scholarly journals Pharmacokinetics-Based Chronoefficacy of Semen Strychni and Tripterygium Glycoside Tablet Against Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingpan Lin ◽  
Lu Gao ◽  
Yanke Lin ◽  
Shuai Wang ◽  
Zemin Yang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Destruction ◽  
Systemic Exposure ◽  
Inflammatory Factors ◽  
Systemic Autoimmune Disease ◽  
Active Ingredients ◽  
Tnf Α ◽  
Exposure Levels ◽  
Semen Strychni

Rheumatoid arthritis is a systemic autoimmune disease characterized by synovial inflammation and bone destruction. Identifying drugs with time-varying efficacy and toxicity, and elucidating the mechanisms would help to improve treatment efficacy and reduce adverse effects. Here, we aimed to determine the chronoefficacy of semen strychni (SS) and tripterygium glycoside tablet (TGT) against rheumatoid arthritis in mice, and to investigate a potential role of circadian pharmacokinetics in generating chronoefficacy. SS extract and TGT suspension were prepared with ultrasonication. Effects of SS and TGT on collagen-induced arthritis (CIA) were evaluated by measuring TNF-α and IL-6 levels. SS dosed at ZT18 was more effective in protecting against CIA than drug dosed at ZT6 (i.e., lower levels of key inflammatory factors at ZT18 than at ZT6). This was accompanied by higher systemic exposure levels of strychnine and brucine (two main putative active ingredients of SS) in ZT18-treated than in ZT6-treated CIA mice. TGT dosing at ZT2 showed a better efficacy against CIA as compared to herb doing at ZT14. Consistently, ZT2 dosing generated a higher exposure of triptolide (a main putative active ingredient of TGT) as compared to ZT14 dosing in CIA mice. Moreover, strychnine, brucine, and triptolide significantly inhibited the proliferation of fibroblast-like synoviocytes, and reduced the production of TNF-α and IL-6 and the mRNAs of TNF-α, IL-6, COX-2, and iNOS, suggesting that they possessed an anti-arthritis activity. In conclusion, SS and TGT display chronoefficacy against rheumatoid arthritis in mice, that is attributed to circadian pharmacokinetics of main active ingredients. Our findings have implications for improving treatment outcomes of SS and TGT via timed delivery.

TLRs Play Crucial Roles in Regulating RA Synoviocyte

2020 ◽  
Vol 20 (8) ◽  
pp. 1156-1165 ◽  
Author(s):  
Xuling Luo ◽  
Juncheng Cui ◽  
Xin Long ◽  
Zhiwei Chen
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Inflammatory Disease ◽  
Chinese Herb ◽  
Bone Destruction ◽  
Inflammatory Factors ◽  
Exact Role ◽  
Autoimmune Inflammatory Disease ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease comparing the inflammation of synovium. Macrophage-like synoviocytes and fibroblast-like synoviocytes (synoviocytes) are crucial ingredients of synovium. Therein, a lot of research has focused on synoviocytes. Researches demonstrated that TLR1, TLR2, TLR3, TLR4, TLR5, TLR6 TLR7 and TLR9 are expressed in synoviocyte. Additionally, the expression of TLR2, TLR3, TLR4 and TLR5 is increased in RA synoviocyte. In this paper, we review the exact role of TLR2, TLR3, TLR4 and TLR5 participate in regulating the production of inflammatory factors in RA synoviocyte. Furthermore, we discuss the role of vasoactive intestinal peptide (VIP), MicroRNA, Monome of Chinese herb and other cells (Monocyte and T cell) influence the function of synoviocyte by regulating TLRs. The activation of toll-like receptors (TLRs) in synoviocyte leads to the aggravation of arthritis, comparing with angiogenesis and bone destruction. Above all, TLRs are promising targets for managing RA.

scholarly journals Multifaceted role of TNF-α during the pathogenesis of rheumatoid arthritis

2013 ◽  
Vol 04 (10) ◽  
pp. 937-940 ◽  
Author(s):  
Ramanjaneya V. R. Mula ◽  
Rangaiah Shashidharamurthy
Keyword(s):  
Rheumatoid Arthritis ◽  
Tnf Α

scholarly journals HIF-1α contributes to Ang II-induced inflammatory cytokine production in podocytes

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Hao Huang ◽  
Yanqin Fan ◽  
Zhao Gao ◽  
Wei Wang ◽  
Ning Shao ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Renin Angiotensin System ◽  
Inflammatory Factors ◽  
Ang Ii ◽  
Angiotensin System ◽  
Inflammatory Injury ◽  
Tnf Α

Abstract Background Studies have indicated that changed expression of hypoxia-inducible factor-1α (HIF-1α) in epithelial cells from the kidney could affect the renal function in chronic kidney disease (CKD). As Angiotensin II (Ang II) is a critical active effector in the renin-angiotensin system (RAS) and was proved to be closely related to the inflammatory injury. Meanwhile, researchers found that Ang II could alter the expression of HIF-1α in the kidney. However, whether HIF-1α is involved in mediating Ang II-induced inflammatory injury in podocytes is not clear. Methods Ang II perfusion animal model were established to assess the potential role of HIF-1α in renal injury in vivo. Ang II stimulated podocytes to observe the corresponding between HIF-1α and inflammatory factors in vitro. Results The expression of inflammatory cytokines such as MCP-1 and TNF-α was increased in the glomeruli from rats treated with Ang II infusion compared with control rats. Increased HIF-1α expression in the glomeruli was also observed in Ang II-infused rats. In vitro, Ang II upregulated the expression of HIF-1α in podocytes. Furthermore, knockdown of HIF-1α by siRNA decreased the expression of MCP-1 and TNF-α. Moreover, HIF-1α siRNA significantly diminished the Ang II-induced overexpression of HIF-1α. Conclusion Collectively, our results suggest that HIF-1α participates in the inflammatory response process caused by Ang II and that downregulation of HIF-1α may be able to partially protect or reverse inflammatory injury in podocytes.

scholarly journals The Role of NLRP3 Inflammasome Activities in Bone Diseases and Vascular Calcification

Inflammation ◽  
2020 ◽  
Author(s):  
Chenyang Yu ◽  
Caihua Zhang ◽  
Zhihui Kuang ◽  
Qiang Zheng
Keyword(s):  
Vascular Calcification ◽  
Nlrp3 Inflammasome ◽  
Periodontal Diseases ◽  
Bone Destruction ◽  
Bone Diseases ◽  
Sterile Inflammation ◽  
Inflammatory Factors ◽  
Bone Homeostasis ◽  
Caspase 1

Abstract Continuous stimulation of inflammation is harmful to tissues of an organism. Inflammatory mediators not only have an effect on metabolic and inflammatory bone diseases but also have an adverse effect on certain genetic and periodontal diseases associated with bone destruction. Inflammatory factors promote vascular calcification in various diseases. Vascular calcification is a pathological process similar to bone development, and vascular diseases play an important role in the loss of bone homeostasis. The NLRP3 inflammasome is an essential component of the natural immune system. It can recognize pathogen-related molecular patterns or host-derived dangerous signaling molecules, recruit, and activate the pro-inflammatory protease caspase-1. Activated caspase-1 cleaves the precursors of IL-1β and IL-18 to produce corresponding mature cytokines or recognizes and cleaves GSDMD to mediate cell pyroptosis. In this review, we discuss the role of NLRP3 inflammasome in bone diseases and vascular calcification caused by sterile or non-sterile inflammation and explore potential treatments to prevent bone loss.

scholarly journals Lipid Peroxidation-Mediated Inflammation Promotes Cell Apoptosis through Activation of NF-κB Pathway in Rheumatoid Arthritis Synovial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Geng Yin ◽  
Ying Wang ◽  
Xiao-min Cen ◽  
Min Yang ◽  
Yan Liang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Apoptosis ◽  
Inflammatory Responses ◽  
Synovial Fibroblasts ◽  
Systemic Autoimmune Disease ◽  
New Strategy ◽  
Significant Clinical Improvement ◽  
Rheumatoid Arthritis Synoviocytes ◽  
Initiation Of Therapy

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of multiple joints. The central pathogenesis of RA is the proliferation of synovial fibroblasts in response to inflammatory cytokines. However, some of the targeted therapies for inflammation reactions do not display significant clinical improvement after initiation of therapy. Thus, the relationship between inflammatory responses and RA therapy is still incompletely understood. In the present study, we proposed to determine whether enhanced inflammations may lead to cell apoptosis in rheumatoid arthritis synoviocytes. Our results indicated that products of lipid peroxidations, 4-HNE, may induce synovial intrinsic inflammations by activating NF-κB pathways and it may lead to cell apoptosis. Pharmacological inhibition of NF-κB activation may reduce the 4-HNE mediated inflammation responses and subsequent cell apoptosis. Our results may help to clarify the role of inflammations on RA development and imply that blocking NF-κB activation may be partly beneficial for human RA therapy. These findings might provide a mechanism-based rationale for developing new strategy to RA clinical therapy.

CHANGES THE CYTOKINE PROFILE AND CALCIUM-REGULATING HORMONES IN RHEUMATOID ARTHRITIS

2019 ◽  
Vol 64 (11) ◽  
pp. 673-676
Author(s):  
Asmaya Saftar Huseynova
Keyword(s):  
Rheumatoid Arthritis ◽  
Parathyroid Hormone ◽  
Bone Loss ◽  
Hypovitaminosis D ◽  
Serum Levels ◽  
Control Group ◽  
Tnf Α ◽  
High Production ◽  
Serological Variant

The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.

scholarly journals The Efficacy of Moxibustion on the Serum Levels of CXCL1 and β-EP in Patients with Rheumatoid Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Siyu Tao ◽  
Xue Wang ◽  
Chenxi Liao ◽  
Yan Xiong ◽  
Jie Tang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Therapy ◽  
Treatment Group ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Control Group ◽  
Tnf Α ◽  
Before And After ◽  
Chemokine Ligand ◽  
Pain Symptoms

Objective. This study aims to evaluate the efficacy of moxibustion on joint swelling and pain and the levels of C-X-C motif chemokine ligand 1 (CXCL1), β-endorphin (β-EP) in serum of rheumatoid arthritis (RA) patients and to investigate the anti-inflammatory and analgesic mechanism of moxibustion on improving RA. Methods. Sixty-eight patients with RA were randomly and equally classified into the control and treatment groups. The control group was treated with routine drug therapy, while the treatment group received routine drug therapy and moxibustion. Both groups were treated for eight weeks. The symptoms and laboratory indicators of RA patients were compared in the two groups before and after intervention. Results. Sixty-one patients completed the study: four patients dropped out from the treatment group and three from the control group. Trial endpoints were change (∆) in symptoms, measured by Ritchie’s articular index (RAI), swollen joint count (SJC), and laboratory indicators, measured by the level of CXCL1, β-EP, tumor necrosis factor-a (TNF-α), and interleukin-1β (IL-1β). ∆RAI, ∆SJC, ∆CXCL1, ∆β-EP, ∆TNF-α, and ∆IL-1β in the treatment group were superior to the control group (13.50 [14.50] versus 6.00 [13.00] in ∆RAI, 4.00 [3.00] versus 2.00 [4.00] in ∆SJC, 0.04 ± 0.79 ng/mL versus -0.01 ± 0.86 ng/mL in ∆CXCL1, -2.43 [5.52] pg/mg versus -0.04 [4.09] pg/mg in ∆β-EP, 3.45 [5.90] pg/mL versus 1.55 [8.29] pg/mL in ∆TNF-α, and 6.15 ± 8.65 pg/mL versus 1.28 ± 8.51 pg/mL in ∆IL-1β; all P  < 0.05). Conclusion. Moxibustion can improve the joint swelling and pain symptoms in patients with RA, which may be related to the fact that moxibustion can reduce the release of inflammatory factors in patients with RA and downregulate the level of CXCL1 and increase the level of β-EP at the same time. This trial is registered with ChiCTR-IOR-17012282.

scholarly journals Myrtenal and β-caryophyllene oxide screened from Liquidambaris Fructus suppress NLRP3 inflammasome components in rheumatoid arthritis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen-xuan Li ◽  
Ping Qian ◽  
Yi-tong Guo ◽  
Li Gu ◽  
Jessore Jurat ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Docking ◽  
Nlrp3 Inflammasome ◽  
Network Pharmacology ◽  
Caryophyllene Oxide ◽  
Active Ingredients ◽  
Caspase 1 ◽  
Tnf Α ◽  
Cartilage Erosion ◽  
And Cartilage

Abstract Background Liquidambaris Fructus (LF) is the infructescence of Liquidambar formosana. In Traditional Chinese Medicine, LF has been used to treat joint pain, a common symptom of arthritis and rheumatism; however, a lack of pharmacological evidence has limited its applications in modern clinics. Therefore, this study aims to explore the protective effect of LF on rheumatoid arthritis (RA) and to identify its active ingredients. Methods Rats with adjuvant-induced arthritis (AIA) were divided into 4 groups and administered petroleum ether extract of LF (PEL), ethyl acetate extract of LF (EEL), water extract of LF (WEL), or piroxicam (PIR) respectively for 3 weeks. Two additional groups were used as normal control (NC) and model control (MC) and administered distilled water as a placebo. The clinical scores for arthritis, bone surface, synovial inflammation and cartilage erosion were used to evaluate the therapeutic efficacy of each treatment. The serum IL-1β and TNF-α level and the expression of NLRP3, IL-1β and caspase-1 p20 in the synovial tissue of AIA rats were evaluated by ELISA and Western blot. The active ingredients of LF were investigated using network pharmacology and molecular docking methods, and their inhibition of NLRP3 inflammasome activation was verified in the human rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) model. Results PEL could alleviate paw swelling, bone and joint destruction, synovial inflammation and cartilage erosion in the AIA rats, with significantly superior efficacy to that of EEL and WEL. PEL reduced IL-1β and TNF-α serum levels, and attenuated the upregulation of NLRP3, IL-1β and caspase-1 p20 expression in the synovial tissue of AIA rats. Network pharmacology and molecular docking results indicated that myrtenal and β-caryophyllene oxide were the main two active ingredients of PEL, and these two compounds showed significant inhibition on TNF-α, NLRP3, IL-1β and caspase-1 p20 expression in RA-FLS. Conclusions Myrtenal and β-caryophyllene oxide screened from PEL could suppress the activation of NLRP3 inflammasome, thereby alleviating RA symptoms.

scholarly journals Klotho protects chondrocyte viability via FOXO1/3 in osteoarthritis

2021 ◽  
Vol 20 (9) ◽  
pp. 1961-1968
Author(s):  
Wei Wei ◽  
Liefeng Ji ◽  
Wanli Duan ◽  
Jiang Zhu
Keyword(s):  
Oxidative Stress ◽  
Survival Rate ◽  
Protective Effect ◽  
Collagen I ◽  
Inflammatory Factors ◽  
Ros Production ◽  
Chondrocyte Viability ◽  
Tnf Α ◽  
Collagen Ii

Purpose: To investigate the effect of Klotho and FOXO1/3 on the CH viability in OA.Methods: The survival rate of CHs, Klotho and FOXO1/3 protein expression, and ROS production were measured in the OA cartilages of different degenerative phases. H2O2 was also used to injure CHs, and the cell viability, Klotho and FOXO1/3 expressions, as well as ROS levels were investigated to clarify the effect of exogenic Klotho on the injured CHs. Additionally, in order to verify the role of FOXO1/3 in Klotho-treated CHs, SOD2, GPX1, inflammatory factors, collagen I/II, SOX9, and Runx-2 levels were analyzed by silencing FOXO1 and FOXO3 expression via siRNA transfection.Results: Klotho and FOXO1/3 expressions significantly decreased, and ROS production increased in severely human OA cartilage (p <0.05). Besides, H2O2 affected CHs viability with the suppression of Klotho and FOXO1/3 expression but ROS production was elevated. Exogenic Klotho application partly reversed the injury caused by H2O2. Furthermore, Klotho treatment of the injured CHs contributed to SOD2 and GPX1 expressions, and suppressed IL-1β, IL-6, TNF-α and MMP-13 production, resulting in  the upregulation of collagen II and SOX9 as well as downregulation of collagen I and Runx-2. However, the protective effect of Klotho was weakened by FOXO1 and FOXO3 gene silencing.Conclusion: Klotho protects CHs viability by suppressing oxidative stress and inflammation, which is associated with the mediation of FOXO1 and FOXO3. These findings provide new insights into the treatment of OA.

scholarly journals Systemic Inflammation and Clinical Outcomes in COVID-19: a retrospective study

2020 ◽  
Author(s):  
Meijia Wang ◽  
Zhenli Huang ◽  
Kun Tang ◽  
Pengfei Gao ◽  
Yanjiao Lu ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Clinical Outcomes ◽  
Systemic Inflammation ◽  
Trial Registration ◽  
Inflammatory Factors ◽  
Reactive Protein ◽  
Tnf Α ◽  
Registration Number ◽  
Factor Α

Abstract Background：COVID-19 causes epidemics and pandemics worldwide, but the role of pathophysiological parameters particularly systemic inflammation in COVID-19 has not been understood. We aimed to investigate clinical outcomes in view of systemic inflammation in COVID-19.Methods：In this retrospective study, the demographic and clinical data of 225 confirmed COVID-19 cases on admission at Tongji Hospital from January 28 to February 15, 2020, were extracted and analyzed. These patients were categorized by inflammation state on the basis of the expression of inflammatory factors or classified as severe and non-severe according to 2019 American Thoracic Society / Infectious Disease Society of America guidelines.Results: Among 225 patients with confirmed COVID-19, 155 patients (68.9%) categorized into hyperinflammation group and 70 (31.1%) were non- hyperinflammation group. Compared to non-hyperinflammation group, hyperinflammation group more frequently had chest tightness/dyspnea and lymphopenia, aberrant multiple indexes of organ function including the heart, liver, kidney, and coagulation, with higher level of C-reactive protein (hsCRP) as well as interleukin (IL)-6, IL-8, tumour necrosis factor α (TNF-α), etc. Hyperinflammation group were more likely to admit to intensive care unit (ICU) (52.3% vs 5.7%), receive ventilation (84.5% vs 10.0%) and be with higher mortality (44.5% vs 5.7%) than non-hyperinflammation group. The mortality of severe patients with hyperinflammation (60/99, 60.6%) was significantly higher than without hyperinflammation (2/20, 10.0%). Non-severe patients with hyperinflammation even tended to have higher mortality (9/56, 16.1%) than those in severe cases without hyperinflammation (2/20, 10%).Conclusion: Excessive systemic inflammation was correlated highly with poor clinical outcomes in COVID-19, particularly in severe cases. Non-severe patients with hyperinflammation even tended to have higher mortality than those in severe cases without hyperinflammation.Trial registration: This is a retrospective observational study without a trial registration number.

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