Sulfated Pelvetia siliquosa Polysaccharides Inhibit CaOx Stone Formation by Inhibiting Calcium Oxalate Crystallization, Cellular Inflammation, and Crystal Adhesion

Hyperoxaluria can easily induce calcium oxalate (CaOx) crystals and cause cell damage, thereby increasing the risk of kidney stone formation. In this study, three sulfated Pelvetia siliquosa polysaccharides (PSPs) were obtained by the sulfur trioxide-pyridine method. The antioxidant activity of PSPs and the inhibitory effects of PSPs on CaOx crystallization, cellular oxidative damage, and cellular inflammation were explored in vitro, and PSPs were used to treat hyperoxaluria-induced crystallization model mice in order to validate the stone-preventive effect of PSPs in vivo. PSPs can inhibit CaOx crystal formation, as well as reduce reactive oxygen species (ROS) levels through their own antioxidant properties and up-regulation of antioxidant enzyme (SOD and CAT) expression, which in turn reduces the release of lactate dehydrogenase (LDH) and malondialdehyde (MDA), improves lysosomal integrity, cellular morphology, and cytoskeleton, inhibits the decrease of mitochondrial membrane potential, reduces adhesion protein (CD44 and OPN) expression, alleviates cellular inflammatory factor (IL-6, TNF-α, and IL-1β) levels, and inhibits apoptosis. PSP3, which has the highest degree of sulfation, had the best protection capacity. PSP3 also showed good antistone ability in mice, and it may be a potential drug for kidney stone prevention.