di Gesso Jessica L, Kerr Jason S, Zhang Qingzhi, Raheem Saki, Yalamanchili Sai Krishna, O'Hagan David, Kay Colin D, O'Connell Maria A
School of Pharmacy, University of East Anglia, Norwich, UK.
Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.
Mol Nutr Food Res. 2015 Jun;59(6):1143-54. doi: 10.1002/mnfr.201400799. Epub 2015 May 3.
Flavonoids are generally studied in vitro, in isolation, and as unmetabolized precursor structures. However, in the habitual diet, multiple flavonoids are consumed together and found present in the circulation as complex mixtures of metabolites. Using a unique study design, we investigated the potential for singular or additive anti-inflammatory effects of flavonoid metabolites relative to their precursor structures.
Six flavonoids, 14 flavonoid metabolites, and 29 combinations of flavonoids and their metabolites (0.1-10 μM) were screened for their ability to reduce LPS-induced tumor necrosis factor-α (TNF-α) secretion in THP-1 monocytes. One micromolar peonidin-3-glucoside, cyanidin-3-glucoside, and the metabolites isovanillic acid (IVA), IVA-glucuronide, vanillic acid-glucuronide, protocatechuic acid-3-sulfate, and benzoic acid-sulfate significantly reduced TNF-α secretion when in isolation, while there was no effect on TNF-α mRNA expression. Four combinations of metabolites that included 4-hydroxybenzoic acid (4HBA) and/or protocatechuic acid also significantly reduced TNF-α secretion to a greater extent than the precursors or metabolites alone. The effects on LPS-induced IL-1β and IL-10 secretion and mRNA expression were also examined. 4HBA significantly reduced IL-1β secretion but none of the flavonoids or metabolites significantly modified IL-10 secretion.
This study provides novel evidence suggesting flavonoid bioactivity results from cumulative or additive effects of circulating metabolites.
黄酮类化合物通常在体外进行研究，是单独研究且作为未代谢的前体结构。然而，在日常饮食中，多种黄酮类化合物会一起被摄入，并以代谢物的复杂混合物形式存在于循环中。我们采用独特的研究设计，研究了黄酮类代谢物相对于其前体结构的单一或相加抗炎作用的潜力。
筛选了六种黄酮类化合物、十四种黄酮类代谢物以及二十九个黄酮类化合物与其代谢物的组合（0.1 - 10 μM），考察它们在THP - 1单核细胞中降低脂多糖诱导的肿瘤坏死因子-α（TNF-α）分泌的能力。1 μM的芍药色素-3-葡萄糖苷、花青素-3-葡萄糖苷以及代谢物异香草酸（IVA）、IVA - 葡萄糖醛酸、香草酸-葡萄糖醛酸、原儿茶酸-3-硫酸盐和苯甲酸-硫酸盐单独存在时能显著降低TNF-α分泌，但对TNF-α mRNA表达无影响。四种包含4-羟基苯甲酸（4HBA）和/或原儿茶酸的代谢物组合也比单独的前体或代谢物更显著地降低了TNF-α分泌。还研究了对脂多糖诱导的白细胞介素-1β（IL-1β）和白细胞介素-10（IL-10）分泌及mRNA表达的影响。4HBA显著降低了IL-1β分泌，但没有一种黄酮类化合物或代谢物能显著改变IL-10分泌。
本研究提供了新的证据，表明黄酮类生物活性源于循环代谢物的累积或相加作用。
