The rock oyster, Saccostrea cucullata, native to the Indo-Pacific region, is widely recognized for its nutritional and therapeutic benefits. A sulfated glycosaminoglycan (SCP-2) with β-(1 → 3)-GlcNSp and α-(1 → 4)-GlcAp as recurring units was isolated from S. cucullata. SCP-2 exhibited substantial 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) inhibition potential (IC50 0.65 mg/mL) in comparison with atorvastatin (IC50 0.72 mg/mL). An in vitro study of SCP-2 (0.1–160 μg/dL) revealed a 77–89 % reduction in triglyceride levels in Caco-2 cells after 4 days of incubation, similar to atorvastatin-treated cells (90 %). The efficacy of SCP-2 (at 90 mg/kg body weight) showed timely alleviation of triglyceride and cholesterol levels in tyloxapol-induced dyslipidemic rats (∼43 % and 81 % inhibition at 5 h), which was analogous to the atorvastatin treatment group (∼66 % and 71 %). Furthermore, SCP-2 (at 90 mg/kg body weight) showed mitigation in triglyceride (>50 %) and cholesterol levels (>25 %) in high-fat high-cholesterol (HFHC) diet-induced rats, similar to the lovastatin treatment group (approximately 62 % and 33 % inhibition on the 45th day). Histopathological studies of SCP-2 also showed recovery in ballooning degeneration, steatosis, and inflammation in liver tissues. Structure-activity relationship analysis suggested the importance of sulfate group in SCP-2 in contributing to its anti-dyslipidemic efficacy. The capability of SCP-2 to mitigate cholesterol, triglyceride, and HMGCR levels positions it as a promising functional food against dyslipidemia-related disorders
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