Yuan Yi-Feng, Wang Shen, Zhou Hang, Tang Bin-Bin, Liu Yang, Huang Hai, He Cai-Jian, Chen Tian-Peng, Fang Mou-Hao, Liang Bo-Cheng, Mao Ying-De-Long, Qie Feng-Qin, Liu Kang, Shi Xiao-Lin
The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
The Second Affiliated Hospital of Zhejiang Chinese Medical University (Xinhua Hospital of Zhejiang Province), Hangzhou, China.
Front Pharmacol. 2022 Oct 11;13:994995. doi: 10.3389/fphar.2022.994995. eCollection 2022.
Sea buckthorn (SBT) is a traditional Chinese medicine (TCM), rich in calcium, phosphorus, and vitamins, which can potentially prevent and treat osteoporosis. However, no research has been conducted to confirm these hypotheses. QiangGuYin (QGY) is a TCM compound used to treat osteoporosis. There is a need to investigate whether SBT enhances QGY efficacy. The aim of this study was to explore whether SBT enhances QGY efficacy by inhibiting CKIP-1 and Notum expression through the Wnt/β-catenin pathway. The study also aimed to explore the active components of SBT. Experimental animals were divided into control, model, QGY, SBT, SBT + (EU), and SBT + QGY groups. After treatment, bone morphometric parameters, such as estrogen, PINP, and S-CTX levels, and Notum, CKIP-1, and β-catenin expression were examined. Screening of SBT active components was conducted by molecular docking to obtain small molecules that bind Notum and CKIP-1. The results showed that all the drug groups could elevate the estrogen, PINP, and S-CTX levels, improve femoral bone morphometric parameters, inhibit Notum and CKIP-1 expression, and promote β-catenin expression. The effect of SBT + EU and SBT + QGY was superior to the others. Molecular docking identified that SBT contains seven small molecules (folic acid, rhein, quercetin, kaempferol, mandenol, isorhamnetin, and ent-epicatechin) with potential effects on CKIP-1 and Notum. SBT improves bone morphometric performance in PMOP rats by inhibiting CKIP-1 and Notum expression, increasing estrogen levels, and activating the Wnt/β-catenin signaling pathway. Furthermore, SBT enhances the properties of QGY. Folic acid, rhein, quercetin, kaempferol, mandenol, isorhamnetin, and ent-epicatechin are the most likely active ingredients of SBT. These results provide insight into the pharmacological mechanisms of SBT in treating osteoporosis.
沙棘（SBT）是一种传统中药，富含钙、磷和维生素，具有预防和治疗骨质疏松症的潜力。然而，尚未有研究证实这些假设。强骨饮（QGY）是一种用于治疗骨质疏松症的中药复方。有必要研究沙棘是否能增强强骨饮的疗效。本研究的目的是探讨沙棘是否通过Wnt/β-连环蛋白途径抑制CKIP-1和Notum表达来增强强骨饮的疗效。该研究还旨在探索沙棘的活性成分。将实验动物分为对照组、模型组、强骨饮组、沙棘组、沙棘+依普黄酮（EU）组和沙棘+强骨饮组。治疗后，检测骨形态计量学参数，如雌激素、PINP和S-CTX水平，以及Notum、CKIP-1和β-连环蛋白的表达。通过分子对接对沙棘活性成分进行筛选，以获得与Notum和CKIP-1结合的小分子。结果表明，所有药物组均可提高雌激素、PINP和S-CTX水平，改善股骨骨形态计量学参数，抑制Notum和CKIP-1表达，并促进β-连环蛋白表达。沙棘+依普黄酮组和沙棘+强骨饮组的效果优于其他组。分子对接鉴定出沙棘含有七种对CKIP-1和Notum有潜在作用的小分子（叶酸、大黄酸、槲皮素、山奈酚、曼德醇、异鼠李素和表儿茶素）。沙棘通过抑制CKIP-1和Notum表达、增加雌激素水平和激活Wnt/β-连环蛋白信号通路来改善绝经后骨质疏松症大鼠的骨形态计量学表现。此外，沙棘增强了强骨饮的性能。叶酸、大黄酸、槲皮素、山奈酚、曼德醇、异鼠李素和表儿茶素是沙棘最可能的活性成分。这些结果为沙棘治疗骨质疏松症的药理机制提供了见解。
