Effect of Nepeta Adenophyta Hedge Extract and Its Fractions on Polycystic Ovarian Syndrome (PCOS)

Polycystic Ovarian Syndrome indicates an increasing health challenge for women of reproductive age, with global prevalence estimates between 6% and 14%. Individuals affected often experience psychological distress, metabolic issues, and difficulties with fertility. The pathophysiology of PCOS consists of three interrelated axes: (i) heightened GnRH pulse frequency results in an increased LH/FSH ratio and theca cell hyperplasia, driving ovarian hyperandrogenism; (ii) peripheral insulin resistance coupled with compensatory hyperinsulinemia further enhances ovarian androgen production; and (iii) chronic oxidative stress and inflammation, driven by cytokines from adipose tissue (TNF α, IL 6) and reactive oxygen species, which hinder follicular development and exacerbate metabolic dysfunction.

Traditional first-line therapies - metformin (insulin sensitizer), clomiphene citrate (ovulation stimulant), and spironolactone (anti-androgen) - each address only a single facet of the syndrome and have notable drawbacks: metformin can lead to dose-dependent gastrointestinal issues; clomiphene elevates the risk of multiple pregnancies and presents anti-estrogenic side effects; spironolactone is teratogenic and is unsuitable for women attempting to conceive. Additionally, none of these agents concurrently tackle hyperandrogenism, insulin resistance, inflammation, and oxidative stress.

Herbal remedies provide a multifaceted, multi-target strategy that corresponds effectively with the intricate pathophysiology of PCOS. NAE shows considerable potential. Its flavonoid fraction (luteolin, apigenin, quercetin) acts as a free radical scavenger, inhibits lipid peroxidation, enhances endogenous antioxidant enzymes (superoxide dismutase, glutathione peroxidase), and down regulates 17α hydroxylase, thereby reducing ovarian testosterone production. The phenolic acids (caffeic acid, rosmarinic acid) inhibit pro-inflammatory cytokines TNF α and IL 6, while improving insulin sensitivity through the enhancement of GLUT 4 translocation in adipose tissue and skeletal muscle. Terpenoids (nepetalactones) influence the hypothalamic pituitary gonadal axis, aiding in the normalization of the LH/FSH ratio, while also offering anxiolytic effects that might alleviate stress-related hormonal disturbances. Glycosides and reducing sugars enhance insulin receptor signaling, stimulate hepatic glycogen production, and block gluconeogenic enzymes like glucose 6 phosphatase.

These mechanistic predictions were confirmed in a carefully regulated animal study. PCOS was established in female Albino Wistar rats through Letrozole (1 mg/kg) given orally dissolved in 0.5% carboxymethylcellulose (CMC) for 21 days. The animals were split into 07 categories, which included untreated control, PCOS control, metformin standard (350 mg/kg), crude NAE (low dose 350 mg/kg, high dose 500 mg/kg), methanol fraction (64 mg/kg), and butanol fraction (12.5 mg/kg), given orally for 30 days. Essential discoveries comprised:

• Hormonal: Significant reduction in serum LH and total testosterone, with normalisation of the LH/FSH ratio (p < 0.01).
• Metabolic: Decreased fasting blood sugar, reduced HOMA IR, enhanced lipid profile (lowered total cholesterol, triglycerides, LDL; raised HDL).
• Ovarian structure: Normal follicular arrangement on H&E staining.
• Gene expression: qRT PCR of ovarian tissue showed an increase in the anti-inflammatory cytokine IL-4, whereas androgen receptor (AR), toll-like receptor 4 (TLR4), Cytochrome-17 (CYP-17), tumor necrosis factor α (TNF-α), and nuclear factor κB (NF-κB) were significantly decreased.