Compounds from Sorindeia juglandifolia (Anacardiaceae) exhibit potent anti-plasmodial activities in vitro and in vivo

• Published in: Malaria Journal
• Main Authors: Kamkumo Raceline G, Ngoutane Alvine M, Tchokouaha Lauve RY, Fokou Patrick VT, Madiesse Eugénie AK, Legac Jennifer, Kezetas Jean JB, Lenta Bruno N, Boyom Fabrice F, Dimo Theophile, Mbacham Wilfred F, Gut Jiri, Rosenthal Philip J
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2012
• Subjects: Malaria; Drug discovery; Sorindeia juglandifolia; Plasmodium falciparum; Plasmodium berghei; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-11-382; https://doaj.org/article/c028660102ac4120ae298828604327d0

Abstract Background Discovering new lead compounds against malaria parasites is a crucial step to ensuring a sustainable global pipeline for effective anti-malarial drugs. As far as we know, no previous phytochemical or pharmacological investigations have been carried out on Sorindeia juglandifolia. This paper describes the results of an anti-malarial activity-driven investigation of the fruits of this Cameroonian plant. Methods Air-dried fruits were extracted by maceration using methanol. The extract was fractionated by flash chromatography followed by column chromatography over silica gel, eluting with gradients of hexane-ethyl acetate mixtures. Resulting fractions and compounds were tested in vitro against the Plasmodium falciparum chloroquine-resistant strain W2, against field isolates of P. falciparum , and against the P. falciparum recombinant cysteine protease falcipain-2. Promising fractions were assessed for acute toxicity after oral administration in mice. One of the promising isolated compounds was assessed in vivo against the rodent malaria parasite Plasmodium berghei . Results The main end-products of the activity-guided fractionation were 2,3,6-trihydroxy benzoic acid (1) and 2,3,6-trihydroxy methyl benzoate (2). Overall, nine fractions tested against P. falciparum W2 and falcipain-2 were active, with IC 50 values of 2.3-11.6 μg/ml for W2, and 1.1-21.9 μg/ml for falcipain-2. Purified compounds (1) and (2) also showed inhibitory effects against P. falciparum W2 (IC50s 16.5 μM and 13.0 μM) and falcipain-2 (IC50s 35.4 and 6.1 μM). In studies of P. falciparum isolates from Cameroon, the plant fractions demonstrated IC 50 values of 0.14-19.4 μg/ml and compounds (1) and (2) values of 6.3 and 36.1 μM. In vivo assessment of compound (1) showed activity against P. berghei strain B, with mean parasitaemia suppressive dose and curative dose of 44.9 mg/kg and 42.2 mg/kg, respectively. Active fractions were found to be safe in mice after oral administration of 7 g/kg body weight. Conclusions Fractions of ...