促进成骨细胞介导的骨形成：天然产物治疗骨质疏松症的一种更有前景的方法

摘要(中文译文)

骨质疏松症是一种以骨量减少、骨微结构受损和骨折风险增加为特征的全身性骨骼疾病，其主要原因是破骨细胞介导的骨吸收相对于成骨细胞介导的骨形成过度活跃。尽管目前的抗骨质疏松药物，如双膦酸盐和地舒单抗，主要侧重于减少骨吸收，但骨合成代谢方法对于恢复骨微结构和最终降低骨折风险至关重要。中药及其活性成分在中国长期以来被用于骨质疏松症的预防和治疗。本综述全面评估了24个类别共65种天然产物对成骨细胞介导的骨形成的作用及其分子机制。这些化合物通过调控关键转录因子（RUNX2和Osterix）以及信号通路，包括WNT/β-连环蛋白（WNT/β-catenin）、骨形态发生蛋白（BMP）、丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/AKT）、氧化应激、自噬和表观遗传调控，来促进骨形成。值得注意的是，某些天然产物[如淫羊藿苷（ICA）]通过多靶点和多通路发挥其作用。许多此类天然产物已在动物模型（如去卵巢（OVX）小鼠）中展现出显著的治疗效果。我们的研究结果表明，具有补肾、抗炎和抗氧化特性的天然产物，以及抑制脂肪细胞分化的天然产物，可能对骨质疏松症的治疗具有前景。此外，我们指出了当前研究的不足，并提出了未来的研究方向，包括高通量筛选和在多种动物模型中的验证、新型骨靶向递送系统的开发，以及靶向骨细胞的天然化合物的鉴定。

Abstract

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass, compromised bone microstructure, and an increased risk of fractures, primarily due to excessive osteoclast-mediated bone resorption relative to osteoblast-mediated bone formation. While current anti-osteoporosis drugs, such as bisphosphonates and denosumab, predominantly focus on reducing bone resorption, osteoanabolic approaches are essential for restoring bone microarchitecture and ultimately reducing fracture risk. Traditional Chinese medicines (TCMs) and their active ingredients have long been used in China for osteoporosis prevention and treatment. This review provides a comprehensive evaluation of the effects and molecular mechanisms of 65 natural products across 24 categories on osteoblast-mediated bone formation. These compounds promote bone formation by regulating key transcription factors (RUNX2 and Osterix) and signaling pathways, including WNT/β-catenin, bone morphogenic protein (BMP), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), oxidative stress, autophagy, and epigenetic regulation. Notably, certain natural products [e.g., icariin (ICA)] exert their effects through multiple targets and pathways. Many of these natural products have demonstrated significant therapeutic efficacy in animal models, such as ovariectomized (OVX) mice. Our findings suggest that natural products with kidney-tonifying, anti-inflammatory, and antioxidant properties, as well as those inhibiting adipocyte differentiation, may hold promise for osteoporosis treatment. Additionally, we highlight current research gaps and propose future directions, including high-throughput screening and validation in diverse animal models, development of novel bone-targeting delivery systems, and identification of natural compounds targeting osteocytes.

如何引用

Chinese journal of natural medicines 的其他文献

• 癌症治疗中的中药现代化：“3D”创新中药