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.