Lotfi Mohammad-Sadegh, Jamali Hamidreza, B Rassouli Fatemeh
Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
Arch Physiol Biochem. 2025 Aug;131(4):658-669. doi: 10.1080/13813455.2025.2483910. Epub 2025 Mar 31.
Osteoporosis poses a global health challenge, particularly with an ageing population. Quercetin, isorhamnetin, avicularin, isoquercetin, quercitrin, and taxifolin are natural flavonoids with similar structure that induce ontogenesis.
In the present study, proteins in oestrogen signalling and bone morphogenesis were analysed, and hub genes were identified with Cytoscape, followed by pathway analysis. Then, molecular targets of flavonoids and osteoporosis-related targets were identified, and overlaps were detected. Molecular docking and dynamics simulations assessed flavonoid interactions with ERs.
The study identified 14 gene products linked to osteoporosis, including ESR1 and ESR2. Enrichment analyses confirmed ESR involvement in various biological processes. SwissTargetPrediction highlighted quercetin and isorhamnetin as favourable targets for ESR1 and ESR2. Molecular docking and dynamics revealed favourable and stable binding of flavonoids to ERα and ERβ.
These interactions suggest therapeutic potential of natural flavonoids for osteoporosis treatment by targeting ERs, laying a foundation for future research in preclinical and clinical settings.
骨质疏松症对全球健康构成挑战，尤其是在人口老龄化的情况下。槲皮素、异鼠李素、扁蓄苷、异槲皮苷、槲皮苷和花旗松素是具有相似结构的天然黄酮类化合物，可诱导个体发育。
在本研究中，分析了雌激素信号传导和骨形态发生中的蛋白质，并用Cytoscape鉴定了枢纽基因，随后进行了通路分析。然后，鉴定了黄酮类化合物的分子靶点和骨质疏松症相关靶点，并检测了重叠部分。分子对接和动力学模拟评估了黄酮类化合物与雌激素受体的相互作用。
该研究确定了14种与骨质疏松症相关的基因产物，包括ESR1和ESR2。富集分析证实ESR参与了各种生物学过程。SwissTargetPrediction突出显示槲皮素和异鼠李素是ESR1和ESR2的有利靶点。分子对接和动力学显示黄酮类化合物与ERα和ERβ具有良好且稳定的结合。
这些相互作用表明天然黄酮类化合物通过靶向雌激素受体治疗骨质疏松症具有潜在的治疗价值，为未来临床前和临床研究奠定了基础。
