Abstract: In this study, monomeric compounds from the fruiting bodies of fresh Lactarius hatsudake were obtained by sequential organic solvent extraction, ethyl acetate extraction, and silica gel column chromatography, and were structurally characterized by ultraviolet-visible (UV-Vis) spectroscopy, high performance liquid chromatography, mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. The effect of the compounds on the mRNA and protein expression of inflammatory factors and the mitogen-activated protein kinase (MAPK) signaling pathway in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells was determined by polymerase chain reaction (PCR) and Western blot. Results indicated that monomeric compounds with strong anti-inflammatory activity were extracted from Lactarius hatsudake and preliminarily identified as guaiane sesquiterpenoids. The guaiane sesquiterpenoids could significantly inhibit the mRNA expression of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) in LPS-stimulated macrophages (P < 0.01). The guaiane sesquiterpenoids could also reduce the protein expression of inflammatory factors such as cyclooxygenase-2 (COX-2), IL-1β, IL-6, iNOS and TNF-α in LPS-stimulated macrophages in a concentration-dependent manner. Therefore, the guaiane sesquiterpenoids can significantly reduce the phosphorylation levels of p44/42, p38 MAPK (p38 protein) and c-Jun N-terminal kinase (JNK), thereby inhibiting the activity of the MAPK signaling pathway.

Key words: Lactarius hatsudake; guaiane; sesquiterpenoids; inflammation