scholarly journals Cimiracemate A confers protection on arthritic neonatal rats via regulation of iNOS/NF-κB/TLR-4 pathway

2021 ◽  
Vol 18 (5) ◽  
pp. 949-954
Author(s):  
Jun Zou ◽  
Kun Peng ◽  
Tao Xiong ◽  
Zhi G. Xiong ◽  
Niya Hu
Keyword(s):  
Rheumatoid Arthritis ◽  
Plasma Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Neonatal Rats ◽  
Oxidative Stress Biomarkers ◽  
Sod Activity ◽  
Tnf Α ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

Purpose: To investigate the protective effect of cimiracemate A on Freund’s adjuvant-induced rheumatoid arthritis (RA) in neonatal rats, and the underlying mechanism. Methods: Rheumatoid arthritis was induced in rat pups using Complete Freund’s adjuvant (100 µg/100 µL/body weight) which was intra-dermally injected at the tail region. After 21 days of establishment of RA, the rats were randomly assigned to four groups of ten rats each: control group, RA group, 5 mg/kg cimiracemate A group, and 10 mg/kg cimiracemate A group. Cimiracemate A was orally administered for 45 days. The effect of cimiracemate A on oxidative stress biomarkers, superoxide dismutase (SOD), malondialdehyde (MDA) and reduced glutathione (GSH) were determined using standard methods. Plasma levels of the inflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE-2) and matrix metalloproteinase-3 (MMP-3) were determined using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to determine the levels of protein expressions of iNOS, NF-κB and TLR-4. Results: The level of MDA significantly increased and the level of GSH significantly decreased in RA group relative to control group (p < 0.05) following treatment with cimiracemate A. SOD activity was significantly reduced in RA group, when compared with control group (p < 0.05). However, treatment with cimiracemate A significantly and dose-dependently reversed the altered levels of MDA and GSH and SOD activity, when compared with RA group (p < 0.05). Plasma levels of IL-1β, TNF-α, PGE-2 and MMP-3 were significantly higher in RA group than in control group, but were significantly and dosedependently reduced after treatment with cimiracemate A (p < 0.05). There were significant increases in the levels of expression of iNOS, NF-κB and TLR-4 proteins in the chondrocytes of RA group, relative to control group (p < 0.05). However, treatment with cimiracemate A significantly and dose-dependently down-regulated the expressions of these proteins, when compared with RA group (p < 0.05). Conclusion: The results of this study indicate that cimiracemate A confers some degree of protection on arthritic neonatal rats via a mechanism that involves regulation of iNOS/NF-κB/TLR-4 pathway.

scholarly journals FUNCTIONAL ANALYSIS OF AGERATUM CONYZOIDES L. (BABANDOTAN) LEAVES EXTRACT ON RHEUMATOID ARTHRITIS MODEL RAT

2017 ◽  
Vol 10 (3) ◽  
pp. 429
Author(s):  
Erna Harfiani ◽  
Riri Nurul Suci ◽  
Ade Arsianti ◽  
Anton Bahtiar ◽  
Katrin Basah
Keyword(s):  
Rheumatoid Arthritis ◽  
Normal Control ◽  
Rat Model ◽  
Control Group ◽  
Paw Edema ◽  
Ageratum Conyzoides ◽  
Tnf Α ◽  
Freund’S Adjuvant ◽  
Complete Freund's Adjuvant ◽  
Freund's Adjuvant

ABSTRACTObjective: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints. Ageratum conyzoides L. (Babandotan)leaves are proven to be used in inflammation therapy, yet there is a little data regarding the effects of the leaves on RA. The aim of this study is toinvestigate anti-RA activity of the ethanolic extract of A. conyzoides L. leaves (EEAL) harvested from Bogor, Indonesia, in rats.Methods: The phytochemical screening analysis and thin-layer chromatography were performed to analyze the constituents of the EEAL. This studyused white male Sprague Dawley rats which were divided into 6 groups; normal control and negative control groups, both given 0.5% carboxymethylcellulose; the positive control group, given methotrexate suspension (0.05 mg/200 g bw.); the dose variation extract is 40 mg, 80 mg, and 160 mg/200 gbody weight. All the groups were induced with 0.1 ml Complete Freund’s adjuvant on day 1, except normal control group. Some parameters will bemeasured, such as paw edema, levels of leukocyte and lymphocyte, concentrations of tumor necrosis factor-α (TNF-α), and the number of osteoclastsper mm2.Results: For 21 days the rats have given treated the EEAL in three doses, was showed the decreasing volume of paw edema, levels of blood leukocytesand lymphocytes, concentrations of TNF-α and the number of osteoclasts, compared to the rat model of RA.Conclusion: This study showed that the leaves of A. conyzoides L. harvested from Bogor, Indonesia, have activity as anti-RA in a rat model, in whichflavonoid plays a role in inhibition of chronic inflammatory processes.Keywords: Ageratum conyzoides L. leaves, Anti-rheumatoid arthritis, Complete Freund’s adjuvant, Flavonoids.

scholarly journals Comparison of therapeutic effects of different mesenchymal stem cells on rheumatoid arthritis in mice

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7023 ◽  
Author(s):  
Qing Zhang ◽  
Qihong Li ◽  
Jun Zhu ◽  
Hao Guo ◽  
Qiming Zhai ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Effect ◽  
Joint Destruction ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Therapeutic Effects ◽  
Micro Ct ◽  
Tnf Α

Background Rheumatoid arthritis (RA) is a chronic and nonspecific autoimmune disease, which leads to joint destruction and deformity. To investigate the potential of human mesenchymal stem cells (MSCs) as a new therapeutic strategy for patients with RA, we compared the therapeutic effects of bone marrow derived MSCs (BMSCs), umbilical cord derived MSCs (UCs), and stem cells derived from human exfoliated deciduous teeth (SHED) on collagen-induced arthritis (CIA) in mice. Methods A total of 24 DBA/1 mice were infused with type II collagen to induce RA in the experimental model. MSC-treated mice were infused with UCs, BMSCs, and SHED, respectively. Bone erosion and joint destruction were measured by micro-computed tomographic (micro-CT) analysis and hematoxylin and eosin staining. The levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were measured by immunohistochemistry and Enzyme-Linked Immunosorbent Assay (ELISA). Results Systemic delivery of MSCs significantly improved the severity of the symptoms related to CIA to greater extent compared with the untreated control group. Micro-CT revealed reduced bone erosions in the metatarsophalangeal joints upon treatment with MSCs. Additionally, according to histologic evaluation, reduced synovitis and articular destruction were observed in MSC-treated groups. The levels of TNF-α and IL-1β in the serum and joints decreased with treatment by MSCs. Conclusion Our findings suggest that systemic infusion of UCs, BMSCs, and SHED may significantly alleviate the effects of RA. The therapeutic effect of BMSCs was greater than that of SHED, while the UCs were shown to have the best therapeutic effect on CIA mice. In conclusion, compared with BMSCs and SHED, UCs may be a more suitable source of MSCs for the treatment of patients with RA.

scholarly journals Effect of Moxibustion on β-EP and Dyn Levels of Pain-Related Indicators in Patients with Rheumatoid Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yingni Wang ◽  
Siyu Tao ◽  
Zeyun Yu ◽  
Yun Luo ◽  
Yuan Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Group ◽  
Clinical Symptoms ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Tnf Α ◽  
Significant Difference ◽  
Routine Inspection ◽  
Anti Inflammatory

Background. Rheumatoid arthritis (RA) is a systemic immunodeficiency disease characterized by persistent synovial inflammation, pannus formation, and bone and cartilage destruction, resulting in joint malformations and function decline. Objective. The purpose of this study is to evaluate the effect of moxibustion on clinical symptoms and levels of pain-related indicators beta-endorphin (β-EP) and dynorphin (Dyn) in patients with RA and to explore the potential anti-inflammatory and analgesic mechanisms of moxibustion in RA treatment. Methods. A total of 64 patients with RA who met the inclusion criteria were randomly and equally classified into the control and treatment groups. The control group received conventional treatment (oral methotrexate, folate, or leflunomide prescribed for a long time). The treatment group was treated with moxibustion at ST36 (Zusanli), BL23 (Shenshu), and Ashi points with respect to the control group. Patients’ clinical symptoms and routine inspection indexes (rheumatoid factor [RF], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]) were recorded before and after treatment. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), β-EP, and Dyn were determined by enzyme-linked immunosorbent assay (ELISA). The software SPSS24.0 was used for statistical analysis. Results. (1) Compared with the pretreatment result, both of the two groups’ clinical symptoms and routine inspection indexes (RF, ESR, and CRP) improved ( P  < 0.05), and the improvement of clinical symptoms in the treatment group outperformed that in the control group ( P  < 0.05). (2) TNF-α and IL-1β levels decreased significantly in the treatment group after treatment ( P  < 0.01), while no significant difference was observed in the control group ( P  > 0.05). (3) β-EP and Dyn levels in the treatment group were significantly increased after treatment ( P  < 0.01, P  < 0.01), but the control group showed no significant difference ( P  > 0.05, P  > 0.05). It is worth mentioning that the serum TNF-α, IL-1β, β-EP, and Dyn levels between the two groups were significantly different after 8 weeks of treatment ( P  < 0.05). (4) Differences in the serum β-EP and Dyn levels in the patients of the treatment group were correlated with TNF-α and IL-1β levels after treatment, and the correlation was mainly negative (r < 0). Conclusion. Moxibustion can improve joint pain in patients with RA using conventional western medicine. One of the mechanisms may affect the serum β-EP and Dyn levels by downregulating the inflammatory factors to play an anti-inflammatory and analgesic role.

Expression and Significance of Th17 Cells and Related Factors in Patients with Autoimmune Hepatitis

2019 ◽  
Vol 22 (4) ◽  
pp. 232-237 ◽  
Author(s):  
Jihong An
Keyword(s):  
Autoimmune Hepatitis ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Treg Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Serum Total Bilirubin ◽  
Study Group ◽  
Related Factors ◽  
Tnf Α

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH). Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry. Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels. Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.

Can Cytokines be used as an Activation Marker in Rheumatoid Arthritis?

2020 ◽  
Vol 20 ◽  
Author(s):  
Fatih Öner Kaya ◽  
Yeşim Ceylaner ◽  
Belkız Öngen İpek ◽  
Zeynep Güneş Özünal ◽  
Gülbüz Sezgin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Healthy Volunteers ◽  
Venous Blood ◽  
Cross Sectional Study ◽  
Joint Disease ◽  
Control Group ◽  
Cross Sectional ◽  
Positive Correlation ◽  
Das 28 ◽  
Tnf Α

Aims: The etiopathogenesis of Rheumatoid Arthritis (RA) is not clearly understood. However, the role of the cytokines takes an important part in this mechanism. We aimed to bring a new approach to the concept of 'remission' in patients with RA. Background: RA is a chronic, autoimmune, inflammatory disease that involves small joints in the form of symmetrical polyarthritis and progresses with exacerbations and remissions. Pain, swelling, tenderness and morning stiffness are typical of the joints involved. Although it is approached as a primary joint disease, a wide variety of extra-articular involvements may also occur. It is an interesting pathophysiological process, the exact cause of which is still unknown, with many environmental, genetic and potentially undiscovered possible factors in a chaotic manner. Objective: In this cross-sectional study, sedimentation rate (ESR), C- Reactive protein (CRP), Tumor necrosis factor (TNF)-α, soluble-TNF-α receptor (TNF-R), Interleukin (IL)-1B and IL-10 were measured in three groups which were healthy volunteers, patients with RA in the active period, and patients with RA in remission. Disease activity score-28 (DAS-28) was calculated in active RA and RA in remission. Methods: This study included 20 healthy volunteers, 20 remission patients with RA and 20 active RA patients. Venous blood samples were collected from patients in both healthy and RA groups. Results: RA group consisted 43 (71.6%) female and 17 (28.4%) male. Control group consisted 11 (55%) female and 9 (45%) male. TNF-R was significantly high only in the active group according to the healthy group (p=0.002). IL-10 was significantly high in active RA according to RA in remission (p=0.03). DAS-28 was significantly high in active RA according to RA in remission (p=0.001). In the active RA group, ESR and TNF-R had a positive correlation (r:0.442; p=0.048). In the active RA group, there was also a positive correlation between TNF-R and CRP (r:0.621; p=0,003). Both healthy and active RA group had significant positive correlation between ESR and CRP (r: 0.481; p=0.032 and r: 0,697; p=0,001 respectively). Conclusion: TNF-R can be the main pathophysiological factor and a marker showing activation. TNF-R can be very important in revealing the effect of TNF on the disease and the value of this effect in the treatment and ensuring the follow-up of the disease with CRP instead of ESR in activation.

scholarly journals Glycyrrhizin Attenuates Carcinogenesis by Inhibiting the Inflammatory Response in a Murine Model of Colorectal Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2609
Author(s):  
Guifeng Wang ◽  
Keiichi Hiramoto ◽  
Ning Ma ◽  
Nobuji Yoshikawa ◽  
Shiho Ohnishi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Stem Cell ◽  
Inflammatory Response ◽  
Murine Model ◽  
Licorice Root ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Stem Cell Markers ◽  
Tnf Α

Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups (n = 5, each)—control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks. Plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using an enzyme-linked immunosorbent assay. The colonic tissue samples were immunohistochemically stained with DNA damage markers (8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxy-guanosine), inflammatory markers (COX-2 and HMGB1), and stem cell markers (YAP1 and SOX9). The average number of colonic tumors and the levels of IL-6 and TNF-α in the CC + GL group were significantly lower than those in the CC group. The levels of all inflammatory and cancer markers were significantly reduced in the CC + GL group. These results suggest that GL inhibits the inflammatory response by binding HMGB1, thereby inhibiting DNA damage and cancer stem cell proliferation and dedifferentiation. In conclusion, GL significantly attenuates the pathogenesis of AOM/DSS-induced colorectal cancer by inhibiting HMGB1-TLR4-NF-κB signaling.

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