Low molecular weight fucoidan

Low molecular weight fucoidan (LMWF) has been proved to be more potent than its prototype, many degradation methods have been used to prepare LMWF. This study is conducted to further explore the biological activities of LMWF prepared by ultrasound based on anticoagulation, antioxidation, and inhibition of urate induced pyroptosis and reabsorption transporters overexpression in human renal tubular epithelial cells. Data revealed that ultrasound successfully degraded fucoidan to be LMWF, the product treated for no more than 2.5 h has stronger in vitro anticoagulant activity that reached the peak value at 2.5 h demonstrated by notably increased activated partial thromboplastin time (APTT) and prothrombin time (PT), but antioxidation progressively reduced along with treatment time indicated by decreased scavenging capacity of DPPH and hydroxyl radicals. LMWF with higher content of sulfate acid group possesses stronger inhibitory activity of urate-induced overexpression of urate-reabsorption transporters and pyroptosis in human renal tubular epithelial cells than native fucoidan. Degradation kinetics model of fucoidan exposed to ultrasonic treatment was best fitted to the second-order kinetic equation. These results indicate that LMWF is more effective for renal protection and anticoagulation than high molecular weight fucoidan, suggesting LMWF is a more promising marine drug.

Fucoidan, a sulfated polysaccharide with a complex structure, has gradually become the focus of biomedical research due to its remarkable biological activity and low toxicity. In this research, it was noted that low molecular weight fucoidan (LMWF) exhibited significant antimicrobial effects on Methicillin-resistant Staphylococcus aureus (MRSA) and promoted polarization towards M2 macrophages, leading to a substantial reduction in inflammatory responses within the lipopolysaccharide (LPS)-activated macrophages. We further explored the mechanism underlying the anti-inflammation activity. Our findings indicated that LMWF significantly enhanced the phosphorylation level of AMP-activated protein kinase (AMPK), inhibited the phosphorylation of the mammalian target of rapamycin (mTOR), and enhanced the expression of LC3II. Meanwhile, Compound C (CC) substantially reversed the anti-inflammation effect of LMWF, indicating that the AMPK pathway plays a pivotal role in this effect. In in vivo research, LMWF revealed impressive anti-inflammatory potential. LMWF treatment significantly eliminated MRSA and ameliorated inflammatory symptoms in mice's MRSA-infected skin wound model. Further analysis using Western Blot (WB) indicated significant AMPK/mTOR signaling pathway activation in mice treated with LMWF, which led to accelerated polarization of macrophages from the M1 to the M2 phenotype. In summary, we systematically explored the mechanism by which LMWF exerts anti-inflammatory effects through in vitro and in vivo experiments. It was confirmed that LMWF effectively induced the conversion of macrophages to an anti-inflammatory M2 phenotype by activating the AMPK/mTOR pathway. Simultaneously, LMWF effectively eradicated MRSA and accelerated wound healing in mice. This finding provides an important theoretical basis for further research on fucoidan.