Anti-Osteoporotic Activity of Harpagoside by Upregulation of the BMP2 and Wnt Signaling Pathways in Osteoblasts and Suppression of Differentiation in Osteoclasts
Anti-Osteoporotic Activity of Harpagoside by Upregulation of the BMP2 and Wnt Signaling Pathways in Osteoblasts and Suppression of Differentiation in Osteoclasts
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DOI：
10.1021/acs.jnatprod.6b00964
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发表时间：
2017-02-01
影响因子：
5.1
通讯作者：
Lee, Sang Kook
中科院分区：
文献类型：
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作者：
Chung, Hwa-Jin;Kim, Won Kyung;Lee, Sang Kook
哈巴俄苷（Harpagophytum procumbens var.）亚裂叶，俗称魔鬼爪。在体外细胞培养物中和使用卵巢切除（OVX）小鼠模型在体内研究了1的抗卵巢增生作用。化合物1通过刺激成骨细胞MC 3 T3-E1细胞中的成骨细胞增殖、碱性磷酸酶活性和矿化来诱导骨形成。用1处理通过调节MC 3 T3-E1细胞中的BMP 2和Wnt信号通路增加骨形成生物标志物的mRNA和蛋白质表达。化合物1还抑制培养的小鼠骨髓细胞的RANKL诱导的破骨细胞生成。口服1可恢复OVX引起的骨小梁破坏。股骨的骨密度也显著增加了1。用1. 5 mg/kg剂量的1. 5 mg/kg的去卵巢小鼠血清中骨钙素、C末端肽和抗酒石酸酸性磷酸酶的升高水平降低。这些发现表明，化合物1可以通过调节成骨细胞分化的刺激和破骨细胞再吸收的抑制来保护小鼠免受OVX诱导的骨丢失。因此，哈巴俄苷（1）是治疗绝经后骨质疏松症的潜在候选药物。
Harpagoside (1) is an iridoid glycoside isolated from the radix of Harpagophytum procumbens var. sublobatum, commonly called Devil's claw. The anti-osteoporotic effect of 1 was investigated in both in vitro cell cultures and in vivo using an ovariectomized (OVX) mouse model. Compound 1 induced bone formation by stimulating osteoblast proliferation, alkaline phosphatase activity, and mineralization in osteoblastic MC3T3-E1 cells. Treatment with 1 increased the mRNA and protein expression of bone formation biomarkers through regulation of the BMP2 and Wnt signaling pathway in MC3T3-E1 cells. Compound 1 also suppressed the RANKL-induced osteoclastogenesis of cultured mouse bone marrow cells. Oral administration of 1 restored the OVX-induced destruction of trabecular bone. The bone mineral density of the femur was also increased significantly by 1. The elevated serum levels of osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase in the OVX mice were decreased by treatment with 1. These findings suggest that compound 1 may protect against bone loss induced by OVX in mice by regulating stimulation of osteoblast differentiation and inhibition of osteoclast resorption. Therefore, harpagoside (1) is a potential candidate for management of postmenopausal osteoporosis.