Alizarin as a New Activator of the Aryl Hydrocarbon Receptor Signaling Pathway

• Published in: Natural product communications Vol. 17; no. 11; p. 1934578
• Main Authors: Lu, Yin-Che, Kuan, Yu-Hsiang, Lin, Chih-Yi, Chou, Yu-Ting, Chen, Shan-Chun, Gao, Guan-Lun, Hsu, Chiang Wei, Su, Jyan-Gwo Joseph
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.11.2022
• Subjects: AHRE transcriptional activity; CYP1A1; AhR; AhR nuclear localization; alizarin
• ISSN: 1934-578X; 1555-9475
• DOI: 10.1177/1934578X221136669

Alizarin (1,2-dihydroxyanthraquinone) is a natural red dye extracted from the roots of Rubia cordifolia L. (family Rubiaceae). Alizarin has been used as a biological red stain for calcium. The aryl hydrocarbon receptor (AhR) has critical roles in multiple physiological pathways. This study aimed to determine whether alizarin is an unreported ligand of AhR. In the present study, we investigated the effects on cytochrome P450 (CYP) 1A1 mRNA, protein expression, AhR nuclear translocation, aryl hydrocarbon response element (AHRE) reporter activity, and AhR-specific antagonist following alizarin treatment of cells of the human hepatoma cell line, HepG2, and murine hepatoma cell line, Hepa-1c1c7. Alizarin induced CYP1A1 mRNA and protein expression in HepG2 and Hep-1c1c7 cells. Such induction was not present in C4 (B13NBii1) cells, which are AhR signal deficient, C12 (B15ECiii2) cells, which reduce AhR protein levels. The alizarin-induced responses were blocked by CH-223191, which is an AhR antagonist. Alizarin, the same as with the AhR ligand, induced the nuclear localization of AhR, as well as stimulated the transcriptional activity of AHRE. The results of this study suggest that alizarin is an AhR agonist.