Anti-inflammatory activity of isobutylamides from zanthoxylum nitidum var. tomentosum

Abstract Inflammation is a very common and important basic pathological process. There is still a great need for the isolation of effective anti-inflammatory agents from plants. In this paper, five new isobutylamides, zanthoxylumamides E–I (1–5), and four known isobutylamides (6–9) were isolated from Zanthoxylum nitidum var. tomentosum (Rutaceae). Chiral resolution of seven racemic isobutylamides (1–4 and 6–8) was successfully performed, and the absolute configurations of two stereoisomers of 1–4 were validated by ECD and NMR. The obtained isobutylamides were evaluated in vitro anti-inflammatory activity with the lipopolysaccharide (LPS)-stimulated production of nitric oxide (NO) in murine macrophage RAW264.7 cells. Compound 8 exhibited significant inhibition of LPS-induced NO production. The underlying molecular mechanisms of the anti-inflammatory activity of 8 revealed that it suppressed the NO production through the modulation of myeloid differentiation factor 88 (MyD88) and interferon regulatory factor 3 (IRF3) signaling pathways.