Eucommia ulmoides Polysaccharides Attenuate Rabbit Osteoarthritis by Regulating the Function of Macrophages

Sun, Yaqiong; Huang, Kui; Mo, Linhai; Ahmad, Akhlaq; Wang, Dejia; Rong, Zijie; Peng, Honghui; Cai, Heng; Liu, Guihua

doi:10.3389/fphar.2021.730557

Cited by 13 publications

(14 citation statements)

References 31 publications

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“…Pharmacological studies have shown that the extracts of EU inhibit the progression of OA by inhibiting the PI3K/Akt pathway (Xie et al, 2015). EU extract can promote articular cartilage repair and subchondral bone reconstruction by regulating the function of macrophages (Sun, Huang, et al, 2021). Therefore, it is expected that EULs are capable of having potent anti‐osteoarthritis effects.…”

Section: Introductionmentioning

confidence: 99%

Combination of UHPLC‐Q Exactive‐Orbitrap MS and network pharmacology to reveal the mechanism of Eucommia ulmoides leaves in the treatment of osteoarthritis

Liu

Cao

2022

Journal of Food Biochemistry

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Osteoarthritis (OA) is a disabling disease and seriously affects the quality of life of patients. is A potential medicine for the treatment of OA is Eucommia ulmoides leaves (EULs). However, its active compounds and therapeutic mechanisms are unclear. Therefore, it is necessary to develop a method using LC–MS and network pharmacology for the detection and identification of compounds and the mechanisms of action of EULs. The compounds were detected and identified based on ultra‐high‐performance liquid chromatography coupled with Quadrupole Exactive‐Orbitrap MS (UHPLC‐Q Exactive‐Orbitrap MS) and followed by the network pharmacology analysis. Seventy‐three compounds, including 15 flavonoids, 8 iridoids, 10 lignans, 24 phenolic acids, and 16 additional compounds, were identified by UHPLC‐Q Exactive‐Orbitrap MS. The network of the pharmacological analysis revealed that 29 active compounds regulated 17 main pathways through 38 target genes, including NF‐kappa B signaling pathway, PI3K‐Akt signaling pathway, AMPK signaling pathway, etc. In conclusion, EULs were effective in the treatment of OA by regulating the abovementioned key pathways. This study showed that LC–MS/MS followed by network pharmacology analysis is useful to elucidate the complex mechanisms of action of Chinese herb. Practical applications This study describes a rapid method of detecting and identifying the constituents and systematic mechanism of Eucommia ulmoides based on LC–MS and network pharmacology. Our results show that 73 compounds of E. ulmoides leaves were identified and predicted that E. ulmoides leaves were effective in the treatment of OA by regulating key pathways, including NF‐kappa B signaling pathway, PI3K‐Akt signaling pathway, and AMPK signaling pathway by network pharmacology, which lays the foundation for subsequent research.

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Section: Introductionmentioning

confidence: 99%

Combination of UHPLC‐Q Exactive‐Orbitrap MS and network pharmacology to reveal the mechanism of Eucommia ulmoides leaves in the treatment of osteoarthritis

Liu

Cao

2022

Journal of Food Biochemistry

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“…Six of the ten active ingredients with high degree values were from Eucommia tulipifera (E. tulipifera) and the associated components of E. tulipifera, such as quercetin and kaempferol, were connected to drug-disease common targets with high density, suggesting that E. tulipifera may play a good role in the treatment of PMO. The lignans and phenylpropanoids in Eucommia are immuneenhancing, and the sterol in bone marrow is used as a raw material for the production of vitamin D3, so it is assumed that QEP may prevent PMO exacerbation to some extent [28][29][30][31][32][33][34] . The topological analysis of the main compounds and the major intersecting targets revealed the highest binding of the target CYP3A4 and hirsutine.…”

Section: Resultsmentioning

confidence: 99%

Network Pharmacology Prediction to Explore the Potential Mechanism of Qing'E Pills

Dong¹,

Ma²,

Pan³

2023

IJPS

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To Explore the Potential Mechanism of Qing'E PillsQing'E pills are a classical formula in traditional Chinese medicine that has the effect of tonifying the kidneys and strengthening the bones, first appearing in the tonic formulae in prescriptions of peaceful benevolent dispensary (10 th century CE). To preliminarily elucidate the potential mechanisms of Qing'E pills in the treatment of postmenopausal osteoporosis based on network pharmacology. The principal components and corresponding protein targets of Qing'E pills were searched on traditional Chinese medicine systems pharmacology, bioinformatics analysis tool for molecular mechanism-traditional Chinese medicine, SymMap and encyclopedia of traditional Chinese medicine and the compound-target network was constructed by Cytoscape 3.9.1. The targets of postmenopausal osteoporosis were searched on online mendelian inheritance in man, GeneCards, histidine triad nucleotide binding protein and DisGeNET databases. The intersection of compound target and disease target was obtained and the coincidence target was imported into the search tool for retrieval of interacting genes database to construct a protein-protein interaction network. We further performed gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses on the targets. The 33 active compounds in Qing'E pills corresponded to 433 targets. 1647 targets were associated with postmenopausal osteoporosis disease. The active compounds with high degree values were quercetin, stearic acid and marine. The proteins with higher values in the protein-protein interaction network were mitogenactivated protein kinase 1, protein kinase B, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, phosphoinositide-3-kinase regulatory 1, amyloid beta precursor protein, Src proto-oncogene, nonreceptor tyrosine kinase, mitogen-activated protein kinase 8, heat shock protein 90 alpha family class A member 1, epidermal growth factor receptor, and Janus kinase 2. Gene ontology and Kyoto encyclopedia of genes and genomes analysis showed that Qing'E pills treatment of postmenopausal osteoporosis involves signaling pathways that mainly include the tumor necrosis factor signaling pathway, osteoclast differentiation, Wnt signaling pathway and estrogen signaling pathway. We revealed the active ingredients and potential molecular mechanism of Qing'E pills in the treatment of postmenopausal osteoporosis and provided a reference for subsequent basic research.

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“…is an important warming and toxifying kidney-yang herb for the treatment of waist and knee pain, joint disadvantage and muscle and bone weakness. [29][30][31] Glycyrrhiza uralensis Fisch. is a qi-invigorating herb, which has been proven to enhance the functions of immunity, anti-inflammatory, anti-gastric ulcer, anti-arrhythmia and regulate blood glucose.…”

Section: Discussionmentioning

confidence: 99%

Chondroprotective Mechanism of Eucommia ulmoides Oliv.-Glycyrrhiza uralensis Fisch. Couplet Medicines in Knee Osteoarthritis via Experimental Study and Network Pharmacology Analysis

Wang¹,

Xu²,

Sun³

et al. 2023

DDDT

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Background: Knee osteoarthritis (KOA) is the primary prevalent disabling joint disorder among osteoarthritis (OA), and there is no particularly effective treatment at the clinic. Traditional Chinese medicine (TCM) herbs, such as Eucommia ulmoides Oliv. and Glycyrrhiza uralensis Fisch. (E.G.) couplet medicines, have been reported to exhibit beneficial health effects on KOA, exact mechanism of E.G. nevertheless is not fully elucidated. Purpose: We assess the therapeutic effects of E.G. on KOA and explore its underlying molecular mechanism. Methods: UPLC-Q-TOF/MS technique was used to analyze the active chemical constituents of E.G. The destabilization of the medial meniscus model (DMM) was employed to evaluate the chondroprotective action of E.G. in KOA mice using histomorphometry, μCT, behavioral testing and immunohistochemical staining. Additionally, network pharmacology and molecular docking were used to predict potential targets for anti-KOA activities of E.G., which was further verified through in vitro experiments. Results: In vivo studies have shown that E.G. could significantly ameliorate DMM-induced KOA phenotypes including subchondral bone sclerosis, cartilage degradation, gait abnormality and thermal pain reaction sensibility. E.G. treatment could also promote extracellular matrix synthesis to protect articular chondrocytes, which was indicated by Col2 and Aggrecan expressions, as well as reducing matrix degradation by inhibiting MMP13 expression. Interestingly, network pharmacologic analysis showed that PPARG might be a therapeutic center. Further study proved that E.G.-containing serum (EGS) could up-regulate PPARG mRNA level in IL-1β-induced chondrocytes. Notably, significant effects of EGS on the increment of anabolic gene expressions (Col2, Aggrecan) and the decrement of catabolic gene expressions (MMP13, Adamts5) in KOA chondrocytes were abolished due to the silence of PPARG. Conclusion: E.G. played a chondroprotective role in anti-KOA by inhibiting extracellular matrix degradation, which might be related to PPARG.

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Eucommia ulmoides Polysaccharides Attenuate Rabbit Osteoarthritis by Regulating the Function of Macrophages

Cited by 13 publications

References 31 publications

Combination of UHPLC‐Q Exactive‐Orbitrap MS and network pharmacology to reveal the mechanism of Eucommia ulmoides leaves in the treatment of osteoarthritis

Combination of UHPLC‐Q Exactive‐Orbitrap MS and network pharmacology to reveal the mechanism of Eucommia ulmoides leaves in the treatment of osteoarthritis

Network Pharmacology Prediction to Explore the Potential Mechanism of Qing'E Pills

Chondroprotective Mechanism of Eucommia ulmoides Oliv.-Glycyrrhiza uralensis Fisch. Couplet Medicines in Knee Osteoarthritis via Experimental Study and Network Pharmacology Analysis

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