Centella asiatica modulates cancer cachexia associated inflammatory cytokines and cell death in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC’s)

BACKGROUND: Cancer cachexia is associated with increased pro-inflammatory cytokine levels. Centella asiatica (C. asiatica) possesses antioxidant, anti-inflammatory and anti-tumour potential. We investigated the modulation of antioxidants, cytokines and cell death by C. asiatica ethanolic leaf extract (C(LE)) in leukaemic THP-1 cells and normal peripheral blood mononuclear cells (PBMC’s). METHODS: Cytotoxcity of C(LE) was determined at 24 and 72 h (h). Oxidant scavenging activity of C(LE) was evaluated using the 2, 2-diphenyl-1 picrylhydrazyl (DPPH) assay. Glutathione (GSH) levels, caspase (−8, −9, −3/7) activities and adenosine triphosphate (ATP) levels (Luminometry) were then assayed. The levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and IL-10 were also assessed using enzyme-linked immunosorbant assay. RESULTS: C(LE) decreased PBMC viability between 33.25–74.55% (24 h: 0.2–0.8 mg/ml C(LE) and 72 h: 0.4–0.8 mg/ml C(LE)) and THP-1 viability by 28.404% (72 h: 0.8 mg/ml C(LE)) (p < 0.0001). Oxidant scavenging activity was increased by C(LE) (0.05–0.8 mg/ml) (p < 0.0001). PBMC TNF-α and IL-10 levels were decreased by C(LE) (0.05–0.8 mg/ml) (p < 0.0001). However, PBMC IL-6 and IL-1β concentrations were increased at 0.05–0.2 mg/ml C(LE) but decreased at 0.4 mg/ml C(LE) (p < 0.0001). In THP-1 cells, C(LE) (0.2–0.8 mg/ml) decreased IL-1β and IL-6 whereas increased IL-10 levels (p < 0.0001). In both cell lines, C(LE) (0.05–0.2 mg/ml, 24 and 72 h) increased GSH concentrations (p < 0.0001). At 24 h, caspase (−9, −3/7) activities was increased by C(LE) (0.05–0.8 mg/ml) in PBMC’s whereas decreased by C(LE) (0.2–0.4 mg/ml) in THP-1 cells (p < 0.0001). At 72 h, C(LE) (0.05–0.8 mg/ml) decreased caspase (−9, −3/7) activities and ATP levels in both cell lines (p < 0.0001). CONCLUSION: In PBMC’s and THP-1 cells, C(LE) proved to effectively modulate antioxidant activity, inflammatory cytokines and cell death. In THP-1 cells, C(LE) decreased pro-inflammatory cytokine levels whereas it increased anti-inflammatory cytokine levels which may alleviate cancer cachexia.