Abstract：
The drugs used for treating bone diseases (BDs), at present, elicit hazardous side effects that include certain types of cancers and strokes, hence the ongoing quest for the discovery of alternatives with little or no side effects. Natural products (NPs), mainly of plant origin, have shown compelling promise in the treatments of BDs, with little or no side effects. However, the paucity in knowledge of the mechanisms behind their activities on bone remodeling has remained a hindrance to NPs\' adoption. This review discusses the pathological development of some BDs, the NP-targeted components, and the actions exerted on bone remodeling signaling pathways (e.g., Receptor Activator of Nuclear Factor κ B-ligand (RANKL)/monocyte/macrophage colony-stimulating factor (M-CSF)/osteoprotegerin (OPG), mitogen-activated protein kinase (MAPK)s/c-Jun N-terminal kinase (JNK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1), Bone Morphogenetic Protein 2 (BMP2)-Wnt/β-catenin, PhosphatidylInositol 3-Kinase (PI3K)/protein kinase B (Akt)/Glycogen Synthase Kinase 3 Beta (GSK3β), and other signaling pathways). Although majority of the studies on the osteoprotective properties of NPs against BDs were conducted ex vivo and mostly on animals, the use of NPs for treating human BDs and the prospects for future development remain promising.
摘要：
用于治疗骨骼疾病（BD）的药物，目前,引起危险的副作用，包括某些类型的癌症和中风，因此，不断寻求发现几乎没有副作用的替代品。天然产物（NPs），主要来自植物，在BD的治疗中显示出令人信服的希望，几乎没有副作用。然而,对其骨重塑活动背后机制的了解不足仍然是NPs采用的障碍。这篇综述讨论了一些BD的病理发展，NP目标组件，以及对骨重塑信号通路的作用(例如，核因子κB-配体受体激活剂(RANKL)/单核细胞/巨噬细胞集落刺激因子(M-CSF)/骨保护素(OPG),丝裂原活化蛋白激酶(MAPK)s/c-Jun氨基末端激酶(JNK)/核因子κ-活化B细胞轻链增强子(NF-κB),Kelch样ECH相关蛋白1(Keap-1)/核因子红系2相关因子2(Nrf2)/血红素氧合酶-1(HO-1),骨形态发生蛋白2(BMP2)-Wnt/β-catenin,磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/糖原合成酶激酶3β(GSK3β),和其他信号通路)。尽管大多数NPs对BD的骨保护特性的研究都是在离体进行的，而且大多是在动物身上进行的。使用NPs治疗人类BDs和未来发展前景仍然很有希望。
