Cistanche-Based Herbal Formula Alleviates Type III Chronic Prostatitis By Inhibiting NLRP3 Inflammasome Activation And Pyroptosis

3. Results

3.1 Animal Experiment

3.1.1 Effect of Cistanche-Based Formula on Prostate Tissue Pathology in CP Rats

In the control group, the prostate gland epithelium and stroma appeared normal, with well-arranged and regular acini, and no inflammatory cell infiltration. In contrast, the model group showed significant pathological damage, including epithelial degeneration, thickened capsule, stromal edema, and massive inflammatory cell infiltration, particularly in the stroma. Enlarged blood vessels and congestion were also observed.

Compared to the model group, rats in the low, medium, and high-dose Cistanche groups showed reduced inflammatory cell infiltration, alleviated epithelial degeneration and stromal edema, and overall milder tissue damage (Figure 1).

Figure 1: Histopathological changes in prostate tissue assessed by HE staining (×100 magnification)

A: Control group

B: Model group

C: Low-dose Cistanche group

D: Medium-dose Cistanche group

E: High-dose Cistanche group

 

3.1.2 Effect of Cistanche Formula on Serum IL-1β and IL-18 Levels in CP Rats

Compared to the control group, the model group showed significantly elevated serum IL-1β and IL-18 levels (P < 0.01). Treatment with Cistanche at all three doses significantly reduced these cytokines (P < 0.01) (Table 1).

Table 1: Effect of Cistanche on IL-1β and IL-18 levels (𝑥̅ ± s, n = 10)

3.1.3 Effect of Cistanche Formula on Serum MDA, SOD, and GSH-Px Levels

In the model group, MDA levels were significantly increased (P < 0.01), while SOD and GSH-Px levels were significantly decreased (P < 0.05), indicating oxidative stress.

Treatment with Cistanche significantly:

Reduced MDA levels (P < 0.01)

Increased SOD levels (P < 0.01)

Increased GSH-Px levels (P < 0.05)

Table 2: Effect of Cistanche formula on oxidative stress markers in CP rats

 

 

Cistanche Formula Supplements For chronic prostatitis (CP)

Buy Now

 

 

 

4. Discussion

With shifts in modern lifestyle, the incidence of chronic prostatitis (CP), especially Type III prostatitis (CP/CPPS), is steadily increasing. CP/CPPS is characterized by pelvic pain, urinary dysfunction, and can lead to psychological disorders and sexual dysfunction, severely impacting quality of life. Current therapies (e.g., α-blockers, antibiotics, NSAIDs) often yield unsatisfactory results or frequent relapse, leading to low treatment satisfaction [18].

The Cistanche-based herbal formula was developed based on TCM principles targeting damp-heat and blood stasis syndromes. Cistanche, traditionally used for its tonifying, anti-inflammatory, and antioxidative properties, replaces other primary herbs in this optimized formula. It is combined with detoxifying and blood-activating herbs to achieve synergistic therapeutic effects.

Recent pharmacological studies have emphasized the role of immune dysfunction, oxidative stress, and proinflammatory cytokine imbalance in CP pathogenesis [19–20]. Among these, IL-1β and IL-18 are key proinflammatory mediators that contribute to inflammatory cascades in CP development [21–22]. Their overexpression correlates with disease severity [23–25].

The NLRP3 inflammasome plays a central role in mediating the release of IL-1β and IL-18 and triggers pyroptosis - a form of programmed cell death associated with inflammation [26–27]. Upon activation, NLRP3 activates Caspase-1, which cleaves GSDMD, forming pores in the cell membrane, leading to cell lysis and release of inflammatory contents such as LDH, IL-1β, and IL-18 [28–30].

This study demonstrated that Cistanche treatment:

Reduced inflammatory cell infiltration and tissue damage in the prostate.

Significantly lowered serum IL-1β, IL-18, and MDA levels.

Upregulated SOD and GSH-Px, reducing oxidative stress.

Decreased NLRP3 expression, as confirmed by immunohistochemistry and Western blot.

Furthermore, Western blot analysis revealed significantly elevated levels of NLRP3, Caspase-1, and GSDMD in the model group, all of which were markedly reduced following Cistanche intervention. These findings align with previous research indicating that Cistanche may inhibit NF-κB signaling, thereby suppressing NLRP3 inflammasome assembly [14].

In cellular assays, LPS and ATP stimulation led to activation of the classic pyroptosis pathway, evidenced by increased protein expression of NLRP3, Caspase-1, and GSDMD, along with elevated IL-1β and IL-18 release. Treatment with Cistanche-containing serum significantly suppressed these markers, reduced cell death, and inhibited pyroptosis.

Conclusion

This study confirms that the Cistanche-based herbal formula exerts its therapeutic effect on Type III chronic prostatitis by:

Inhibiting NLRP3 inflammasome activation

Suppressing Caspase-1 and GSDMD expression

Reducing the release of IL-1β and IL-18

Alleviating oxidative stress and pyroptosis-induced inflammation

These results suggest that Cistanche is a promising natural treatment for chronic prostatitis, offering multi-targeted anti-inflammatory and antioxidant actions through modulation of the NLRP3/Caspase-1/GSDMD signaling pathway.