The anti-osteoporotic effect of naringenin is clear, and its mechanism involves multi-pathway regulation, which is analyzed below:
Anti-osteoporosis effect
Inhibit osteoclast differentiation and function: naringin can inhibit specific gene expression during osteoclast differentiation, down-regulate the expression of RANK, TRAP, MMP-9. NFATc1 mRNA, and up-regulate the expression of C-fos mRNA, which can reduce the number and activity of osteoclasts and inhibit bone resorption.
Promote osteoblast proliferation and differentiation: Naringin can increase the expression of osteoblast marker proteins (e.g. osteocalcin, osteoblastin, osteoprotegerin, and bone-forming protein-2), and up-regulate the expression of osteogenesis-related genes (e.g. Runx2. Osx, and collagen type I α1 chain), thus promoting osteoblast proliferation, differentiation and mineralization.
Regulation of bone metabolism-related signaling pathways: Naringin can regulate ERK, PI3K/Akt, Wnt/β-catenin and other related signaling pathways, activate osteoblast signaling, inhibit osteoclastogenesis, thus regulating the balance of bone metabolism.
Anti-osteoporosis mechanism
Estrogen-like effect: Naringin has phytoestrogenic activity, which can stimulate osteoblast proliferation through estrogen receptor mimicking estradiol, up-regulate alkaline phosphatase mRNA expression activity, promote osteogenesis, enhance osteoprotegerin/RANKL mRNA expression activity, and inhibit osteoclastogenesis.
Activation of Wnt/β-catenin signaling pathway: Naringin activates the Wnt/β-catenin signaling pathway by promoting the secretion of Sema3A from osteoblasts and osteoclasts, which enhances bone formation in osteoblasts and inhibits osteoclastogenesis.
Regulation of autophagy-related proteins: Naringin can increase the expression of autophagy-related factor Beclin-1 in osteoblasts, decrease the expression of p62. increase the rate of positive cells and the number of autophagic vesicles, promote autophagy in osteoblasts, maintain the stable state of osteoblasts, and improve the proliferation and differentiation of osteoblasts.
Anti-oxidative stress: Naringin can remove free radicals (such as DPPH, AAPH, ABTS, etc.), antagonize their attack on cells, inhibit the generation of ROS, block the oxidative reaction of the body, regulate the content of many oxidative enzymes in the body, such as SOD, GSH, GST, MDA, MPO, etc., and repair the damage caused by oxidative stress in the body, thus protecting osteoblasts from oxidative damage.
Improve bone microstructure and mechanical properties: Naringin can increase bone density, trabecular thickness, bone mineralization and mechanical strength, reduce in vitro bone resorption, improve bone microstructure, and improve the biomechanical strength of bone.