Multi-target therapeutic mechanism of Qianlie Shule granule against chronic prostatitis: network pharmacology-guided experimental validation

To elucidate the active constituents and multi-target mechanisms underlying the therapeutic effects of Qianlie Shule granules (, QG) against chronic prostatitis (CP).

QG constituents were profiled by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Putative targets were predicted using network pharmacology and enrichment analyses. Male Sprague-Dawley rats were assigned to control, sham, model, and QG-treated groups (low/medium/high doses). Prostatic injury, inflammation, oxidative stress, and apoptosis were assessed by histology, biochemical assays, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) signaling was evaluated by reverse transcription quantitative polymerase chain reaction and Western blot.

Fifty-nine compounds in QG were identified, and 92 potential targets of QG for CP were predicted. The results indicated that apoptosis-related genes and the PI3K/Akt/mTOR signaling pathway were identified as major targets of QG against CP. Further, the results in vivo showed that QG effectively alleviated the histological damage in the prostate, decreased the pro-inflammatory cytokines, and increased the antioxidant capacity. QG reduced apoptosis by reducing the expression of Caspase 3 and Caspase 8. QG upregulated the mRNA levels of PI3K, AKT and mTOR and promoted the phosphorylation of PI3K, AKT and mTOR.

QG could ameliorate CP in rats by inhibiting inflammation, oxidative stress, and apoptosis. Moreover, QG could upregulate the anti-apoptotic PI3K/ Akt/mTOR pathway in CP rats.