Effect of Shakuyaku-Kanzo-To, Shakuyaku, Kanzo, Paeoniflorin, Glycyrrhetinic Acid and Glycyrrhizin on Ovarian Function in Rats

Abstract

It is known that amenorrhea, oligomenorrhea, irregular menstrual cycles, luteal insufficiency and infertility are frequently associated with hyperandrogenism. It has been reported in previous studies that the traditional herbal medicine, Shakuyaku-Kanzo-To(SKT) can lower high serum testosterone levels in oligomenorrheic or amenorrheic women, and that some of these sterile women conceive. SKT contains Shakuyaku (S) and Kanzo (K) in equal amounts. The main component of S and K is paeoniflorin and glycyrrhizin, respectively. This study was designed to investigate the mechanism in lowering serum testosterone (T) levels by SKT. Experiment I: Female Wistar rats were injected subcutaneously with 500 micrograms of testosterone propionate at the age of 2 days, becoming androgen-sterilized rats (ASR). Fifty-six-day-old ASR were given orally SKT (22.5, 45, 90 and 180 mg/kg body weight), S or K (11.25, 22.5, 45 and 90 mg/kg b.w.) in water through a tube every day for 2 weeks. Control ASR were given only water. Each group consisted of 10 rats. Serum total and free T levels in SKT and S groups were significantly lower than those in the controls, and these decreases were dose-dependent. Experiment II: Female Wistar rats were oophorectomized at the age of 60 days. From one week later they were given orally SKT (90 and 180 mg/kg b.w.), S or K (45 and 90 mg/kg b.w.) every day for 2 weeks. Control rats were given only water. Each group consisted of 11 rats. There was no change in serum T, LH and FSH levels in either groups. The results from experiment I and II suggest that SKT influences the T production by ovaries but not by adrenal glands. Experiment III: The minced tissues of one ovary obtained from proestrous Wistar rats were incubated with media containing Paeoniflorin(P), Glycyrrhetinic acid(GA) or Glycyrrhizin(GL) (GL) (1, 50 and 100 micrograms/ml, respectively, n = 5 in each group) for 270 minutes at 37 degrees C under an atmosphere of 95%O2 and 5%CO2. The T production by ovaries was significantly decreased in each treated group in comparison with the control, and this decrease was dose-dependent. However, the delta 4-androstenedione (delta 4-A) production by ovaries was increased in each treated group. The ratio of T to delta 4-A was significantly lower in each treated group than in the control. The estradiol(E2) production by ovaries in each treated group was not changed in comparison with the control.(ABSTRACT TRUNCATED AT 400 WORDS)

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].…”

“…In Oriental herbal medicine, licorice-containing Kanzo and Kampo preparations have been used to induce [3,6,18,30,37,44]. This testosterone-lowering effect was also experimentally confirmed in ovarian culture of licorice-treated female rats [37,38].…”

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

“…[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.…”

Comparative pharmacokinetics and metabolites study of seven major bioactive components of Shaoyao‐Gancao decoction in normal and polycystic ovary syndrome rats by ultra high pressure liquid chromatography with tandem mass spectrometry

“…It has been in the widespread treatment of gynecological disorders such as dysmenorrheal , PCOS , endometriosis, and adenomyosis for thousands of years in Asia. Since 1980s, Japanese researchers have conducted the experimental studies on the therapeutic effects of SGD on PCOS and shown that the formula was effective for achieving pregnancy in patients with PCOS and improving their hyperandrogenism symptoms . Modern studies have showed that the main bioactive compounds of SGD including monoterpene glucosides, flavonoids, and triterpenoid saponins contribute a lot to the pharmacodynamic material basis in therapy of PCOS .…”