[Ningmitai Capsules alleviate CP/CPPS symptoms by regulating Nrf2 and NF-κB signaling pathways]

Abstract

Objective: To investigate the therapeutic effect of Ningmitai Capsules (NMT) on chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) and its action mechanism.

Methods: We equally randomized fifteen 6－8 weeks old male Wistar rats into a sham operation, a model control and an NMT group, and established a CP/CPPS model in the rats by intra-prostatic injection of complete Freund adjuvant (CFA). We treated the rats in the sham operation and model control groups by injection of aseptic phosphate buffer saline (PBS) and 50 μl complete Freund adjuvant (CFA), respectively, into the ventral lobe of the prostate followed by gavage with purified water from the second day after surgery, and those in the NMT group with 50 μl CFA injected into the ventral lobe of the prostate followed by gavage with 3 ml NMT suspension at 400 mg/kg/d from the second day after surgery. After 4 weeks of treatment, we killed the animals and collected the serum and prostatic tissue samples for evaluation of the severity of prostatitis by histopathological grading of chronic prostatitis through HE staining, determination of the mRNA expressions of inflammatory factors by real-time quantitative PCR, measurement of the activities of related antioxidant enzymes with testing kits, and detection of the expressions of the related targets in the signaling pathways by Western blot.

Results: Histopathological examination revealed different degrees of inflammatory cell infiltration in the mesenchyme, inflammatory vacuoles, irregularly shaped acini in the model control group, with a significantly higher inflammation score than in the sham operation group (P<0.05), and reduced infiltrating lymphocytes, inflammatory vacuoles and inflammation score in the NMT group compared with those in the model controls (P<0.05). Compared with the rats in the sham operation group, the model controls showed remarkably up-regulated expressions of IL-1β, IL-6, IL-10, IL-17A, TNF-α and IFN-γ (P<0.05), decreased contents of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) (P<0.05), and increased content of malondialdehyde (MDA) (P<0.05). Compared with the model controls, the rats treated with NMT exhibited markedly reduced expressions of IL-1β, IL-6, IL-10, IL-17A, TNF-α and IFN-γ (P<0.05), increased contents of SOD, CAT and GSH-Px (P<0.05), decreased content of MDA (P<0.05), up-regulated expressions of nuclear factor red 2-related factor 2 (n-Nrf2) and heme oxygenase-1 (HO-1) (P<0.05), and down-regulated expression of NF-κB P-P65 (P<0.05).

Conclusion: NMT plays anti-oxidation and anti-inflammation roles in the pathogenesis of CP/CPPS, possibly by activation of Nrf2 and suppression of NF-κB signaling pathways.

Keywords: Ningmitai Capsules; chronic prostatitis / chronic pelvic pain syndrome; anti-inflammation; anti-oxidation; Nrf2 and NF-κB signaling pathways; rat.