Wide-range screening of anti-inflammatory compounds in tomato using LC-MS and elucidating the mechanism of their functions

Obesity-induced chronic inflammation is a key factor in type 2 diabetes. A vicious cycle involving pro-inflammatory mediators between adipocytes and macrophages is a common cause of chronic inflammation in the adipose tissue. Tomato is one of the most popular vegetables and is associated with a reduced risk of diabetes. However, the molecular mechanism underlying the effect of tomato on diabetes is unclear. In this study, we focused on anti-inflammatory compounds in tomato. We found that the extract of tomato reduced plasma glucose and inflammatory markers in mice. We screened anti-inflammatory fractions in tomato using lipopolysaccharide-stimulated RAW264.7 macrophages, and active compounds were estimated by liquid chromatography-mass spectrometry over a wide range. Surprisingly, a large number of compounds including oxylipin and coumarin derivatives were estimated as anti-inflammatory compounds. Especially, 9-oxo-octadecadienoic acid and daphnetin suppressed pro-inflammatory cytokines in RAW264.7 macrophages inhibiting mitogen-activated protein kinase phosphorylation and inhibitor of kappa B α protein degradation. These findings suggest that tomato containing diverse anti-inflammatory compounds ameliorates chronic inflammation in obese adipose tissue.

肥胖诱导的慢性炎症是2型糖尿病的关键致病因素。脂肪细胞与巨噬细胞间由促炎介质介导的恶性循环，是脂肪组织慢性炎症的常见诱因。番茄是最受大众喜爱的蔬菜之一，且与糖尿病患病风险降低存在关联。然而，番茄发挥抗糖尿病作用的分子机制目前仍不明确。本研究聚焦于番茄中的抗炎活性化合物，研究发现番茄提取物可降低小鼠的血糖水平与炎症标志物水平。本研究采用脂多糖（lipopolysaccharide）诱导的RAW264.7巨噬细胞模型，筛选番茄中的抗炎活性组分，并通过液相色谱-质谱联用法（liquid chromatography-mass spectrometry）对广谱活性成分进行鉴定。令人意外的是，经鉴定得到的抗炎活性化合物涵盖多个类别，包括氧化脂类（oxylipin）与香豆素（coumarin）衍生物。其中，9-氧代十八碳二烯酸（9-oxo-octadecadienoic acid）与瑞香素（daphnetin）可通过抑制RAW264.7巨噬细胞中的丝裂原活化蛋白激酶（mitogen-activated protein kinase）磷酸化以及核因子κB抑制蛋白α（inhibitor of kappa B α）的降解，下调促炎细胞因子的表达。上述研究结果表明，富含多种抗炎活性成分的番茄，可改善肥胖状态下的脂肪组织慢性炎症。