Anti-Osteoporosis Activity of Lycopene Through ESR1: Network Pharmacology, Molecular Docking, Imaging Technology, and
Benqian Zhao1, Lulu Chen1, Wei Wang1
1Department of Radiology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou City, Zhejiang Province, China.
Abstract:
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.
Insights
Lycopene (LYC) combats osteoporosis by promoting bone growth through the estrogen receptor 1 (ESR1) and PI3K/AKT pathway. This natural compound enhances osteogenic differentiation, offering a potential therapeutic strategy for bone loss.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Osteoporosis is a prevalent metabolic bone disease.
- Lycopene (LYC), a tomato-derived antioxidant, shows promise in treating osteoporosis.
- Understanding LYC's molecular mechanisms is crucial for its therapeutic application.
Purpose of the Study:
- To elucidate the molecular targets and pathways through which Lycopene exerts its anti-osteoporosis effects.
- To investigate LYC's impact on osteogenic differentiation and bone metabolism.
- To validate the role of estrogen receptor 1 (ESR1) and the PI3K/AKT pathway in LYC's action.
Main Methods:
- Network pharmacology and molecular docking to identify LYC's protein targets in osteoporosis.
- KEGG pathway and GO enrichment analyses to determine biological functions.
- In vitro studies using human marrow-derived mesenchymal stem cells (hBMSCs) to assess osteogenic differentiation.
- In vivo studies using an ovariectomy-induced osteoporosis mouse model.
Main Results:
- Estrogen receptor 1 (ESR1) was identified as a key therapeutic target of LYC.
- LYC promoted osteogenic differentiation of hBMSCs and increased ESR1 expression in vitro.
- LYC treatment reduced bone loss and elevated ESR1 levels in OVX mice.
- LYC activated the PI3K/AKT pathway by upregulating ESR1, crucial for osteogenic differentiation.
Conclusions:
- Lycopene exerts anti-osteoporosis effects by promoting osteogenic differentiation of hBMSCs via the ESR1/PI3K/AKT signaling pathway.
- ESR1 is a critical mediator of LYC's beneficial effects on bone metabolism.
- These findings provide a molecular foundation for utilizing Lycopene as a therapeutic agent for osteoporosis.
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