Traditional Medicine (Mahuang-Tang) Improves Ovarian Dysfunction and the Regulation of Steroidogenic Genes in Letrozole-Induced PCOS Rats.

Mahuang-Tang (MHT) has traditionally been used in Asia to treat a variety of diseases, such as fever without sweating, joint pain, lower back pain, asthma, and gynecological conditions. Polycystic ovary syndrome (PCOS) is a kind of gynecological disease that causes amenorrhea, infertility, and menopausal and urogenital disorders that could benefit from MHT treatment. In this study, we examined the effects of MHT on ovarian hormones and steroidogenic enzymes in female PCOS rats. The PCOS rat model was induced by Letrozole, and an in vivo evaluation of whether the dietary consumption of MHT improved the PCOS-like symptoms was conducted. The luteinizing hormone (LH) level and luteinizing hormone/follicular-stimulating hormone (LH/FSH) ratio increased in PCOS rats but decreased following MHT treatment. In the PCOS rats, the reduced estrogen level was restored to that of normal controls with MHT treatment in serum. The transcription level(s) of gonadotropin receptors (Fshr and Lhr), steroid receptors (Pgr, and Esr1) and steroidogenic enzymes (Cyp19a1, Hsd3b1, Hsd17a1, and Cyp11a1) changed under the PCOS condition, and were regulated by MHT treatment in the ovaries of PCOS rats. The reproductive tissues of Letrozole-induced PCOS rats were restored into estrogenic condition from androgen environments. These results suggest that MHT ameliorates the symptoms of PCOS by improving the dysregulation of ovarian steroids and steroidogenic enzymes in PCOS rats.

Yang H ，Lee YH ，Lee SR ，Kaya P ，Hong EJ ，Lee HW ... -  《-》

Crocus sativus (saffron) petals extract and its active ingredient, anthocyanin improves ovarian dysfunction, regulation of inflammatory genes and antioxidant factors in testosterone-induced PCOS mice.

Saffron petal has traditionally been used to treat a variety of diseases, such as gynecological disease such as primary dysmenorrhea and premenstrual tension. Polycystic Ovary Syndrome (PCOS) is a form of gynecological disease that causes amenorrhea, infertility, menopausal and urogenital disorders. This disease may be treated with saffron petals. In this study, the effects of saffron petal extract (SPE) and saffron petal anthocyanins (SPA) on ovarian hormones, steroidogenic enzymes, ovarian dysfunction, regulation of anti-inflammatory genes, and antioxidant factors in female PCOS mice were studied. The PCOS mouse model was induced by testosterone enanthate (TE), and an in vivo evaluation of whether the dietary consumption of SPE and SPA improved the PCOS-like symptoms was conducted. The luteinizing hormone (LH), testosterone, and estrogen levels increased in PCOS mice, but decreased following SPE and SPA treatment. In the PCOS mice, the reduced follicular-stimulating hormone (FSH) progesterone levels were restored to that of normal controls with SPE and SPA treatment in serum. The transcription level(s) of gonadotropin receptors (Fshr and Lhr), steroid receptors (Pgr, and Esr1), inflammatory markers (TNFα, IL1ß, IL6 and IL18), inflammatory-related factors (NF-κB, NF-κB p65, IκB) and antioxidant enzymes (GPx, SOD, CAT, GST, and GSH) changed under the PCOS condition. Moreover, they were regulated by SPE and SPA treatment in PCOS mice ovaries. The reproductive tissues of TE induced PCOS mice were restored into estrogenic conditions from androgen environments. The study of antioxidant activity of SPE and SPA using FRAP and DPPH tests showed high antioxidant activity. These results suggest that SPE and SPA ameliorates symptoms of PCOS by improving dysregulation of ovarian steroids, steroidogenic, antioxidant enzymes and inflammatory markers in PCOS mice.

Moshfegh F ，Balanejad SZ ，Shahrokhabady K ，Attaranzadeh A ... -  《-》

Liuwei Dihuang Pills alleviate the polycystic ovary syndrome with improved insulin sensitivity through PI3K/Akt signaling pathway.

Polycystic ovary syndrome (PCOS) is a complex gynecological endocrine disease commonly occurred in women of childbearing age. The main hallmark of PCOS includes elevated androgen production and insulin resistance (IR). Liuwei Dihuang Pills (LWDH Pills), a commonly prescribed traditional Chinese medicine (TCM) is widely used as a tonic prescription to treat diabetes, female menopause syndrome and other symptoms with'Kidney-Yin' deficiency. It has been reported the effects LWDH pills on PI3K/Akt signaling pathway in T2DM treatment. Recent studies have also indicated that the treatment of menopausal syndrome may be associated with the ovarian sexual hormone levels regulated by LWDH pills to alleviate female infertility. However, its potential benefits on PCOS have not been fully elucidated. The primary aim of this study was to investigate the alterations of PI3K/Akt pathway in polycystic ovary syndrome-insulin resistance (PCOS-IR) progression induced by letrozole combined with high fat diet (HFD) and then to explore the detailed mechanism of LWDH Pills to alleviate PCOS. The female Sprague-Dawley rats were continuously treated with letrozole (p.o administration at 1 mg kg-1·day-1) and HFD for 21 days to establish the PCOS-IR model. Concurrently, metformin (200 mg kg-1·day-1) or LWDH Pills was orally administrated (1.2 or 3.6 g kg-1·day-1) to intervene disease progression. The ovarian pathology was evaluated by HE (hematoxylin-eosin) staining. The serum sexual hormones, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, progesterone and fasting insulin (FINS) were determined by radioimmunoassay. The protein expressions of IRS-1, PI3Kp85α, Akt and FoxO1a were analyzed by western blotting, while the mRNA levels of follicle-stimulating hormone receptor (FSHR) and Cyp19a1 in ovarian tissue were measured by qPCR. The upregulated phosphorylation of IRS-1 (S307), down-regulated phosphorylation of PI3Kp85α, Akt, and FoxO1a were significantly reversed by LWDH Pills (3.6 g kg-1·day-1) in PCOS-IR rats with up-regulated mRNA levels of FSHR and Cyp19a1 in ovary. Also, the index of insulin resistance was gradually adjusted to normal by LWDH Pills. The serum levels of FSH, estradiol, progesterone levels were significantly raised while LH, testosterone were reduced. The ovarian polycystic changes were alleviated while the atresia follicles were reduced. LWDH Pills therapy obviously improved the ovarian polycystic pathogenesis and regained the development of follicles via upregulating Cyp19a1, alleviated insulin resistance through acting on PI3K/Akt signaling pathway. These findings have provided scientific evidence for LWDH Pills to treat PCOS.

Qiu Z ，Dong J ，Xue C ，Li X ，Liu K ，Liu B ，Cheng J ，Huang F ... -  《-》

Partially purified non-polar phytocomponents from Aloe barbadensis Mill. gel restores metabolic and reproductive comorbidities in letrozole-induced polycystic ovary syndrome rodent model- an "in-vivo" study.

In India, Kumaryasava, a popular Aloe barbadensis Mill. gel preparation has therapeutic value in treatment of female reproductive disorders like menstrual disturbances and menopausal problems. Despite their widespread use, only a limited number of studies have probed into the scientific evidence for their varied bioactivities. In this regard, studies have demonstrated that Aloe vera gel has the potential to modulate steroidogenic activity in letrozole induced polycystic ovary syndrome (PCOS) rat. However, isolation and identification of the bioactive molecule/s from Aloe vera gel and studying their molecular targets will underpin the treatment regime for PCOS. The Partially Purified Non-Polar Phytocomponents (PPNPP)- LP1 and LP3 were isolated from the petroleum ether extract of Aloe vera gel by column chromatography. Based upon the GC-MS analysis, LP1 and LP3 comprised of n-Hexadecanoic acid and Campesterol acetate with an abundance of 97.07%, and 96.07% respectively. For evaluation of their bioactivities, eighty 3-4 months female Balb/c mice were classified as 10 groups with 8 animals in each group. Groups were control (C), PCOS (0.5 mg/kg/day Letrozole orally for 21days), PCOS treated orally for 60 days with Aloe vera gel (AVG) (10 mg/kg/day) (PCOS + AVG), PCOS treated orally for 60 days with petroleum ether extract (PE) of Aloe vera gel (25 μg/kg/day) (PCOS + PE), PCOS treated orally for 60 days with LP1 (0.5 μg/kg/day) (PCOS + LP1), PCOS treated orally for 60 days with commercially available pure compound-n-Hexadecanoic acid (HA) (0.5 μg/kg/day) (PCOS + HA), PCOS treated orally for 60 days with LP3 (0.01 μg/kg/day) (PCOS + LP3), PCOS treated orally for 60 days with commercially available pure compound- Campesterol acetate (CA) (0.01 μg/kg/day) (PCOS + CA), PCOS treated orally for 60 days with Metformin (100 mg/kg/day) (PCOS + Metformin) and PCOS treated orally for 60 days with DMSO (Vehicle) (PCOS + DMSO). Body weight, Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, gene expression of gonadotropin receptors (Fshr and Lhr), steroid receptors (Ar, Esr1, Esr2 and Pgr) and steroidogenic markers (Star, Hsd3b1, Cyp19a1 and Amh) were analysed in the ovaries. Polycystic ovarian morphology was assessed through histopathological changes of ovary. Toxicity markers- SGOT, SGPT and creatinine were also measured at the end of the study. Mice treated with letrozole demonstrated significant increase in body weight, glucose intolerance, fasting insulin levels, HOMA-IR, triglycerides levels as well as testosterone levels, and a significant decline in the progesterone levels as compared to the control animals. PCOS animals also exhibited arrested estrus cyclicity, disrupted ovarian histopathology with the presence of multiple peripheral cysts and abnormal gene expression of gonadotropin receptor, steroid receptor and steroid markers. Oral administration of AVG, PE extract of AVG, LP3 and metformin greatly alleviated these complications in PCOS animals. The above findings indicate the effectiveness of LP3, isolated from Aloe vera gel against letrozole induced PCOS in mice and may be used in the treatment of PCOS as an alternative to metformin.

Dey A ，Dhadhal S ，Maharjan R ，Nagar PS ，Nampoothiri L ... -  《-》

Novel promising reproductive and metabolic effects of Cicer arietinum L. extract on letrozole induced polycystic ovary syndrome in rat model.

Ali SE ，El Badawy SA ，Elmosalamy SH ，Emam SR ，Azouz AA ，Galal MK ，Abd-Elsalam RM ，Issa MY ，Hassan BB ... -  《-》