A kaempferol-3-O-β-d-glucoside, intervention effect of astragalin on estradiol metabolism.

Kaempherol-3-O-β-d-glucoside, known as astragalin, is one of flavonoids found in a variety of plants including Cuscuta australis R.Br. In recent studies, astragalin possess many biological functions. Although astragalin is formed by linking glucose to kaempherol, its biological activity is not the same as kaempferol. In vivo, 17 β-estradiol (E2) is hydroxylated by cytochrome P450 (CYP) 1B1 to form 4-hydroxy-E2 (4-OH-E2). This metabolite 4-OH-E2 is highly expressed in tumor tissues and has a strong tumorigenic effect. In this paper, the inhibition of astragalin and kaempferol on the activity of cytochrome 1B1 catalyzing estradiol to form 4-hydroxy-estradiol was studied, and the structure-activity relationship between astragalin and kaempferol due to their structural differences was discussed. This study showed that astragalin could inhibit the activity of CYP1B1. The inhibitory effect of astragalin (IC50 5.36 ± 1.13 μM) was weaker than kaempferol (IC50 0.45 ± 0.11 μM). For astragalin, Ki and Vmax values were 4.061 ± 0.737 μM and 1.457 pmol/μg protein/min, while for kaempferol, Ki and Vmax values were 2.631 ± 0.381 μM protein/min and 1.023 ± 0.231 pmol/μg. By kinetic analysis, astragalin and kaempferol were all mixed inhibition, indicating that although astragalin is formed by linking glucose to kaempherol, its inhibitory mechanism on CYP1B1 remained unchanged, and still belonged to a mixed inhibition. The data indicated that astragalin has been able to inhibit the metabolism of estradiol into the carcinogenic metabolite 4-hydroxyl-estradiol in vivo and illustrated an anti-tumor mechanism of astragalin. This study helps to reveal the structure-activity relationship between CYP1B1 activity and its inhibitors.