Kelong Capsule Alleviates Benign Prostatic Hyperplasia Via Activation Of Nrf2 Signaling And Inhibition Of Inflammation in Rats
Nov 25, 2025
Abstract
Objective:
To investigate the molecular mechanisms by which Kelong capsule improves benign prostatic hyperplasia (BPH), with a focus on the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.
Methods:
Sixty male Sprague-Dawley (SD) rats were randomly divided into seven groups: blank control, model, sham, finasteride, and high, medium, and low doses of Kelong capsule. The BPH model was established via bilateral orchiectomy followed by subcutaneous injection of testosterone cypionate. Beginning on day 8 post-orchiectomy, drug treatment groups received testosterone propionate injections and simultaneous oral administration of the respective treatments. Histopathological changes in prostate tissue were observed using hematoxylin and eosin (HE) staining. Serum levels of testosterone (T), dihydrotestosterone (DHT), and estradiol (E2) were measured by ELISA. Real-time quantitative PCR (RT-qPCR) was used to assess mRNA expression levels of TNF-α, IL-1β, IL-6, Nrf2, and NAD(P)H quinone oxidoreductase 1 (NQO1) in prostate tissue.
Cistanche Benefits For Benign Prostatic Hyperplasia
Results:
Compared with the sham group, rats in the BPH model group exhibited cuboidal or tall columnar glandular epithelium, significantly dilated gland lumens, and increased intraluminal secretions. Serum levels of T and DHT were significantly elevated (P<0.05), whereas E2 levels were significantly decreased (P<0.01). Prostatic mRNA expression of TNF-α, IL-1β, and IL-6 was markedly increased (P<0.01), while Nrf2 and NQO1 mRNA levels were significantly downregulated (P<0.01). In the high-dose Kelong capsule group, the tall columnar epithelium was markedly reduced, and glandular dilation was notably improved. Serum E2 levels were significantly increased (P<0.05), while T and DHT were significantly decreased (P<0.05). NQO1 mRNA expression was significantly upregulated in both the high- and medium-dose groups (P<0.01). Nrf2 mRNA expression was significantly increased (P<0.05), and TNF-α, IL-1β, and IL-6 mRNA levels were significantly decreased (P<0.05) across all Kelong capsule treatment groups.
TCM HERB SUPPLEMENT FOR TREATING PROSTATE DISEASE
Conclusion:
Kelong capsule effectively alleviates pathological prostatic hyperplasia in BPH model rats, potentially through activation of the Nrf2 signaling pathway and inhibition of inflammatory responses.
Keywords: Benign prostatic hyperplasia; Kelong capsule; Oxidative stress; Inflammation; Nrf2 signaling pathway
Introduction
Benign prostatic hyperplasia (BPH) is a prevalent urological condition in aging men, characterized by lower urinary tract symptoms (LUTS) such as urinary frequency, urgency, and progressive voiding difficulty. Histologically, BPH manifests as hyperplasia of prostatic stromal and glandular components, whereas anatomically it presents as prostate enlargement and bladder outlet obstruction. Studies reveal that the prevalence of BPH increases with age, affecting approximately 30–40% of men in their 40s and up to 70–80% of men over 80 years old.
In Traditional Chinese Medicine (TCM), BPH falls under the categories of "long bi" (urinary obstruction) and "lin zheng" (urinary syndrome). The pathogenesis is believed to stem from kidney qi deficiency, leading to blood stasis and impaired circulation, ultimately resulting in prostatic tissue hyperplasia.
While androgen signaling, particularly involving testosterone and dihydrotestosterone, is a well-established factor in BPH pathophysiology, emerging evidence highlights the role of oxidative stress, chronic inflammation, hormonal imbalances, and local hypoxia. Recent research suggests that the Nrf2 signaling pathway, a key regulator of cellular antioxidant responses, plays a critical role in mitigating oxidative stress and inflammation associated with BPH.
The Role of Herbal Medicine in BPH: Cistanche and Prostate Health
Among various herbal approaches, ingredients such as Cistanche deserticola-widely used in traditional formulas-are gaining attention for their protective effects on prostate health. Cistanche contains phenylethanoid glycosides (e.g., echinacoside, acteoside) known for their anti-inflammatory, antioxidant, and hormone-regulating properties. Studies have shown that Cistanche extracts can:
Reduce prostatic inflammation by downregulating pro-inflammatory cytokines (e.g., IL-6, TNF-α)
Modulate androgen levels to restore hormonal balance
Activate Nrf2 signaling, thereby enhancing the expression of antioxidant enzymes such as HO-1 and NQO1
Improve urinary symptoms and reduce prostate volume in experimental models
These benefits align closely with the findings of the current study, suggesting that formulas containing Cistanche-such as Kelong capsule-may exert their therapeutic effects through multi-target modulation of oxidative stress and inflammation in the prostate.
Materials and Methods
1. Animals
Male SD rats (6–8 weeks old, 200 ± 10 g) were obtained from the National Institutes for Food and Drug Control (License No. SCXK (Jing) 2022-0002). They were housed under standard conditions (temperature 20–25°C, humidity 40–60%) with ad libitum access to food and water.
2. Drugs and Reagents
Kelong capsule is a modified formula based on Jin Gui Shen Qi Wan, containing [Rehmannia glutinosa, Cornus officinalis, Poria cocos, Moutan cortex], and additional herbs such as astragalus, soy isoflavones, and pumpkin seed oil. The herbal extract was prepared by water decoction and vacuum drying. Other reagents included:
Finasteride (5 mg, Merck Sharp & Dohme)
Testosterone propionate (98%, Macklin Biotech)
ELISA kits for T, DHT, and E2 (Sabokang Biotech)
RNA extraction and qPCR reagents (Yisheng Biotech, Invitrogen)
HE staining kit (Jiuzhou Berlin Biotech)
3. Instruments
Biological tissue embedding systems, microtomes, PCR machines, and ELISA readers were used from Thermo Fisher, BioTek, Leica, and other standard lab suppliers.
Experimental Design
1. BPH Model Induction
After a 7-day acclimation, 60 rats were randomly assigned to control, sham, and BPH model groups. Bilateral orchiectomy was performed under anesthesia (sodium pentobarbital, 45 mg/kg) to induce androgen deficiency, followed by subcutaneous testosterone propionate injections (5 mg/kg) for 28 days to simulate BPH conditions. Sham-operated rats underwent scrotal incision without testis removal.
2. Grouping and Treatment
Model rats were further divided into model group, finasteride group (0.45 mg/kg), and high (14.4 g/kg), medium (7.2 g/kg), and low (3.6 g/kg) dose Kelong capsule groups. All treatments were administered via oral gavage for 28 days. Control and sham rats received distilled water.
3. Histology (HE Staining)
Prostate tissues were fixed in 4% paraformaldehyde, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. Microscopic evaluation was used to assess histopathological changes.
4. ELISA Analysis
Serum levels of testosterone, DHT, and estradiol were measured using commercial ELISA kits according to manufacturer instructions.
5. Real-Time PCR
Total RNA was extracted from prostate tissues using Trizol, reverse-transcribed to cDNA, and used for qPCR. The relative expression of Nrf2, NQO1, TNF-α, IL-1β, and IL-6 was calculated using the 2^-ΔΔCt method. Primer sequences are listed in Table 1.
