Sea cucumber enzymatic hydrolysates relieve osteoporosis through OPG/RANK/RANKL system in ovariectomized rats

Osteoporosis harms human health and has a variety of causes, among which the imbalance of bone metabolism caused by menopause is an important one. Studies have shown that sea cucumbers have a variety of physiological activities such as anti-inflammation. Sea cucumber enzymatic hydrolysates (SCEH) were prepared and characterized for peptides and polysaccharides, and then the effects on relieving osteoporosis were explored by feeding ovariectomized Sprague-Dawley rats for 90 days. Bone density and microstructure were measured using micro-CT and pathological sectioning. Serum markers for bone metabolism, and inflammation were measured using ELISA kits. Gene transcription and expression of the OPG/RANKL system in bone were measured using qRT-PCR and western blots. Results showed that SCEH could improve the bone density, strength, microstructure and mass, and inhibit the generation of osteoclasts. The abnormally elevated markers for bone resorption, formation and inflammation were reduced with the intake of SCEH. The mRNA and protein expressions of RANKL were also decreased by feeding SCEH, thereby up-regulating the ratio of OPG to RANKL. These results suggested that SCEH could inhibit the bone resorption by inhibiting the NF-κB pathway related to osteoclast generation via the down-regulation of both the RANKL level and inflammatory response, and also improve the balance of bone metabolism, thus obtaining the effects of increasing bone density and relieving osteoporosis. SCEH with a medium-dose (1000 mg/kg body weight) had the best remission effect and could be used as a potential starting material to develop healthy foods that can assist in treating osteoporosis.