PubMedZhonghua nan ke xue = National journal of andrology2026-11-11
[Qianlie Shukang tablet ameliorates prostatic hyperplasia in rats: Mechanistic exploration integrating network pharmacology with experimental validation].
Liang Qiying Q, Wei Yanyun Y, Zhao Lijuan L, Sa Rina R et al.
Objective To evaluate the therapeutic efficacy of Qianlie Shukang (QLSK) tablet on benign prostatic hyperplasia (BPH) by establishing a rat model of BPH. Methods Forty SPF-grade male Sprague-Dawley (SD) rats were divided into six groups by random number table method: control (sham surgery, equal volume of CMC-Na solution), BPH model (equal volume of CMC-Na solution), positive control (finasteride 0.5 mg/kg), and QLSK low- (145.94 mg/kg), medium- (291.88 mg/kg), and high-dose (583.76 mg/kg) groups. Except for the control group which underwent sham surgery modeling (subcutaneous injection of peanut oil 0.5 mg/［kg·d］ ), the BPH rat model was established in all other groups through castration surgery combined with testosterone propionate injection (0.5 mg/［kg·d］, subcutaneously). All groups were intragastrically administered their respective drug solutions dissolved in carboxymethylcellulose sodium (CMC-Na) once daily. After 28 consecutive days of intervention, the rats were sacrificed for sample collection. The pathological changes in prostate tissue were observed using hematoxylin and eosin (HE) staining. Levels of inflammatory and oxidative stress factors in rat prostate tissue including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, IL-2, IL-1β, IL-10, prostaglandin E2 (PGE2), superoxide dismutase (SOD), and malondialdehyde (MDA) as well as levels of sex hormones and growth factors including dihydrotestosterone (DHT), testosterone (T), estradiol (E2), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1) and immunoglobulin G (IgG) were measured by ELISA. Serum creatinine (CREA), urea (UREA), and glucose (GLU) levels were detected using an automatic biochemical analyzer. Network pharmacology technology was employed to screen for potential core targets of QLSK in treating BPH in rats (key molecules in pathways such as PI3K/AKT and NF-κB). The protein expression levels of Bax, PI3K, IL-1β, and TNF-α in rat prostate tissue were detected by immunohistochemistry (IHC). Results The increases of prostate wet weight and volume index in BPH rats were significantly inhibital by QLSK(P<0.05). Histopathological analysis demonstrated marked improvement in glandular epithelial hyperplasia and interstitial inflammatory infiltration, with no significant effects on renal function markers (CREA, UREA) or blood glucose levels (P>0.05). Medium- and high-dose QLSK groups exhibited decreased prostatic levels of pro-inflammatory factors (IL-8, IL-2, TGF-β1; P<0.05) and androgens (DHT, T; P<0.05), while elevating anti-inflammatory cytokines (IL-6, IL-10; P<0.01) and SOD activity (P<0.05). Based on TCMSP database and literature database, 35 active ingredients (ginsenoside Rb1, ginsenoside Rd, etc.) were screened and obtained, involving 44 core targets (PIK3CA, IL-1β, AKT1, TNF, etc.) and 72 KEGG pathways. The DAVID enrichment analysis showed that the PI3K-Akt and NF-κB signaling pathways (P<0.01) had a significant correlation. Immunohistochemical results showed that the expression of pro-apoptotic protein Bax was up-regulated (P<0.01) and the expression of PI3K and TNF-α was down-regulated (P<0.01) in prostate tissues after the intervention of QLSK, and the medium dose of QLSK could significantly reduce the expression level of IL-1β (P<0.01). Conclusion This study integrates experimental and bioinformatics approaches to reveal the "multi-component, multi-target, multi-pathway" therapeutic mode of QLSK against BPH. The anti-hyperplastic effects are mediated through dual inhibition of PI3K-Akt pathway activation and NF-κB-mediated inflammatory response. However, the in vivo validation of the key active ingredients and the mechanism of multi-target synergistic regulation still need to be further elucidated.