisole [PubChem CID. 198119] (Drugfield Pharmaceuticals Ltd., Nigeria).

Plant material

The leaf and fruit of Uvaria chamae (P. Beauv.) Annonaceae were collected in June 2012 on Hill Two, Obafemi Awolowo University (OAU) campus, Ile-Ife (7.5183°N,

Acute toxicity test

No sign of toxicity or mortality was observed in the experimental animals given UCL on single and twice-daily drug administration as well as during the 14-day period of observation. Therefore, the median lethal dose (LD₅₀) was greater than 5 g/kg.

Antimalarial activities of the leaf and fruit

The outcomes of the antimalarial activity were the average parasitaemia/percentage chemosuppression (four-day and prophylactic tests), parasite clearance (curative test) and survival rate.

Discussion

U. chamae is reported in ethnomedicine as a febrifuge and particularly a constituent of antimalarial mixtures in Nigeria (Burkill, 1985). The root was investigated for antimalarial properties both in vitro and in vivo (Addae-Kyereme et al., 2001, Okokon et al., 2006). In the present study, it was observed that the leaf and fruit of the plant exhibited moderate antimalarial activities in both suppressive and curative test models. However, the two extracts showed considerable prophylactic

Conclusion

The study concluded that the leaf and fruit extracts of U. chamae exhibited moderate antimalarial activities in both suppressive and curative models while there was a significant antimalarial effect using the prophylactic model. There was no significant difference in the activity of the leaf when administered as a twice-daily drug administration. In addition, potentiation effect was observed with the combination of the leaf and amodiaquine in low doses while no significant activity was observed

Acknowledgment

The authors are grateful to Professor O.G. Ademowo (University of Ibadan) and Dr. G. Olayiwola (Obafemi Awolowo University) for access to the P. berghei NK 65 and ANKA parasites, respectively. The technical assistance of Mr. D. Dada, Mr. E. Taiwo, Mr. K. Quadri, Miss B. Akinrinade and Miss K. Agbaje is appreciated.

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Evaluation of the combination of Uvaria chamae (P. Beauv.) and amodiaquine in murine malaria

Abstract

Ethnopharmacological relevance

Materials and methods

Result

Conclusion

Graphical abstract

Introduction

Section snippets

Drugs, reagents and chemicals

Plant material

Acute toxicity test

Antimalarial activities of the leaf and fruit

Discussion

Conclusion

Acknowledgment

J. Ethnopharmacol.

Phytochemistry

J. Ethnopharmacol.

Exp. Parasitol.

Cancer Lett.

In vitro antisickling activities and phytochemical evaluation of Plumbago zeylanica and Uvaria chamae

Afr. J. Biotechnol.

Evaluation of antitrypanosomal and antiinflammatory activities of selected Nigerian medicinal plants in mice

Afr. J. Tradit. Complement. Altern. Med.

Evaluation of the in vivo antimalarial potentials of the leaf and fruit of Uvaria chamae P. Beauv (Annonaceae)

Planta Med.

Prevalence of concurrent use of herbal and synthetic medicines among outpatients in a mission hospital in Nigeria

Int. J. Drug Dev. Res.

In vivo interaction between extracts of Khaya grandifoliola (Welw.) CDC (Meliaceae) and artemisinin in a murine malarial model

J. Med. Plants

Azadirachta indica-artesunic acid combination produces an increased cure rate of Plasmodium berghei-infected mice

Pharm. Biol.

The Useful Plants of West Tropical Africa

Amodiaquine dosage and tolerability for intermittent preventive treatment to prevent malaria in children

Antimicrob. Agents Chemother.

Effect of high-dose or split-dose artesunate on parasite clearance in artemisinin-resistant falciparum malaria

Clin. Infect. Dis.

Cis-bullatencin, a linear acetogenin from roots of Uvaria chamae

Nat. Prod. Lett.

Chamuvarinin, an acetogenin bearing a tetrahydropyran ring from the roots of Uvaria chamae

J. Nat. Prod.

A new adjacent bis-tetrahydrofuran annonaceous acetogenin from the seeds of Uvaria chamae

Planta Med.

Cytotoxic C-benzylated flavonoids from Uvaria chamae

J. Org. Chem.

Alkaloids of the Annonaceae XXVIII. Alkaloids from Uvaria chamae

Plant. Med. Phytother.