Zhenwu Decoction ameliorates experimental benign prostatic hyperplasia: association with mitochondrial quality control, oxidative stress and apoptosis regulation.
Zhenwu Decoction shows potential in reducing prostate enlargement and modulating oxidative stress and apoptosis in a rat model of BPH, but human studies are needed to confirm its efficacy.
Where it sits
this study against the rest of the mots-c corpusSummary and findings
The study evaluated the effects of Zhenwu Decoction (ZWD) on testosterone propionate-induced benign prostatic hyperplasia (BPH) in rats. ZWD reduced prostate volume and weight, improved tissue architecture, and modulated oxidative stress and apoptosis markers. The study also assessed mitochondrial quality control markers in both in vivo and in vitro models.
Abstract
<h4>Ethnopharmacological relevance</h4>Zhenwu Decoction (ZWD), first recorded in the Shang Han Lun, is a classical formula used to warm Yang and promote water metabolism. It has traditionally been used for Yang deficiency with water retention, impaired Qi transformation and dysuria. Benign prostatic hyperplasia (BPH) can be classified under the traditional categories of "Longbi" and "dysuria", and its pathogenesis is closely related to kidney Yang deficiency, impaired bladder Qi transformation and water retention in the lower Jiao. Given that BPH is not merely a proliferative lesion but a chronic process involving androgenic stimulation, oxidative stress, insufficient apoptosis and tissue remodelling, investigating the modern pharmacological basis by which ZWD improves BPH through multiple pathological links has clear ethnopharmacological relevance.<h4>Aim of the study</h4>This study aimed to evaluate the therapeutic effect of ZWD on TP-induced experimental BPH and to determine whether this effect is accompanied by changes in oxidative stress, apoptosis and markers of HIF-1α/BNIP3-related mitochondrial quality control.<h4>Materials and methods</h4>UPLC-MS/MS was used to characterise the chemical constituents of ZWD, and network pharmacology analysis was performed based on the experimentally detected candidate compounds. A testosterone propionate (TP)-induced rat model of BPH was established to evaluate the effects of ZWD on prostatic hyperplasia, tissue remodelling, androgen levels, oxidative stress and apoptosis. Western blotting, qPCR, immunohistochemistry, immunofluorescence co-localisation, mCherry-GFP-LC3 autophagy flux-related assays and medicated serum experiments in BPH-1 cells were further used to assess changes associated with mitochondrial quality control.<h4>Results</h4>UPLC-MS/MS combined with database cross-matching identified 49 ZWD-related candidate compounds, of which 24 met the criteria of OB ≥ 20% and DL ≥ 0.10. Network pharmacology analysis identified 135 overlapping ZWD-BPH targets. These targets were mainly enriched in processes related to the MAPK cascade, reactive oxygen species response, AGE-RAGE signalling, HIF-1 signalling, EGFR-related signalling and endocrine regulation. In vivo, ZWD reduced prostate volume, prostate weight and prostate index in TP-induced BPH rats. It also improved epithelial thickening, glandular architectural disruption and collagen deposition, decreased serum T, DHT and prostatic MDA levels, and increased SOD activity. ZWD treatment also enhanced TUNEL-positive signals, up-regulated Bax and cleaved caspase-3, down-regulated Bcl-2, and was accompanied by changes in mitochondrial quality control-related markers, including HIF-1α, BNIP3, Beclin-1, LC3B-II/LC3B-I and p62. In vitro, ZWD-medicated serum reduced BPH-1 cell viability and ROS accumulation, improved mitochondrial membrane potential status, promoted apoptosis-related changes, and enhanced the spatial association between mitochondria and the autophagy-lysosome system.<h4>Conclusion</h4>ZWD ameliorated prostatic hyperplasia and tissue remodelling in experimental BPH. These effects were accompanied by reduced androgenic stimulation, decreased oxidative stress, enhanced apoptosis-related changes and restoration of mitochondrial quality control-related markers. HIF-1α/BNIP3-related mitochondrial quality control may represent an important observational node in the action of ZWD, although its causal role requires further clarification through targeted intervention and dynamic flux validation.
Background
Benign prostatic hyperplasia (BPH) is a common condition characterized by prostate enlargement and associated urinary symptoms. Traditional Chinese medicine, such as Zhenwu Decoction (ZWD), has been used to address conditions like BPH, which are linked to Yang deficiency and impaired Qi transformation. This study explores the pharmacological effects of ZWD on BPH, focusing on oxidative stress, apoptosis, and mitochondrial quality control.
Methods
The study used a testosterone propionate-induced rat model of BPH to evaluate the effects of ZWD. Chemical constituents of ZWD were characterized using UPLC-MS/MS, and network pharmacology analysis was conducted. The study assessed changes in prostate volume, tissue architecture, androgen levels, oxidative stress, and apoptosis. Various assays, including Western blotting and qPCR, were used to evaluate mitochondrial quality control markers.
Results
ZWD treatment resulted in a reduction of prostate volume and weight in the rat model of BPH. There was a decrease in serum testosterone, dihydrotestosterone, and prostatic malondialdehyde levels, alongside an increase in superoxide dismutase activity. Apoptosis-related changes were observed, including increased TUNEL-positive signals and up-regulation of Bax and cleaved caspase-3. Mitochondrial quality control markers such as HIF-1α and BNIP3 were modulated.
Interpretation
The findings suggest that ZWD may have a therapeutic effect on BPH by modulating oxidative stress, apoptosis, and mitochondrial quality control. While the study shows statistically significant changes, the clinical relevance remains uncertain due to the animal model. Further research is needed to confirm these effects in humans and to clarify the role of mitochondrial quality control.
Key findings
- 49 ZWD-related candidate compounds identified, 24 met OB ≥ 20% and DL ≥ 0.10.
- 135 overlapping ZWD-BPH targets enriched in MAPK cascade and ROS response.
- ZWD reduced prostate volume and weight in TP-induced BPH rats.
- Decreased serum T, DHT, and prostatic MDA levels, increased SOD activity.
- Enhanced TUNEL-positive signals, up-regulated Bax and cleaved caspase-3.
Limitations
- rat model, not human
- mechanistic focus, not clinical outcomes
- unreported sample size
- no long-term follow-up