The formulation of three phytopharmaceutical products of Andrographispaniculata fractions (AP fraction A and B) containing diterpene lactones as an active substance were developed and their antimalarial activities against Plasmodium bergheihas been examined. In vivo antimalarial assay on P. berghei infected mice was carried out by oral administration,twice a dayfor four consecutive days of the AP fractions product, which were Tablet I : wet granulated formula of AP fraction A; Tablet II : wet granulated formula of AP fraction B; Tablet III : solid dispersion formula of AP fraction B.. The results revealed that three phytopharmaceutical products of A.paniculata were inhibited parasite's growth with inhibition range of 70.15% to 80.35%. There was no significant difference of antimalarial activities between Tablet II and III, meanwhile there was significant difference among Tablet I with Tablet II and Tablet III.It was concluded that antimalarial activity depending on raw material form of A. paniculata active substance.

Background New agents for developing alternative or complementary medicine to treat the hepatitis C virus (HCV) are still needed due to high rates of HCV infection globally and the current limitations of available treatments. Treatment of HCV with a combination of direct acting antivirals have been shown to be approximately 90% effective but will be limited in the future due to the emergence of drug resistance and high cost. The leaves of Melicope latifolia have previously been reported to have anti-HCV activity and are a potential source of bioactive compounds for future novel drug development. This study aimed to evaluate the efficacy of the extract of M. latifolia fruit to treat HCV and to isolate its active compounds. Method M. latifolia fruit was extracted using methanol and purified using vacuum liquid chromatography (VLC) and Radial Chromatography. The anti-HCV activity was analyzed using cell culture lines Huh7it-1 and JFH1 (genotype 2a). Time-of-addition and immunoblotting studies were performed to identify the mode of action of the isolated active compounds. The structures of the active compounds were determined using nuclear magnetic resonance (NMR) spectra, UV, IR, and Mass Spectra. Results Six known compounds were isolated from M. latifolia fruit: O-methyloktadrenolon, alloevodionol, isopimpinellin, alloxanthoxyletin, methylevodionol, and N-methylflindersine. N-methylflidersine was the most active compound with IC50 value of 3.8 μg/ml while methylevodionol, isopimpinellin, and alloevodionol were less active. O-methyloktadrenolon and alloxanthoxyletin were moderately active with IC50 values of 10.9 and 21.72 μg/ml, respectively. N-methylflidersine decreased level of HCV NS3 protein expression in the cells. Conclusion The alkaloid compound, N-methylflindersine which was isolated from M. latifolia possesses anti-HCV activity through post-entry inhibition and suppressed NS3 protein expression.

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Objectives. To determine the analgesic and antipyretic activities of a tablet derived from Andrographis paniculata ethyl acetate fraction (AS201-01) in animal models. Methods. The tablet derived from AS201-01 contains an equivalent of 35 mg andrographolide per tablet. Analgesic activity was determined using an acetic acid-induced writhing test on adult male mice. A writhe was recorded by a stopwatch and was defined as the stretching of the abdomen and/or stretching of at least one hind limb. For the determination of antipyretic activity, pyrexia was induced by subcutaneous injection of 15% w/v Brewer’s yeast into adult male rats. Rectal temperature was monitored at 1, 2, 3, and 4 hours after treatment. Results. The results showed that the AS201-01 tablet had analgesic and antipyretic activity. In the acetic acid-induced writhing model, AS201-01 tablet exhibited significant analgesic effect with a 66.73% reduction in writhing response at a dose of 50 mg andrographolide/kg body weight compared to the negative control group. The tablet also showed a significant antipyretic effect. The maximum antipyretic effect was observed after the third hour of administration of the AS201-01 tablet at a dose of 100 mg andrographolide/kg body weight. Conclusion. Tablet of Andrographis paniculata ethyl acetate fraction (AS201-01) exhibited analgesic and antipyretic activities.

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Background. The ethanol extract of Artocarpus champeden stem bark (ACEE) has been proven to exhibit antimalarial activity. Despite the antimalarial effects observed, mechanisms of immune response to explain the antimalarial activity of ACEE remain poorly characterized. Here, we show the production of pro- and anti-inflammatory cytokines T helper 1 (Th1: IFN-γ, TNF-α) and T helper 2 (Th2: IL-10) from Plasmodium berghei-infected mice treated with formulated ACEE in order to better characterize the mechanism behind ACEE’s antimalarial activity. In addition, we have also determined the effect of formulated ACEE on parasite growth and liver function. Methods. Balb/c mice were infected with P. berghei strain ANKA and then administered daily doses of ACEE at a dose of 20, 50, and 100 mg/kg BW, and survival time was recorded. We determined the presence of P. berghei in the blood of the infected mice and inhibition of P. berghei growth. In order to assess the liver function of infected mice, we determined aspartate transaminase (AST) and alanine transaminase (ALT) levels. Determination of cytokines Th1 (IFN-γ, TNF-α) and Th2 (IL-10) levels was conducted using enzyme-linked immunosorbent assay (ELISA). Results. We found that formulated ACEE inhibited parasite growth and showed the highest antimalarial activity at 100 mg/kg BW. AST and ALT levels were found to be in the normal range, and there was no significant difference among control and treatment groups (P>0.05). Infected mice treated with formulated ACEE showed a significant increase in the production of IFN-γ on day 7 and an increased production of TNF-α on day 4 and day 7. No effect on IL-10 production was observed. Decreased parasitemia and longer survival time were observed when compared with untreated infected mice. Conclusion. This study suggests that the administration of ACEE was effective in inhibiting P. berghei growth in infected mice and extending survival time. No effect on liver function was observed based on AST and ALT levels. The antimalarial effects of ACEE could be explained in part by the enhanced production of the proinflammatory cytokines IFN-γ and TNF-α. ACEE treatment may provide novel therapeutic strategies for malaria in future.

Background: A phytochemical study on medicinal plants used for the treatment of fever and malaria in Africa yielded metabolites with potential antiplasmodial activity, many of which are Anthraquinones (AQ). AQs have similar sub-structure as naphthoquinones and xanthones, which were previously reported as novel antiplasmodial agents. </P><P> Objective: The present study aimed to investigate the structural requirements of 9,10- anthraquinones with hydroxy, methoxy and methyl substituents to exert strong antiplasmodial activity and to investigate their possible mode of action. </P><P> Methods: Thirty-one AQs were synthesized through Friedel-Crafts reaction and assayed for antiplasmodial activity in vitro against Plasmodium falciparum (3D7). The selected compounds were tested for toxicity and probed for their mode of action against β-hematin dimerization through HRP2 and lipid catalyses. The most active compounds were subjected to a docking study using AutoDock 4.2. </P><P> Results: The active AQs have similar common structural characteristics. However, it is difficult to establish a structure-activity relationship as certain compounds are active despite the absence of the structural features exhibited by other active AQs. They have either ortho- or meta-arranged substituents and one free hydroxyl and/or carbonyl groups. When C-6 is substituted with a methyl group, the activity of AQs generally increased. 1,3-DihydroxyAQ (15) showed good antiplasmodial activity with an IC50 value of 1.08 &#181;M, and when C-6 was substituted with a methyl group, 1,3- dihydroxy-6-methylAQ (24) showed stronger antiplasmodial activity with an IC50 value of 0.02 &#181;M, with better selectivity index. Compounds 15 and 24 showed strong HRP2 activity and mild toxicity against hepatocyte cells. Molecular docking studies showed that the hydroxyl groups at the ortho (23) and meta (24) positions are able to form hydrogen bonds with heme, of 3.49 Å and 3.02 Å, respectively. </P><P> Conclusion: The activity of 1,3-dihydroxy-6-methylAQ (24) could be due to their inhibition against the free heme dimerization by inhibiting the HRP2 protein. It was further observed that the anthraquinone moiety of compound 24 bind in parallel to the heme ring through hydrophobic interactions, thus preventing crystallization of heme into hemozoin.