BACKGROUND:Recent studies have shown that the Notch signaling pathway plays a varying role in osteoporosis,and in-depth research in this field is of great significance to the prevention and treatment of osteoporosis.Traditional Chinese medicine has become the focus of research in today's society due to its obvious multi-faceted,multi-level benefits in alleviating osteoporosis with less adverse effects. OBJECTIVE:To analyze and summarize domestic and international literature to further understand the connection between the Notch signaling pathway and osteoporosis and to elucidate the mechanism by which traditional Chinese medicine prevents and treats osteoporosis via the Notch signaling pathway. METHODS:CNKI,WanFang,and VIP were searched with the keywords of"Notch,osteoporosis,osteoblasts,osteoclasts,bone marrow mesenchymal stem cells,signaling pathway,traditional Chinese medicine,pill,experiment"in Chinese.PubMed,Nature,and Embase were retrieved using the keywords of"Notch,osteoporosis,osteoblasts,osteoclasts,mesenchymal stem cells,signal pathway,traditional Chinese medicine,pill,experiment"in English.The search time was from database inception to October 2022. RESULTS AND CONCLUSION:The Notch signaling pathway plays a role in the development and progression of osteoporosis to varying degrees by regulating the differentiation and proliferation of mesenchymal stem cells,osteoblasts and osteoclasts.The Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells,osteoblasts and osteoclasts by directly or indirectly regulating key cytokines such as Notch1,Jagged1,Hes,Hey,macrophage colony-stimulating factor and nuclear factor-κB receptor-activating factor ligand,which in turn promotes or inhibits bone formation and ultimately has a certain effect on the prevention and treatment of osteoporosis.The active ingredients of Chinese herbs are mostly extracted from herbs for kidney tonifying,such as Epimedium,Cortex Eucommiae,Malaytea Scurfpea Fruit,Eleutherococcus Senticosus,Ligustrum Lucidum.Moreover,herbal compounds and preparations have the effect of tonifying kidney and strengthening bone,which provides more herbal options and directions for the subsequent study of Notch signaling pathway toward the prevention and treatment of osteoporosis.Current studies on traditional Chinese medicine mainly focus on active ingredients and single herbal extracts,with relatively few clinical trials on Chinese herbal compounds and preparations.Fewer studies have been conducted on the regulation of Notch signaling pathways by acupuncture,manipulation,and integrated Chinese and Western medicine to prevent and treat osteoporosis.Therefore,there is a need to explore the mechanisms by which traditional Chinese medicine technology-based therapies and integrated Chinese and Western medicine regulate the Notch signaling pathway to treat osteoporosis.

BACKGROUND:The nuclear factor-κB signaling pathway plays an important role in the pathogenesis of osteoporosis.In recent years,increasing studies have shown that terpenoid herbal monomer compounds can inhibit the activity of bone resorbing cells and promote the differentiation of bone forming cells via the nuclear factor-κB signaling pathway,thus reducing bone resorption and increasing bone formation,which has certain preventive and therapeutic effects on osteoporosis. OBJECTIVE:By analyzing and summarizing the domestic and international literature,to investigate the relationship between nuclear factor-κB signaling pathway and osteoporosis in depth,elucidate the mechanism of terpenoid monomer compounds in regulating the nuclear factor-κB signaling pathway to prevent osteoporosis,and systematically summarize the terpenoid monomer compounds targeting to regulate the nuclear factor-κB signaling pathway to prevent osteoporosis. METHODS:According to the proposed inclusion and exclusion criteria,two researchers searched for relevant articles published from database inception to December 2022 in CNKI and PubMed using the search terms"NF-κB,osteoporosis,osteoblasts,osteoclasts,angiogenesis,traditional Chinese medicine,terpenoid"in Chinese and English,respectively.A third researcher summarized and organized the literature and 75 articles were finally included for a systematic review. RESULTS AND CONCLUSION:The nuclear factor-κB signaling pathway mediates the onset and progression of osteoporosis by regulating the differentiation and proliferation of osteoblasts and osteoclasts,as well as angiogenesis.Activation of the nuclear factor-κB signaling pathway negatively regulates the proliferation and differentiation of osteoblasts.Activation of the nuclear factor-κB signaling pathway enhances osteoclast activity and inhibits osteoblast growth,thereby inhibiting compensatory bone production to maintain bone homeostasis.However,over-activation of the nuclear factor-κB signaling pathway can lead to osteoporosis.The nuclear factor-κB signaling pathway is involved in the"angiogenesis-osteogenesis"coupling by upregulating the expression levels of cytokines such as angiopoietin-1,platelet-derived growth factor BB and vascular endothelial growth factor,which promote the growth of blood vessels in bone.The terpenoid herbal monomer compounds are used in the field of tissue engineering to promote the proliferation and differentiation of bone cells,thereby promoting the growth and repair of bone tissue.Terpenoid herbal monomer compounds can prevent and treat osteoporosis by inhibiting the degradation of nuclear factor-κB inhibitor,blocking nuclear factor-κB/p65 phosphorylation and nuclear translocation,thereby weakening the nuclear factor-κB signaling pathway,promoting osteoblast differentiation and inhibiting osteoclast formation.Currently,research on the regulation of nuclear factor-κB signaling pathway by monomeric compounds of terpenoids to prevent osteoporosis is mainly based on in vitro cellular experiments and animal models,and there is a lack of research on the complex physiological and pathological processes in humans.In the future,more clinical trials and studies are needed to further clarify the mechanism of action and efficacy of the nuclear factor-κB signaling pathway involved in the intervention of osteoporosis.