Anti-inflammatory effect of a triterpenoid from Balanophora laxiflora: results of bioactivity-guided isolation

Balanophora laxiflora, a medicinal plant traditionally used to treat fever, pain, and inflammation in Vietnam, has been reported to possess prominent anti-inflammatory activity. This study examined the active constituents and molecular mechanisms underlying these anti-inflammatory effects using bioactivity-guided isolation in combination with cell-based assays and animal models of inflammation. Among the isolated compounds, the triterpenoid (21α)-22-hydroxyhopan-3-one (1) showed the most potent inhibitory effect on COX-2 expression in LPS-stimulated Raw 264.7 macrophages. Furthermore, 1 suppressed the expression of the inflammatory mediators iNOS, IL-1β, INFβ, and TNFα in activated Raw 264.7 macrophages and alleviated the inflammatory response in carrageenan-induced paw oedema and a cotton pellet-induced granuloma model. Mechanistically, the anti-inflammatory effects of 1 were mediated via decreasing cellular reactive oxygen species (ROS) levels by inhibiting NADPH oxidases (NOXs) and free radical scavenging activities. By downregulating ROS signalling, 1 reduced the activation of MAPK signalling pathways, leading to decreased AP-1-dependent transcription of inflammatory mediators. These findings shed light on the chemical constituents that contribute to the anti-inflammatory actions of B. laxiflora and suggest that 1 is a promising candidate for treating inflammation-related diseases. Anti-inflammatory; Anti-oxidant; Balanophora laxiflora; Reactive oxygen species; Triterpenoids.