Kaempferol Attenuates the Effects of XIST/miR-130a/STAT3 on Inflammation and Extracellular Matrix Degradation in Osteoarthritis

Xiao, Yaosheng; Liu, Lulin; Zheng, Yizhou; Liu, Wuyang; Xu, Youjia

doi:10.4155/fmc-2021-0127

Cited by 22 publications

(17 citation statements)

References 39 publications

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“…A previous study reported that quercetin could BioMed Research International alleviate rat osteoarthritis by inhibiting inflammation and apoptosis of chondrocytes [33]. Similarly, kaempferol could also inhibit inflammation and extracellular matrix degrada-tion in OA [34]. Moreover, the present study confirmed that both the top core compounds of the formula and each herb had high binding energy with IL6 and AKT1 through (e-j) The adamts5 (e), MMP13 (f), aggrecan (g), col2 (h), col10a1 (i), AKT1(j), and TNF-α (k) mRNA expression in control and TNF-α-induced (10 ng/mL) chondrocytes treated with different concentrations of GJ serum and BAY 11-7082 (2 μM) for 24 hours.…”

Section: Discussionmentioning

confidence: 98%

“…A previous study reported that quercetin could alleviate rat osteoarthritis by inhibiting inflammation and apoptosis of chondrocytes [ 33 ]. Similarly, kaempferol could also inhibit inflammation and extracellular matrix degradation in OA [ 34 ]. Moreover, the present study confirmed that both the top core compounds of the formula and each herb had high binding energy with IL6 and AKT1 through molecular docking.…”

Section: Discussionmentioning

confidence: 99%

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Elucidation of the Underlying Mechanism of Gujian Oral Liquid Acting on Osteoarthritis through Network Pharmacology, Molecular Docking, and Experiment

Shi

et al. 2022

BioMed Research International

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Gujian oral liquid (GJ), a traditional herbal formula in China, has been widely used to treat patients with osteoarthritis (OA). Nevertheless, the active component and potential mechanism of GJ are not fully elucidated. Thus, we investigate the effect of GJ and explore its underlying mechanism on OA through network pharmacology and experimental validation. First, a total of 175 bioactive compounds were identified, and 134 overlapping targets were acquired after comparing the targets of the GJ with those of OA. 8 hub targets, including IL6 and AKT1, were obtained in PPI network analysis. Then, we built up GJ-target-OA network and protein-protein interaction (PPI) network, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The results underlined inflammatory tumor necrosis factor (TNF) as a promising signaling pathway of GJ for OA treatment. Moreover, molecular docking also verified the top two active compounds had direct bindings with the top three target genes. Finally, we verified the effect of GJ on OA in vivo and in vitro. In vivo experiments validated that GJ not only significantly attenuated OA phenotypes including articular cartilage degeneration and subchondral bone sclerosis but also reduced the expressions of tumor necrosis factor-α (TNF-α) and p-p65 in articular chondrocytes. Besides, GJ serum also had a protective effect on chondrocytes against inflammation caused by TNF-α in vitro. Hence, our study predicted and verified that GJ could exert anti-inflammation and anticatabolism effects partially via regulating TNF-α/NF-kappa B (NF-κB) signaling.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Elucidation of the Underlying Mechanism of Gujian Oral Liquid Acting on Osteoarthritis through Network Pharmacology, Molecular Docking, and Experiment

Shi

et al. 2022

BioMed Research International

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“…Subsequently, Ding et al reported that emodin (MOL000471) attenuated OA progression by suppressing the NF- κ B and Wnt/ β -catenin pathways [ 23 ]. Xiao et al implicated that Kaempferol (MOL000422) reduced the effects on inflammation by XIST/miR-130a/STAT3 pathway in chondrocytes, as well as promoted secretion of extracellular matrix (ECM) [ 24 ]. Collectively, our study indicated that the main compounds in SJDTR had various pharmacological effects, such as inhibiting inflammatory and apoptotic, as well as promoting ECM secretion for the treatment of OA.…”

Section: Discussionmentioning

confidence: 99%

A Study on the Potential Mechanism of Shujin Dingtong Recipe against Osteoarthritis Based on Network Pharmacology and Molecular Docking

Yuan

Yang

2022

Computational and Mathematical Methods in Medicine

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Background. With the aging of the social population, Osteoarthritis (OA) has already become a vital health and economic problem globally. Shujin Dingtong recipe (SJDTR) is an effective formula to treat OA in China. Although studies have shown that SJDTR can significantly alleviate OA symptoms, its mechanism still remains unclear. Purpose. This study is aimed at investigating the potential mechanism of SJDTR for the treatment of OA based on network pharmacology and molecular docking. Methods. Main ingredients of SJDTR were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. OA disease targets were obtained from the Gene Expression Omnibus (GEO) database. The overlapped targets and signaling pathways were explored using Protein-Protein Interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Following this, the core targets were employed to dock with corresponding components via molecular docking in order to further explore the mechanism of SJDTR in the treatment of OA. Results. From network pharmacology, we found 100 active components of SJDTR, 31 drug and OA-related targets, 1161 GO items, and 91 signaling pathways. Based on the analysis with PPI network and molecular docking, TP53, CCNB1, and MMP-2 were selected for the core targets of SJDTR against OA. Molecular docking demonstrated that Quercetin, Baicalein, and Luteolin, had good binding with the TP53, CCNB1, and MMP-2 protein, respectively. Conclusion. To conclude, our study suggested the main ingredients of SJDTR might alleviate the progression of OA through multiple targets and pathways. Additionally, network pharmacology and molecular docking, as new approaches, were adopted for systematically exploring the potential mechanism of SJDTR for the treatment of OA.

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“…Notably, the consistency results could be seen in the studies of XIST in terms of repressing the development of OA as indicated by different models. For instance, in IL-1b induced human C28/I2 chondrocyte cells, the knockdown of XIST expression suppressed the production of IL-6, TNF-α, PGE2 and NO through the interaction with miR130a ( 187 ). XIST regulated IL-1β-induced chondrocyte growth, apoptosis and ECM synthesis through sponging with miR-142-5p in human chondrosarcoma cell line SW1353 ( 188 ).…”

Section: Biological Functions Of Lncrnas In Oa Pathogenesismentioning

confidence: 99%

Emerging role of lncRNAs in osteoarthritis: An updated review

2022

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Osteoarthritis (OA) is a prevalent joint disease, which is associated with progressive articular cartilage loss, synovial inflammation, subchondral sclerosis and meniscus injury. The molecular mechanism underlying OA pathogenesis is multifactorial. Long non-coding RNAs (lncRNAs) are non-protein coding RNAs with length more than 200 nucleotides. They have various functions such as modulating transcription and protein activity, as well as forming endogenous small interfering RNAs (siRNAs) and microRNA (miRNA) sponges. Emerging evidence suggests that lncRNAs might be involved in the pathogenesis of OA which opens up a new avenue for the development of new biomarkers and therapeutic strategies. The purpose of this review is to summarize the current clinical and basic experiments related to lncRNAs and OA with a focus on the extensively studied H19, GAS5, MALAT1, XIST and HOTAIR. The potential translational value of these lncRNAs as therapeutic targets for OA is also discussed.

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Kaempferol Attenuates the Effects of XIST/miR-130a/STAT3 on Inflammation and Extracellular Matrix Degradation in Osteoarthritis

Cited by 22 publications

References 39 publications

Elucidation of the Underlying Mechanism of Gujian Oral Liquid Acting on Osteoarthritis through Network Pharmacology, Molecular Docking, and Experiment

Elucidation of the Underlying Mechanism of Gujian Oral Liquid Acting on Osteoarthritis through Network Pharmacology, Molecular Docking, and Experiment

A Study on the Potential Mechanism of Shujin Dingtong Recipe against Osteoarthritis Based on Network Pharmacology and Molecular Docking

Emerging role of lncRNAs in osteoarthritis: An updated review

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