Inhibition of cystathionine-γ-lyase-mediated hydrogen sulfide production in LPS-stimulated RAW 264.7 macrophages by polyherbal extract

Abstract

The polyherbal formulation chandraprabha vati (CV) comprising 29 herbs is traditionally used as an anti-inflammatory agent for arthritis and urinary ailments in Indian Siddha medicine. Earlier, we reported that lipopolysaccharide (LPS) induced apoptosis in RAW 264.7 macrophages is mediated by hydrogen sulfide (H₂S), a potential target for many inflammatory diseases. Here, we hypothesized that pretreatment with CV decreases H₂S level and thereby alleviate the inflammatory conditions induced by LPS in RAW 264.7 macrophages, and this protective effect occurs through alterations in cystathionine-γ-lyase (CSE), a H₂S synthesizing enzyme. Accordingly, we evaluated the anti-inflammatory effect of CV in LPS-stimulated RAW 264.7 macrophages in vitro. The CV pretreatment followed by 12 h of LPS-stimulation showed significantly decreased TNF-α, H₂S production possibly through CSE gene expression and NF-кB activation compared to the non pretreated macrophages. Our results further confirm that the polyherbal extract chandraprabha vati may be a useful therapy for inflammatory disorders by reducing H₂S levels.