Chen Xiaoling, Patterson Andrew D, Perdew Gary H, Murray Iain A, Kellogg Joshua J
Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United States.
J Funct Foods. 2023 Jul;106. doi: 10.1016/j.jff.2023.105602. Epub 2023 Jun 7.
Diet-derived aryl hydrocarbon receptor (AHR) ligands have potential to maintain gut health. However, among the myriad bioactive compounds from foods, identifying novel functional ligands which would significantly impact gastrointestinal health is a challenge. In this study, a novel AHR modulator is predicted, identified, and characterized in the white button mushroom (). Using a molecular networking approach, a methylated analog to benzothiazole was indicated in white button mushrooms, which was subsequently isolated and identified as 2-amino-4-methyl-benzothiazole(2A4). Cell-based AHR transcriptional assays revealed that 2-amino-4-methyl-benzothiazole possesses agonistic activity and upregulated CYP1A1 expression. This contrasts with previous findings that whole white button mushroom extract has overall antagonistic activity , underscoring the importance of studying the roles each chemical component plays in a whole food. The findings suggest that 2-amino-4-methyl-benzothiazole is a previously unidentified AHR modulator from white button mushroom and demonstrate that molecular networking has potential to identify novel receptor modulators from natural products.
饮食来源的芳烃受体（AHR）配体具有维持肠道健康的潜力。然而，在众多来自食物的生物活性化合物中，识别出能对胃肠道健康产生显著影响的新型功能性配体是一项挑战。在本研究中，一种新型AHR调节剂在双孢蘑菇中得到预测、鉴定和表征。使用分子网络方法，在双孢蘑菇中发现了一种苯并噻唑的甲基化类似物，随后将其分离并鉴定为2-氨基-4-甲基苯并噻唑（2A4）。基于细胞的AHR转录分析表明，2-氨基-4-甲基苯并噻唑具有激动活性并上调CYP1A1表达。这与之前关于双孢蘑菇全提取物具有总体拮抗活性的研究结果形成对比，凸显了研究每种化学成分在完整食物中所起作用的重要性。这些发现表明，2-氨基-4-甲基苯并噻唑是一种先前未被识别的来自双孢蘑菇的AHR调节剂，并证明分子网络有潜力从天然产物中识别新型受体调节剂。
