Punicalagin Exerts Protective Effects against Ankylosing Spondylitis by Regulating NF-B-TH17/JAK2/STAT3 Signaling and Oxidative Stress.
Biomed Res Int. 2020 ;2020:4918239. Epub 2020 Sep 23. PMID: 33029510
Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by sacroiliitis and spinal rigidity of the axial joints. The role of oxidative stress and increased proinflammatory cytokines is well documented in AS pathogenesis. Punicalagin (2,3-hexahydroxydiphenoyl-gallagyl-D-glucose), an ellagitannin widely present in pomegranates, is found to exhibit potent anti-inflammatory, antiproliferative, and antioxidative effects. The present study was undertaken to investigate the effects of punicalagin in a rodent model of AS.
Methods: BALB/c mice induced spondylitis were sacrificed 24 h after the last injection of proteoglycan extract. Histological scoring was done to assess the degree of the disease. The expression of JAK2/STAT3 proteins and proteins of the nuclear factor-B (NF-B) pathway was determined by immunoblotting. Serum levels of inflammatory mediators-TNF-, IL-1, IL-6, IL-17A, and IL-23-were assessed. Levels of lipid peroxidation and reactive oxygen species (ROS) were quantified. Antioxidant status as a measure of activities of antioxidant enzymes-catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)-was determined.
Results: Punicalagin effectively improved antioxidant status and decreased lipid peroxidation, ROS production, and serum levels of inflammatory mediators. NF-B pathway and JAK2/STAT3 signaling were significantly (<0.05) downregulated. Punicalagin effectively regulated the production of cytokines by the Th17 cells and the IL-17A/IL-23 axis.
Conclusion: The observations suggest that punicalagin exerts a protective role in AS via reducing oxidative stress and regulating NF-B/TH17/JAK2/STAT3 signal. Punicalagin thus could be explored further as a potent candidate compound in the treatment of AS.