Protective effects of a polysaccharide BLE0 isolated from barley leaf on bone loss in ovariectomized mice

Potent anti-osteoporotic drugs have been developed over the past decades; however, the substantial need for treatments that can effectively and safely manage osteoporosis remains unmet. Barley leaf-derived products are one of best functional foods that can be used as nutritional supplements and detoxifiers in humans and are beneficial in improving bone disease. However, little information is available regarding the anti-osteoporotic effects of polysaccharides as the main component of barley leaf. This study aimed to clarify the beneficial effects of barley leaf (BLE0) polysaccharides on bone loss in ovariectomized mice and osteoclast differentiation in bone marrow-derived macrophages. BLE0 remarkably inhibited receptor activator of the nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in a dose-dependent manner. It also blocked RANKL-induced activation of osteoclastogenic signals including ERK and p38 and the expression of nuclear factor of activated T cells cytoplasmic 1, as a master regulator of osteoclast differentiation, leading to decreased expression of osteoclast-specific marker genes such as Atp6v0d2, DC-STAMP and cathepsin K. Micro-computed tomography revealed that a seven-week oral administration of BLE0 dramatically improved ovariectomy-induced trabecular bone loss. Anti-osteoporotic effects were confirmed using morphometric analysis. Taken together, BLE0 is a bioactive polysaccharide; it mitigates estrogen deficiency-induced bone loss by directly inhibiting osteoclast differentiation.