Induction of Nrf2-EpRE-mediated gene expression by hydroxyanthraquinones present in extracts from traditional Chinese medicine and herbs.

Hydroxyanthraquinones that can be present in traditional Chinese medicine (TCM) and herbal extracts have claimed beneficial intestinal effects. We examined the ability of a panel hydroxyanthraquinones, and methanolic extracts from selected TCM and herbal granules to activate Nrf2-EpRE mediated gene expression using a reporter-gene assay. The results indicate that purpurin, aloe-emodin, 2-hydroxy-3-methylanthraquinone and rhein induced Nrf2 mediated gene expressions with a high induction factor (IFs>10), with BMCL10 values (the lower confidence limit of the concentration giving 10% added response above background) of 16 µM, 1.1 µM, 23 µM and 2.3 µM, respectively, while aurantio-obtusin, obtusifolin, rubiadin 1-methyl ether and emodin were less potent (IFs<5), with BMCL10 values for added response above background level of 4.6 µM, 15 µM, 9.8 µM and 3.8 µM, respectively. All TCM extracts and the herbal extracts of Aloe Vera, Polygonum multiflorum, Rubia (cordifolia) and Rheum officinale activated the Nrf2-EpRE pathway. Of the TCM extracts, Chuan-Xin-Lian-Kang-Yan-Pian was the most potent Nrf2-inducer. LC-MS/MS analysis indicated the presence of selected hydroxyanthraquinones in the extracts and herbs, in part explaining their Nrf2-EpRE mediated activity. In conclusion, different hydroxyanthraquinones have different potencies of Nrf2 activation. The Nrf2 activation by extracts from TCM and herbs can be partially explained by the presence of selected hydroxyanthraquinones.