Mechanistic Study On The Improvement Of Chronic Prostatitis By A Cistanche-Based Herbal Formula Via The STAT3/HIF-1α/Glycolysis Axis

 

WANG Chen¹², JIANG Xiao-han¹², WANG Ya-hong¹², GE Hai-tao²³, WANG Fu-jiang²³**
¹ Nanjing University of Chinese Medicine, Nanjing, China
² Jiangsu Suzhong Pharmaceutical Research Institute, Nanjing, China
³ R&D System Research Center, Jiangsu Suzhong Pharmaceutical Group

 

 

 

 

 

Abstract

This study explores the molecular mechanism of a Cistanche-centered herbal formulation for the treatment of chronic prostatitis (CP), focusing on the STAT3/HIF-1α/glycolysis signaling axis. We employed a validated experimental autoimmune prostatitis (EAP) rat model, mimicking the complex inflammatory and immune features of CP.

Male Wistar rats were randomly assigned to six groups (n=7 per group):

Normal control

Model group (EAP)

Low, medium, and high doses of the Cistanche-based formula (197.2, 591.5, 1,774.4 mg/kg/day)

Positive control group (finasteride analog, 34.2 mg/kg/day)

All treatments were administered for 28 consecutive days via oral gavage.

Key Evaluations & Methods

Histopathology (Hematoxylin & Eosin staining):
To assess inflammatory cell infiltration and prostate tissue damage.

Serum Biomarkers (ELISA):
Levels of Interleukin-8 (IL-8), Interleukin-1β (IL-1β), and Immunoglobulin G (IgG) were quantified.

Protein Expression (Western Blot & Immunohistochemistry):
Expression of phosphorylated STAT3 (p-STAT3), HIF-1α, hexokinase (HK), and multiple inositol polyphosphate phosphatase 1 (MINPP1) in prostate tissues.

Untargeted Metabolomics (UPLC-MS/MS):
Serum samples from control, model, and treatment groups were analyzed to identify key metabolic pathways and differential metabolites related to glycolysis, inflammation, and oxidative stress.

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Results Summary

Histological improvement:
The Cistanche-based formulation notably reduced glandular damage and immune infiltration in prostate tissues.

Inflammatory cytokines:
Serum IL-8, IL-1β, and IgG levels were significantly decreased in treatment groups vs. model.

Signaling axis modulation:
The formulation downregulated p-STAT3, HIF-1α, and HK, while upregulating MINPP1, indicating suppression of inflammatory and glycolytic pathways.

Metabolic reprogramming:
Metabolomic profiling identified 96 differential metabolites, suggesting regulation of glycolysis, arachidonic acid metabolism, and amino acid biosynthesis.

Conclusion

This Cistanche-based herbal formula exhibits therapeutic potential against chronic prostatitis by targeting the STAT3/HIF-1α/glycolysis metabolic axis. It offers a multi-targeted, low-toxicity approach to modulate immune response, reduce inflammation, and restore prostate homeostasis.

The findings provide scientific support for integrating traditional botanical medicine with modern molecular pharmacology, paving the way for functional supplement development in men's urological health.

 

🔬 Why Cistanche?

Cistanche has been extensively studied for its effects on:

Androgen receptor modulation

Immune regulation

Anti-fatigue and anti-oxidant properties

Spermatogenesis support

Its inclusion in this prostate-targeted formula reflects both traditional wisdom and modern pharmacological promise.

🚀 Application Potential

This formula presents a market-ready opportunity for companies interested in:

Functional foods & nutraceuticals for men's health

Adjunct therapy for chronic prostatitis or BPH

Herbal-based metabolic and immune modulation

Integrative medicine clinical trials

 

📎 Available Upon Request:

Full study protocol and data

Pharmacokinetic & safety preclinical data

Formulation IP status

Potential for clinical translation or licensing partnership