Antiplasmodial and antimalarial evaluation of a Nigerian hepta-herbal Agbo-iba decoction: Identification of magic bullets and possible facilitators of drug action.

Malaria remains one of the most important pathogenic infectious diseases. Although Africa suffers the greatest brunt, a sizeable proportion of her population still relies on herbal medicines for reasons of cost as well as the belief etched in the minds of consumers that herbal medicines are safer and more efficacious than Modern medicines. Agbo-iba ; a concoction of two or more than two plants is commonly used for the management of malaria in Nigeria. This study assessed the safety and efficacy of a hepta-herbal Agbo-iba (HHA) antimalarial decoction used for the management of malaria in Benin city, Nigeria. Assessment was done against malaria parasite in culture as well as in vivo in pre-clinical murine model of malaria. HHA (IC 50 Pf 3D7 50 μg/ml) was moderately potent and only one of its constituent plants Annickia affinis (IC 50 Pf 3D7 1.49 μg/ml) was far more potent, while all others were moderately active to inactive against the parasite in vitro. HHA showed good selectivity in vitro and was safe at 2 g/kg in mice. However, at 100 mg/kg oral dose, while HHA suppressed parasite growth by 56.76%, the suppression caused by A.affinis was only 32.46% in mice malaria suggesting the existence of synergistic partner(s) in the herbal formula. LCMS revealed the presence of quaternary protoberberine alkaloids (QPAs) in A.affinis and HHA. Although QPAs have strong in vitro antiplasmodial activity, their in vivo antimalarial activity is undermined by being substrates of Permeability glycoprotein (Pgp) efflux pump. Our study suggests that inhibitor(s) of Pgp in HHA could improve the bioavailability of QPAs in mice fed the herbal combo. Further, molecules from other HHA constituent plants may also contribute to the better potency observed for the polyherbal in vivo. These possibilities were validated by the curative antimalarial study at 100 mg/kg, where A.affinis was inactive but the HHA suppressed parasite growth by 44.45%. [Display omitted] [ABSTRACT FROM AUTHOR]