Yonger Chen

Current evidences suggest that hyperuricemia is closely related to the overproduction or underexcretion of uric acid (UA). Curcumin (CUR), a natural polyphenol component extracted from the rhizome of Curcuma longa, has been reported to treat various symptoms such inflammation disease, seems to be efficacious in hyperuricemia. In this study, we aimed to investigate the effect of CUR on hyperuricemia and kidney inflammation in hyperuricemic mice. Administration with CUR (20 or 40 mg/kg) or allopurinol (ALL, 5 mg/kg) was given to mice orally one hour later after the injection of potassium oxonate (PO) (300 mg/kg, i.p.) for 14 days. CUR administration decreased the levels of uric acid (UA), creatinine (CRE) and blood urea nitrogen (BUN) in serum. Meanwhile, treatment with CUR effectively inhibited serum and liver xanthine oxidase (XOD) levels, and further renewed normal antioxidant enzymes activities (SOD, GSH-Px), reduced MDA accumulation in serum. Further studies showed that CUR decreased inflammatory cytokines productions (IL-1β, IL-18) in serum, as well as inhibited PO-induced the activation of NLRP3 inflammasome signaling in the kidney. In conclusion, the study revealed that CUR exhibited anti-hyperuricemic and anti-inflammatory effects through suppressing NLRP3 inflammasome activation in kidney and provided the evidence for treating hyperuricemia and associated renal inflammation.

Colitis-associated colorectal cancer (CAC) frequently develops in patients with inflammatory bowel disease (IBD) who have been exposed to a prolonged state of chronic inflammation. The investigation of pharmacological agents and their mechanisms to prevent precancerous lesions and inhibit their progression remains a significant focus and challenge in CAC research. Previous studies have demonstrated that vitexin effectively mitigates CAC, however, its precise mechanism of action warrants further exploration. This study reveals that the absence of the Vitamin D receptor (VDR) accelerates the progression from chronic colitis to colorectal cancer. Our findings indicate that vitexin can specifically target the VDR protein, facilitating its translocation into the cell nucleus to exert transcriptional activity. Additionally, through a co-culture model of macrophages and cancer cells, we observed that vitexin promotes the polarization of macrophages towards the M1 phenotype, a process that is dependent on VDR. Furthermore, ChIP-seq analysis revealed that vitexin regulates the transcriptional activation of phenazine biosynthesis-like domain protein (PBLD) via VDR. ChIP assays and dual luciferase reporter assays were employed to identify the functional PBLD regulatory region, confirming that the VDR/PBLD pathway is critical for vitexin-mediated regulation of macrophage polarization. Finally, in a mouse model with myeloid VDR gene knockout, we found that the protective effects of vitexin were abolished in mid-stage CAC. In summary, our study establishes that vitexin targets VDR and modulates macrophage polarization through the VDR/PBLD pathway, thereby alleviating the transition from chronic colitis to colorectal cancer.