Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) affects an estimated 35–50% of the male population at some point in their lives (COLLINS M M, STAFFORD R S, O′LEARY M P, et al., 1998, SCHWARTZ et al., 2015, REES et al., 2015). This disorder also has negative impacts on sperm and the quality of life (Schaeffer et al., 2006), which is often marked by pelvic or perineal pain, urinary discomfort, mental health problems, and sexual impairment. Therapeutic options, such as physiotherapy, α-blockers, drugs for inflammation, and neuroleptics, are not adequate for addressing the needs of both patients and clinicians due to the incomplete understanding of the etiology of CP/CPPS (MAGISTRO et al., 2016, POLACKWICH and SHOSKES, 2016). Thus, there is an urgent need for a novel therapeutic intervention for CP/CPPS and an improved understanding of its etiology.

Isoliquiritigenin (ISL), a simple chalcone flavonoid extracted from the roots of Glycyrrhiza species, has a variety of properties, including antioxidant, antiviral, anti-inflammatory, and antitumor functions (YAMAMOTO et al., 1991, YADAV et al., 2011, JIN et al., 2016). It is worth noting that ISL exhibits a remarkable anti-inflammatory impact on intracranial hemorrhage, diabetic nephropathy, and liver damage in animal experiments (Leeet al., 2009). Recently, Honda et al. (2014) reported that ISL can significantly reduce NLRP3 inflammasome activation by inhibiting caspase recruitment domain (ASC) oligomerization in bone marrow-derived macrophages in mice. Therefore, this study aimed to assess the anti-inflammatory effects of ISL on the experimental autoimmune prostatitis (EAP) model and explore the possible anti-inflammatory mechanism.

The NLRP3 inflammasome is formed by the complexation of ASC, procaspase-1, and NOD-like receptor protein 3 (NLRP3) (Jo et al., 2016). After triggering the NLRP3 inflammasome, procaspase-1 is spontaneously cleaved and reactivated to form caspase-1 which stimulates the production of pro-inflammatory mediators including IL-18 and IL-1β that induce tissue injury and inflammation (Strowig et al., 2012). Recent research suggests that activation of the NLRP3 inflammasome complicates the pelvic pain and inflammation of prostate tissue in EAP (ZHANG et al., 2019, ZANG et al., 2021). Consequently, therapeutic options that prevent inflammasome activation may represent novel alternative treatments for patients with CP/CPPS. In addition, an imbalance between peroxides and antioxidants, or oxidative stress (OS), also contributes to CP/CPPS development (Chen et al., 2020). Increased levels of OS in patients with CP/CPPS can induce inflammatory reactions and trigger several detrimental consequences, such as erectile dysfunction and infertility (HU et al., 2016, POTTS and PASQUALOTTO, 2003). Hence, targeting these mechanisms could potentially serve as a viable treatment modality for patients diagnosed with CP/CPPS (Shahed and Shoskes, 2000).

Here, a mouse model of EAP was established to explore the anti-inflammatory mechanism of ISL in CP/CPPS. Plasma inflammatory cytokine expression levels were determined, the level of pelvic pain was evaluated, and the histological characteristics of prostate tissues were examined following ISL treatment. Corresponding cellular experiments were performed for the systematic investigation of the mechanism underlying ISL inhibition of the inflammatory response.