1-Monopalmitin (1-Mono) is the principal active component found in natural plants such as Mougeotia nummuloides and Spirulina major, which has been shown to promote apoptosis in lung cancer cells through the PI3K/AKT pathway. However, the effects of 1-Mono on benign prostatic hyperplasia (BPH) remain unclear. This study aims to investigate the therapeutic effects of 1-Mono in BPH models and its underlying molecular mechanisms.

This study first utilized two-sample Mendelian randomization to screen for key metabolites with a causal relationship to BPH from 486 serum metabolites, identifying 1-Mono. Subsequently, various in vitro techniques, including CCK-8, EdU assays, apoptosis detection, Western Blot (WB), and qRT-PCR, were employed to evaluate the effects of 1-Mono on proliferation, apoptosis, and inflammatory responses in BPH-1 and WPMY-1 cells. In vivo, a rat BPH model was established, and the impact of 1-Mono on prostate enlargement and cell proliferation was assessed through H&E staining, immunohistochemistry, immunofluorescence, and WB. Mechanistic studies were conducted using RNA sequencing, molecular docking, and rescue experiments to explore the regulatory mechanisms of 1-Mono in BPH.

The study found that elevated genetic susceptibility levels of 1-Mono significantly reduced susceptibility to BPH. In vitro experiments demonstrated that 1-Mono significantly inhibited proliferation and inflammatory responses in BPH-1 and WPMY-1 cells while promoting apoptosis. In the testosterone-induced BPH rat model, 1-Mono effectively alleviated pathological prostate enlargement. Mechanistic studies revealed that 1-Mono inhibited the androgen/androgen receptor (AR) signaling pathway and suppressed the upregulation of pro-inflammatory molecules by alleviating endoplasmic reticulum stress (ER-stress). AR knockdown experiments partially abolished the beneficial effects of 1-Mono in prostate cells, indicating that its action is AR-dependent.

As an inhibitor of AR and ER-stress, 1-Mono demonstrates considerable therapeutic potential and may serve as an effective treatment for BPH.