Anti-rheumatic activity of Phenethyl isothiocyanate via inhibition of histone deacetylase-1

Choudhary, Narayan; Gupta, Riya; Bhatt, Lokesh Kumar

doi:10.1016/j.cbi.2020.109095

Cited by 9 publications

(5 citation statements)

References 28 publications

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“…Moreover, HDAC1 inhibition reduced joint swelling, cartilage, and bone damage in joint tissues of CIA rats [ 19 ]. More importantly, nonselective HDAC inhibitors were found to have anti-inflammatory properties in both in vitro and in vivo models of RA [ 20 , 21 ]. Similarly, our results demonstrated that MTA1 was upregulated in TNF- α -treated MH7A cells, and MTA1 knockdown inhibited proliferation, inflammation, and oxidative stress and promoted apoptosis in MH7A cells.…”

Section: Discussionmentioning

confidence: 99%

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

Song

Dong

et al. 2021

Mediators of Inflammation

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Ellagic acid (EA) was reported to play protective roles in rheumatoid arthritis (RA). It was found that the level of metastasis-associated gene 1 (MTA1)/histone deacetylase 1 (HDAC1) protein complex was downregulated by polyphenols in several human disorders. Notably, inhibition of MTA1 or HDAC1 has anti-inflammatory effects on RA. Therefore, our study is aimed at investigating whether EA prevents RA progression through regulating the MTA1/HDAC1 complex. Herein, the human fibroblast-like synoviocyte (FLS) cell line MH7A was treated with TNF-α to induce an inflammation model in vitro and then incubated with different concentrations of EA. Western blot analysis showed that EA reduced MTA1 expression in a dose-dependent manner in MH7A cells. Then, TNF-α-treated MH7A cells were incubated with EA alone or together with MTA1 overexpression plasmid (pcDNA-MTA1), and we found that EA inhibited proliferation, inflammation cytokine levels, and oxidative stress marker protein levels and promoted apoptosis in MH7A cells, while MTA1 overexpression abolished these effects. Moreover, coimmunoprecipitation assay verified the interaction between MTA1 and HDAC1. EA downregulated the MTA1/HDAC1 complex in MH7A cells. MTA1 knockdown inhibited proliferation, inflammation, and oxidative stress and promoted apoptosis in MH7A cells, while HDAC1 overexpression reversed these effects. Moreover, chromatin immunoprecipitation assay indicated that EA inhibited HDAC1-mediated Nur77 deacetylation. Rescue experiments demonstrated that Nur77 knockdown reversed the effects of EA on MH7A cell biological behaviors. Additionally, EA treatment attenuated arthritis index, paw swelling, synovial hyperplasia, and inflammation in collagen-induced arthritis (CIA) rats. In conclusion, EA inhibited proliferation, inflammation, and oxidative stress and promoted apoptosis in MH7A cells and alleviated the severity of RA in CIA rats though downregulating MTA1/HDAC1 complex and promoting HDAC1 deacetylation-mediated Nur77 expression.

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Section: Discussionmentioning

confidence: 99%

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

Song

Dong

et al. 2021

Mediators of Inflammation

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“…The pharmacokinetic feature of PEITC includes first-order linear absorption with a high protein binding nature . A recent study on PEITC (as a potent inhibitor of HDAC1) also demonstrated ameliorated RA by downregulation of TNF-alpha as well as HDAC 1 levels in synovial tissue of CFA-induced arthritic rats . On the other hand, SFN is a natural, aliphatic ITC, primarily derived from broccoli, belonging to Brassicaceae family.…”

Section: Introductionmentioning

confidence: 99%

“…12 A recent study on PEITC (as a potent inhibitor of HDAC1) also demonstrated ameliorated RA by downregulation of TNFalpha as well as HDAC 1 levels in synovial tissue of CFAinduced arthritic rats. 13 On the other hand, SFN is a natural, aliphatic ITC, primarily derived from broccoli, belonging to Brassicaceae family. SFN has also been studied for its inflammatory and antiarthritic activities.…”

Section: Introductionmentioning

confidence: 99%

Naringin in Combination with Isothiocyanates as Liposomal Formulations Potentiates the Anti-inflammatory Activity in Different Acute and Chronic Animal Models of Rheumatoid Arthritis

et al. 2020

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Combination of drugs is extensively used to treat chronic inflammatory disease. Naringin (NAR), sulforaphane (SFN), and phenethyl isothiocyanate (PEITC) are nutraceuticals with promising anti-inflammatory properties. However, their clinical effectiveness gets hindered because of low aqueous solubility and poor bioavailability. In the current study, two combinations of liposome (NAR + SFN and NAR + PEITC) were prepared and studied thoroughly in different in vivo models of acute and chronic models of inflammation. The encapsulation efficiency of NAR, SFN, and PEITC in the combination liposomal formulations (CLFs) prepared with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-distearoyl-sn-glycero-3-phosphoethanolamine -020CN (15:4:1 M ratio) was determined to be 79.8 ± 4.2, 46.5 ± 3.6, and 78.5 ± 3.2%, respectively. The CLFs were characterized by differential scanning calorimetry, Xray diffraction, dynamic light scattering, and Fourier transform infrared spectroscopy. The physicochemical results showed that the preparations were monodisperse (PDI 0.062−0.248) in water with an average size from 140.5 to 165.6 nm and a zeta potential of −47.3 to −53.3 mV. Dissolution studies in vitro showed a slower release of PEITC (>90%, 6 h) in comparison to that of SFN (3 h). Here, we are the first to report the antiarthritic activity of CLF of NAR + SFN and NAR + PEITC in the Freund's complete adjuvant (FCA)-induced arthritic model. At an intraperitoneal dose (375 + 375 μg/mL) for 3 weeks, the NAR + PEITC liposome significantly improves both % paw edema and arthritic score compared to their free drug combinations in FCA rats. Most importantly, hematological and biochemical results showed improved anemic conditions with significant changes in the SGOT, SGPT, and ALP levels. The ELISA results showed similar trends of increased cytokine (IL-10) and decreased inflammation markers (TNF-α, IL-6, IFN-γ). Histological evaluations showing reduction in cell infiltration, pannus formation, and bone and cartilage destruction further confirm and validate the antiarthritic activity of the CLF. This comprehensive study reveals the effectiveness of combination liposomes of poorly soluble antiinflammatory molecules (NAR, SFN, PEITC) in the treatment of arthritis.

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“…The preventive treatment using PEITC reduces paw edema, total arthritis index, mobility score, stair climbing ability, behavioral parameters, and bone erosion in rats with CFA-induced arthritis in a dose-dependent manner. In addition, PEITC expressively downregulates the level of TNF-α in the synovial tissues of the CFA rats ( 71 ).…”

Section: The Effects Of Compounds On Epigenetic Regulation Of Ramentioning

confidence: 99%

Epigenetic Regulation in the Pathogenesis of Rheumatoid Arthritis

Yang

Teng

et al. 2022

Front. Immunol.

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Rheumatoid arthritis (RA) is an autoimmune disease. The etiology of RA remains undetermined and the pathogenesis is complex. There remains a paucity of ideal therapeutic drugs and treatment strategies. The epigenetic modifications affect and regulate the function and characteristics of genes through mechanisms, including DNA methylation, histone modification, chromosome remodeling, and RNAi, thereby exerting a significant impact on the living state of the body. Recently, the phenomenon of epigenetic modification in RA has garnered growing research interest. The application of epigenetically modified methods is the frontier field in the research of RA pathogenesis. This review highlights the research on the pathogenesis of RA based on epigenetic modification in the recent five years, thereby suggesting new methods and strategies for the diagnosis and treatment of RA.

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Anti-rheumatic activity of Phenethyl isothiocyanate via inhibition of histone deacetylase-1

Cited by 9 publications

References 28 publications

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

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

Naringin in Combination with Isothiocyanates as Liposomal Formulations Potentiates the Anti-inflammatory Activity in Different Acute and Chronic Animal Models of Rheumatoid Arthritis

Epigenetic Regulation in the Pathogenesis of Rheumatoid Arthritis

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