Zhang Min, Zhang Juan, Wang Chao, Yan Jian-Kun, Yi Jing, Ning Jing, Huo Xiao-Kui, Yu Zhen-Long, Zhang Bao-Jing, Sun Cheng-Peng, Ma Xiao-Chi
College of Pharmacy, Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China.
School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China.
J Agric Food Chem. 2022 Dec 7;70(48):15104-15115. doi: 10.1021/acs.jafc.2c05455. Epub 2022 Nov 22.
18-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 RG13B1, finally leading to the isolation and identification of three new metabolites () and three known metabolites () based on 1D and 2D NMR and high-resolution electrospray ionization mass spectroscopy spectra. Metabolite 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 interacted with MD2 through the hydrogen bond of amino acid residue Arg90. These findings demonstrated that metabolite could serve as a potential candidate to develop the new inhibitors of MD2.
18-β-甘草次酸（GA）是一种在体内具有抗炎活性的三萜类化合物，但其低生物利用度因在肠道蓄积而限制了其应用。为了研究GA在肠道微生物中的代谢情况，将其与人肠道真菌RG13B1一起孵育，最终基于一维和二维核磁共振以及高分辨率电喷雾电离质谱光谱分离并鉴定出三种新代谢产物（）和三种已知代谢产物（）。代谢产物可靶向髓样分化蛋白2（MD2），通过抑制p65的核转位，在脂多糖（LPS）介导的RAW264.7细胞中下调其靶蛋白和基因，从而抑制核因子-κB（NF-κB）信号通路的激活。分子动力学表明，代谢产物通过氨基酸残基Arg90的氢键与MD2相互作用。这些发现表明，代谢产物可作为开发新型MD2抑制剂的潜在候选物。
