title: In vitro antiplasmodial activities and synergistic combinations of differential solvent extracts of the polyherbal product, Nefang.
abstract: Nefang, a polyherbal product composed of Mangifera indica (bark and leaf), Psidium guajava, Carica papaya, Cymbopogon citratus, Citrus sinensis, and Ocimum gratissimum (leaves), is a potential therapy against P. falciparum malaria. In vitro antiplasmodial activities of its constituent solvent extracts were analyzed on CQ-sensitive (3D7) and multidrug resistant (Dd2) P. falciparum strains. The interactions involving the differential solvent extracts were further analyzed using a variable potency ratio drug combination approach. Effective concentration 50 (EC50) values were determined by nonlinear regression curve-fitting of the dose-response data and used in calculating the fractional inhibitory concentration 50 (FIC50) and combination indices (CI) for each pair. The derived EC50 values (3D7/Dd2, μ g/mL) are Nefang-96.96/55.08, MiB-65.33/34.58, MiL-82.56/40.04, Pg-47.02/25.79, Cp-1188/317.5, Cc-723.3/141, Cs-184.4/105.1, and Og-778.5/118.9. Synergism was obtained with MiB/Pg (CI = 0.351), MiL/Pg (0.358), MiB/Cs (0.366), MiL/Cs (0.482), Pg/Cs (0.483), and Cs/Og (0.414) when analyzed at equipotency ratios. Cytotoxicity testing of Nefang and the solvent extracts on two human cell lines (Hep G2 and U2OS) revealed no significant toxicity relative to their antiplasmodial activities (SI > 20). Taken together, our data confirm the antimalarial activities of Nefang and its constituent plant extracts and identified extract pairs with promising synergistic interactions for exploitation towards a rational phytotherapeutic and evidence-based antimalarial drug discovery.
authors.affiliation: Centre for Research on Medicinal Plants and Traditional Medicine, Institute of Medical Research and Medicinal Plants Studies (IMPM), P.O. Box 6163, Yaoundé, Cameroon ; Department of Pharmacology and Pharmacognosy, University of Nairobi, P.O. Box 19676-00202, Nairobi 0800, Kenya.
authors.forename: Protus
authors.initials: P
authors.lastname: Arrey Tarkang
authors.affiliation: Early Drug Discovery Program, Institut Pasteur Korea, Republic of Korea.
authors.forename: Kathrin Diehl
authors.initials: KD
authors.lastname: Franzoi
authors.affiliation: Early Drug Discovery Program, Institut Pasteur Korea, Republic of Korea.
authors.forename: Sukjun
authors.identifier: 0000-0001-6448-8103
authors.initials: S
authors.lastname: Lee
authors.affiliation: Early Drug Discovery Program, Institut Pasteur Korea, Republic of Korea.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Lee
authors.affiliation: Early Drug Discovery Program, Institut Pasteur Korea, Republic of Korea.
authors.forename: Diego
authors.identifier: 0000-0003-1225-1299
authors.initials: D
authors.lastname: Vivarelli
authors.affiliation: Centre for Neglected Diseases Drug Discovery, Institut Pasteur Korea, Republic of Korea.
authors.forename: Lucio
authors.initials: L
authors.lastname: Freitas-Junior
authors.affiliation: Early Drug Discovery Program, Institut Pasteur Korea, Republic of Korea.
authors.forename: Michel
authors.initials: M
authors.lastname: Liuzzi
authors.affiliation: Centre for Research on Medicinal Plants and Traditional Medicine, Institute of Medical Research and Medicinal Plants Studies (IMPM), P.O. Box 6163, Yaoundé, Cameroon.
authors.forename: Tsabang
authors.initials: T
authors.lastname: Nolé
authors.affiliation: Early Drug Discovery Program, Institut Pasteur Korea, Republic of Korea.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Ayong
authors.affiliation: Centre for Research on Medicinal Plants and Traditional Medicine, Institute of Medical Research and Medicinal Plants Studies (IMPM), P.O. Box 6163, Yaoundé, Cameroon.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Agbor
authors.affiliation: Department of Pharmacology and Pharmacognosy, University of Nairobi, P.O. Box 19676-00202, Nairobi 0800, Kenya.
authors.forename: Faith A
authors.initials: FA
authors.lastname: Okalebo
authors.affiliation: Department of Pharmacology and Pharmacognosy, University of Nairobi, P.O. Box 19676-00202, Nairobi 0800, Kenya.
authors.forename: Anastasia N
authors.initials: AN
authors.lastname: Guantai
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D056945:Hep G2 Cells; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010963:Plasmodium falciparum; D012997:Solvents / Q000737:chemistry*
chemical_list: D000962:Antimalarials; D010936:Plant Extracts; D012997:Solvents