Ellagic Acid Alleviates Rheumatoid Arthritis in Rats through Inhibiting MTA1/HDAC1-Mediated Nur77 Deacetylation

Song, Huanjin; Wu, Hao; Dong, Jing; Huang, Sihua; Ye, Jintao; Liu, Ruoxi

doi:10.1155/2021/6359652

Cited by 16 publications

(13 citation statements)

References 25 publications

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“…Moreover, an improvement in oxidative markers was observed, such as MPO activity, NO release, GSH levels, and lipid peroxidation. Similar doses of EA were used by Song et al (25, 50, 100 mg/kg/d), who confirmed the reduction of paw swelling, synovial hyperplasia, and inflammation in a collagen-induced arthritis (CIA) model [ 35 ]. Moreover, EA was treated in TNF-α-induced FLS cells, at the range of 10 to 100 μM, thus inhibiting the levels of cytokines (IL-6, IL-1β) and oxidative markers (MDA).…”

Section: Resultsmentioning

confidence: 66%

“…Plausibly, products from hydrolysis and metabolism, such as GA, EA, and UroA, participate in the biological effect, although their formation at the gut level has rarely been addressed. This evidence is supported by several in vivo experiments, in which HTs and metabolites were administered as individual compounds through the oral route at comparable doses: EA (50 mg/kg) ameliorated the inflammatory profile in RA models [ 31 , 32 , 33 , 34 , 35 ]; similarly EA, GA, and UroA (10–20 mg/kg) inhibited gut inflammation in IBD models [ 64 , 65 , 66 , 70 , 71 , 72 ], while EA (10 mg/kg) and GA (20–80 mg/kg) reduced allergic inflammation in AD, asthma, and rhinitis [ 86 , 88 , 96 , 102 ]. Remarkably, HTs have frequently been mentioned for direct antibacterial and antiviral activity [ 106 ], which may suggest a restrained impact on infection risk.…”

Section: Discussionmentioning

confidence: 68%

“…Moreover, EA was treated in TNF-α-induced FLS cells, at the range of 10 to 100 μM, thus inhibiting the levels of cytokines (IL-6, IL-1β) and oxidative markers (MDA). The authors suggested that EA may interfere with the metastasis-associated gene 1 (MTA1)/HDAC-1 pathway, involved in RA development, reflecting the inhibition of Nur77 deacetylation [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

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Hydrolyzable Tannins in the Management of Th1, Th2 and Th17 Inflammatory-Related Diseases

et al. 2022

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Plants rich in hydrolyzable tannins were traditionally used all over the world for a variety of chronic inflammatory disorders, including arthritis, colitis, and dermatitis. However, the knowledge of their immunological targets is still limited though fundamental for their rational use in phytotherapy. The recent advances regarding the pathogenesis of inflammatory-based diseases represent an opportunity to elucidate the pharmacological mechanism of plant-derived metabolites with immunomodulatory activity. This review collects recent articles regarding the role of hydrolyzable tannins and their gut metabolites in Th1, Th2, and Th17 inflammatory responses. In line with the traditional use, rheumatoid arthritis (RA), inflammatory bowel diseases (IBDs), psoriasis, atopic dermatitis (AD), and asthma were the most investigated diseases. A substantial body of in vivo studies suggests that, beside innate response, hydrolyzable tannins may reduce the levels of Th-derived cytokines, including IFN-γ, IL-17, and IL-4, following oral administration. The mode of action is multitarget and may involve the impairment of inflammatory transcription factors (NF-κB, NFAT, STAT), enzymes (MAPKs, COX-2, iNOS), and ion channels. However, their potential impact on pathways with renewed interest for inflammation, such as JAK/STAT, or the modulation of the gut microbiota demands dedicate studies.

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Section: Resultsmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 99%

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Hydrolyzable Tannins in the Management of Th1, Th2 and Th17 Inflammatory-Related Diseases

et al. 2022

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“…There are relevant studies on the relationship between HDAC1 and inflammation. For example, down-regulation of HDAC1 can restore myocardial injury in septic mice to a certain extent ( Nong, Qin et al, 2022 ), and ellagic acid can alleviate rheumatoid arthritis in rats by inhibiting HDAC1 ( Song, Wu et al, 2021 ), and HDAC1 can control the metabolism of intestinal epithelial cells by regulating the supply of acetyl groups, resulting in impaired response to oxidative stress, AMPK kinase activation and mitochondrial biogenesis ( Gonneaud, Turgeon et al, 2015 ). Our study found that the expression of HDAC1 was significantly increased in the aorta of T2DM mice as well as HG-induced HUVEC cells ( Figures 3D, E, H , Figures 5A–C ).…”

Section: Discussionmentioning

confidence: 99%

Vaccarin alleviates endothelial inflammatory injury in diabetes by mediating miR-570-3p/HDAC1 pathway

Zhu

et al. 2022

Front. Pharmacol.

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Vaccarin is a flavonoid glycoside, which has a variety of pharmacological properties and plays a protective role in diabetes and its complications, but its mechanism is unclear. In this study, we aim to investigate whether histone deacetylase 1(HDAC1), a gene that plays a pivotal role in regulating eukaryotic gene expression, is the target of miR-570-3p in diabetic vascular endothelium, and the potential molecular mechanism of vaccarin regulating endothelial inflammatory injury through miR-570-3p/HDAC1 pathway. The HFD and streptozotocin (STZ) induced diabetes mice model, a classical type 2 diabetic model, was established. The aorta of diabetic mice displayed a decrease of miR-570-3p, the elevation of HDAC1, and inflammatory injury, which were alleviated by vaccarin. Next, we employed the role of vaccarin in regulating endothelial cells miR-570-3p and HDAC1 under hyperglycemia conditions in vitro. We discovered that overexpression of HDAC1 counteracted the inhibitory effect of vaccarin on inflammatory injury in human umbilical vein endothelial cells (HUVECs). Manipulation of miRNA levels in HUVECs was achieved by transfecting cells with miR-570-3p mimic and inhibitor. Overexpression of miR-570-3p could decrease the expression of downstream components of HDAC1 including TNF-α, IL-1β, and malondialdehyde, while increasing GSH-Px activity in HUVECs under hyperglycemic conditions. Nevertheless, such phenomenon was completely reversed by miR-570-3p inhibitor, and administration of miR-570-3p inhibitor could block the inhibition of vaccarin on HDAC1 and inflammatory injury. Luciferase reporter assay confirmed the 3′- UTR of the HDAC1 gene was a direct target of miR-570-3p. In summary, our findings suggest that vaccarin alleviates endothelial inflammatory injury in diabetes by mediating miR-570-3p/HDAC1 pathway. Our study provides a new pathogenic link between deregulation of miRNA expression in the vascular endothelium of diabetes and inflammatory injury and provides new ideas, insights, and choices for the scope of application and medicinal value of vaccarin and some potential biomarkers or targets in diabetic endothelial dysfunction and vascular complications.

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“…Overexpressed HDAC1 promotes the pathological process of bone destruction in RA. 17,18 Additionally, HDAC affects the differentiation of osteoclast progenitors by regulating NF-κB and RANKL/RANK signaling pathways. As potential antiinflammatory and immune drugs, HDAC inhibitors are promising in RA therapy.…”

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confidence: 99%

HDAC2 exacerbates rheumatoid arthritis progression via the IL‐17‐CCL7 signaling pathway

Mao

Jin

Zhang

et al. 2023

Environmental Toxicology

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Histone deacetylases (HDACs) have been reported to regulate the immune response in rheumatoid arthritis (RA). The current study aimed to explore key HDACs and their molecular mechanism in RA. First, the expression of HDAC1, HDAC2, HDAC3 and HDAC8 in RA synovial tissue was determined by qRT‐PCR. The effects of HDAC2 on the proliferation, migration, invasion, and apoptosis of fibroblast‐like synoviocytes (FLS) in vitro were studied. Furthermore, collagen‐induced arthritis (CIA) rat models were established to evaluate the severity of arthritis in joints, and the levels of inflammatory factors were examined by immunohistochemistry staining, ELISA, and qRT‐PCR. Transcriptome sequencing was used to screen differentially expressed genes (DEGs) with HDAC2 silencing in the synovial tissue of CIA rat, and downstream signaling pathways were predicted by enrichment analysis. The results showed that HDAC2 was highly expressed in the synovial tissue of RA patients and CIA rats. Overexpressed HDAC2 promoted FLS proliferation, migration, and invasion and inhibited FLS apoptosis in vitro, resulting in secretion of inflammatory factors and RA exacerbation in vivo. There were 176 DEGs, including 57 downregulated and 119 upregulated genes, after silencing HDAC2 in CIA rats. DEGs were primarily enriched in Platinum drug resistance, IL‐17 as well as the PI3K‐Akt signaling pathways. CCL7, which was implicated in the IL‐17 signaling pathway, was downregulated after HDAC2 silencing. Furthermore, CCL7 overexpression aggravated the development of RA, which was demonstrated to be effectively attenuated by HDAC2 suppression. In conclusion, this study demonstrated that HDAC2 exacerbated the progression of RA by regulating the IL‐17‐CCL7 signaling pathway, suggesting that HDAC2 may be a promising therapeutic target for RA treatment.

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Ellagic Acid Alleviates Rheumatoid Arthritis in Rats through Inhibiting MTA1/HDAC1-Mediated Nur77 Deacetylation

Cited by 16 publications

References 25 publications

Hydrolyzable Tannins in the Management of Th1, Th2 and Th17 Inflammatory-Related Diseases

Hydrolyzable Tannins in the Management of Th1, Th2 and Th17 Inflammatory-Related Diseases

Vaccarin alleviates endothelial inflammatory injury in diabetes by mediating miR-570-3p/HDAC1 pathway

HDAC2 exacerbates rheumatoid arthritis progression via the IL‐17‐CCL7 signaling pathway

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