Xue Liming, Jiang Yiping, Han Ting, Zhang Naidan, Qin Luping, Xin Hailiang, Zhang Qiaoyan
Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Institute of Chemical Toxicity, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; Department of Oral Biological and Medical Sciences, The University of British Columbia, Vancouver, BC, Canada V6T1Z3.
Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
J Ethnopharmacol. 2016 Nov 4;192:370-381. doi: 10.1016/j.jep.2016.07.037. Epub 2016 Jul 12.
Icariin, a principal flavonoid glycoside of Epimedium brevicornu Maxim, has been widely proved to possess antiosteoporotic activity with promoting bone formation and decreasing bone resorption. However, the involving mechanisms remain unclear.
To clear a global insight of signal pathways involved in anti-osteoporotic mechanism of icariin at proteins and metabolites level by integrating the proteomics and NMR metabonomics, in a systems biology approach.
Mice were divided into sham, OVX model and icariin-treated OVX group, after 90 days treatment, difference gel electrophoresis combined with MALDI-TOF/TOF proteomics analysis on bone femur and serum metabolomics were carried out for monitor intracellular processes and elucidate anti-osteoporotic mechanism of icariin. Osteoblast and osteoclast were applied to evaluate the potential signal pathways.
Twenty three proteins in bone femur, and 8 metabolites in serum, were significantly altered and identified, involving in bone remodeling, energy metabolism, cytoskeleton, lipid metabolism, MAPK signaling, Ca signaling et, al. Furthermore, animal experiment show icariin could enhance the BMD and BMC, decrease CTX-I level in ovariectomized mice. The mitochondrial membrane potential and the intracellular ATP levels were increased significantly, and the cytoskeleton were improved in icariin-treatment osteoblast and osteoclast. Icariin also increased mRNA expression of Runx2 and osterix of OB, decreased CTR and CAII mRNA expression and protein expression of P38 and JNK. However, icariin did not reveal any inhibition of the collagenolytic activity of cathepsin K, mRNA expression of MMP-9 and protein expression of ERK in osteoclast.
we consider icariin as multi-targeting compounds for treating with osteoporosis, involve initiating osteoblastogenesis, inhibiting adipogenesis, and preventing osteoclast differentiation.
淫羊藿苷是短角淫羊藿的主要黄酮苷类成分，已被广泛证明具有抗骨质疏松活性，可促进骨形成并减少骨吸收。然而，其相关机制仍不清楚。
采用系统生物学方法，通过整合蛋白质组学和核磁共振代谢组学，在蛋白质和代谢物水平上全面了解淫羊藿苷抗骨质疏松机制中涉及的信号通路。
将小鼠分为假手术组、去卵巢模型组和淫羊藿苷治疗去卵巢组，治疗90天后，对股骨进行差异凝胶电泳结合基质辅助激光解吸电离飞行时间串联质谱蛋白质组学分析，并对血清进行代谢组学分析，以监测细胞内过程并阐明淫羊藿苷的抗骨质疏松机制。应用成骨细胞和破骨细胞评估潜在的信号通路。
股骨中有23种蛋白质和血清中的8种代谢物发生了显著变化并被鉴定出来，涉及骨重塑、能量代谢、细胞骨架、脂质代谢、丝裂原活化蛋白激酶信号通路、钙信号等。此外，动物实验表明淫羊藿苷可提高去卵巢小鼠的骨密度和骨矿含量，降低I型胶原交联C端肽水平。淫羊藿苷治疗的成骨细胞和破骨细胞中线粒体膜电位和细胞内ATP水平显著升高，细胞骨架得到改善。淫羊藿苷还增加了成骨细胞中Runx2和osterix的mRNA表达，降低了破骨细胞中CTR和CAII的mRNA表达以及P38和JNK的蛋白表达。然而，淫羊藿苷对破骨细胞中组织蛋白酶K的胶原olytic活性、MMP-9的mRNA表达和ERK的蛋白表达没有任何抑制作用。
我们认为淫羊藿苷是治疗骨质疏松症的多靶点化合物，涉及启动成骨细胞生成、抑制脂肪生成和防止破骨细胞分化。
