Article Type: Apigenin alleviated peritoneal dialysis-related peritoneal fibrosis by regulating pyroptosis

Prolonged exposure of the peritoneum to peritoneal dialysis fluid, peritonitis, and peritoneal blood accumulation can cause peritoneal inflammation and injury, followed by progressive fibrosis, ultimately leading to the cessation of peritoneal dialysis. Apigenin is an herbal medicine with anti-inflammatory, antioxidant, and anti-fibrotic properties. Our previous study found that apigenin could inhibit the process of peritoneal fibrosis, but whether apigenin could treat fibrosis by inhibiting pyroptosis is not known. This study aimed to investigate the protective effects of apigenin against peritoneal mesothelial cell pyroptosis and fibrosis. First, we observed changes in peritoneal mesothelial cells using VX-765, an inhibitor of cellular pyroptosis. Western blotting, immunoblotting, and electron microscopy showed that cellular pyroptosis was significantly inhibited, and peritoneal mesothelial cell fibrosis was reduced accordingly. Secondly, when the cells were co-treated with high glucose medium and apigenin, apigenin attenuated the activation of cellular pyroptosis by decreasing the levels of Gasdermin D, NOD-like receptor protein 3 inflammatory niche activation, caspase-1 and IL-1β and also inhibited the development of peritoneal fibrosis. Thus, our results suggest that apigenin plays a protective role against peritoneal fibrosis by inhibiting pyroptosis.