Anti-inflammatory activity of an anthraquinone derivative from Chamaecrista pumila (Lam.) K. Larsen in macrophages

Tóm tắt

Chamaecrista pumila has empirically been used to treat inflammation-associated complications. However, the molecular mechanism and chemical components underlying the anti-inflammatory activity of this medicinal plant are poorly understood. Hence, the present study aimed to identify main bioactive compounds from the ethyl acetate fraction of C. pumila extract, which was demonstrated to possess the strongest anti-inflammatory effect in a previous study, and provide mechanistic insights into modulation of inflammatory responses by the compound of interest. Using lipopolysaccharide (LPS)-induced murine macrophage models, we found that 4,7-dihydroxy-2-hydroxymethyl-5,6-dimethoxyanthraquinone (ML-6) exhibited the most effective inhibitory effect on the production of nitric oxide (NO) in peritoneal and Raw 264.7 macrophages with the 50% inhibitory concentrations (IC₅₀) of 3.822 and 19.12 μM, respectively. In addition, the secretion of pro-inflammatory cytokines including interleukin (IL)-6 and IL-1β in peritoneal macrophages stimulated with LPS with or without ATP attenuated by 40.4 and 47.6% in presence of ML6 at 10 μM. Mechanistically, ML6 suppressed the activation and nuclear translocation of the transcriptional factor NF-κB, a master regulator of inflammation. Furthermore, ML6 potently inhibited a form of inflammation-induced programmed cell death called pyroptosis. This compound also protected macrophages from LPS-induced cellular oxidative stress by decreasing total ROS levels. These findings suggest that ML6 may serve as a promising anti-inflammatory drug candidate and further studies should be performed to unravel its roles in the treatment of inflammatory disorders.