Fei Wang

Key Laboratory of Natural Medicine and Clinical Translation, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China

Estrogens play crucial roles in the normal physiology of a variety of tissues. The actions of estrogens are mediated by the estrogen receptors (ER α/β), which function as ligand-regulated transcriptional factors. The biosynthesis of estrogen in humans is controlled by aromatase (encoded by CYP19A1), which is the only enzyme that catalyzes the formation of estrogens by using androgens, such as testosterone and androstenedione as substrates. Overexposure to estrogen can lead to the occurrence of breast or ovarian cancer, but estrogen deficiency is also associated with a variety of diseases, including osteoporosis, atherosclerosis and Alzheimer’s disease. Some of natural products, such as flavonoids, have been considered as potent inhibitors of aromatase activity, but new natural products that can modulate the expression of aromatase in transcriptional and post-transcriptional level are needed, which are important for the understanding of still unresolved tissue-specificity of aromatase expression. By establishing a human granulosa-like KGN cell-based screening platform, we identified several natural products which modulate the estrogen biosynthesis through distinct mechanisms, including luteolin (1) which inhibits the aromatase expression and promotes the aromatase protein degradation without the effect on its catalytic activity [1], egonol gentiotrioside (2) from Styrax perkinsiae which allosterically promote aromatase activity without the effect on its expression [2], icariin (3) from Epimedium brevicornum Maxim which only promotes aromatase expression possibly through phosphodiesterase 5 [3], phytol (4) and (22E)-ergosta-6,9,22-triene-3β,5α,8α-trio (5) from Sinocalamus affinis which inhibit promoter II-driven aromatase transcription by p38 MAPK [4].

References

[1] Lu DF., Yang LJ., Wang F.,* Zhang GL.* J. Agric. Food Chem. 2012, 60, 8411-8418.

[2] Lu DF., Yang LJ., Li QL., Gao XP., Wang F.,* Zhang GL.* Eur. J. Pharmacol. 2012, 691, 275-282.

[3] Yang LJ., Lu DF., Guo JJ., Meng XL., Zhang GL.,* Wang F.* J Ethnopharmacol 2013, 145, 715-721.

[4] Guo JJ., Yuan Y., Lu DF., Du BW., Xiong L., Shi JG., Yang LJ., Liu WL., Yuan XH., Zhang GL*., Wang F*. Toxicol App Pharmacol. 2014, 279, 23-32.