柚皮苷防治骨质疏松症的分子机制

Molecular mechanism of naringin in prevention and treatment of osteoporosis

背景:近年研究表明,柚皮苷抗骨质疏松的研究大多停留在体内外实验当中,了解相关信号通路的作用机制以及相关蛋白与某些特定基因的表达是深入了解柚皮苷发挥抗骨质疏松症的重要途径。目前,中医药已被证实在抗骨质疏松方面具有显著作用,柚皮苷是骨碎补中的主要有效成分之一,其抗骨质疏松的有效性及作用机制逐渐得到学者们认可,其临床与基础研究逐渐被大家重视。目的:分析总结柚皮苷在体内外发挥抗骨质疏松作用的研究进展,为下一步研究其相关的作用机制提供一些思路。方法:检索中国知网、万方、维普数据库及PubMed数据库收录的相关文献,中文检索词为“柚皮苷,骨质疏松症,中药单体,发病机制,信号通路,骨髓间充质干细胞,成骨细胞,破骨细胞”等;英文检索词为“Naringin,Osteoporosis,Chinese medicine monomer,pathogenesis,Signal path,Bmscs,Osteoblast,Osteoclast”等,并根据研究需要确立相应的标准,对最终所得文献进行筛选,最终纳入69篇文献进行综述。结果与结论:(1)柚皮苷阻断了富含果糖饮食引起的破骨细胞和脂肪细胞数量的增加以及骨细胞和骨钙素(+)细胞数量的减少、并且通过促进成骨细胞和骨细胞分泌Sema3A,从而激活Wnt/β-catenin信号通路局部增强成骨细胞骨形成,同时抑制破骨细胞生成。(2)柚皮苷通过诱导成骨细胞自噬是一种重要的形式,然而自噬相关蛋白参与成骨细胞分化和骨形成,当成骨细胞缺乏自噬会降低矿化能力,并导致成骨细胞和破骨细胞数量不平衡,从而导致骨量丢失,骨密度下降。(3)搭载柚皮苷的复合支架可为骨缺损修复提供必要的载体,并且柚皮苷还能增加局部骨形态发生蛋白2和血管内皮生长因子的含量,从而加速新生骨组织的生长,具备优异的骨修复性能。(4)柚皮苷可调控ERK、PI3K/Akt和Wnt等相关信号通路来发挥调节骨代谢以及抑制氧化应激等作用,进而调控骨质疏松症,对该病起到良好的防治作用,但目前相关研究深度和广度不足,在未来应基于目前的机制研究,深入探究柚皮苷调控该病不同通路的具体机制及通路间相互作用,将有利于运用柚皮苷治疗骨质疏松症的多元发展。

BACKGROUND:Recent studies have shown that research on naringin anti-osteoporosis mostly stays in in vitro and in vivo experiments.Understanding the mechanism of related signaling pathways and the expression of related proteins and some specific genes is an important way to deeply understand naringin anti-osteoporosis.At present,traditional Chinese medicine has been confirmed to have a significant role in anti-osteoporosis.Naringin is one of the main active ingredients in Rhizoma Drynariae.Its effectiveness and mechanism of action against osteoporosis have been gradually recognized by scholars,and its clinical and basic research has been gradually emphasized.OBJECTIVE:To analyze and summarize the research progress of naringin in anti-osteoporosis in vitro and in vivo,thereby providing some ideas for the next step to study its related mechanism of action.METHODS:The relevant literatures included in CNKI and PubMed database were searched with the Chinese search terms of“naringin,osteoporosis,traditional Chinese medicine compound,pathogenesis,signaling pathway,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts”in Chinese and English,respectively.The corresponding criteria were established according to the research needs,and finally 69 articles were included for review.RESULTS AND CONCLUSION:Naringin blocks the increase in the number of osteoclasts and adipocytes,the decrease in the number of osteocytes and osteocalcin(+)cells induced by fructose-rich diet,and promotes the secretion of Sema3A from osteoblasts and osteocytes,thereby enhancing local bone formation and inhibiting osteoclast production by activating the Wnt/β-catenin pathway.Naringin is an important way to induce autophagy of osteoblasts,but autophagy-related proteins participate in osteoblast differentiation and bone formation.Lack of autophagy in osteoblasts reduces mineralization and leads to an imbalance in the number of osteoblasts and osteoclasts,which results in bone loss and decreased bone density.The composite scaffold loaded with naringin can be used as a necessary carrier for bone defect repair and has excellent bone repair properties.Naringin can also accelerate the growth of new bone tissue by increasing the local contents of bone morphogenetic protein 2 and vascular endothelial growth factor.Naringin can regulate bone metabolism and inhibit oxidative stress via ERK,PI3K/Akt and Wnt signaling pathways to improve osteoporosis,which can play a good role in preventing and controlling the disease.However,the depth and breadth of the relevant research is insufficient.Based on the mechanism of the current study,we should investigate the specific mechanisms by which naringin regulates different pathways and inter-pathway interactions in the future,which will be beneficial to the multifaceted development of naringin used in the treatment of osteoporosis..