Butylphthalide identified via Samul-tang-induced transcriptomic signatures improves oocyte quality in aged mice

Samul-tang (SM) is a traditional prescription widely used in clinical practice for the management of gynecological diseases, especially for menstrual regulation and infertility treatment. We previously reported its efficacy in increasing mature oocyte production and improving ovarian reserves, potentially regulated by rat sarcoma virus (Ras) signaling in the ovaries of aged mice. Although the main ingredients of SM are known, the bioactive compounds responsible for protecting ovarian function during aging remain unidentified. This study aimed to identify the active compounds that significantly contribute to the therapeutic potential of SM against age-related decline in ovarian function. The combination of butylphthalide and oleanolic acid improved mature oocyte production similar to that in SM-administered aged mice. Subsequently, we identified butylphthalide as an active compound that mimicked SM's effect on enhancing ovarian reserve. This study introduces a novel strategy for identifying active compounds in multi-component herbal medicines by evaluating compound combinations in an in vivo model, offering promising therapeutic avenues for age-related female infertility through targeted gene expression modulation.