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

Abstract

BackgroundDiscovering 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.MethodsAir-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.ResultsThe 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 IC50 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 IC50 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.ConclusionsFractions of Sorindeia juglandifolia and two compounds isolated from these fractions were active against cultured malaria parasites, the P. falciparum protease falcipain-2, and in a rodent malaria model. These results suggest that further investigation of the anti-malarial activities of natural products from S. juglandifolia will be appropriate.

Potent antiplasmodial extracts and fractions from Terminalia mantaly and Terminalia superba

“…Furthermore, recent reports on phytochemical studies of Terminalia mantaly mainly showed the presence of phenols, flavonoids, tannins, saponins, and steroids [ 25 , 26 ]. Many compounds belonging to these classes of phytochemicals have been found to be highly potent against several sensitive and resistant strains of P. falciparum [ 4 , 19 , 27 – 30 ]. Moreover, studies on their potential mechanisms of action revealed that phenolic compounds and derivatives are very active as enzymes inhibitors.…”

“…Plasmodium falciparum is the causative agent of all reported cases of malaria in Cameroon [ 1 ]. Overall, thousands of people continue to die from malaria each year and despite extensive efforts to control the disease, it remains a major public health threat [ 4 , 5 ]. With persistent severe malarial morbidity and increasing resistance to malaria drugs, including the recently introduced, first-line, artemisinin-based combination therapy (ACT) [ 6 , 7 ], there is a compelling need for new and improved treatments for malaria.…”

Phytochemical Screening, Antibacterial Activity and Bioautography of <i>Sorindeia madagascariensis</i>, <i>Mucuna stans</i>, and <i>Albizia harveyi</i>

“…Specifically, flavonoids, tannins, and saponins have been intensely detected in a leaf extract of S. grandifolia [43]. Similarly, a fruit extract of S. juglandifolia has been found to possess phenolics, tannins, flavonoids, saponins, glycosides, triterpenes and anthraquinones but not alkaloids [19,44,45].…”

A New C-Glucosylflavone from Sorindeia juglandifolia

“…, and 2,3,6-trihydroxy benzoic acid and 2,3,6-trihydroxy (methyl) benzoate from Sorindeia (Kamkumo et al, 2012). The results showed that the Sorindeia genus is also a source of phenolic compounds such as fl avonoids which have been reported from other species within the family Anacardiaceae.…”

“…In traditional folk medicine, the plant is used for the treatment of liver diseases, and a decoction of its leaves is used as gargle for mouth sores in children (Berhaut, 1971). Recently, the fruit extracts have been indicated to contain 2,3,6-trihydroxy benzoic acid and 2,3,6-trihydroxy (methyl) benzoate exhibiting potent antiplasmodial activities in vitro and in vivo (Kamkumo et al, 2012). As part of our continuing chemical investigations of Cameroon medicinal plants (Pegnyemb et al, 2005;Ngo Mbing et al, 2009;Ndongo et al, 2010), a new C-glucosylfl avone, 2'',6''-di-O-acetyl-7-O-methyl vitexin (1), along with seven known compounds, 2''-O-acetyl-7-O-methyl vitexin (2), mearnsitrin (3), robustafl avone (4), 3-O-galloyl catechin (5), tachioside (2-methoxy-benzene-1,4-diol-1-O-β-glucopyranoside) (6), 3β-O-Dglucopyranosyl-β-stigmasterol (7), and methyl gallate (8), were isolated from the leaves of S. juglandifolia (Fig.…”