The Mechanism of anti-inflammatory effect of water-soluble components of tea tree oil in LPS-induced murine macrophage

• Main Authors: Po-Yu Chen, 陳柏諭
• Other Authors: Tsu-Chung Chang
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/06173804302631978471

碩士 === 國防醫學院 === 生物化學研究所 === 97 === Tea tree oil (MAC) is the essential oil from the Australian native plant, Melaleuca alternifolia. Previous studies indicated that MAC and its’ main water-soluble component, terpinen-4-ol, suppressed the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF-) in human monocytes stimulated with lipopolysaccharide (LPS). Heme oxygenase-1 (HO-1), an inducible rate-limiting enzyme, catalyzes heme into carbon monoxide (CO), free iron, and biliverdin. This enzyme has been suggested to play a regulatory role in the resolution phase of inflammation and is considered as a potential therapeutic target for treating inflammatory diseases. Moreover, it is known that HO-1 and CO can inhibit inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in activated macrophages via inactivation of nuclear factor-kappa B (NF-κB). This study aims to delineate the mechanism of anti-inflammatory activity of MAC and terpinen-4-ol in LPS-treated Raw264.7 cells, a model system of macrophages. Our results showed that MAC increased HO-1 expression in Raw264.7 cells in a concentration- and time-dependent manner. Western blot analysis showed that HO-1 was induced via p38 and JNK activation, evident at 3h, and reached maximal after 12 h. In addition to, we showed that MAC increased activation and nuclear translocation of important transcription facot Nrf2 of HO-1 induction via MAPK and PI-3K signal transduction pathway. Addition of MAC for 12h prior to LPS treatment of marcophages significantly decreased iNOS expression, NO production, and NF-κB activation. Use of Tin protoporphyrin IX (SnPPIX), an HO-1 inhibitor, abolished the inhibitory effects of MAC on iNOS expression, NO production and NF-κB activation. Collectively, our results suggest that MAC inhibit iNOS expression, NO production, and NF-κB activation in LPS-stimulated macrophages through a mechanism that involves the action of HO-1.