Therapeutic effects of Chinese medicine Di-Long (Pheretima vulgaris) on rheumatoid arthritis through inhibiting NF-κB activation and regulating Th1/Th2 balance

Background. Traditional Chinese medicine considers that rheumatoid arthritis (RA) is caused by blood stasis, heat, and toxins. Xuebijing (XBJ), a traditional Chinese medicine compound injection, activates blood circulation to dissipate blood stasis, eliminating pathogenic heat from the blood and degrading toxins. XBJ was approved by the China FDA to treat for many years. This study examined the potential therapeutic effects of XBJ on RA and rat collagen-induced arthritis (CIA). Methods. XBJ was cultured with the synovial fluid (SF) of RA patients. XBJ was also injected into CIA rats. Changes in Treg and Th17 cell levels in the peripheral blood (PB), SF, and spleen and changes in Th1/Th2 and cytokine levels in PB were detected using flow cytometry. Four RA patients were treated using XBJ based on Chinese medical theory and Chinese medicine indications. Results. Following culture with XBJ, the proportion of Treg cells (P=0.007) was significantly increased in RA SF, while the Th1/Th2 ratio remained unchanged. After XBJ treatment, CIA in rats was significantly relieved (P<0.001). The Treg cell proportion was significantly increased in the PB, SF, and spleen in the treated rats, while the number of Th17 cells decreased. The ratio of Th1/Th2 remained unchanged in PB, and the levels of IL-1β, IL-6, IL-17A, IFN-γ, and TNF-α decreased (P=0.031, P<0.001, P<0.001, P<0.001, and P=0.001, respectively). After XBJ treatment, the disease activity score-28 (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Th17 cell number, and Th1/Th2 cell ratio in the four RA patients were significantly decreased, while the Treg cell proportion was increased. Conclusion. XBJ can restore the immune balance to treat RA and CIA. Therefore, XBJ could be a potential therapeutic drug for RA.

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SAT0007 BLOCKING HISTAMINE-RELEASING FACTOR/TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (HRF/TCTP) ATTENUATES AGGRESSIVENESS OF FIBROBLAST-LIKE SYNOVIOCYTES AND AMELIORATES COLLAGEN-INDUCED ARTHRITIS IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5088 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 934.3-934

Author(s):

M. Kim ◽

Y. Choe ◽

H. Lee ◽

Y. H. Cheon ◽

S. I. Lee

Keyword(s):

Rheumatoid Arthritis ◽

Cancer Progression ◽

Inflammatory Responses ◽

Joint Destruction ◽

Serum Levels ◽

Therapeutic Effects ◽

Collagen Induced Arthritis ◽

Translationally Controlled Tumor Protein ◽

Biochemical Analyses ◽

Fibroblast Like Synoviocytes

Background:Histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses. Increased expression of HRF/TCTP occurs in joints of rheumatoid arthritis (RA) patients, but the role of HRF/TCTP in RA remains undefinedObjectives:In this study, we explored the pathogenic significance of HRF/TCTP and evaluated therapeutic effects of HRF/TCTP blockade in RA.Methods:HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine experimental phenotypes of RA. HRF/TCTP levels were measured in sera and joint fluids in patients with RA and compared to those with osteoarthritis, ankylosing spondylitis, Behcet disease, and healthy controls. HRF/TCTP expression was also assessed in synovium and fibroblast-like synoviocytes (FLS) obtained from RA or OA patients. Finally, we assessed effects of HRF/TCTP and dimerized HRF/TCTP binding peptide-2 (dTBP2), an inhibitor of HRF/TCTP, in RA-FLS and CIA mice.Results:Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were increased in HRF/TCTP TG mice, and decreased in KD mice compared to wild-type littermates. HRF/TCTP levels were higher in sera, synovial fluid, synovium, and FLS of patients with RA than in control groups. Serum levels of HRF/TCTP correlated well with disease activity in RA. Tumor-like aggressiveness of RA-FLS was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice, and had no detrimental effect in a murine tuberculosis model.Conclusion:Our results indicate that HRF/TCTP represents a novel biomarker and therapeutic target for diagnosis and treatment of RA.References:N/AAcknowledgments :National Research Foundation of KoreaKorea Health Industry Development InstituteDisclosure of Interests:None declared

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Comparative study on the antituberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan

Military Medical Research ◽

10.1186/s40779-021-00324-5 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Li-Yao Duan ◽

Yan Liang ◽

Wen-Ping Gong ◽

Yong Xue ◽

Jie Mi ◽

...

Keyword(s):

Gene Expression ◽

Chinese Medicine ◽

Treatment Group ◽

Mechanism Of Action ◽

Cell Damage ◽

Control Group ◽

Therapeutic Effects ◽

Model Group ◽

Lung Histopathology ◽

Th17 Cytokines

Abstract Background The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis effects. The anti- tuberculosis effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH. Methods BALB/c mice aged 6-8 weeks were randomly divided into a normal control group, Tuberculosis (TB) model group, JHW treatment group, and NBXH treatment group. After 3 and 13 weeks of treatment, the therapeutic effect in each group was evaluated by comparing lung histopathology, lung and liver colony counts, the number of spots representing effector T cells secreting IFN-γ in an ELISPOT, and the levels of Th1, Th2, and Th17 cytokines, which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing. Results After 13 weeks of treatment, the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (P < 0.05). Compared with those in the TB model group, the lung colony counts in the JHW and NBXH groups were significantly decreased (P < 0.05), and the IL-2 and IL-4 levels in the NBXH group were significantly increased (P < 0.05). NBXH partly restored significant changes in gene expression caused by Mycobacterium tuberculosis (M. tuberculosis) infection. According to GO and KEGG analyses, the changes in biological process (BP), cell composition (CC) and molecular function (MF) terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent, but they were mainly related to the immune response and inflammatory response in the mouse TB model. Conclusions NBXH had therapeutic effects similar to those of JHW in improving lung histopathology, reducing lung colony counts, and regulating the levels of cytokines. NBXH restored significant changes in gene expression and repaired cell damage caused by M. tuberculosis infection by regulating immune-related pathways, which clarified the mechanism of action of NBXH.

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Metabolomics study of the therapeutic mechanism of a Chinese herbal formula on collagen-induced arthritis mice

RSC Advances ◽

10.1039/c8ra05528a ◽

2019 ◽

Vol 9 (7) ◽

pp. 3716-3725 ◽

Cited By ~ 1

Author(s):

Zhen Jin ◽

Ji-da Zhang ◽

Xin Wu ◽

Gang Cao

Keyword(s):

Rheumatoid Arthritis ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Herbal Formula ◽

Collagen Induced Arthritis ◽

Chinese Herbal Formula ◽

Chinese Herbal ◽

Therapeutic Mechanism ◽

Metabolomics Study

Wenjinghuoluo (WJHL) prescription, the typical rheumatoid arthritis (RA) treatment compound in traditional Chinese medicine, shows favorable efficacy.

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Treatment of Rheumatoid Arthritis with Traditional Chinese Medicine

BioMed Research International ◽

10.1155/2014/528018 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

Wen-Yuan Lee ◽

Hsin-Yi Chen ◽

Kuan-Chung Chen ◽

Calvin Yu-Chian Chen

Keyword(s):

Rheumatoid Arthritis ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Protein Complex ◽

Chronic Inflammatory Disease ◽

Dynamics Simulation ◽

Current Therapy ◽

Potential Candidate ◽

Interleukin 6 Receptor ◽

The Stability

Rheumatoid arthritis (RA) is a chronic inflammatory disease that will affect quality of life and, working efficiency, and produce negative thoughts for patients. Current therapy of RA is treated with disease-modifying antirheumatic drugs (DMARDs). Although most of these treatment methods are effective, most patients still have a pleasant experience either due to poor efficacy or side effects or both. Interleukin-6 receptor (IL6R) is important in the pathogenesis of RA. In this study, we would like to detect the potential candidates which inhibit IL6R against RA from traditional Chinese medicine (TCM). We use TCM compounds from the TCM Database@Taiwan for virtually screening the potential IL6R inhibitors. The TCM candidate compound, calycosin, has potent binding affinity with IL6R protein. The molecular dynamics simulation was employed to validate the stability of interaction in the protein complex with calycosin. The analysis indicates that protein complex with calycosin is more stable. In addition, calycosin is known to be one of the components ofAngelica sinensis, which has been indicated to have an important role in the treatment of rheumatoid arthritis. Therefore, calycosin is a potential candidate as lead compounds for further study in drug development process with IL6R protein against rheumatoid arthritis.

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AB0043 EFFECT OF ANTI-INFLAMMATORY MEDICATION ON INTERACTION OF SYNOVIAL FIBROBLASTS WITH MACROPHAGES IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.247 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1054.1-1054

Author(s):

M. Schmeller ◽

M. Diller ◽

R. Hasseli ◽

A. Knothe ◽

S. Rehart ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mononuclear Cells ◽

Joint Inflammation ◽

Synovial Fibroblasts ◽

Therapeutic Effects ◽

Synergistic Activity ◽

M1 Macrophages ◽

Healthy Donors ◽

Proinflammatory Activity ◽

Anti Inflammatory

Background:One of the key mechanisms in the pathogenesis of rheumatoid arthritis (RA) is the interaction of macrophages and synovial fibroblasts during joint inflammation. Increased synergistic proinflammatory activity of both cell types leads to the release of high levels of proinflammatory cytokines, especially of interleukin-6 (IL-6), and of matrix degrading enzymes. If this mechanism is uncontrolled, progressive destruction of articular cartilage and bone will take place.In active disease, immediate anti-inflammatory treatment with glucocorticoids is usually replaced by disease-modifying anti-rheumatic drugs (DMARDS), especially by methotrexate (MTX) and biologics such as TNF-α- or IL-6-inhibitors. This led to great improvements in prognosis and outcome for RA patients. However, about 40% of patients experience no remission or suffer from side effects of medication. To optimize established substances and to develop new treatment strategies, it is necessary to understand the mechanisms underlying the limited therapeutic effects.Objectives:Evaluation of the effect of prednisolone, MTX, adalimumab, tocilizumab on IL-6 secretion by RA synovial fibroblasts (RASF) and macrophages.Methods:RA synovium was used for RASF isolation. Peripheral blood mononuclear cells (PBMCs) were isolated from blood of healthy donors and RA patients by using Ficoll© medium followed by density gradient centrifugation. Mononuclear cells were seeded on six well plates (6x10^6/well) and incubated for one week. Then they were stimulated with Interferon-у (20 ng/ml) and LPS (50 ng/ml) for 48h to initiate differentiation into proinflammatory M1 macrophages. The M1 macrophages were co-cultured with RASF (100.000/well) and different treatments added (prednisolone: 10, 25, 50, 75, 100 nM, 1 µM; adalimumab: 100, 500 µg/ml; tocilizumab: 1, 5 µg/ml; MTX: 0,5, 1, 5, 10, 100 nM, 1µM). After 24h culture supernatants were collected and IL-6- and TNFα-ELISAs were performed.Results:IL-6 concentrations of untreated controls were comparable, regardless whether M1 macrophages from healthy donors or RA-patients were used for co-culture. Prednisolone reduced co-culture-induced IL-6 up to 56% (p<0.001) in co-culture of RASF and M1 macrophages of healthy donors and up to 60% (p<0.001) in co-culture of RASF and RA M1 macrophages. Adalimumab reduced IL-6 up to 28% (p<0.05) in M1 of healthy donors and up to 45% (p<0.01) in RA M1 macrophage co-cultures. A minor reduction by 10-20% of IL-6 was observed with tocilizumab and no significant effect could be achieved after treatment with MTX.Conclusion:Prednisolone and adalimumab clearly decrease but do not eliminate proinflammatory synergistic activity of RASF and M1 macrophages. These results confirm the clinical observation, that there is a large number of RA-patients that independent of anti-inflammatory treatment still suffer from low-level joint inflammation.The synergistic proinflammatory activity of M1 macrophages and RASF seems to be a complex and multifactorial mechanism that is difficult to eliminate by a single treatment substance. Since it is one of the key mechanisms in RA pathogenesis, there is a critical need to investigate how therapy effects could be optimized. This study confirmed RASFs as one of the leading effector cells of increased synergistic proinflammatory activity, thus underlining their promising role as a treatment target in rheumatoid arthritis.Disclosure of Interests:None declared

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Therapeutic Effects of Traditional Chinese Medicine on Spinal Cord Injury: A Promising Supplementary Treatment in Future

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/8958721 ◽

2016 ◽

Vol 2016 ◽

pp. 1-18 ◽

Cited By ~ 14

Author(s):

Qian Zhang ◽

Hao Yang ◽

Jing An ◽

Rui Zhang ◽

Bo Chen ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Epigallocatechin Gallate ◽

Therapeutic Effects ◽

Cord Injury ◽

Supplementary Treatment ◽

Natural Drugs ◽

Doctoral Dissertations

Objective. Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM) attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy.Methods. Information was collected from articles published in peer-reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI), as well as from master’s dissertations, doctoral dissertations, and Chinese Pharmacopoeia.Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti-inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin) and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix) was elucidated and summarized.Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment.

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Clinical Therapeutic Effects of Aspirin in Combination with Fufang Danshen Diwan, a Traditional Chinese Medicine Formula, on Coronary Heart Disease: A Systematic Review and Meta-Analysis

Cellular Physiology and Biochemistry ◽

10.1159/000447892 ◽

2016 ◽

Vol 39 (5) ◽

pp. 1955-1963 ◽

Cited By ~ 16

Author(s):

Jianchun Huang ◽

Xiaojun Tang ◽

Fangxing Ye ◽

Junhui He ◽

Xiaolong Kong

Keyword(s):

Systematic Review ◽

Coronary Heart Disease ◽

Heart Disease ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Aspirin Therapy ◽

Therapeutic Effects ◽

Chinese Medicine Formula

Background/Aims: Coronary heart disease is characterized by vascular stenosis or occlusion resulting in myocardial ischemia, hypoxia and necrosis. In China, the combination of aspirin and Fufang Danshen Diwan (FDD), a traditional Chinese medicine formula, has been suggested in the treatment of coronary heart disease. There have been several studies comparing the effectiveness of aspirin alone and in combination with FDD to treat coronary artery disease; however, it remains unclear whether combined aspirin therapy is superior. This study was thus designed to clarify this issue through a systematic review and meta-analysis. Methods: Databases including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) database, Wanfang Data and VIP Information were searched. Papers were reviewed systematically by two researchers and analyzed using Cochrane software Revman 5.1. Results: Fourteen randomized controlled trials enrolling 1367 subjects were included. Meta-analyses revealed that aspirin in combination with FDD was significantly more effective at alleviating angina pectoris and improving electrocardiogram (ECG) results relative to aspirin therapy alone, reflected by the summary effects for the clinical markedly effective (OR = 2.45; 95% CI 1.95-3.08) and the total effective (OR = 3.92; 95% CI 2.87-5.36) rates. In addition, combined aspirin and FDD was significantly more efficacious than aspirin monotherapy at improving blood lipid levels, as indicated by the following outcomes: 1) reduction of TC level (SMD −1.12; 95% CI −1.49 to −0.76); 2) reduction of TG level (SMD −0.94; 95% CI −1.15 to -0.74); 3) reduction of LDL level (SMD -0.68; 95% CI -0.88 to -0.48); and 4) improvement of HDL level (SMD 0.52; 95% CI 0.04 to 0.99 ). No serious adverse events were reported in any of the included trials. Conclusion: The present meta-analysis demonstrated that aspirin in combination with FDD was more effective than aspirin alone for treating coronary heart disease. More full-scale randomized clinical trials with reliable designs are recommended to further evaluate the clinical benefits and long-term effectiveness of FDD for the treatment of coronary heart disease.

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