Prunella vulgaris L. ameliorates goiter in Wistar rats is associated with changes in Rap1GAP/CREB3L1/PI3K-AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE Prunella vulgaris L. (PV), known as Xia Ku Cao, has traditionally been used in Chinese medicine to dissipate nodules and reduce swelling and is widely used for thyroid disorders. However, its efficacy and mechanisms in iodine-deficiency-induced goiter remain unclear.

Aim

OF THE STUDY This study investigated the therapeutic effects of PV aqueous extract on iodine-deficiency-induced goiter and explored its potential molecular mechanisms.

Materials And Methods

Forty-eight Wistar rats were used. Eight received a standard diet, whereas 40 received an iodine-deficient diet for 12 weeks and were subsequently assigned to the model, levothyroxine, or low-, medium-, and high-dose PV groups (n = 8). Treatments were administered orally for 16 weeks. Thyroid volume, thyroid weight, hormone levels, histopathology, ultrastructure, and hepatorenal biomarkers were evaluated. Chemical profiling and Deep DIA proteomics were performed, and selected proteins were validated by Western blotting.

Results

PV extract contained rosmarinic acid, salvianic acid A, and other potentially bioactive constituents. Medium- and high-dose PV significantly reduced thyroid volume and attenuated thyroid inflammatory infiltration and ultrastructural injury. Proteomic and Western blot analyses showed that these effects were associated with increased Rap1GAP expression, decreased CREB3L1 expression, and reduced PI3K-AKT pathway activation. PV produced no detectable alterations in thyroid hormone levels or the measured hepatorenal biomarkers.

Conclusions

PV alleviated iodine-deficiency-induced goiter while preserving systemic thyroid function. Its effects were associated with modulation of the Rap1GAP/CREB3L1/PI3K-AKT signaling axis, supporting the traditional use of PV for thyroid enlargement.