# Thymol Mitigates Oxidative Stress-Induced Ovarian Aging and Restores Steroidogenesis via the JAK1–STAT3 Pathway

## TL;DR

Thymol, a natural compound, helps reduce ovarian aging by fighting oxidative stress and restoring hormone production through a specific cellular pathway.

## Contribution

This study identifies thymol's novel role in mitigating ovarian aging via the JAK1–STAT3 pathway.

## Key findings

- Thymol increased cell viability and antioxidant enzyme activity in ovarian cells.
- Thymol reduced oxidative stress and senescence markers in both cell and mouse models.
- Thymol improved steroid hormone levels and reduced ovarian aging markers in aged mice.

## Abstract

Premature ovarian failure (POF) is characterized by oxidative stress, cellular senescence, and impaired steroidogenesis, yet current therapies remain limited in effectiveness. Thymol, a natural monoterpene, exhibits antioxidant and anti-inflammatory properties. Network pharmacology and molecular docking identified multiple potential targets, notably the Janus kinase 1 (JAK1)-signal transducer and activator of transcription 3 (STAT3) pathway. In tert-butyl hydroperoxide (t-BHP)-induced human granulosa-like tumor cells (n = 3), 40 μg/mL thymol increased cell viability by approximately 45%, restored superoxide dismutase, catalase, and glutathione peroxidase activities to nearly twice those of the model group, and reduced reactive oxygen species accumulation by about 35% (p < 0.05). It also decreased senescence markers p53, p21, and p16 by 40–60% and inhibited JAK1–STAT3 phosphorylation (n = 3, p < 0.05). In aged pregnant mice (n = 4 per group), thymol increased viable fetus numbers by about 40%, elevated serum estradiol and progesterone levels to 1.6–1.8-fold of aged controls, and downregulated ovarian aging markers (p < 0.05). Collectively, these findings indicate that thymol mitigates oxidative stress-induced ovarian aging by modulating JAK1–STAT3 signaling and restoring steroidogenic function, supporting its potential as a natural candidate for delaying ovarian senescence.