Glioblastoma is an aggressive cancer, against which medical professionals are still quite helpless, due to its resistance to current treatments. Scorpion toxins have been proposed as a promising alternative for the development of effective targeted glioblastoma therapy and diagnostic. However, the exploitation of the long peptides could present disadvantages. In this work, we identified and synthetized AaTs-1, the first tetrapeptide from Androctonus australis scorpion venom (Aa), which exhibited an antiproliferative effect specifically against human glioblastoma cells. Both the native and synthetic AaTs-1 were endowed with the same inhibiting effect on the proliferation of U87 cells with an IC50 of 0.56 mM. Interestingly, AaTs-1 was about two times more active than the anti-glioblastoma conventional chemotherapeutic drug, temozolomide (TMZ), and enhanced its efficacy on U87 cells. AaTs-1 showed a significant similarity with the synthetic peptide WKYMVm, an agonist of a G-coupled formyl-peptide receptor, FPRL-1, known to be involved in the proliferation of glioma cells. Interestingly, the tetrapeptide triggered the dephosphorylation of ERK, p38, and JNK kinases. It also enhanced the expression of p53 and FPRL-1, likely leading to the inhibition of the store operated calcium entry. Overall, our work uncovered AaTs-1 as a first natural potential FPRL-1 antagonist, which could be proposed as a promising target to develop new generation of innovative molecules used alone or in combination with TMZ to improve glioblastoma treatment response. Its chemical synthesis in non-limiting quantity represents a valuable advantage to design and develop low-cost active analogues to treat glioblastoma cancer.
Introduction:Schistosomiasis is an important parasitic disease in the tropics. Praziquantel is unable to treat the migrating juvenile which stressed the need for new drugs.
Objective:To evaluate the effectiveness of a plant (Randia nilotica) used traditionally to treat migrating juvenile form of schistosoma mansoni.
Methods:Sets of experiments were carried out using both aqueous and methanol extracts of R. nilotica and Praziquantel drug to evaluate their efficacy against migrating schistosomulae by different routes of administration and regimens. First group given was 1 ml of 10 000 ppm of aqueous extract orally and intrapratonially from day 2-8 post infection. Second group was given three doses of 1 ml of 500 ppm of methanol extract on day 7, 21 and 35 after infection. The third group of mice was given 7 doses of Praziquantel at 60 mg /kg orally from day 2-8 post infection.
Results:It resulted in significant reduction in total worm burden at 50% and 73% respectively. The size of worms was very small. Obvious reduction result in mean eggs counts in liver and intestine per mouse in first group. The total worm burden reduction was 83% but the worms were normal, very active (high motility rate) and no dead worms in second group. The third group of mice, showed non significant reduction in total worm burden which was (29%).The worms were normal, very active.
Conclusion:We concluded that the aqueous extract of R. nilotica is highly effective against immature worms of S. mansoni.
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