Lemongrass ( <i>Cymbopogon citratus</i> ) Extracts Ameliorate Polycystic Ovary Syndrome in Rats by Inhibiting Follicular Atresia and Modulating Ghrelin and Leptin

Polycystic ovary syndrome (PCOS) accelerates ovarian follicular depletion through atresia. This study investigated the therapeutic potential of aqueous (AE) and hydroethanolic (HEE) extracts of <i>Cymbopogon citratus</i> in mitigating PCOS-induced ovarian damage (specifically ferroptosis, apoptosis, and oxidative stress) in a rat model of PCOS. PCOS was induced by oral administration of letrozole (1 mg/kg/day for 21 days), followed by treatment with AE or HEE (100, 200, or 400 mg/kg/day for 20 days) with metformin (200 mg/kg) as a positive control. The results showed that HEE contains 5 times more alkaloids than AE. In experimental animals, <i>C. citratus</i> corrected ovarian damage caused by PCOS, compared to the disease control treated with distilled water. Indeed, <i>C. citratus</i> decreased serum testosterone levels [maximum decrease rate of 37.10% (<i>p</i> < 0.0001) obtained with HEE100] and increased estradiol levels [maximum increase rate of 56.15% (<i>p</i> < 0.0001) obtained with AE200]. An increase in serum ghrelin levels [maximum increase rate of 129.38% (<i>p</i> < 0.0001) obtained with AE400] and a decrease in leptin levels [maximum decrease rate of 43.85% (<i>p</i> < 0.0001) obtained with AE400] were observed. In the ovaries, <i>C. citratus</i> decreased Fe²⁺ [maximum decrease rate of 31.57% (<i>p</i> < 0.01) obtained with HEE200], caspase 3 [maximum decrease rate of 24.47% (<i>p</i> < 0.05) obtained with HEE400], oxidative stress markers [MDA: up to 23.28% decrease (<i>p</i> < 0.05) induced by AE100], and increased antioxidants [catalase: up to 29.99% increase (<i>p</i> < 0.05) induced by HEE100 and GSH: up to 42.37% increase (<i>p</i> < 0.01) induced by HEE200]. <i>C. citratus</i> also decreased cystic and atretic follicles and promoted follicle growth and ovulation. In conclusion, <i>C. citratus</i> extracts are capable of protecting the ovaries from the adverse effects of PCOS, primarily ferroptosis, and apoptosis of follicular cells. Of the two extracts, AE seems ideal due to its low alkaloid content.