MATERIALS AND METHOD: In this experiment, the potential of embelin, isolated from Embelia ribes, to inhibit the growth and sensitize CQ action was screened using SYBRE-green-I based drug sensitivity and isobologram assays, respectively. Its effect on red blood cells stability was screened to assess its safety. To explore its molecular mechanism, its effect on plasmodial Hemozoin and the in vitro β-hematin formation was screened as well. Furthermore, its anti-oxidant activity was measured using the conventional in vitro tests and its molecular characters were obtained using Molispiration program.
RESULTS: The results showed that its anti-plasmodial effect was weaker than CQ but synergism was obtained when they were combined at ratios lower than 5:5 CQ/embelin. Furthermore, β-hematin formation was inhibited by embelin without showing any synergism after mixing with CQ.
CONCLUSION: Overall, embelin is not ideal to be suggested as a conventional antiplasmodium but it has a potential to ameliorate CQ resistance. Furthermore, its action is not related to its impact on hemozoin formation. Further, investigations are recommended to illustrate its detailed mechanism of action. Abbreviation used: CQ-DV-PBS-HEPES: Chloroquine-Digestive vacuole-Phosphate-buffer-saline-4-(2-hydroxyethyl-1-piperazin-ethan-sulphoni-acid), EDTA: Ethylen-diamin-tetra-acetic-acid, g.m.wt: Gram molecular weight, cMCM: Complete-malaria-culture-medium, Hct: Hematocrite, PRBCs: Parasitized-redblood-cells, nRBCs: Normal-red-blood-cells, RT: Room temperature, IC: Inhibitory concentration, FIC: Fractional inhibitory concentration, iCM: Incomplete-culturemedium, BSA: Bovin serum albumin, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, DPPH: 2,2-diphenyl-1- picrylhydrazy, BHT: Butylatedhydroxyl-toleuen, PSA: Polar surface area, ClogP: Log partition coefficient (octanol/water), GPCR: G-protein-coupled-receptors, DMSO: Dimethylsulphoxide, NaOH: Sodium hydroxide.
OBJECTIVE: This study investigates the effect of methanol extract of M. calabura leaves (MMCL) on hepatic antioxidant and anti-inflammatory activities in CCl4-induced hepatotoxic rat.
MATERIALS AND METHODS: Sprague Dawley rats (n = 6) were treated (p.o.) with 10% DMSO (Groups 1 and 2), 50 mg/kg N-acetylcysteine (Group 3) or, 50, 250, or 500 mg/kg MMCL (Groups 4-6) for 7 consecutive days followed by pretreatment (i.p.) with vehicle (Group 1) or 50% CCl4 in olive oil (v/v) (Groups 2-6) on day 7th. Plasma liver enzymes and hepatic antioxidant enzymes and pro-inflammatory cytokines concentrations were measured while liver histopathology was examined.
RESULTS: MMCL, at 500 mg/kg, significantly (p
METHODS: Plasmodium berghei infection in male ICR mice was used as the rodent model of choice. The time course of IL-35 expression in the systemic circulation and tissues of P. berghei infected mice as well as their healthy control counterparts was assessed by enzyme linked immunosorbent assay and immunohistochemistry respectively. The effect of modulating IL-35 by recombinant IL-35 protein or neutralizing anti-Epstein-Barr virus-induced gene 3 antibody on the cytokine environment during P. berghei infection was assessed by flow cytometry. Furthermore, the influence of modulating IL-35 on histopathological hallmarks of malaria and disease progression was evaluated.
RESULTS: Interleukin-35 was significantly up regulated in serum and tissues of P. berghei infected mice and correlated with parasitaemia. Neutralization of IL-35 significantly enhanced the release of IFN-γ, decreased the expression of IL-6 and decreased parasitaemia patency. Neutralization of IL-35 was also associated with a tendency towards increased survival as well as the absence of pathological features associated with malaria infection unlike recombinant IL-35 protein administration which sustained a normal course of infection and unfavourable malaria associated histological outcomes in P. berghei infected mice.
CONCLUSION: These results indicate the involvement of IL-35 in P. berghei induced malaria infection. IL-35 neutralization strategies may represent viable therapeutic modalities beneficial for the resolution of malaria infection.