Liposome-encapsulated dimethyl curcumin inhibits over-activation of rat lymphocyte to relieve collagen-induced arthritis by regulating intracellular proteolysis and PCNA/p21/caspase-3 pathway

Abstract Background: Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, can reduce the symptoms of rheumatoid arthritis (RA), but its pharmacological mechanism is unclear. The aims of this study were to investigate the therapeutic mechanisms of WJT for RA in vivo.Methods: The effects of WJT on the joint pathology, and the levels of Bax, Bcl-2,caspase-3, cleaved-caspase-3, ERK1/2, pERK1/2, TNF-α, IL-1β, and IL-6 were demonstrated based on several experiments in the model of collagen-induced arthritis (CIA) in rats. 16S rDNA high-throughput sequencing was used to investigate the effect of WJT on the overall structure and composition of gut microbiota. Meanwhile, metabolite changes in faeces were analyzed by metabolomics techniques. Results: The results showed that WJT restored the joint pathology in CIA rats, upregulated Bax and cleaved-caspase-3, downregulated Bcl-2, caspase-3, and pERK1/2, and reduced the levels of pro-inflammatory cytokines. The overall gut microbial structure in CIA rats was altered after WJT treatment. Three bacterial phyla were prominently restored: Bacteroidetes,Tenericutes and Deferribacteres, and three bacterial genera were significantly reversed: Vibrio, Macrococcus and Vagococcus. Furthermore, five specific metabolites associated with these specific bacterial genera were identified by correlation analysis. In addition, WJT supplement trended to down-regulate the other five metabolites according to metabolomic analyses. Conclusions: These results revealed that WJT restored the pathological changes of RA might through activating the mitochondrial apoptosis pathway, inhibited MEK/ERK signaling, and modulating the special bacteria and the special metabolites.

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Arsenic Trioxide Induces Apoptosis of Fibroblast-like Synoviocytes and Represents Antiarthritis Effect in Experimental Model of Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.100299 ◽

2010 ◽

Vol 38 (1) ◽

pp. 36-43 ◽

Cited By ~ 9

Author(s):

YIFANG MEI ◽

YINING ZHENG ◽

HUI WANG ◽

JUAN GAO ◽

DIANXIN LIU ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mrna Expression ◽

Arsenic Trioxide ◽

Messenger Rna ◽

Caspase 3 ◽

Joint Destruction ◽

Flow Cytometric Analysis ◽

Caspase 8 ◽

Collagen Induced Arthritis ◽

Fibroblast Like Synoviocytes

Objective.Recent studies have demonstrated that rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) proliferate as fiercely as tumor cells. Induction of apoptosis in RA FLS therefore provides a new approach for the inhibition of joint destruction. Arsenic trioxide (As2O3) was reported to be an effective apoptosis inducer in a variety of cell types. We investigated the possible effect of As2O3on apoptosis induction of RA FLS and the mechanisms involved in this process.Methods.Apoptosis was determined by flow cytometric analysis, terminal deoxynucleotide transferase-mediated dUTP nick end-labeling, and transmission electron microscopy. The activity and messenger RNA (mRNA) expression of nuclear factor-κB (NF-κB) was then detected by ELISA and real-time polymerase chain reaction, respectively. Activities of caspase-3 and caspase-8 were evaluated using luminogenic substrates. The effect of As2O3on the morphology of rats with collagen-induced arthritis was evaluated under a light microscope after H&E staining.Results.As2O3significantly enhanced the apoptosis of RA FLS. It suppressed the DNA-binding activity and mRNA expression level of NF-κB, probably by inhibiting tumor necrosis factor-α-induced activation of NF-κB. As2O3treatment significantly increased the activity of both caspase-3 and caspase-8. Morphological analysis revealed histological recovery in the synovial membrane. Synovial hyperplasia and inflammation in the joints were effectively inhibited.Conclusion.As2O3represents an apoptotic effect on RA FLS through NF-κB signaling pathway, and this process is mediated by the activation of caspase cascade. Treatment with As2O3significantly improved the pathologic changes of collagen-induced arthritis and may have potential for treatment of RA.

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IL-6 Promotes Islet β-Cell Dysfunction in Rat Collagen-Induced Arthritis

Journal of Diabetes Research ◽

10.1155/2016/7592931 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Huan Jin ◽

Yaogui Ning ◽

Haotong Zhou ◽

Youlian Wang

Keyword(s):

Glucose Metabolism ◽

Caspase 3 ◽

Islet Cells ◽

Type Ii Collagen ◽

Intradermal Injection ◽

Control Group ◽

Collagen Induced Arthritis ◽

Abnormal Glucose Metabolism ◽

Pancreas Islet ◽

Related Enzyme

The aim of this study was to explore the possible mechanism of rheumatoid arthritis- (RA-) related abnormal glucose metabolism. The model of collagen-induced arthritis (CIA) was established by intradermal injection of type II collagen into Wistar rats; complete Freund’s adjuvant injections were used as the control group. Fasting plasma glucose (FBG) was measured by the glucose oxidase method. Fasting insulin (FIns) and the expressions of IL-6 were detected by ELISA. Islet caspase-3 was examined by immunohistochemistry. On day 17 after immunization, FBG of the CIA group showed an elevated FBG value compared with the control group. Meanwhile, the FIns of group CIA was lower when compared with the control group. Interestingly, the inflammatory cytokine IL-6 expression was significantly increased when compared with the control group. As expected, the abnormal glucose metabolism was accompanied by the increased IL-6 expression. Furthermore, in line with the upregulated IL-6 expression, the apoptosis related enzyme caspase-3 was also markedly increased. These data showed that the elevated FBG in CIA may be associated with the reduced FIns level secondary to the overapoptosis of pancreas islet cells induced by IL-6.

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Inhibition of nitric oxide and caspase-3 mediated apoptosis by a tetrapeptide derivative (PEP1261) in cultured synovial fibroblasts from collagen-induced arthritis

Molecular and Cellular Biochemistry ◽

10.1007/s11010-006-1737-4 ◽

2006 ◽

Vol 282 (1-2) ◽

pp. 125-139 ◽

Cited By ~ 6

Author(s):

Dilly Ashok Kumar ◽

K. Settu ◽

Kalidindi V. S. Narayana Raju ◽

K. Kumanan ◽

Bhakthavatchalam Murali Manohar ◽

...

Keyword(s):

Nitric Oxide ◽

Caspase 3 ◽

Synovial Fibroblasts ◽

Collagen Induced Arthritis

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Identification of drug targets and potential molecular mechanisms of Wantong Jingu Tablet in treatment of rats with collagen-induced arthritis based on 16S rDNA high-throughput sequencing and metabolomic analysis

10.21203/rs.3.rs-40544/v1 ◽

2020 ◽

Author(s):

Zhaodong Li ◽

Fangyuan Qi ◽

Fan Li

Keyword(s):

Rheumatoid Arthritis ◽

16S Rdna ◽

High Throughput ◽

Drug Targets ◽

Molecular Mechanisms ◽

High Throughput Sequencing ◽

Caspase 3 ◽

Collagen Induced Arthritis ◽

Apoptosis Pathway ◽

Joint Pathology

Abstract Background: Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, can reduce the symptoms of rheumatoid arthritis (RA), but its pharmacological mechanism is unclear. The aims of this study were to investigate the therapeutic mechanisms of WJT for RA in vivo.Methods: The effects of WJT on the joint pathology, and the levels of Bax, Bcl-2,caspase-3, cleaved-caspase-3, ERK1/2, pERK1/2, TNF-α, IL-1β, and IL-6 were demonstrated based on several experiments in the model of collagen-induced arthritis (CIA) in rats. 16S rDNA high-throughput sequencing was used to investigate the effect of WJT on the overall structure and composition of gut microbiota. Meanwhile, metabolite changes in faeces were analyzed by metabolomics techniques.Results: The results showed that WJT restored the joint pathology in CIA rats, upregulated Bax and cleaved-caspase-3, downregulated Bcl-2, caspase-3, and pERK1/2, and reduced the levels of pro-inflammatory cytokines. The overall gut microbial structure in CIA rats was altered after WJT treatment. Three bacterial phyla were prominently restored: Bacteroidetes,Tenericutes and Deferribacteres, and three bacterial genera were significantly reversed: Vibrio, Macrococcus and Vagococcus. Furthermore, five specific metabolites associated with these specific bacterial genera were identified by correlation analysis. In addition, WJT supplement trended to down-regulate the other five metabolites according to metabolomic analyses.Conclusions: These results revealed that WJT restored the pathological changes of RA might through activating the mitochondrial apoptosis pathway, inhibited MEK/ERK signaling, and modulating the special bacteria and the special metabolites.Keywords: Rheumatoid arthritis; 16S rDNA high-throughput sequencing; metabolomics; drug targets; Wantong Jingu Tablet

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