Cardiac Glycosides Inhibit LPS-induced Activation of Pro-inflammatory Cytokines in Whole Blood through an NF-kB-dependent Mechanism

Summary: Chemotherapy of African trypanosomiasis still remains far from being satisfactory, being severely limited by a number of factors including unacceptable toxicity, increasing parasite resistance, high cost and unavailability. There is an urgent need for therapeutic agents that are effective, affordable and accessible to the rural poor in Africa who bear most of the disease burden. The objective of this study was to evaluate the therapeutic effects of Acacia nilotica in experimental Trypanosoma brucei brucei infection in mice.  Methanol extract of stem bark of the plant was investigated for its therapeutic effects in experimental African trypanosomiasis. Acute toxicity studies were also conducted. Crude extract of 70% v/v (Methanol/Water) at a dose of 400mg kg -1 body weight per day completely cured the experimental T.b. brucei infection in mice, while doses of 50, 100, 200, 300, and 400mgkg -1 body weight per day of the partially purified extract completely cured the experimental infection in mice within two days.  Sub inoculation of blood and cerebrospinal fluid drawn from the cured mice into healthy mice failed to produce any infection within 28 days of post inoculation. Phytochemical analysis showed the presence of carbohydrates, saponin, tannin and cardiac glycoside. LD 50 of the partially purified extract was found to be 2000mg/kg body weight, the extract being acutely toxic at a dose of 1600mgkg -1 body weight. It is concluded that methanol extract of stem bark of A. nilotica cures experimental T. b. brucei infection in mice. Industrial relevance: The findings in this study provide very useful clue for biopharmaceutical industries and drug manufacturers for the development of phytotherapeutic agents from this plant, not only for therapeutic intervention in the control of African trypanosomiasis but also for the treatment of cancer. This is because of the strong link between Chemotherapy of human African trypanosomiasis (sleeping sickness) and cancer chemotherapy as every drug currently used for the treatment of sleeping sickness has some form of anticancer activity. Moreover, the plant is used in folk medicine for the treatment of cancer. The potential is also very high for the manufacture of highly efficacious drugs for the treatment of sleeping sickness and/or cancer through synthetic modification of isolated bioactive phytoconstituents from this plant. The possibility also exists for the development of anti-diabetic drugs from extracts of this plant.