Puerarin inhibits inflammation and oxidative stress in female BALB/c mouse models of Graves' disease

Background: Graves' disease (GD) is an autoimmune thyroid disorder. Our previous study has demonstrated a significant decrease in flavone levels among children with GD compared to the control group. Puerarin, a well-known flavonoid with anti-inflammatory and antioxidant properties. We wanted to investigate its potential impact on GD pathogenesis, aiming to determine whether increasing puerarin intake could prevent or delay the onset of GD. Methods: Adenovirus with TSHR-289 subunit was used to establish a GD mice model, and mice were intragastrically administered with puerarin or sterilized water daily. Thyroid function and inflammatory cytokine levels were quantified using ELISA, lymphocyte subsets were analyzed via flow cytometry, oxidative stress (OS) markers were measured with a microplate reader, and the expression of pertinent signaling pathway proteins were assessed by Western blot. Results: The results demonstrated that puerarin treatment significantly decreased thyroxin levels and alleviated thyroid pathological changes in GD mice. Furthermore, the immune imbalance of GD mice was improved, as evidenced by reduced inflammatory indexes, elevated antioxidant levels, and decreased malondialdehyde (MDA) levels compared to untreated GD mice. Puerarin-treated GD mice exhibited significantly lower expressions of heat shock protein (HSP): HSP70, HSP90, phosphorylated extracellular regulated kinases (p-ERK) and phosphorylated protein kinase B (p-AKT) than untreated GD mice. Moreover, low dosage puerarin (400 mg/kg) was associated with a better protective effect than high dosage (1,200 mg/kg). Conclusions: Puerarin may have the potential to mitigate GD by inhibiting inflammatory and OS, through downregulating the expression of HSP70 and HSP90 and suppressing the activation of the PI3K/ AKT/ERK signaling pathway. Furthermore, a lower dose exhibited superior protective effects compared to a higher dose.