Arachis hypogaea L. Root Extract Mitigates Testosterone Propionate-Induced Benign Prostatic Hyperplasia in ICR Mice...

In traditional Chinese medicine, Arachis hypogaea L. root extract (AHRE), and other parts of the plant historically have been used to manage benign prostatic hyperplasia (BPH). Hence, to evaluate the therapeutic effect of AHRE on testosterone-induced BPH in ICR mice, BPH was induced by daily subcutaneous testosterone propionate injections (6 mg/kg BW) in olive oil for 30 days. AHRE was orally administered at 100, 200, and 300 mg/kg BW daily, with finasteride (1 mg/kg BW) used as the positive control. HPLC-qTOF-MS/MS identified 19 compounds in 70% ethanolic AHRE, with resveratrol quantified at 1.12 mg/g dry weight. Prostate weight (PW), prostatic index (PI), histopathological changes, serum concentrations of prostatic acid phosphatase (PAP), dihydrotestosterone (DHT), testosterone (T), estradiol (E₂), and T/E₂ ratio, along with androgen receptor (AR) levels and the relative mRNA expression of hypoxia-inducible factor-1α (HIF-1α), estrogen receptors (ER-α and ER-β), lipoxygenase-5 (LOX-5), and cyclooxygenase-2 (COX-2) were measured. High-dose AHRE (300 mg/kg) reduced PW by 84.07%, significantly reduced glandular hyperplasia, prostatic cell counts, PAP, DHT, and AR levels (p < 0.05). It also downregulated relative mRNA expression of inflammation-related genes, including ER-α (1.6-fold), 5-LOX (1.65-fold), and COX-2 (1.36-fold). Preliminary gut microbiota analysis revealed treatment-associated increases in the relative abundance of Bifidobacterium, which showed robust negative correlations with PW (ρ = -0.95, q < 0.001), PI (ρ = -0.96, q < 0.001), and inflammatory markers, a genus linked to enhanced gut barrier function and control of systemic inflammation, potentially contributing to the observed improvements in BPH phenotypes.