Potential anti-inflammatory and anti-apoptotic effect of Coccinia grandis plant extract in LPS stimulated-THP-1 cells.

Coccinia grandis (C. grandis) L is an Indian medicinal plant from the Cucurbitaceae family whose extracts possess anti-oxidant, anti-infective, and anti-inflammatory properties. The objective of the present study was to probe the potential immunomodulatory of C. grandis crude extract on different pathways in THP-1 cells as probed by changes in expression of several proteins. THP-1 cells were differentiated into macrophages after treatment with phorbol-12-myristate 13-acetate, followed by exposure to lipopolysaccharide (LPS) with or without 50 or 100 µg/ml of C. grandis extract. Treatment of the cells with the extract significantly downregulated the expression and release of pro-inflammatory cytokines (IL-6, IL-1ß, CCL2, CCL22, CXCL10/IP-10, CX3CL1 and CXCL8/IL-8), proteins (ERK5, BAX, BCL2, Cyclin D, ERK1, NF-κB, P-IκBα,P- NF-κB and P-p38) and molecular signaling pathways (NF-κB, p38 MAPK, ERK1/2 and IL-6/JAK/STAT3 signaling cascades). This study is the first to highlight the ability of C. grandis extract to modulate several pathways, including proliferation, the expression of inflammatory cytokines, phagocytosis, migration properties and apoptosis, in human monocytic THP-1 cells.

In Vitro Studies on the Immunomodulatory Effects of Pulicaria crispa Extract on Human THP-1 Monocytes.

BACKGROUND: Pulicaria crispa (P. crispa) is a plant from the Compositae family that exhibits antioxidant, anti-inflammatory, antibacterial, and cytotoxic activities. OBJECTIVE: The current study aimed at investigating the immunomodulatory effects of P. crispa extract in lipopolysaccharide- (LPS-) stimulated human monocytic THP-1 cells. METHODS: To induce macrophage differentiation, THP-1 cell lines were treated with phorbol-12-myristate 13-acetate, followed by exposure to LPS with or without 50 or 100 µg/ml of P. crispa extract. The following tests were employed to test the immunomodulatory effects of the extract: MTT assay, ELISA, Western blotting analysis, cell migration and phagocytosis assays, and Annexin V staining method. RESULTS: Exposure to 100 µg/ml P. crispa extract significantly reduced THP-1 cell proliferation, migration, and phagocytosis (in LPS-stimulated cells, but not in unstimulated cells). Moreover, the extract alone significantly reduced the rate of THP-1 cell apoptosis, while it increased the rate of late apoptosis. Molecular investigations showed that treatment with P. crispa extract significantly upregulated the expression of ERK1, p-MAPK, P-P38, and Bcl2, while it significantly reduced the expression of ERK5, Bax, NF-κB, P-NF-κB, CCL1, CCL2, CCL5, CCL22, CXCL1, and CXCL10. CONCLUSION: Pulicaria crispa extract exhibited anti-inflammatory, antiproliferative, antimigratory, and antiphagocytic effects in LPS-stimulated THP-1 cells. Future studies should investigate these mechanisms in animal models with chronic inflammatory diseases.

Structure activity relationship (SAR) and quantitative structure activity relationship (QSAR) studies showed plant flavonoids as potential inhibitors of dengue NS2B-NS3 protease.

BACKGROUND: Due to dengue virus disease, half of the world population is at severe health risk. Viral encoded NS2B-NS3 protease complex causes cleavage in the nonstructural region of the viral polyprotein. The cleavage is essentially required for fully functional viral protein. It has already been reported that if function of NS2B-NS3 complex is disrupted, viral replication is inhibited. Therefore, the NS2B-NS3 is a well-characterized target for designing antiviral drug. RESULTS: In this study docking analysis was performed with active site of dengue NS2B-NS3 protein with selected plant flavonoids. More than 100 flavonoids were used for docking analysis. On the basis of docking results 10 flavonoids might be considered as the best inhibitors of NS2B-NS3 protein. The interaction studies showed resilient interactions between ligand and receptor atoms. Furthermore, QSAR and SAR studies were conducted on the basis of NS2B-NS3 protease complex docking results. The value of correlation coefficient (r) 0.95 shows that there was a good correlation between flavonoid structures and selected properties. CONCLUSION: We hereby suggest that plant flavonoids could be used as potent inhibitors of dengue NS2B-NS3 protein and can be used as antiviral agents against dengue virus. Out of more than hundred plant flavonoids, ten flavonoid structures are presented in this study. On the basis of best docking results, QSAR and SAR studies were performed. These flavonoids can directly work as anti-dengue drug or with little modifications in their structures.

Effect of pyrazoloquinoline derivatives on the growth of Leishmania donovani promastigotes.

A screening study was conducted to examine the effect of a series of synthesized pyrazoloquinoline derivatives on the growth of Leishmania donovani promastigotes. Sixteen compounds were tested, ten of which showed an inhibitory effect on the growth of promastigotes. Compound 1 demonstrated potent antileishmanial activity, followed by compounds 3 and 7. Some compounds showed less significant activities, while others exhibited little or no activity. Some of these compounds may be potential candidates for future treatment of leishmaniasis.