Indigofera oblongifolia regulates the hepatic gene expression profile induced by blood stage malaria.

Malaria is still a major health problem worldwide. This study aimed to investigate the hepatoprotective role of Indigofera oblongifolia leaf extracts (ILE) against mice hepatic injury induced by Plasmodium chabaudi. Female C57BL/6 mice were treated with 100 mg/kg of ILE after infection with erythrocytes parasitized by P. chabaudi. On day 7 post-infection, the extract improved the histological alteration induced by the parasite. This was evidenced by the decreased histological index induced by ILE. Moreover, ILE was able to increase the hepatic antioxidant capacity and could significantly improve the decrease in erythrocyte count and hemoglobin content in mice blood plasma due to infection. ILE was also able to upregulate the expression of 24 genes related to metabolism and of 3 genes related to the immune response. Furthermore, the extract was able to downregulate the expression of 35 genes related to metabolism and of 82 genes related to immune response. Moreover, the microarray study showed that ILE regulated the change in gene expression induced by the parasite. Among these genes, we quantified the expression of cd209f, cyp7a1, Hsd3b5, Sult2a3, Lcn2, CcI8, Nos2, and saa3-mRNAs. These genes were regulated by ILE. Therefore, our results revealed the protective role of Indigofera oblongifolia against hepatic injury induced by blood stage malaria.

Exploring the antimalarial potential of whole Cymbopogon citratus plant therapy.

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (lemon grass) has been used in traditional medicine as an herbal infusion to treat fever and malaria. Generally, whole plant extracts possess higher biological activity than purified compounds. However, the antimalarial activity of the whole C. citratus plant has not been experimentally tested. AIM OF THE STUDY: To evaluate the antimalarial activity of an herbal infusion and the whole Cymbopogon citratus plant in two experimental models of malaria. MATERIAL AND METHODS: The plant was dried for 10 days at room temperature and was then milled and passed through brass sieves to obtain a powder, which was administered to CBA/Ca mice with a patent Plasmodium chabaudi AS or P. berghei ANKA infection. We analysed the effects of two different doses (1600 and 3200mg/kg) compared with those of the herbal infusion and chloroquine, used as a positive control. We also assessed the prophylactic antimalarial activities of the whole C. citratus plant and the combination of the whole plant and chloroquine. RESULTS: The C. citratus whole plant exhibited prolonged antimalarial activity against both P. chabaudi AS and P. berghei ANKA. The low dose of the whole C. citratus plant displayed higher antimalarial activity than the high dose against P. berghei ANKA. As a prophylactic treatment, the whole plant exhibited higher antimalarial activity than either the herbal infusion or chloroquine. In addition, the combination of the whole C. citratus plant and chloroquine displayed higher activity than chloroquine alone against P. berghei ANKA patent infection. CONCLUSIONS: We demonstrated the antimalarial activity of the whole C. citratus plant in two experimental models. The whole C. citratus plant elicited higher anti-malarial activity than the herbal infusion or chloroquine when used as a prophylactic treatment. The antimalarial activity of the whole C. citratus plant supports continued efforts towards developing whole plant therapies for the management of malaria and other infectious diseases prevalent in resource-poor communities.

Immunobiologic and antiinflammatory properties of a bark extract from Ampelozizyphus amazonicus Ducke.

Ampelozizyphus amazonicus is used in the treatment and prevention of malaria. The effect of an aqueous extract from this plant (SART) on the immune response was investigated by measuring immunoglobulin production induced by immunization with the antigen TNP-Ficoll in Plasmodium chabaudi-infected mice. SART treatment increased antigen-specific IgM and IgG levels in TNP-Ficoll-immunized mice. The B cell response during malarial infection was also modified by SART. There was an increase in total serum IgM and IgG and a decrease in the percentage of splenic plasma cells (CD138+ cells) in P. chabaudi-infected, SART-treated animals. SART (1, 3 or 10 mg/kg, p.o.) and the reference drug dexamethasone (5 mg/kg) were also tested in carrageenan-induced leukocyte migration to the subcutaneous air pouch (SAP). All SART doses significantly reduced leukocyte migration into the SAP. The protein concentration resulting from extravasation into the peritoneum was also significantly reduced. Our data indicate that SART possesses immunomodulatory properties, inducing an in vivo modification of the B lymphocyte response and anti-inflammatory properties, which are partly due to a reduction in cell migration and are most likely due to an inhibition of the production of inflammatory mediators. Preliminary HPLC-ESI-MS/MS analysis of SART shows a complex saponin profile with deprotonated molecule [M-H](-) ions in the range of m/z 800-1000.

Dried whole plant Artemisia annua as an antimalarial therapy.

Drugs are primary weapons for reducing malaria in human populations. However emergence of resistant parasites has repeatedly curtailed the lifespan of each drug that is developed and deployed. Currently the most effective anti-malarial is artemisinin, which is extracted from the leaves of Artemisia annua. Due to poor pharmacokinetic properties and prudent efforts to curtail resistance to monotherapies, artemisinin is prescribed only in combination with other anti-malarials composing an Artemisinin Combination Therapy (ACT). Low yield in the plant, and the added cost of secondary anti-malarials in the ACT, make artemisinin costly for the developing world. As an alternative, we compared the efficacy of oral delivery of the dried leaves of whole plant (WP) A. annua to a comparable dose of pure artemisinin in a rodent malaria model (Plasmodium chabaudi). We found that a single dose of WP (containing 24 mg/kg artemisinin) reduces parasitemia more effectively than a comparable dose of purified drug. This increased efficacy may result from a documented 40-fold increase in the bioavailability of artemisinin in the blood of mice fed the whole plant, in comparison to those administered synthetic drug. Synergistic benefits may derive from the presence of other anti-malarial compounds in A. annua. If shown to be clinically efficacious, well-tolerated, and compatible with the public health imperative of forestalling evolution of drug resistance, inexpensive, locally grown and processed A. annua might prove to be an effective addition to the global effort to reduce malaria morbidity and mortality.