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

• Published in: Chemistry & biodiversity Vol. 11; no. 6; pp. 949 - 961
• Main Authors: Chang, Chun-Wei, Chang, Hsun-Shuo, Cheng, Ming-Jen, Liu, Ta-Wei, Hsieh, Sung-Yuan, Yuan, Gwo-Fang, Chen, Ih-Sheng
• Format: Journal Article
• Language: English
• Published: Zürich WILEY-VCH Verlag 01-06-2014; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Animals; Dose-Response Relationship, Drug; Endophytes - chemistry; Hypoxylon investiens; Interleukin-6 - biosynthesis; Interleukin-6 inhibitory activity; Litsea; Litsea - microbiology; Macrophages - drug effects; Macrophages - metabolism; Metabolites; Mice; Molecular Structure; Nitric Oxide - biosynthesis; Nitric oxide inhibitory activity; Plant Stems - microbiology; Sesquiterpenes, Guaiane - chemistry; Sesquiterpenes, Guaiane - isolation & purification; Sesquiterpenes, Guaiane - pharmacology; Structure-Activity Relationship; Xylariales - chemistry; Interleukin-6 inhibitory activity; Nitric oxide inhibitory activity; Metabolites; Hypoxylon investiens
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.201300364

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‐O‐methylmellein (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 IC50 values of 11.8±0.9, 17.8±1.1, and 13.3±0.5 μM, respectively, stronger than the positive control quercetin (IC50 36.8±1.3 μM). Compounds 2, 15, and 16 also showed interleukin‐6 (IL‐6) inhibitory activity with IC50 values of 9.2±1.7, 18.0±0.6, and 2.0±0.1 μM, stronger than the positive control quercetin (IC50 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.