Wu Peitong, Lv Qingguo, Wang Shuo, Feng Xueqin, Zhang Kaiyue, Li Chunnan, Li Yishan, Gao Xiaochen, Sun Jiaming
Jilin Institute of Ginseng Science, Changchun University of Chinese Medicine, Changchun, 130117, P.R. China.
Jilin Ginseng Academy, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130117, P.R. China.
Comb Chem High Throughput Screen. 2024 Sep 6. doi: 10.2174/0113862073312956240826053228.
Verbascoside, a compound classified as a phenylethanol glycoside in Dihuang, has been the subject of modern pharmacological investigations. These studies have revealed its noteworthy antioxidant, anti-inflammatory, memory-enhancing, neuroprotective, antitumor, and various other pharmacological properties. While verbascoside exhibits favorable antioxidant effects, its precise mechanism of action in ameliorating osteoporosis through the treatment of oxidative stress remains unclear.
This study employed CCK8, ALP, ELISA, and ROS staining techniques to examine the osteoporotic effects of verbascoside on zebrafish and MC3T3-E1 cells. Additionally, this study aimed to investigate the molecular mechanism by which verbascoside improves osteoporosis by mitigating oxidative stress. To identify the common targets of verbascoside in relation to oxidative stress and osteoporosis, network pharmacology and molecular dynamics simulation were employed. The construction of the verbascoside - oxidative stress - osteoporosis - potential target gene network aimed to identify the core targets, while the mechanism of action was elucidated through KEGG analysis, and the accuracy was confirmed by assessing the mRNA expression of the targets.
In vivo experiments demonstrated that verbascoside exhibited therapeutic effects on osteoporosis and reduced ROS production in zebrafish. In vitro experiments further revealed that verbascoside enhanced the proliferation and differentiation of MC3T3-E1 cells, thereby improving the oxidative stress status of osteoblasts. Thirteen core targets and estrogen signaling pathways were identified through the application of network pharmacology. The pivotal role of the estrogen signaling pathway in facilitating the ability of verbascoside to mitigate oxidative stressinduced osteoporosis was substantiated by the modulation of target protein mRNA expression.
The findings underscore the considerable therapeutic potential of verbascoside in ameliorating osteoporosis through the alleviation of oxidative stress, thus establishing it as a promising compound for the treatment of this condition.
地黄中的苯乙醇苷类化合物毛蕊花糖苷一直是现代药理学研究的对象。这些研究揭示了其显著的抗氧化、抗炎、增强记忆、神经保护、抗肿瘤及其他多种药理特性。虽然毛蕊花糖苷具有良好的抗氧化作用，但其通过治疗氧化应激改善骨质疏松的确切作用机制尚不清楚。
本研究采用CCK8、碱性磷酸酶（ALP）、酶联免疫吸附测定（ELISA）和活性氧（ROS）染色技术，研究毛蕊花糖苷对斑马鱼和MC3T3-E1细胞骨质疏松的影响。此外，本研究旨在探讨毛蕊花糖苷通过减轻氧化应激改善骨质疏松的分子机制。为了确定毛蕊花糖苷与氧化应激和骨质疏松相关的共同靶点，采用了网络药理学和分子动力学模拟。构建毛蕊花糖苷-氧化应激-骨质疏松-潜在靶基因网络以确定核心靶点，通过京都基因与基因组百科全书（KEGG）分析阐明作用机制，并通过评估靶点的mRNA表达来确认准确性。
体内实验表明，毛蕊花糖苷对骨质疏松具有治疗作用，并降低了斑马鱼体内ROS的产生。体外实验进一步表明，毛蕊花糖苷增强了MC3T3-E1细胞的增殖和分化，从而改善了成骨细胞的氧化应激状态。通过网络药理学应用确定了13个核心靶点和雌激素信号通路。靶蛋白mRNA表达的调节证实了雌激素信号通路在促进毛蕊花糖苷减轻氧化应激诱导的骨质疏松能力方面的关键作用。
研究结果强调了毛蕊花糖苷通过减轻氧化应激改善骨质疏松的巨大治疗潜力，从而使其成为治疗这种疾病的有前景的化合物。
