Magnolia officinalis Ameliorates Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome in Rats

Abstract

Background: Polycystic ovary syndrome (PCOS) is a prevalent reproductive and metabolic disorder. Insulin resistance (IR) is highly associated with PCOS and aggravates its symptoms. Thiazolidinediones (TZDs), as insulin sensitizing agents, are PPARγ agonists that improve many of the symptoms of PCOS. The Magnolia officinalis extract (MOE) is a natural peroxisome proliferator activated receptor gamma (PPARγ) agonist that improves insulin sensitivity in experimental models. Objectives: Using a dehydroepiandrosterone (DHEA)-induced rat model of PCOS and IR, this study aimed to explore both the potential beneficial effects and the molecular mechanisms of action of MOE. Methods: Post-pubertal female Sprague Dawley rats were subcutaneously injected daily with DHEA (6 mg/100 g body weight) dissolved in sesame oil for 28 days (n = 30). Age- and weight-matched control rats received only sesame oil (n = 12). Afterward, 16 of the DHEA-injected rats, along with five control rats, were sacrificed for blood and tissue collection. The 14 remaining DHEA-injected rats received either treatment of 30 days of oral MOE (500 mg/kg) dissolved in dimethyl sulfoxide (DMSO) (n = 7), or oral DMSO only (n = 7). Meanwhile, the remaining control rats (n = 7) continued to receive daily oral DMSO for 30 days. At the end of the treatments, the rats were sacrificed for blood and tissue collection. Results: After 28 days, the DHEA-treated rats exhibited an increase in body weight as compared to controls (P < 0.05). DHEA injection induced a PCOS phenotype as evident by a statistically significant (P < 0.05) elevated serum luteinizing hormone (LH), and an increased number of cystically dilated follicles with thicker granulosa compared to controls. PCOS rats showed a statistically significant rise in fasting insulin with an increased homeostatic model assessment index of insulin resistance (HOMA-IR) as compared to controls (P < 0.05). Compared to the control group, PCOS rats had a statistically significant lower ovarian protein expression of PPARγ, insulin receptor substrate 1 (IRS1), and protein kinase B (Akt) by Western Blot (P < 0.05). Conversely, the PCOS group showed an increased mammalian target of rapamycin (mTOR) pathway activity as evident by an increase in the fraction of phosphorylated mTOR to total mTOR compared to the control group (P < 0.05). When treated for 30 days with oral MOE (500 mg/kg), the PCOS rats showed a statistically significant decrease in body weight and serum LH levels as compared to the non-treated PCOS rats (P < 0.05). The number of cystically dilated follicles in the MOE-treated PCOS rats was significantly reduced compared to the non-treated PCOS rats. In the MOE-treated PCOS rats, the ovarian protein expression of PPARγ, IRS1, and Akt was significantly increased, while the p-mTOR/mTOR expression was decreased compared to the non-treated PCOS group (P < 0.05). Conclusions: According to our results, the MOE ameliorated the DHEA-induced PCOS phenotype histologically, hormonally, and metabolically. Fundamentally, this explores the elusive pathophysiologic association between IR and PCOS by targeting pathways common to both disorders.

Effectiveness of Magnolol, a Lignan from Magnolia Bark, in Diabetes, Its Complications and Comorbidities—A Review

“…In another study, the same animal model of PCOS and insulin resistance was treated with magnolia extract. The obtained results revealed that this extract led to the decrease in the serum insulin and testosterone levels and the increase in the ovarian expression of IRS1, PKB and PPARγ [63]. Both these studies demonstrate that magnolol and magnolia extract are natural PPAR-γ agonists [46,63].…”

Regulation of Insulin Resistance, Lipid Profile and Glucose Metabolism Associated with Polycystic Ovary Syndrome by Tinospora cordifolia

“…PCOS and weight gain were associated with DHEA injections. There is a lot of evidence linking PCOS and being overweight [ 27 ]. In this study, the BW of mice treated with DHEA was significantly increased due to abdominal fat compared to the normal mice [ 37 ].…”

“…After blood collection, animals were euthanized with an overdose of ketamine and their ovarian weight, size, and morphology were assessed [ 27 ].…”

Nasturtium officinale L. and metformin alleviate the estradiol‐ induced polycystic ovary syndrome with synergistic effects through modulation of Bax/Bcl‐2/p53/caspase‐3 signaling pathway and anti‐inflammatory and anti‐oxidative effects

“…These compounds through antioxidant, anti‐inflammatory and apoptotic pathways help to stimulate the onset of normal ovarian cycles, HPO (Hypothalamic–Pituitary‐Ovarian axis) (regulation of androgens and modulation of LH/FSH level), mitochondrial apoptosis of granulosa cells and eventually ovulation in PCOS patients (Jazani, Azgomi, Azgomi, & Azgomi, 2019). Nassar, Khachab, Zaatiti, and Kanaan (2021) showed that Magnolia officinalis L. extract in DHEA‐induced PCOS in rats regulated the ovarian cycle and normal ovulation by reducing the LH/FSH ratio and stimulating the IRS‐1 and AKT pathways (Nassar et al, 2021).…”

“…These compounds through antioxidant, anti-inflammatory and apoptotic pathways help to stimulate the onset of normal ovarian cycles, HPO (Hypothalamic-Pituitary-Ovarian axis) (regulation of androgens and modulation of LH/FSH level), mitochondrial apoptosis of granulosa cells and eventually ovulation in PCOS patients (Jazani, Azgomi, Azgomi, & Azgomi, 2019). Nassar, Khachab, Zaatiti, and Kanaan (2021) showed that Magnolia officinalis L. extract in DHEA-induced PCOS in rats regulated the ovarian cycle and normal ovulation by reducing the LH/FSH ratio and stimulating the IRS-1and AKT pathways(Nassar et al, 2021).Nasturtium officinale L. (N. officinale) or Watercress belongs tothe Brassicaceae and aquatic family, with a height of 20-80 cm and simple leaves that are native to Eastern Europe, Southeast Asia and the Middle East. The leaves of this plant are used as a vegetable in soups, stews, teas and additives in various foods.…”