Effect of Paeoniflorin, Glycyrrhizin and Glycyrrhetic acid on Ovarian Androgen Production

Abstract

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.

A Randomized, Crossover Comparison of Herbal Medicine and Bromocriptine Against Risperidone-Induced Hyperprolactinemia in Patients With Schizophrenia

“…First, both in vivo and in vitro studies in experimental animals have found that paeoniflorin, glycyrrhetinic acid, and glycyrrhizin directly reduce PRL and testosterone production by inhibiting their conversion processes and relevant enzymes, but enhance estradiol synthesis. [21][22][23] Similar effects were also observed in clinical studies, showing that glycyrrhetic acid and glycyrrhizin treatments reduce serum testosterone concentrations in healthy women 38 and in male patients with type 2 diabetes. 39 Second, it has been reported that paeoniflorin can alleviate dopaminergic neurodegeneration and Parkinson disease-like behavior, 40,41 indicating dopamine-enhancing effects of this compound.…”

“…[8][9][10][11] Animal studies further demonstrated that PGD and its major constituents possess a capacity of modulating synthesis and release of several sexual and reproductive hormones, including PRL. [21][22][23][24][25] The observations have led to a hypothesis that PGD may possess comparable efficacy and a safer profile compared with conventional dopamine agonists in the treatment of hyperprolactinemia associated with antipsychotic therapy. To test this hypothesis, we conducted a comparative study of PGD versus BMT as additional therapy in schizophrenic females with risperidone-induced hyperprolactinemia using a randomized crossover design.…”

Licorice Extract Does Not Impair the Male Reproductive Function of Rats

“…This testosterone-lowering effect was also experimentally confirmed in ovarian culture of licorice-treated female rats [37,38]. Therefore, it was proposed that licorice could cause the deficiency of serum testosterone, leading to sexual dysfunction or decline of libido in men [1,2].…”

“…Interestingly, however, Sakamoto & Wakabayashi [30] showed that oral administration of a Kanzo preparation, glycyrrhizin or glycyrrhetinic acid decreased in vitro testosterone production in Leydig cells of rats stimulated by luteinizing hormone. The testosterone-reducing effect of glycyrrhizin and glycyrrhetinic acid was observed in female rats [37,38], but not in males [the present study], and there is controversy over the influence of licorice in men [1,2,16,25]. It is hypothesized that, in spite of partial suppression of the basal production of testosterone following the inhibition of steroid-metabolizing enzymes by licorice, production of testosterone stimulated by luteinizing hormone is significantly blocked in the testes, or in the ovaries in the proestrous cycle [3,6,18,30,37,38,44].…”

Effects of Bushen Tianjing Recipe in a rat model of tripterygium glycoside-induced premature ovarian failure

“…In vitro and in vivo studies have revealed that the major bioactive compounds isolated from these components have ovarian failure-resistant effects or pharmacological activities against gynaecological disorders [21, 22]. More importantly, pro-angiogenic and anti-apoptotic signaling cascades have been implicated in the bioactivities of these compounds [23–26].…”