Effects of synthetic organic compounds and zerumbone on in vitro anti-inflammatory actions and their molecular mechanisms

• Main Authors: Hui-Jung Lin, 林慧蓉
• Other Authors: Chin-Lin Hsu
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/vt2w8d

碩士 === 中山醫學大學 === 營養學研究所 === 104 === The inflammatory response provides the first line of host defense against a variety of exogenous and endogenous stimuli. The progression of chronic inflammation to diseases (such as cancer, cardiovascular diseases, and metabolic diseases) is a complex process involving multiple biological factors. Obesity-associated chronic inflammation is characterized by macrophage infiltration while occurs mainly in adipose tissues, and leads to an increased release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and macrophage chemo-attractant protein-1 (MCP-1). The overproduction of pro-inflammatory cytokines seem to be important causes of morbidity and some relative diseases, such as type 2 diabetes and atherosclerosis. Synthetic organic compounds and zerumbone have been reported to possess multiple biological functions, including anti-cancer, anti-oxidant, and anti-inflammatory activities. However, the anti-inflammatory effects of synthetic organic compounds and zerumbone in cell culture model remain unclear. Therefore, there are two topics included in this study, (1) Effects of synthetic organic compounds on LPS-induced inflammatory response in RAW 264.7 macrophages, and TNF-α-induced inflammatory response in 3T3-L1 adipocytes and their molecular mechanisms. (2) Effect of zerumbone on LPS-induced inflammatory response in RAW 264.7 macrophages, and TNF-α-induced inflammatory response in 3T3-L1 adipocytes and their molecular mechanisms. (1) The result showed that BZT-21 and BZT-26 had the highest inhibition on LPS-induced nitric oxide (NO) in RAW 264.7 macrophages among 24 synthetic organic compounds tested. Moreover, BZT-21 and BZT-26 inhibited LPS-induced inflammatory cytokines (IL-6, IL-1β, PGE2, and MCP-1) and inflammatory-related gene expressions (TLR-4, p65, JAK-2, STAT-3, IL-6, IL-1β, MCP-1, COX-2, and iNOS) in RAW 264.7 macrophages among the compounds tested. BZT-21 and BZT-26 also inhibited TNF-α-induced inflammatory cytokines (IL-6 and MCP-1), and inflammatory-related gene expressions (IL-6, MCP-1, CRP, and NF-κB), as well as increased the gene expressions of SIRT-1, AMPK, and Adiponectin in 3T3-L1 adipocytes. (2) The result showed that zerumbone inhibits LPS-induced inflammatory cytokines (NO, IL-6, IL-1β, PGE2, TNF-α, and MCP-1) and inflammatory-related gene expressions (TLR-4, p65, JAK-2, STAT-3, IL-6, IL-1β, MCP-1, TNF-α, COX-2, and iNOS) in RAW 264.7 macrophages. Moreover, zerumbone inhibited TNF-α-induced inflammatory cytokines (IL-6 and MCP-1), and inflammatory-related gene expressions (IL-6, MCP-1, CRP, and NF-κB), as well as increased the gene expressions of SIRT-1, AMPK, and Adiponectin in 3T3-L1 adipocytes. These results indicated that BZT-21, BZT-26, and zerumbone are suppressed LPS-induced inflammatory response in RAW 264.7 macrophages, and TNF-α-induced inflammatory response in 3T3-L1 adipocytes. Therefore, BZT-21, BZT-26, and zerumbone have great anti-inflammatory actions and improvement of obesity-related inflammatory response.