Glycine tabacina ethanol extract ameliorates collagen-induced arthritis in rats via inhibiting pro-inflammatory cytokines and oxidation

Abstract Background Macrophages play a crucial role in inflammation. Astilbe chinensis is one of perennial herbs belonging to the genus Astilbe. Plants in the genus have been used for pain, headaches, arthralgia, and chronic bronchitis. However, the effect of A.chinensis on inflammation remains unclear. To study the anti-inflammatory action of A.chinensis ethanol extract (ACE), we investigated the effect of ACE on the production of pro-inflammatory mediators and cytokines in macrophages. Methods We evaluated the effectiveness of ACE in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and thioglycollate (TG)-elicited peritoneal macrophages from male C57BL/6 mice. We measured the levels of pro-inflammatory mediators and cytokines, and examined the anti-inflammatory actions of ACE on nuclear factor κB (NF-κB) pathway in the macrophages. Western blot analysis and immunofluorescence microscopy were used to determine protein level and translocation, respectively. Results ACE suppressed the output of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines in stimulated macrophages via inhibiting the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. ACE suppressed mRNA expression of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α). We examined the efficacies of ACE on NF-κB activation by measuring the expressions including IκB kinase (IKK), inhibitor of κB (IκB), and nuclear p65 proteins. In addition, the inhibition of NF-κB p65’s translocation was determined with immunofluorescence assay. Conclusion Our findings manifested that ACE inhibited LPS or TG-induced inflammation by blocking the NF-κB signaling pathway in macrophages. It indicated that ACE is a potential therapeutic mean for inflammation and related diseases.

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Honokiol Inhibits the Progression of Collagen-Induced Arthritis by Reducing Levels of Pro-inflammatory Cytokines and Matrix Metalloproteinases and Blocking Oxidative Tissue Damage

Journal of Pharmacological Sciences ◽

10.1254/jphs.10070fp ◽

2010 ◽

Vol 114 (1) ◽

pp. 69-78 ◽

Cited By ~ 17

Author(s):

Ki Rim Kim ◽

Kwang-Kyun Park ◽

Kyung-Soo Chun ◽

Won-Yoon Chung

Keyword(s):

Matrix Metalloproteinases ◽

Inflammatory Cytokines ◽

Tissue Damage ◽

Collagen Induced Arthritis ◽

Pro Inflammatory Cytokines

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Osteostatin Inhibits Collagen-Induced Arthritis by Regulation of Immune Activation, Pro-Inflammatory Cytokines, and Osteoclastogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms20163845 ◽

2019 ◽

Vol 20 (16) ◽

pp. 3845 ◽

Cited By ~ 2

Author(s):

Josep Nácher-Juan ◽

María Carmen Terencio ◽

María José Alcaraz ◽

María Luisa Ferrándiz

Keyword(s):

T Cells ◽

Bone Loss ◽

Inflammatory Cytokines ◽

T Cell Activation ◽

Immune Activation ◽

Joint Destruction ◽

Related Protein ◽

Collagen Induced Arthritis ◽

Parathyroid Hormone Related Protein ◽

Pro Inflammatory Cytokines

In chronic inflammatory joint diseases, such as rheumatoid arthritis, there is an important bone loss. Parathyroid hormone-related protein (PTHrP) and related peptides have shown osteoinductive properties in bone regeneration models, but there are no data on inflammatory joint destruction. We have investigated whether the PTHrP (107-111) C-terminal peptide (osteostatin) could control the development of collagen-induced arthritis in mice. Administration of osteostatin (80 or 120 μg/kg s.c.) after the onset of disease decreased the severity of arthritis as well as cartilage and bone degradation. This peptide reduced serum IgG2a levels as well as T cell activation, with the downregulation of RORγt+CD4+ T cells and upregulation of FoxP3+CD8+ T cells in lymph nodes. The levels of key cytokines, such as interleukin(IL)-1β, IL-2, IL-6, IL-17, and tumor necrosis factor-α in mice paws were decreased by osteostatin treatment, whereas IL-10 was enhanced. Bone protection was related to reductions in receptor activator of nuclear factor-κB ligand, Dickkopf-related protein 1, and joint osteoclast area. Osteostatin improves arthritis and controls bone loss by inhibiting immune activation, pro-inflammatory cytokines, and osteoclastogenesis. Our results support the interest of osteostatin for the treatment of inflammatory joint conditions.

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Sustained Hypoxia Suppresses Joint Destruction in a Rat Model of Rheumatoid Arthritis via Negative Feedback of Hypoxia Inducible Factor-1α

International Journal of Molecular Sciences ◽

10.3390/ijms22083898 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3898

Author(s):

Kenta Kaihara ◽

Shuji Nakagawa ◽

Yuji Arai ◽

Hiroaki Inoue ◽

Shinji Tsuchida ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Inflammatory Cytokines ◽

Joint Destruction ◽

Hypoxia Inducible Factor ◽

Inhibitory Effect ◽

Dependent Manner ◽

Collagen Induced Arthritis ◽

Risk Patients ◽

Sustained Hypoxia ◽

Pro Inflammatory Cytokines

Hypoxia inducible factor (HIF)-1α has been implicated in the pathogenesis of rheumatoid arthritis (RA). HIF-1α, which is expressed in hypoxia, is reversely suppressed in sustained hypoxia. Here, we investigated the inhibitory effect of hypoxia on arthritis by controlling HIF-1α. Rheumatoid fibroblast-like synoviocyte MH7A cells were cultured in a hypoxic incubator for up to 72 h to evaluate the expression of HIF-1. Furthermore, collagen-induced arthritis (CIA) model rats were maintained under 12% hypoxia in a hypoxic chamber for 28 days to evaluate the effect on arthritis. In MH7A cells, HIF-1α protein level increased at 3 h, peaked at 6 h, and subsequently decreased in a time-dependent manner. The transcription of pro-inflammatory cytokines increased at 1 h; however, they decreased after 3 h (p < 0.05). Deferoxamine-mediated activation of HIF-1α abolished the inhibitory effect of sustained hypoxia on pro-inflammatory cytokines. In the rat CIA model, the onset of joint swelling was delayed and arthritis was suppressed in the hypoxia group compared with the normoxia group (p < 0.05). Histologically, joint destruction was suppressed primarily in the cartilage. Thus, sustained hypoxia may represent a new safe, and potent therapeutic approach for high-risk patients with RA by suppressing HIF-1α expression.

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