Zhao Benqian, Chen Lulu, Wang Wei, Xu Weinan, Xu Bing
Department of Radiology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou City, Zhejiang Province, China.
Department of Orthopedics, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou City, Zhejiang Province, China.
Chem Biol Drug Des. 2025 Jun;105(6):e70135. doi: 10.1111/cbdd.70135.
Osteoporosis is a widespread metabolic bone disorder. Lycopene (LYC), a potent antioxidant in tomatoes, has been shown to exhibit anti-osteoporosis effects. Here, we elucidated its molecular determinants in treating osteoporosis. Network pharmacology and molecular docking were utilized to screen target proteins of LYC in osteoporosis treatment. KEGG pathway and GO enrichment analyses were used to observe biological functions of these target proteins. The osteoblastic differentiation of human marrow-derived mesenchymal stem cells (hBMSCs) was induced and evaluated by ALP staining and activity assay, Alizarin Red S (ARS) staining, and related protein expression analysis. An osteoporotic mouse model was induced by ovariectomy (OVX). For the anti-osteoporosis effect of LYC, network pharmacology and molecular docking showed estrogen receptor 1 (ESR1) as a potential therapeutic target, and KEGG pathway enrichment analysis suggested the involvement of the PI3K/AKT pathway. LYC promoted osteogenic differentiation of hBMSCs and increased ESR1 expression in the hBMSC osteogenic differentiation process in vitro. LYC diminished bone loss and increased ESR1 expression in OVX mice. Reduction of ESR1 attenuated LYC-induced osteogenic differentiation of hBMSCs. Moreover, LYC activated the PI3K/AKT pathway in the hBMSC osteogenic differentiation process by upregulating ESR1. Our findings suggest that LYC induces osteogenic differentiation of hBMSCs by the ESR1/PI3K/AKT pathway, thereby contributing to its anti-osteoporosis effect. Our study provides a molecular basis for the potential application of LYC as a therapeutic agent in osteoporosis.
骨质疏松症是一种广泛存在的代谢性骨病。番茄红素（LYC）是番茄中一种强大的抗氧化剂，已被证明具有抗骨质疏松作用。在此，我们阐明了其治疗骨质疏松症的分子决定因素。利用网络药理学和分子对接技术筛选LYC在骨质疏松症治疗中的靶蛋白。采用KEGG通路和GO富集分析观察这些靶蛋白的生物学功能。通过碱性磷酸酶（ALP）染色和活性测定、茜素红S（ARS）染色以及相关蛋白表达分析，诱导并评估人骨髓间充质干细胞（hBMSCs）向成骨细胞分化。通过卵巢切除术（OVX）建立骨质疏松小鼠模型。对于LYC的抗骨质疏松作用，网络药理学和分子对接显示雌激素受体1（ESR1）是一个潜在的治疗靶点，KEGG通路富集分析表明PI3K/AKT通路参与其中。LYC促进hBMSCs的成骨分化，并在体外hBMSCs成骨分化过程中增加ESR1表达。LYC减少OVX小鼠的骨质流失并增加ESR1表达。ESR1的减少减弱了LYC诱导的hBMSCs成骨分化。此外，LYC通过上调ESR1在hBMSCs成骨分化过程中激活PI3K/AKT通路。我们的研究结果表明，LYC通过ESR1/PI3K/AKT通路诱导hBMSCs成骨分化，从而发挥其抗骨质疏松作用。我们的研究为LYC作为治疗骨质疏松症的潜在药物提供了分子基础。
