N-Butanol Extract of Modified You-Gui-Yin Attenuates Osteoclastogenesis and Ameliorates Osteoporosis by Inhibiting RANKL-Mediated NF-κB Signaling

Zeng, Qinghe; Xu, Rui; Ling, Houfu; Zhao, Shan; Wang, Xu; Yuan, Wenhua; Gu, Mancang; Xu, Taotao; Wang, Pinger; Ruan, Hongfeng; Jin, Hongting; Qu, Hang-Bo; Ye, Fusheng; Chen, Jiali

doi:10.3389/fendo.2022.925848

Cited by 5 publications

(3 citation statements)

References 48 publications

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“…All these indicated that the female reproductive system especially the ovary is closely related to bone, and YGY can inhibit bone loss by promoting osteogenic proliferation and differentiation and attenuating osteoclastogenesis. [ 20 , 21 ] In western medicine, ONFH is a disease involving changes in local stem cell activity of the femoral head. [ 22 ] The researchers found a decrease in the number, activity, or osteogenic differentiation of mesenchymal stem cells in the bone marrow in patients with ONFH.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology-based and molecular docking-based analysis of You-Gui-Yin for the treatment of osteonecrosis of the femoral head

Yao,

Fan,

Song

et al. 2023

Medicine

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You-Gui-Yin (YGY) is a classic prescription for warming up kidney-Yang and filling in kidney essence in traditional Chinese medicine, and has been used to treat osteonecrosis of the femoral head (ONFH) effectively. However, the underlying mechanisms are still unknown. This study is aimed at exploring the possible mechanisms of action of the YGY in the treatment of ONFH based on network pharmacology and molecular docking. TCMSP was used to screen the active components and targets of YGY. The disease targets of ONFH were collected in several public databases. The protein-protein interaction (PPI) Network was constructed using the STRING platform. The Metascape database platform was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The key active components and core target proteins of YGY in the treatment of ONFH were verified by the molecular docking. 120 active components were obtained from YGY, among which 73 components were hit by the 117 drug-disease intersection targets. Key effective components included quercetin, kaempferol, beta-sitosterol, glycitein, beta-carotene, and so on. Core target proteins included ALB, AKT1, TNF, IL6, TP53, and so on. According to GO and KEGG analyses, there were 1762 biological processes, 94 cellular component, 138 molecular function and 187 signaling pathways involved. we selected the top 20 biological processes (BP), cellular components (CC), molecular functions (MF) and signaling pathways to draw the heat maps, showing that Lipid and atherosclerosis signaling pathway, IL-17 signaling pathway, HIF-1 signaling pathway, relaxin signaling pathway and MAPK signaling pathway and other pathways may play a key role in the treatment of ONFH by YGY. The results of molecular docking showed that key effective components and corresponding core target proteins exhibited the good binding activity. YGY can treat ONFH through multicomponents, multitargets, and multipathways, which provides a reference for the subsequent research, development of targeted drugs and clinical application.

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Section: Discussionmentioning

confidence: 99%

Network pharmacology-based and molecular docking-based analysis of You-Gui-Yin for the treatment of osteonecrosis of the femoral head

Yao,

Fan,

Song

et al. 2023

Medicine

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“…TCM formulas, BSHXD, and Jianpi Qingchang Bushen decoction (JQBD) can alleviate bone loss, decrease bone volume, and limit osteoclastogenesis by reducing the RANKL-stimulated NF-κB, ERK, JNK signal transduction pathways in OP model mice ( 93 , 98 ). Bushen Tongluo decoction (BSTLD) and You Gui Yin (YGY) can promote bone generation and attenuate OC activity and bone resorption in the OVX-induced OP mouse model by reducing RANKL/OPG ratio ( 53 , 99 ).…”

Section: Anti-op Effects Of Tcm and Plant-based Natural Compoundsmentioning

confidence: 99%

Mechanisms of action and synergetic formulas of plant-based natural compounds from traditional Chinese medicine for managing osteoporosis: a literature review

Zhou,

Shen,

Zhang

et al. 2023

Front. Med.

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Osteoporosis (OP) is a systemic skeletal disease prevalent in older adults, characterized by substantial bone loss and deterioration of microstructure, resulting in heightened bone fragility and risk of fracture. Traditional Chinese Medicine (TCM) herbs have been widely employed in OP treatment owing to their advantages, such as good tolerance, low toxicity, high efficiency, and minimal adverse reactions. Increasing evidence also reveals that many plant-based compounds (or secondary metabolites) from these TCM formulas, such as resveratrol, naringin, and ginsenoside, have demonstrated beneficial effects in reducing the risk of OP. Nonetheless, the comprehensive roles of these natural products in OP have not been thoroughly clarified, impeding the development of synergistic formulas for optimal OP treatment. In this review, we sum up the pathological mechanisms of OP based on evidence from basic and clinical research; emphasis is placed on the in vitro and preclinical in vivo evidence-based anti-OP mechanisms of TCM formulas and their chemically active plant constituents, especially their effects on imbalanced bone homeostasis regulated by osteoblasts (responsible for bone formation), osteoclasts (responsible for bone resorption), bone marrow mesenchymal stem cells as well as bone microstructure, angiogenesis, and immune system. Furthermore, we prospectively discuss the combinatory ingredients from natural products from these TCM formulas. Our goal is to improve comprehension of the pharmacological mechanisms of TCM formulas and their chemically active constituents, which could inform the development of new strategies for managing OP.

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“…RANKL (osteoprotegerin ligand) activates the formation and activation of osteoclasts by binding to its receptor, thus promoting bone absorption. OPG (osteoprotegerin) is a natural antagonist of RANKL, which can bind to RANKL and prevent it from binding with RANKL, thus inhibiting bone resorption 6 . Activating the Wnt/β- catenin pathway can promote the proliferation and differentiation of osteoblasts and increase bone formation 7 , 8 .…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis

Dong,

Ren,

et al. 2024

Sci Rep

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Osteoporosis (OP) is a prevalent global disease characterized by bone mass loss and microstructural destruction, resulting in increased bone fragility and fracture susceptibility. Our study aims to investigate the potential of kaempferol in preventing and treating OP through a combination of network pharmacology and molecular experiments. Kaempferol and OP-related targets were retrieved from the public database. A protein–protein interaction (PPI) network of common targets was constructed using the STRING database and visualized with Cytoscape 3.9.1 software. Enrichment analyses for GO and KEGG of potential therapeutic targets were conducted using the Hiplot platform. Molecular docking was performed using Molecular operating environment (MOE) software, and cell experiments were conducted to validate the mechanism of kaempferol in treating OP. Network pharmacology analysis identified 54 overlapping targets between kaempferol and OP, with 10 core targets identified. The primarily enriched pathways included atherosclerosis-related signaling pathways, the AGE/RAGE signaling pathway, and the TNF signaling pathway. Molecular docking results indicated stable binding of kaempferol and two target proteins, AKT1 and MMP9. In vitro cell experiments demonstrated significant upregulation of AKT1 expression in MC3T3-E1 cells (p < 0.001) with kaempferol treatment, along with downregulation of MMP9 expression (p < 0.05) compared to the control group. This study predicted the core targets and pathways of kaempferol in OP treatment using network pharmacology, and validated these findings through in vitro experiments, suggesting a promising avenue for future clinical treatment of OP.

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N-Butanol Extract of Modified You-Gui-Yin Attenuates Osteoclastogenesis and Ameliorates Osteoporosis by Inhibiting RANKL-Mediated NF-κB Signaling

Cited by 5 publications

References 48 publications

Network pharmacology-based and molecular docking-based analysis of You-Gui-Yin for the treatment of osteonecrosis of the femoral head

Network pharmacology-based and molecular docking-based analysis of You-Gui-Yin for the treatment of osteonecrosis of the femoral head

Mechanisms of action and synergetic formulas of plant-based natural compounds from traditional Chinese medicine for managing osteoporosis: a literature review

Network pharmacology analysis and experimental validation to explore the mechanism of kaempferol in the treatment of osteoporosis

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