Sesamin Catechol Glucuronides Exert Anti-inflammatory Effects by Suppressing Interferon β and Inducible Nitric Oxide Synthase Expression through Deconjugation in Macrophage-like J774.1 Cells
Sesamin Catechol Glucuronides Exert Anti-inflammatory Effects by Suppressing Interferon β and Inducible Nitric Oxide Synthase Expression through Deconjugation in Macrophage-like J774.1 Cells
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DOI：
10.1021/acs.jafc.8b07227
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发表时间：
2019-07-10
影响因子：
6.1
通讯作者：
Kawai, Yoshichika
中科院分区：
文献类型：
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作者：
Abe-Kanoh, Naomi;Kunimoto, Yumi;Kawai, Yoshichika
芝麻素是芝麻木脂素的代表，具有促进健康的作用。芝麻素在体内可转化为儿茶酚衍生物，并进一步转化为其葡萄糖醛酸盐或硫酸盐，而芝麻素代谢产物的生物活性尚不清楚。我们检测了芝麻素代谢物对脂多糖（LPS）诱导的小鼠巨噬细胞J774.1细胞一氧化氮（NO）产生的抑制作用，发现单儿酚衍生物SC1 (7 α,7' α,8 α,8' α)-3,4-二羟基-3',4'-亚甲基二氧基-7,9':7'，9-二氧基木聚糖)的活性远高于芝麻素和其他代谢物。SC1葡萄糖醛酸酯的抑制作用是时间依赖性的，与SC1的细胞内积累和甲基化形式有关。SC1葡糖苷和SC1可减弱lps刺激的巨噬细胞中诱导型NO合成酶（iNOS）和上游干扰素- β (ifn - β)的表达。SC1葡糖苷类化合物对NO生成的抑制作用被β -葡糖苷酶抑制剂抵消，而被儿茶酚- o -甲基转移酶抑制剂增强。我们的研究结果表明，SC1葡糖苷通过巨噬细胞介导的解结作用抑制ifn - β /iNOS信号通路，从而发挥抗炎作用。
Sesamin, a representative sesame lignan, has health-promoting activities. Sesamin is converted into catechol derivatives and further into their glucuronides or sulfates in vivo, whereas the biological activities of sesamin metabolites remain unclear. We examined the inhibitory effects of sesamin metabolites on the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse macrophage-like J774.1 cells and found that a monocatechol derivative SC1, (7 alpha,7'alpha,8 alpha,8'alpha)-3,4-dihydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane, has a much higher activity than sesamin and other metabolites. The inhibitory effects of SC1 glucuronides were time-dependently enhanced, associated with the intracellular accumulation of SC1 and the methylated form. SC1 glucuronides and SC1 attenuated the expression of inducible NO synthase (iNOS) and upstream interferon-beta (IFN-beta) in the LPS-stimulated macrophages. The inhibitory effects of SC1 glucuronides against NO production were canceled by the beta-glucuronidase inhibitor and enhanced by the catechol-O-methyltransferase inhibitor. Our results suggest that SC1 glucuronides exert the anti-inflammatory effects by inhibiting the IFN-beta/iNOS signaling through macrophage-mediated deconjugation.