Anti-SARS-CoV-2 Activity of Rhamnan Sulfate from Monostroma nitidum.

The COVID-19 pandemic is a major human health concern. The pathogen responsible for COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), invades its host through the interaction of its spike (S) protein with a host cell receptor, angiotensin-converting enzyme 2 (ACE2). In addition to ACE2, heparan sulfate (HS) on the surface of host cells also plays a significant role as a co-receptor. Our previous studies demonstrated that sulfated glycans, such as heparin and fucoidans, show anti-COVID-19 activities. In the current study, rhamnan sulfate (RS), a polysaccharide with a rhamnose backbone from a green seaweed, Monostroma nitidum, was evaluated for binding to the S-protein from SARS-CoV-2 and inhibition of viral infectivity in vitro. The structural characteristics of RS were investigated by determining its monosaccharide composition and performing two-dimensional nuclear magnetic resonance. RS inhibition of the interaction of heparin, a highly sulfated HS, with the SARS-CoV-2 spike protein (from wild type and different mutant variants) was studied using surface plasmon resonance (SPR). In competitive binding studies, the IC50 of RS against the S-protein receptor binding domain (RBD) binding to immobilized heparin was 1.6 ng/mL, which is much lower than the IC50 for heparin (~750 ng/mL). RS showed stronger inhibition than heparin on the S-protein RBD or pseudoviral particles binding to immobilized heparin. Finally, in an in vitro cell-based assay, RS showed strong antiviral activities against wild type SARS-CoV-2 and the delta variant.

Effects of a combined fucoidan and traditional Chinese medicine formula on hyperglycaemia and diabetic nephropathy in a type II diabetes mellitus rat model.

In this study, we innovatively propose a fucoidan mixed with traditional Chinese medicine formula (FCM) and evaluate its effects on hyperglycaemia and diabetic nephropathy in a type II diabetes mellitus Wistar rat model. After treatment with FCM for 8 weeks, the blood glucose, insulin resistance, serum lipid and antioxidant stress levels were significantly decreased (P < 0.05 or P < 0.01, vs. negative group). Via gene expression analysis, we found that three genes (InsR, GCK and GLUT-2) in the glucose metabolism pathway were significantly increased (P < 0.01, vs. negative group) in the FCM-treated groups and play important roles in hypoglycaemic activity. Moreover, FCM treatments alleviated (P < 0.01, vs. negative group) the urine protein, urine creatinine and pathological changes in the kidneys, producing significant improvements in renal function and structure. In summary, FCM exerts protective effects in diabetic rats and could be used in medicinal treatment for diabetes mellitus and its complications.

In vitro and in vivo immunomodulatory effects of fucoidan compound agents.

Fucoidan extracted from brown algae displays diverse biological activities. In the present study, fucoidan was mixed with Chinese herb extracts, and the in vitro and in vivo immunomodulatory effects of two fucoidan compound agents were evaluated. The results showed that fucoidan from Kjellmaniella crassifolia (KF) and Undaria pinnatifida (UF) were sulfated polysaccharides, Astragalus polysaccharide (AP) was composed of α-d-glucose, and Codonopsis pilosula polysaccharide (CPP) was a furanose. Furthermore, fucoidan compound agents stimulated mouse macrophage RAW264.7 cell proliferation and enhanced the secretion of granulocyte-macrophage colony stimulating factor (GM-CSF) and tumour necrosis factor-α (TNF-α) in vitro. In addition, KCA (KF + AP + CPP) and UCA (UF + AP + CPP) could improve the nonspecific immunity and the specific immunity of BALB/c mice. Fucoidan compound agents also increased the secretion of GM-CSF, TNF-α, interleukin (IL)-4 and IL-10 in vivo. Therefore, we confirmed that fucoidan compound agents have promise for development as supplementary immunopotentiators.