Departament de Farmacologia, Facultat de Farmàcia, Universitat de València. Av. Vicente Andrés Estellés, s/n, Burjassot, 46100 Valencia, Spain.
ProtoQSAR SL., CEEI (Centro Europeo de Empresas Innovadoras), Av. Benjamin Franklin 12, Parque Tecnológico de Valencia, Paterna, 46980 Valencia, Spain.
Molecules. 2021 Apr 16;26(8):2315. doi: 10.3390/molecules26082315.
The aryl hydrocarbon receptor (AhR) is a transcription factor deeply implicated in health and diseases. Historically identified as a sensor of xenobiotics and mainly toxic substances, AhR has recently become an emerging pharmacological target in cancer, immunology, inflammatory conditions, and aging. Multiple AhR ligands are recognized, with plant occurring flavonoids being the largest group of natural ligands of AhR in the human diet. The biological implications of the modulatory effects of flavonoids on AhR could be highlighted from a toxicological and environmental concern and for the possible pharmacological applicability. Overall, the possible AhR-mediated harmful and/or beneficial effects of flavonoids need to be further investigated, since in many cases they are contradictory. Similar to other AhR modulators, flavonoids commonly exhibit tissue, organ, and species-specific activities on AhR. Such cellular-context dependency could be probably beneficial in their pharmacotherapeutic use. Flavones, flavonols, flavanones, and isoflavones are the main subclasses of flavonoids reported as AhR modulators. Some of the structural features of these groups of flavonoids that could be influencing their AhR effects are herein summarized. However, limited generalizations, as well as few outright structure-activity relationships can be suggested on the AhR agonism and/or antagonism caused by flavonoids.
芳香烃受体 (AhR) 是一种转录因子，与健康和疾病密切相关。该受体最初被认为是一种对外源化学物质和主要有毒物质的传感器，最近已成为癌症、免疫学、炎症和衰老等领域新兴的药理学靶点。目前已经鉴定出多种 AhR 配体，植物中存在的类黄酮是人类饮食中 AhR 的最大天然配体组。类黄酮对 AhR 的调节作用的生物学意义可能源于对毒理学和环境的关注，以及对可能的药理学适用性的关注。总的来说，需要进一步研究类黄酮可能介导的 AhR 有害和/或有益影响，因为在许多情况下，这些影响是相互矛盾的。与其他 AhR 调节剂类似，类黄酮通常对 AhR 具有组织、器官和物种特异性的活性。这种细胞背景的依赖性可能对其治疗用途有益。黄酮类、黄酮醇类、黄烷酮类和异黄酮类是作为 AhR 调节剂的主要黄酮类亚类。本文总结了这些黄酮类化合物影响 AhR 作用的一些结构特征。然而，对于黄酮类化合物引起的 AhR 激动和/或拮抗作用，目前只能提出一些有限的概括和少数明确的结构-活性关系。
