Therapeutic mechanism of Qingre Tonglin capsules (QRTL) in CNP via inflammasome suppression.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, Qingre Tonglin Capsule (QRTL) has demonstrated efficacy and broad prospects in treating Chronic Non-bacterial Prostatitis (CNP). Experimental studies have demonstrated that QRTL can improve symptoms and alleviate inflammation in CNP rats. However, the mechanisms of action and active components remain unclear. These uncertainties restrict its clinical use and necessitate systematic research to clarify them.

AIM OF THE STUDY: This study aimed to investigate the protective effect of QRTL on a rat model of chronic non-bacterial prostatitis and an inflammation model of human prostate immortalized stromal cells (WPMY-1), and to clarify the underlying mechanisms.

MATERIALS AND

METHODS

In this study, we used carrageenan to establish a rat model of CNP and lipopolysaccharide (LPS) to induce inflammation in WPMY-1. We employed UHPLC-HRMS to identify the bioavailable components of QRTL, and predicted potential mechanisms through network pharmacology. Additionally, we conducted in vitro and ex vivo experiments to further investigate the anti-inflammatory and cell death-modulating effects. The therapeutic mechanism of QRTL on CNP was elucidated by demonstrating its inhibition of inflammatory responses, which in turn reduced pyroptosis.

RESULTS

QRTL treatment significantly reduced the prostate index, serum prostate-specific antigen (PSA) level, and MDA content, increased SOD activity, attenuated prostate tissue damage, and inhibited fibrosis in rats with CNP. QRTL-containing serum lowered the levels of inflammatory cytokines in LPS-induced WPMY-1 cells in a dose-dependent manner. UHPLC-HRMS identified 23 active components of QRTL in the blood. Furthermore, the key components (Justicidin B, Matrine, and Oxymatrine) interacted with 34 inflammation-related targets identified by network pharmacology. These components mainly regulated signaling pathways such as Toll-like receptors and NOD-like receptors, inhibited inflammasome formation, and modulated the Bcl2/BAX pathway to reduce apoptosis.

CONCLUSIONS

The significant therapeutic effect of QRTL and their active ingredients on CNP is likely related to the modulation of the TLR4/NLRP3 signaling pathway, leading to the inhibition of programmed cell death mediated by inflammation. Additionally, the modulation of the BAX pathway exerted a cytoprotective effect. These findings have provided a pharmacological basis for the clinical application of QRTL.