Ha Sang Keun, Lee Jin-Ah, Cho Eun Jung, Choi Inwook
Research Group of Nutraceuticals for Metabolic Syndrome, Korea Food Research Inst., Gyeonggi, 463-746, Republic of Korea.
J Food Sci. 2017 Feb;82(2):545-552. doi: 10.1111/1750-3841.13620. Epub 2017 Jan 10.
Although luteolin is known to have potent anti-inflammatory activities, much less information has been provided on such activities of its hepatic metabolites. Luteolin was subjected to hepatic metabolism in HepG2 cells either without or with catechol O-methyl transferase (COMT) inhibitor. To identify hepatic metabolites of luteolin without (luteolin metabolites, LMs) or with COMT inhibitor (LMs+CI), metabolites were treated by β-glucuronidase and sulfatase, and found that they were composed of glucuronide and sulfate conjugates of diosmetin in LMs or these conjugates of luteolin in LMs+CI. LMs and LMs+CI were examined for their anti-inflammatory activities on LPS stimulated Raw 264.7 cells. Expression of iNOS and production of nitric oxide and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 were suppressed more effectively by the treatment with LMs+CI than LMs. Our data provide a new insight on possible improvement in functional properties of luteolin on target cells by modifying their metabolic pathway in hepatocytes.
尽管已知木犀草素具有强大的抗炎活性，但其肝脏代谢产物的此类活性所提供的信息却少得多。木犀草素在HepG2细胞中进行肝脏代谢，分为不加或加入儿茶酚O - 甲基转移酶（COMT）抑制剂的情况。为了鉴定木犀草素在不加（木犀草素代谢产物，LMs）或加入COMT抑制剂（LMs + CI）时的肝脏代谢产物，代谢产物用β - 葡萄糖醛酸酶和硫酸酯酶处理，发现LMs中它们由香叶木素的葡萄糖醛酸和硫酸酯缀合物组成，而LMs + CI中则由木犀草素的这些缀合物组成。检测了LMs和LMs + CI对脂多糖刺激的Raw 264.7细胞的抗炎活性。与LMs相比，用LMs + CI处理能更有效地抑制诱导型一氧化氮合酶（iNOS）的表达、一氧化氮以及促炎细胞因子如肿瘤坏死因子 - α（TNF - α）、白细胞介素 - 1β（IL - 1β）和白细胞介素 - 6（IL - 6）的产生。我们的数据为通过改变木犀草素在肝细胞中的代谢途径来改善其在靶细胞上的功能特性提供了新的见解。
