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• Euphorbia wallichii carry high antileishmanial potentials. • Euphorbia wallichii kills Leishmania cells via membrane permeability and apoptosis. • Euphorbia wallichii carry low cytotoxicity to human blood erythrocytes. Clinically available synthetic chemotherapeutics to treat the vector-borne protozoan infection, leishmaniasis, are associated with serious complications such as toxicity and emergence of resistance. Natural products from plants consist of interesting biomolecules that may interfere with DNA or membrane integrity of the parasite and can possibly minimise the associated side effects. In the present study, various fractions of Euphorbia wallichii (EW) root extracts including n-hexane (EWNX), ethyl acetate (EWEA), chloroform (EWCH) and aqueous (EWAQ), were evaluated for their antileishmanial potential against Leishmania tropica followed by investigation of the possible mechanism of action via reactive oxygen species (ROS) quantification, membrane permeability (via sytox green dye) and apoptotic assay (via AO/EB method) using fluorescent microscopy. Two of the fractions i.e. EWEA and EWAQ inhibited the growth of promastigotes (IC 50 7.8 and 10.2 μg/mL, respectively) and amastigotes (IC 50 9.9 and 13.3 μg/mL, respectively) forms almost at similar concentrations as found for the standard antileishmanial drugs, tartar emetic (TA) and Glucantime (IC 50 9.4 and 21.5 μg/mL, respectively). Both the active fractions remained non-toxic towards human blood erythrocytes and were able to cause membrane permeability and apoptotic induction (using Triton X-100 as a positive control) leading to death of Leishmania parasites. However, both the fractions could not triger significant and persistent ROS generation, compared to hydrogen peroxide used as a positive control. Antilesihmanial activity of the two active fractions might be attributed to the presence of high quantity of tannins and saponins. [ABSTRACT FROM AUTHOR]

Novel organobismuth(V) and organoantimony(V) complexes of Ph 3 ML 2 type were synthesized, in which L = deprotonated 2-acetylbenzoic acid (2AcBH), 4-acetylbenzoic acid (4AcBH) or 5-acetylsalicylic acid (5AcSH) and M = bismuth(V) or antimony(V). Complexes [Ph 3 Bi(2AcB) 2 ] ( 1 ) [Ph 3 Sb(4AcB) 2 ] ( 2 ), [Ph 3 Bi(4AcB) 2 ] ( 3 ) and [Ph 3 Sb(5AcS) 2 . CHCl 3 ] ( 4 ) were characterized by elemental analysis, IR, and NMR. Crystal structures of 2 and 4 were determined by single crystal X-ray diffraction. In vitro cytotoxic activities against cancerous (human chronic myelogenous leukemia, K562 and murine metastatic melanoma, B16F10) and healthy non-cancerous (murine fibroblasts, L929 and murine melanocytes, Melan-A) cells showed that, compared to free ligands, both of the metal complexes are more active as anticancer agents at low concentration in cancerous cell lines, but also possessed toxic effect at comparatively higher concentration towards the non-cancerous cells. The organobismuth(V) complex Ph 3 Bi(2AcB) 2 was found to be more active than the Ph 3 BiCl 2 metal precursor against the tumor cell lines and exhibited the highest selectivity index. Moreover, evaluation of the pro-apoptotic activity of Ph 3 Bi(2AcB) 2 in B16F10 cells, by quantifying the cellular DNA using flow cytometry, indicates that cell cycle arrest and cell apoptosis contribute to the drug cytotoxicity. This work supports the great potential of organobismuth(V) dicarboxylate complexes as anticancer agents. [ABSTRACT FROM AUTHOR]

• High levels of IL-4 and cell-free mitochondrial DNA were detected in CL patients infected with L. tropica or L. major. • In both groups of patients, the level of CD4+ T - cells was higher while no significant difference in levels of CD8+ T - cells was observed. • Levels of CF mt-DNA and IL-4 in CL can be used to determine the disease progression. • These biomarkers could help in designing vaccine strategies and immunotherapies. The pathophysiology of Cutaneous Leishmaniasis (CL), an infection caused by Leishmania tropica (L. tropica) and Leishmania major (L. major) is primarily determined by inflammation-mediated immune cells. The immune response mainly depends on cells and molecules related to T-cells that influence susceptibility and disease development. Understanding the immunological mechanisms that cause tissue injury or lesion healing is critical for developing appropriate treatment strategies. In the present study, T-cells profile and cell-free mitochondrial DNA (CF mt-DNA) were investigated in CL patients infected with L. tropica (n = 34) and L. major (n = 2) and compared with non-infected healthy controls (n = 20). There was a significant (p <0.0001) difference between CD4+ T - cells among L. tropica and L. major CL-infected groups as compared to control while no significant difference (p = 0.8597) was found in the percentages of CD8+ T - cells. When L. tropica and L. major CL-infected individuals were compared to controls, the levels of IL-4 and expression of CF mt-DNA were significantly higher (p <0.0001). Higher levels of CF mt-DNA were detected in CL patients, irrespective of the infective Leishmania species. We proposed that the levels of CF mt-DNA and IL-4 in CL-infected individuals can be used to determine the disease progression. A better understanding of these biomarkers and evaluation of the immune responses in CL patients might benefit the development of vaccines and immunotherapies. [ABSTRACT FROM AUTHOR]