Inhibitory Effects of Constituents of an Endophytic Fungus Hypoxylon investiens on Nitric Oxide and Interleukin-6 Production in RAW264.7 Macrophages

摘要

Three new compounds, hypoxyloamide (1), 8-methoxynaphthalene-1,7-diol (2), and hypoxylonol (3), together with seven compounds isolated from nature for the first time, investiamide (4), hypoxypropanamide (5), hypoxylonol A (6), investienol (7), 2-heptylfuran (8), (3S)-5-methyl-8-Omethylmellein (9), (4R)-O-methylsclerone (10), along with 19 known compounds, 11 –29, were isolated from the culture broth of Hypoxylon investiens BCRC 10F0115, a fungal endophyte residing in the stems of an endemic Formosan plant Litsea akoensis var. chitouchiaoensis. The structures of the new compounds were established by spectroscopic methods, including UV, IR, HR-ESI-MS, and extensive 1D- and 2D-NMR techniques. Of these isolates, 2, 8-methoxynaphthalen-1-ol (15), and 1,8-dimethoxynaphthalene (16) showed nitric oxide (NO) inhibitory activity with IC_(50) values of 11.8±0.9, 17.8±1.1, and 13.3±0.5 μm, respectively, stronger than the positive control quercetin (IC_(50) 36.8±1.3 μm). Compounds 2, 15, and 16 also showed interleukin-6 (IL-6) inhibitory activity with IC_(50) values of 9.2±1.7, 18.0±0.6, and 2.0±0.1 μm, stronger than the positive control quercetin (IC_(50) 31.3±1.6 μm). To the best of our knowledge, this is the first report on guaiane sesquiterpene metabolites, 3, 6, and 7, from the genus Hypoxylon.