Diosmetin exhibits anti‐proliferative and anti‐inflammatory effects on TNF‐α‐stimulated human rheumatoid arthritis fibroblast‐like synoviocytes through regulating the Akt and NF‐κB signaling pathways

Chen, You; Wang, Yongsheng; Liu, Min; Zhou, Bingkang; Yang, Guangjie

doi:10.1002/ptr.6596

Cited by 60 publications

(31 citation statements)

References 44 publications

(45 reference statements)

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“…Diosmetin is a type of common flavonoids. It is rich in citrus fruits, olive leaves and extracts from common herbs in southern China with a variety of functions such as scavenging free radicals, anti-inflammatory and anti-oxidative stress [ 13 – 15 ]. Recently, it is shown that diosmetin has anti-tumor effect by inhibiting the cell proliferation, inducing cell apoptosis and regulating cell cycle on breast cancer cells, liver cancer cells, colon cancer cells, leukemia cells and other tumors, indicating it is a potential promising treatment for cancers [ 17 , 18 , 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells

et al. 2021

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Background Diosmetin is a bioflavonoid compound naturally abundant in citrus fruits. It is found to perform a variety of activities, while its antitumor property in osteosarcoma, a malignant tumor with unmet clinical treatment, remained unknown. Methods Colony formation assay, cell cycle analysis and apoptosis analysis were conducted respectively to observe the effect of diosmetin on cell proliferation and apoptosis in human osteosarcoma cells. Western blot and immunoprecipitation were used to detect the expression of apoptotic molecules and activation of STAT3/c-Myc pathway in Saos-2 and U2SO cells. Results Diosmetin significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and promoted cell apoptosis in both Saos-2 and U2SO cells. Moreover, Diosmetin downregulated the expression of anti-apoptotic protein Bcl-xL while upregulated the levels of pro-apoptotic proteins including cleaved Caspase-3, cleaved-PARP and Bax. Furthermore, diosmetin dose-dependently inhibited STAT3 phosphorylation, reduced the expression of its downstream protein c-Myc and impeded the interaction between STAT3 molecules. Conclusions These results suggest that diosmetin exerts anti-osteosarcoma effects by suppressing cell proliferation and inducing apoptosis via inhibiting the activation of STAT3/c-Myc signaling pathway, which provide the possibility for diosmetin to be a chemotherapeutic candidate for osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells

et al. 2021

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“…RA FLS with TNFα stimulation was widely served as an in vitro model to explore RA pathogenesis and screen potential therapeutic drugs. 22,23 In this study, we evaluated the effects of lentivirus-mediated AQP1 overexpression or silencing on the proliferation, apoptosis, migration and invasion of TNF-αstimulated MH7A cells, and revealed the underlying mechanisms related to Wnt/β-catenin signaling pathway. Aggressive proliferation of RA FLS has been suggested to contribute to synovial hyperplasia, the basic pathological feature of RA.…”

Section: Discussionmentioning

confidence: 99%

Lentivirus-Mediated Overexpression or Silencing of Aquaporin 1 Affects the Proliferation, Migration and Invasion of TNF-α-Stimulated Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Wnt/β-Catenin Signaling Pathway

Zhou¹,

Cai²,

Feng³

et al. 2021

JIR

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Introduction: Previous studies have confirmed the pathologic role of synovial aquaporin 1 (AQP1) in rheumatoid arthritis (RA), but its associations with the abnormal biologic behaviors of fibroblast-like synoviocytes (FLS) remain unclear. Herein, we examined the roles of AQP1 in the proliferation, migration and invasion of TNF-α-stimulated RA FLS (MH7A cells) and explored the underlying mechanisms. Materials and Methods: Lentivirus-mediated AQP1 overexpression or silencing MH7A cells was constructed. Assays of MTT, flow cytometry (PI staining and Annexin V-PE/ 7-AAD staining), TMRM staining, wound-healing, transwell and phalloidin staining were performed to detect cell proliferation, cycle distribution, apoptosis, migration and invasion. The involvement of Wnt/β-catenin pathway was revealed by Western blot and β-catenin immunofluorescence staining. Results: AQP1 overexpression promoted cell proliferation of TNF-α-stimulated MH7A by facilitating transformation from G0/G1 to S phase and inhibiting cell apoptosis (ie, reduced apoptosis rates, raised mitochondrial membrane potential, increased Bcl-2 protein level and decreased levels of Bax and cleaved caspase 3 protein). Also, AQP1 overexpression increased the migration index as well as the numbers of migrated and invasive cells. Furthermore, AQP1 overexpression promoted the activation of Wnt/β-catenin pathway, and XAV939, an inhibitor of Wnt/β-catenin, canceled the above effects of AQP1 overexpression on MH7A cells. As expected, AQP1 silencing exhibited the opposite effects on TNF-αstimulated MH7A cells, which could be reversed by LiCl, an activator of Wnt/β-catenin. Conclusion: AQP1 can affect the proliferation, migration and invasion of MH7A cells by Wnt/β-catenin signaling pathway, and AQP1 can be as a crucial determiner that can regulate RA FLS biologic behaviors.

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“… 7 At present, MH7A cells as a mature pathological model cells have been widely used in the study of RA. 2 , 8 , 9 Human rheumatoid arthritis fibroblast-like synovial cell line of MH7A was obtained from the Beina Biological Company (Beijing, China), sub-cultured in DMEM (high glucose) containing 10% FBS at 37°C. Cells were passed through every 3–4 days, and only 3–5 generations of MH7A cells were used in the experiment.…”

Section: Methodsmentioning

confidence: 99%

Inducing Apoptosis and Suppressing Inflammatory Reactions in Synovial Fibroblasts are Two Important Ways for Guizhi-Shaoyao-Zhimu Decoction Against Rheumatoid Arthritis

Zhang

Duan

et al. 2021

JIR

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Background and Objectives Guizhi-Shaoyao-Zhimu decoction (GSZD) is often applied to control rheumatoid arthritis (RA), gout, osteoarthritis, etc. In this study, bioinformatic analysis and experimental verification were used to uncover the integral mechanism profile of GSZD against RA. Materials and Methods The chemical compositions of GSZD were identified by UPLC-QTOF-MS/MS. MH7A cell model was established to screen active compounds in GSZD, and potential targets of these compounds were predicted through online database retrieval. The differential expression genes (DEGs) in synovial tissue of RA patients and normal controls were retrieved from the GEO database. DEGs and the predicated compounds targets were overlapped, and the overlapped genes were subsequently enriched by GO and KEGG analysis. The pathways with significant enrichments were further experimentally verified. Results A total of 19 constituents were identified from GSZD, and 11 compounds showed obviously antiproliferative effects on MH7A cells with IC 50 < 100 μg/mL. Bioinformatic analysis indicated that IL-1β, IL-6, MAPK8 , JAK2 , CXCL8 , and CASP3 were the main targets of GSZD, and the integral pharmacological mechanisms profile of GSZD might be related to anti-inflammation and proapoptosis. GSZD can promote the loss of mitochondrial membrane potential (MOMP) and induce apoptosis in MH7A cells. Furthermore, in vitro experiments showed GSZD can not only downregulate mRNA expressions of IL-1β ( p <0.05), IL-6 ( p <0.05), MMPs ( p <0.05) and CCL5 ( p <0.05) but also inhibit the nuclear transcription of NF-κB. GSZD also reduced the expressions of Bcl-2 ( p <0.05), JAK2 ( p <0.05), STAT-3 ( p <0.05), whereas increase Bax ( p <0.05), Caspase-3 ( p <0.05) and caspase-9 ( p <0.05). Conclusion Collectively, inducing synovial fibroblast apoptosis and inhibiting inflammatory response are two important ways for GSZD to RA, and our study proved bioinformatic analysis combined with experimental verification is a feasible method to explore the drug targets and mechanism of actions of TCMs.

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Diosmetin exhibits anti‐proliferative and anti‐inflammatory effects on TNF‐α‐stimulated human rheumatoid arthritis fibroblast‐like synoviocytes through regulating the Akt and NF‐κB signaling pathways

Cited by 60 publications

References 44 publications

Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells

Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells

Lentivirus-Mediated Overexpression or Silencing of Aquaporin 1 Affects the Proliferation, Migration and Invasion of TNF-α-Stimulated Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Wnt/β-Catenin Signaling Pathway

Inducing Apoptosis and Suppressing Inflammatory Reactions in Synovial Fibroblasts are Two Important Ways for Guizhi-Shaoyao-Zhimu Decoction Against Rheumatoid Arthritis

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