Evaluation of Formulated Herbal Syrup (Containing Fennel, Anise, and Celery) on the Letrozole-Induced Polycystic Ovary Syndrome Model

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder associated with irregular menstrual cycles, hyperandrogenism, obesity, and reduced fertility. Objectives: The present study aimed to formulate herbal syrup based on Iranian traditional medicine (ITM) and evaluate its effect on the letrozole-induced PCOS model in female rats. Methods: The herbal syrup contains anise, fennel, and celery seed extracts. Five different formulations were made with different percentages of additive components. Quality control and stability tests were performed on the selected formulation. During the in vivo step, 6 groups of rats were evaluated: The control group (received carboxymethyl cellulose 1% as a vehicle) and the other 5 groups (received letrozole 1 mg/kg orally for 21 days). During 21 days, daily vaginal smears were examined to detect irregularities of the estrous cycle. After induction of PCOS, rats were orally administered with herbal syrup (1, 2, 4 mL/kg) or metformin (200 mg/kg) for 28 days. Moreover, body and ovarian weights, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and testosterone were measured. Finally, ovarian tissues were isolated for histological examination. Results: The best formulation of the syrup contained the plant extract (totally 10%), sugar (50%), sodium benzoate (0.1%), and potassium sorbate (0.1%). Body weight was significantly increased in all groups compared to the control group, and after treatment, a significant weight reduction was seen in the metformin and 1-mL/kg dose group. Following PCOS induction, ovary weight was significantly increased, while after treatment, it showed a significant decrease. After 21 days of letrozole administration, induction of PCOS was confirmed by the irregularities in estrous cycles and an increase in testosterone and LH levels. After treatments with the syrup, LH levels significantly decreased in all groups (P < 0.05), and serum testosterone and FSH levels significantly decreased in the 2-mL/kg dose group compared to the PCOS group (P < 0.05). Estradiol and progesterone levels significantly increased in the treatment groups in a dose-dependent manner. Histological studies of metformin and herbal syrup groups exhibited normal follicular development with fewer and smaller cystic follicles compared to the PCOS group. Conclusions: The herbal syrup made from anise, fennel, and celery seed extracts improved serum levels of sex hormones, recovered the ovarian morphology in PCOS-induced rats, and can be a good candidate for further clinical trials.