Coffee ingredients, hydroquinone, pyrocatechol, and 4-ethylcatechol exhibit anti-inflammatory activity through inhibiting NF-κB and activating Nrf2
Coffee ingredients, hydroquinone, pyrocatechol, and 4-ethylcatechol exhibit anti-inflammatory activity through inhibiting NF-κB and activating Nrf2
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DOI：
10.1016/j.jff.2022.104980
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发表时间：
2022-02-01
影响因子：
5.6
通讯作者：
Tamura, Hiroomi
中科院分区：
文献类型：
--
作者：
Funakoshi-Tago, Megumi;Matsutaka, Mari;Tamura, Hiroomi
邻苯二酚是一种具有抗炎活性的咖啡成分。我们在此发现对苯二酚和4-乙基儿茶酚是抑制lps诱导的炎症反应的新型咖啡成分。与邻苯二酚类似，对苯二酚和4-乙基儿茶酚通过抑制小鼠巨噬细胞样RAW264.7细胞iNOS和CCL2 mRNA的表达，显著抑制lps诱导的一氧化氮（NO）的产生和CCL2的分泌。这些成分还通过阻止NF-kappa B的核定位，抑制lps诱导的炎症关键转录因子NF-kappa B的活化，并诱导Nrf2的表达，Nrf2是lps诱导炎症的负向调节转录因子。利用替换了主要半胱氨酸残基的Keap1突变体重组的Keap1(-/-) mef，我们发现Keap1中的Cys151是邻苯二酚、对苯二酚和4-乙基儿茶酚诱导Nrf2表达的关键传感器。然而，咖啡煎液中对苯二酚和4-乙基儿茶酚的含量明显低于邻苯二酚，这表明邻苯二酚是咖啡中具有抗炎活性的主要成分。
Pyrocatechol is a coffee ingredient that exhibits anti-inflammatory activity. We herein identified hydroquinone and 4-ethylcatechol as novel coffee ingredients inhibiting LPS-induced inflammatory responses. Similar to pyrocatechol, hydroquinone and 4-ethylcatechol significantly inhibited LPS-induced nitric oxide (NO) production and CCL2 secretion by suppressing the mRNA expression of iNOS and CCL2 in murine macrophage-like RAW264.7 cells. These ingredients also inhibited the LPS-induced activation of NF-kappa B, a pivotal transcription factor in inflammation, by preventing its nuclear localization, and induced the expression of Nrf2, a transcription factor negatively regulating LPS-induced inflammation. By utilizing Keap1(-/-)MEFs reconstituted with Keap1 mutants in which major cysteine residues were substituted, we found that Cys151 in Keap1 was a critical sensor for pyrocatechol, hydroquinone, and 4-ethylcatechol to induce Nrf2 expression. However, the amounts of hydroquinone and 4-ethylcatechol in the coffee decoction were markedly lower than that of pyrocatechol, suggesting that pyrocatechol is the main coffee ingredient exhibiting anti-inflammatory activity.