Lessertia frutescens (Sutherlandia) suppresses multiple intracellular signaling pathways associated with inflammatory responses in murine macrophages (830.12)

Abstract

Sutherlandia is an herb native to southern Africa and traditionally used in various inflammatory conditions. Previously, we reported that an ethanolic extract of Sutherlandia (SE) had anti‐inflammatory activity in murine macrophages. This study was designed to investigate the impact of SE on inflammation‐related intracellular signaling pathways, and to identify the bioactive component(s) in this herb. RAW 264.7 cells were exposed to various concentrations of SE for 1 hr, then an inflammatory response was triggered by co‐treatment with LPS and IFNγ. The phosphorylated and total STAT1, ERK1/2, p38, and JNKs in cell lysates were determined by Western blot. Exposure to SE significantly decreased the phosphorylation of STAT1 and ERK1/2 by up to 80% and 70%, respectively. Meanwhile, SE had only a limited effect on the phosphorylation of p38 and JNK. We used nitric oxide (NO) production as a screening tool to evaluate the anti‐inflammatory activities of Sutherlandia‐specific constituents: sutherlandiosides A‐D, sutherlandins A‐D. None of these compounds were able to reduce LPS/IFNγ‐induced NO production. In summary, our crude Sutherlandia extract suppressed several key signaling pathways related to inflammatory responses in macrophages, and we continue to search for the constituent(s) responsible.Grant Funding Source: Supported by NIH P50AT006273