Abstract
This research aims to study the effects of curcuminoids-rich extract (CRE) carried by
hydroxypropyl-β-cyclodextrin-polyvinylpyrrolidone K30, termed CRE-Ter, on bone formation,
osteoclast inhibition, and reduced muscle atrophy on both cellular and animal levels. The cellular
studies found that CRE-Ter can stimulate bone formation by creating Alkaline phosphatase (ALP),
stimulating calcium mineralization, stimulating the bone genes such as Bmp-2, Runx2, collagen
1a and increasing Wnt β-catenin intracellular signaling. In addition, CRE-Ter inhibits the formation
of TRAP and Cathepsin K, which are important for the osteoclast cell differentiation. Furthermore,
CRE-Ter stimulates the formation of atrophied muscle cells by reducing the formation of TNF-α
and IL-6, increasing nitric oxide, stimulating the irisin muscle gene and increasing the intracellular
signaling, p38 and Wnt β-catenin. The insight binding ligands between CRE-Ter and irisin in cell is
demonstrated by molecular docking. The results of animal experiments show that CRE-Ter is not
toxic to the liver and kidneys. CRE-Ter stimulates ALP and osteocalcin which are related to
increased bone formation. CRE-Ter reduces TRAP enzyme which is related to the inhibition of
bone resorption. In addition, studies in sarcopenic mice found that CRE-Ter increased muscle grip
strength, the weight of the gastrocnemius calf muscle and muscle fibers when compared to the
control group. In addition, CRE-Ter reduces the expression of MuRF1 and NF-κB proteins. The
results of all studies at both the cellular and animal levels conclude that CRE-Ter could be
developed as a drug for the treatment of osteoporosis and sarcopenia in the future.
