柚皮苷在骨组织再生领域的应用潜力

Application potential of naringin in bone tissue regeneration

背景:骨组织再生是目前治疗大面积骨缺损的重要研究方向。柚皮苷(Naringin)作为一种天然黄酮类化合物,具有诱导成骨的潜力,引起骨组织再生领域研究者的广泛关注。目的:回顾柚皮苷促进骨再生的主要相关作用、安全有效性及在骨组织工程中的应用进展,为大面积骨缺损的临床治疗提供理论研究依据。方法:第一作者检索2002-2021年期间收录在PubMed数据库、万方数据库及中国知网(CNKI)中国期刊全文数据库关于柚皮苷诱导成骨的文章。英文检索词为“naringin;bone defects;osteoinductive;osteoporosis;bone regeneration;osteoclasts;blood vessel;bone tissue engineering”,中文检索词为“柚皮苷;骨缺损;骨诱导;骨质疏松症;骨再生;破骨细胞;血管;骨组织工程”。共选取55篇文献进行综述。结果与结论:柚皮苷在抗骨质疏松症、促进骨的生成、抑制破骨细胞生成及促进血管生成方面通过发挥雌激素样作用或参与骨形态发生蛋白(BMP)、Wnt/β-catenin、PI3K/Akt及VEGF/VEGFR-2等不同信号通路的调节表现出良好的诱导骨组织生成的潜力,而且具备安全稳定、易提取、成本低等特性,因此柚皮苷是一种非常有潜力的天然骨诱导小分子药物。近年来,柚皮苷与骨组织工程技术结合后改善了药物初始突释的问题,提高了药物的生物利用度。但是,未来仍需更多的实验研究更全面系统的诱导成骨机制,充分利用好骨组织工程技术,深入验证柚皮苷最合适的控释载体及局部应用效果,使柚皮苷早日能成熟、稳定、有效地应用于骨缺损的临床治疗中。

BACKGROUND:Bone tissue regeneration is currently an important research direction in the treatment of large-area bone defects.Naringin,as a natural flavonoid,has the potential to induce osteogenesis,which has attracted extensive attention in the field of bone tissue regeneration.OBJECTIVE:To review the main related effects and safety of naringin in promoting bone regeneration and its application in bone tissue engineering,thereby providing a theoretical basis for the clinical treatment of large-area bone defects.METHODS:The first author searched for articles regarding naringin-induced osteogenesis included in PubMed,WanFang,and CNKI databases from 2002 to 2021.The keywords were“naringin;bone defects;osteoinductive;osteoporosis;bone regeneration;osteoclasts;blood vessel;bone tissue engineering”in English and Chinese,respectively.Fifty-five eligible articles were finally reviewed.RESULTS AND CONCLUSION:Naringin has a good potential of inducing bone tissue production in anti-osteoporosis,promoting bone formation,inhibiting osteoclast formation and promoting angiogenesis by exerting estrogen-like effects or participating in the regulation of different signaling pathways such as bone morphogenetic protein,Wnt/β-catenin,PI3K/Akt and VEGF/VEGFR-2.In addition,naringin has the characteristics of safety,stability,easy extraction,and low cost.Therefore,naringin is a very promising natural bone induction small-molecule drug.In recent years,naringin combined with bone tissue engineering technology has improved the initial sudden release and bioavailability of drugs.However,in the future,we still need more experimental studies on the mechanism of induction osteogenesis in a more comprehensive and systematic way,and make full use of good bone tissue engineering technology to further verify the most suitable controlled-release carrier and local application effect of naringin.Thereby,naringin will be mature,stable and effective in the clinical treatment of bone defects as soon as possible.