Effect of paeoniflorin, glycyrrhizin and glycyrrhetic acid on ovarian androgen production

We have shown that traditional herbal medicine, Shakuyaku-Kanzo-To consisted of Shakuyaku and Kanzo decreased serum testosterone levels in woman and rat. Therefore, paeoniflorin and glycyrrhizin, a main component of Shakuyaku and Kanzo, respectively, and glycyrrhetic acid, a metabolite of glycyrrhizin in vivo, were investigated for the steroid production in the rat ovary on the morning of proestrus. The homogenized tissues of one ovary were incubated in the Dulbecco's modified Eagle medium (pH 7.5) with 100 micrograms/ml of paeoniflorin, glycyrrhetic acid and glycyrrhizin and the medium only (the control) at 37 degrees C for 270 min. After the centrifugation, the concentrations of delta 4-androstenedione, testosterone and estradiol in the supernatants were determined by RIA. The production of the hormones expressed by [concentration x supernatant volume/weight of the ovary] was compared to the control. Paeoniflorin, glycyrrhetic acid and glycyrrhizin decreased significantly the testosterone production but did not change that of delta 4-androstenedione and estradiol. Testosterone/delta 4-androstenedione production ratio was lowered significantly by paeoniflorin, glycyrrhetic acid and glycyrrhizin. Estradiol/testosterone production ratio was increased significantly by glycyrrhetic acid and not changed by paeoniflorin and glycyrrhizin. These results suggest that paeoniflorin, glycyrrhetic acid and glycyrrhizin affect the conversion between delta 4-androstenedione and testosterone to inhibit testosterone synthesis and stimulate the aromatase activity to promote estradiol synthesis by the direct action on the rat proestrous ovary.