Enhanced Antimalarial Effects of Chloroquine by Aqueous Vernonia Amygdalina Leaf Extract in Mice Infected with Chloroquine Resistant and Sensitive Plasmodium berghei strains

Background: The emergence and spread of Plasmodium falciparum with resistance to chloroquine (CQ); the safest and cheapest antimalarial drug coupled with the increasing cost of alternative drugs especially in developing countries have necessitated the need to optimize antimalarial actions of plant extracts and restore chloroquine efficacy. Objective: The present study determines the ability of Vernonia amygdalina leaf extract to enhance the prophylactic and therapeutic efficacy of chloroquine against Plasmo- dium berghei malaria in mice. Methods: Chloroquine sensitive (P. bergheiS) and resistant (P.bergheiR) ANKA clones of Plasmodium berghei maintained by serial passage in mice were used to develop respective experimental rodent malaria models based on intraperitoneal injection of 106 parasitize erythrocyte suspension in PBS (pH 7.2) and subsequent development of parasitaemia. These models were then used to investigate the prophylactic enhancement of chloroquine (CQ) at 5 mg/kg via combination with selected doses (31.25; 62.5; 125mg/kbw) of Vernonia amygdalina leaf extracts using a 4-day suppression test. Effect of these combinations on the therapeutic efficacy of CQ at 30mg/kg over 3 days were evaluated. Treatment outcomes including parasite clearance (PCT) and rescrudescent time (RT) were compared with CQchlorpheniramine com-bination. The acute toxicity of the extract-CQ combinations was also determined enzymatically. Results: Prophylatically; chloroquine (5mg/kg) in combination with vernonia extracts achieved a dose-dependent (57.2 - 72.7) suppression of parasitaemia due to CQ sensitive and resistant P berghei strains in the experimental animals. Therapeutically; chloroquine (30mg/kg for 3 days) combined with vernonia to dose-dependently shorten the parasite clearance times (2.6 - 4.4 vs. 4.8 days; P 0.05 for CQ-V62.5/125 combination); prolong the recrudescent times (8.9 - 18.9 vs. 7.2 days; P 0.05) and improve day 14 cure rate (66.7 - 100 vs. 58.3) in the treated P. bergheiS infected mice compared to CQ monotherapy. Whereas CQ monotherapy failed; resolution of parasitaemia due to the CQ resistant parasite with day 14 cure rates of 25 - 100were also observed with these combinations. In therapeutic terms; the potencies of CQ-V125 combination were comparable to those of CQ-chlorpheniramine (0.25mg/kg; 12hourly; 7 days) in the infected animals. Toxicity testing indicates that these combinations elicited mild to - moderate increases in the liver enzymes measured when adminis- tered orally to mice for 7 days. Conclusion: This study indicates that Vernonia amygdalina leaf extract dose - dependently restore the efficacy of CQ against CQ resistance P. berghei malaria in mice

Phytochemical Screening and Antioxidant Activities of some Selected Medicinal Plants Used for Malaria Therapy in Southwestern Nigeria

Purpose: Oxidative stress has been shown to play an important role in the development of anaemia in malaria. Indeed; increase in total antioxidant status has been shown to be important in recovery from malaria. The antioxidant activities of four medicinal plants traditionally used in the treatment of malaria in southwestern Nigeria were determi- ned. Methods: The ethanolic extracts of the leaves of Carica papaya Linn. [Caricaceae] ; stem bark of Magnifera indica Linn. [Anacardiaceae]; leaves of Psidium guajava Linn. [Myrtaceae] and the leaves of Vernonia amygdalina Del. [Compositae]; were used in the present study. The plant parts commonly used in the locality in malaria therapy were employed in this study. The plants were screened for the presence of phytochemicals and; their effect on 2;2-Diphenyl-1-picryl-hydrazyl radical (DPPH) was used to determine their free radical scavenging activity. Results: Phytochemical screening of the plants showed the presence of flavonoids; terpenoids; saponins; tannins and reducing sugars. M. indica did not contain cardiac glycosides and alkaloids while; P. guajava also showed the absence of alkaloids and anthraquinones. Anthraquinones was similarly absent from V. amygdalina. Concentrations of the plant extracts required for 50inhibition of DPPH radical scavenging effect (IC50) were recorded as 0.04 mg/ml; 0.313 mg/ml; 0.58 mg/ml; 2.30 mg/ml and 0.054 mg/ml for P. guajava; M. Indica; C. papaya; V. amygdalina and Vitamin C; respectively. Conclusion : All the plants showed potent inhibition of DPPH radical scavenging activity; P. guajava being the most potent. The free radical scavenging (antioxidant) activities of these plants probably contribute to the effectiveness of the above plants in malaria therapy