Biotransformation of 18β-Glycyrrhetinic Acid by Human Intestinal Fungus Aspergillus niger RG13B1 and the Potential Anti-Inflammatory Mechanism of Its Metabolites,Journal of Agricultural and Food Chemistry

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Biotransformation of 18β-Glycyrrhetinic Acid by Human Intestinal Fungus Aspergillus niger RG13B1 and the Potential Anti-Inflammatory Mechanism of Its Metabolites
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-11-22 , DOI: 10.1021/acs.jafc.2c05455
Min Zhang ₁ , Juan Zhang _{1,

2} , Chao Wang ₁ , Jian-Kun Yan ₃ , Jing Yi _{1,

4} , Jing Ning ₁ , Xiao-Kui Huo ₁ , Zhen-Long Yu ₁ , Bao-Jing Zhang ₁ , Cheng-Peng Sun ₁ , Xiao-Chi Ma ₁

Affiliation

18β-Glycyrrhetinic acid (GA) is a triterpenoid possessing an anti-inflammatory activity in vivo, while the low bioavailability limits its application due to its intestinal accumulation. In order to investigate the metabolism of GA in intestinal microbes, it was incubated with human intestinal fungus Aspergillus niger RG13B1, finally leading to the isolation and identification of three new metabolites (1–3) and three known metabolites (4–6) based on 1D and 2D NMR and high-resolution electrospray ionization mass spectroscopy spectra. Metabolite 6 could target myeloid differentiation protein 2 (MD2) to suppress the activation of nuclear factor-kappa B (NF-κB) signaling pathway via inhibiting the nuclear translocation of p65 to downregulate its target proteins and genes in lipopolysaccharide (LPS)-mediated RAW264.7 cells. Molecular dynamics suggested that metabolite 6 interacted with MD2 through the hydrogen bond of amino acid residue Arg90. These findings demonstrated that metabolite 6 could serve as a potential candidate to develop the new inhibitors of MD2.

中文翻译：

人肠道真菌黑曲霉RG13B1对18β-甘草次酸的生物转化及其代谢物潜在的抗炎机制

18 β-甘草次酸 (GA) 是一种三萜类化合物，在体内具有抗炎活性，但由于其在肠道内蓄积，生物利用度低，限制了其应用。为了研究 GA 在肠道微生物中的代谢，将其与人肠道真菌Aspergillus niger RG13B1 一起孵育，最终分离和鉴定了三种新代谢物（1-3）和三种已知代谢物（4-6）基于一维和二维核磁共振和高分辨率电喷雾电离质谱。代谢物6可通过抑制 p65 的核转位下调脂多糖 (LPS) 介导的 RAW264.7 中的靶蛋白和基因，靶向髓样分化蛋白 2 (MD2) 以抑制核因子-κB (NF-κB) 信号通路的激活细胞。分子动力学表明代谢物6通过氨基酸残基 Arg90 的氢键与 MD2 相互作用。这些发现表明代谢物6可以作为开发新的 MD2 抑制剂的潜在候选物。

更新日期：2022-11-22

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