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Bai J, Lv T, Yu H, Ji Z, Gu X, Gao Y, Ma L. The combined impact of neutrophil-percentage-to-albumin ratio and depressive symptoms on mortality in US arthritis patients: insights from NHANES (2005-2018). Front Public Health 2025; 13:1545250. [PMID: 40115342 PMCID: PMC11922730 DOI: 10.3389/fpubh.2025.1545250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Accepted: 02/24/2025] [Indexed: 03/23/2025] Open
Abstract
Background The neutrophil-to-albumin ratio (NPAR) reflects inflammation and nutritional status, while depression significantly impacts survival in chronic disease patients. This study examines the independent and combined effects of NPAR and depressive symptoms on all-cause and cardiovascular mortality in arthritis patients. Methods We analyzed a nationally representative sample of people with arthritisaged 40 and older from NHANES (2005-2018). NPAR assessed inflammation and nutritional status, while depressive symptoms were measured by PHQ-9. Weighted Cox regression examined the independent and joint associations of NPAR and PHQ-9 with all-cause and cardiovascular disease (CVD) mortality. Results Our analysis indicated that higher NPAR levels combined with lower depressive symptoms (PHQ-9 < 10) significantly increased all-cause and CVD mortality risks in arthritis patients. In this group, the hazard ratio (HR) for all-cause mortality was 2.087, with a similarly elevated CVD mortality risk (HR = 2.614), underscoring NPAR's predictive strength in non-depressed individuals. Among those with higher depressive symptoms, while elevated NPAR was still associated with increased mortality, its impact on CVD mortality was less marked, highlighting the need for further research into the NPAR-depression interaction. Conclusion This study identifies NPAR as a key predictor of mortality in arthritis patients, particularly those with fewer depressive symptoms. NPAR significantly predicts all-cause and CVD mortality, underscoring its value as an inflammation and nutrition biomarker. Integrating NPAR in clinical practice could enhance individualized risk assessment and intervention for arthritis patients.
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Affiliation(s)
- Jinyue Bai
- Department of General Practice, Aerospace Center Hospital, Beijing, China
| | - Taihong Lv
- Department of General Medicine, Beijing TianTan Hospital, Capital Medical University, Beijing, China
| | - Hanming Yu
- Department of Pulmonary and Critical Care Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Zishuo Ji
- Department of Neurology, Beijing TianTan Hospital, Capital Medical University, Beijing, China
| | - Xiu Gu
- Department of Pulmonary and Critical Care Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Yun Gao
- Department of General Practice, Aerospace Center Hospital, Beijing, China
| | - Li Ma
- Department of General Medicine, Beijing TianTan Hospital, Capital Medical University, Beijing, China
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Shu H, Chen XY, Zhao J, Li P, Sun Z. Efficacy and safety of Tripterygium wilfordii glycosides tablets combined with Western medicine for patients with rheumatic immune diseases. World J Clin Cases 2025; 13:95513. [PMID: 40012824 PMCID: PMC11612673 DOI: 10.12998/wjcc.v13.i6.95513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 10/03/2024] [Accepted: 11/07/2024] [Indexed: 11/25/2024] Open
Abstract
BACKGROUND Rheumatic immune diseases are a group of chronic inflammatory diseases characterized by joint and systemic multi-organ involvement, including rheumatoid arthritis, systemic lupus erythematosus, and Sjogren's syndrome, among others. The pathogenesis of these diseases is related to the abnormal activation and regulatory imbalance of the immune system. The prevalence and morbidity of rheumatic immune diseases are high, imposing a significant burden on patients' quality of life and socio-economic costs. Currently, the treatment of rheumatic immune diseases mainly relies on Western medicine, such as non-steroidal anti-inflammatory drugs, glucocorticoids, disease-modifying antirheumatic drugs, and biologics. However, the therapeutic effects of Western medicine are not ideal, some patients poorly respond or are resistant to Western medicine, and long-term use often causes various adverse reactions. AIM To systematically evaluate the efficacy and safety of Tripterygium wilfordii glycosides tablets combined with Western medicine in the treatment of patients with rheumatic immune diseases. METHODS This study conducted a meta-analysis to systematically evaluate the efficacy and safety of Tripterygium wilfordii glycosides tablets combined with Western medicine for patients with rheumatic immune diseases. Chinese and English databases were searched for randomized controlled trials (RCTs) on the treatment of rheumatic immune diseases with Tripterygium wilfordii glycosides tablets combined with Western medicine. The quality of the included studies was assessed using the Cochrane risk of bias assessment tool. Meta-analysis was performed using RevMan 5.4 software. RESULTS The meta-analysis included 11 RCTs involving 1026 patients with rheumatic immune diseases. The combined treatment significantly reduced the risk of disease recurrence (relative risk = 1.07, 95% confidence interval: 1.01-1.15, P < 0.05) and showed no significant heterogeneity (I 2 = 0%, P = 0.53), indicating that Tripterygium wilfordii glycosides tablets combined with Western medicine is an effective method to reduce the possibility of postoperative recurrence in patients with rheumatic immune diseases. However, due to the limited number and quality of the studies included, these results should be interpreted with caution. CONCLUSION Tripterygium wilfordii glycosides tablets combined with Western medicine is an effective and safe treatment option for patients with rheumatic immune diseases and can be considered a clinical choice. However, more high-quality research is needed to validate this conclusion and provide more solid evidence for clinical practice.
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Affiliation(s)
- Hang Shu
- Department of Traditional Chinese Medicine, Hangzhou Special Service Recuperation Center of Chinese People's Liberation Army Air Force, Nanjing 210000, Jiangsu Province, China
| | - Xiao-Yu Chen
- Department of Convalescence, Hangzhou Special Service Recuperation Center of Chinese People's Liberation Army Air Force, Nanjing 210000, Jiangsu Province, China
| | - Jie Zhao
- Department of Traditional Chinese Medicine, Hangzhou Special Service Recuperation Center of Chinese People's Liberation Army Air Force, Nanjing 210000, Jiangsu Province, China
| | - Pin Li
- Department of Traditional Chinese Medicine, Hangzhou Special Service Recuperation Center of Chinese People's Liberation Army Air Force, Nanjing 210000, Jiangsu Province, China
| | - Zhen Sun
- Department of Traditional Chinese Medicine, Hangzhou Special Service Recuperation Center of Chinese People's Liberation Army Air Force, Nanjing 210000, Jiangsu Province, China
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Zhu BY, Liu ZC, Zhao ZX, Huang HP, Zhang N, Xia J, Chen WW. Pharmacological Mechanism of Chinese Medicine in Systemic Lupus Erythematosus: A Narrative Review. Chin J Integr Med 2025; 31:157-169. [PMID: 39240290 DOI: 10.1007/s11655-024-3762-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/24/2024] [Indexed: 09/07/2024]
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder affecting multiple systems, characterized by the development of harmful autoantibodies and immune complexes that lead to damage in organs and tissues. Chinese medicine (CM) plays a role in mitigating complications, enhancing treatment effectiveness, and reducing toxicity of concurrent medications, and ensuring a safe pregnancy. However, CM mainly solves the disease comprehensively through multi-target and multi-channel regulation process, therefore, its treatment mechanism is often complicated, involving many molecular links. This review introduces the research progress of pathogenesis of SLE from the aspects of genetics, epigenetics, innate immunity and acquired immunity, and then discusses the molecular mechanism and target of single Chinese herbal medicine and prescription that are commonly used and effective in clinic to treat SLE.
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Affiliation(s)
- Bo-Yu Zhu
- Department of Rheumatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China
| | - Zhi-Chao Liu
- Department of Rheumatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China
| | - Zhen-Xi Zhao
- Department of Rheumatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China
| | - Hui-Ping Huang
- Department of Rheumatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China
| | - Na Zhang
- Department of Rheumatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China
| | - Jia Xia
- Department of Rheumatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China
| | - Wei-Wei Chen
- Department of Rheumatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
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Ma J, Sun B, Te LG, Huang X, Zuo X, Han XK, Wang SS. A Dietary Supplement Jinghuosu Ameliorates Reproductive Damage Induced by Tripterygium Glycosides. Chin J Integr Med 2024; 30:330-338. [PMID: 38212501 DOI: 10.1007/s11655-023-3750-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/26/2023] [Indexed: 01/13/2024]
Abstract
OBJECTIVE To determine the possible protective effects of Jinghuosu, a dietary supplement (DS), on tripterygium glycosides (TG)-induced reproductive system injury in rats and its underlying mechanisms. METHODS A reproductive damage model was established in rats by feeding of TGs. Twenty-eight male Sprague Dawley rats were randomly divided into 4 groups using a random number table (n=7 in each): control (C) group, model (M) group, DS group and L-carnitine (LC) group. Rats in M, DS and LC groups received 40 mg/kg TGs orally. Starting from the 5th week, after administration of TGs for 4 h every day, rats in DS and LC groups were administered with 2.7 g/kg DS and 0.21 g/kg LC, respectively, for protective treatment over the next 4 weeks. Rats in Group C continued to receive the control treatment. Hematoxylin-eosin staining was used for histopathological analysis of rat testicular tissues. Enzyme-linked immunosorbent assay was performed to measure alkaline phosphatase (ALP), lactate dehydrogenase, alcohol dehydrogenase, total antioxidant capacity (T-AOC), superoxide dismutase, glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) concentrations. Chemiluminescence assay was used to determine the serum testosterone content. Quantitative real-time PCR and Western blotting were conducted to analyze the expression of genes and proteins related to the testosterone synthesis pathway and the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 antioxidant pathway. RESULTS Oral administration of TGs induced significant increases in the testicular levels of zinc transporter 1 and MDA (P<0.05). On the other hand, sperm concentration, sperm motility, and serum testosterone, serum zinc, testicular zinc, Zrt-, Irt-like protein 1, ALP, luteinizing hormone (LH) receptor, steroidogenic acute regulatory protein, Cytochrome P450 family 11 subfamily A member 1, 3 β -hydroxysteroid dehydrogenase 1 T-AOC, GSH-Px, nuclear factor erythroid 2-related factor 2, heme oxygenase-1 and NAD (P)H: quinone oxidoreductase 1 levels decreased following TGs exposure (P<0.05). All of these phenotypes were evidently reversed by DS (P<0.05). CONCLUSION DS Jinghuosu protects against TG-induced reproductive system injury in rats, probably by improving zinc homeostasis, enhancing the testosterone synthesis and attenuating oxidative stress.
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Affiliation(s)
- Jing Ma
- Hebei Key Laboratory of Reproductive Medicine, Hebei Institute of Reproductive Health, Hebei Reproductive Health Hospital, Shijiazhuang, 050071, China
| | - Bo Sun
- Graduate School of Hebei Medical University, Shijiazhuang, 050017, China
| | - Li-Ger Te
- Graduate School of Hebei Medical University, Shijiazhuang, 050017, China
| | - Xin Huang
- School of Chemistry and Materials Science, Hebei Normal University, Shijiazhuang, 050024, China
| | - Xin Zuo
- School of Chemistry and Materials Science, Hebei Normal University, Shijiazhuang, 050024, China
| | - Xiao-Ke Han
- Xingtai Infertility Specialist Hospital, Xingtai, Hebei Province, 054000, China
| | - Shu-Song Wang
- Hebei Key Laboratory of Reproductive Medicine, Hebei Institute of Reproductive Health, Hebei Reproductive Health Hospital, Shijiazhuang, 050071, China.
- Graduate School of Hebei Medical University, Shijiazhuang, 050017, China.
- School of Chemistry and Materials Science, Hebei Normal University, Shijiazhuang, 050024, China.
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Lin J, Liu J, O’Fee A, Pandey C, Benna-Doyle S, Maunder A, Rao V, Alesi S, Ng B, Ee C. The effectiveness and safety of lifestyle medicine and integrative therapies in inflammatory arthritis: an umbrella review using a hierarchical evidence gathering approach. Front Med (Lausanne) 2024; 11:1357914. [PMID: 38545510 PMCID: PMC10965540 DOI: 10.3389/fmed.2024.1357914] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 02/13/2024] [Indexed: 11/11/2024] Open
Abstract
Objective An umbrella review was conducted to provide a comprehensive evaluation of the evidence on lifestyle medicine and integrative therapies for inflammatory arthritis. Methods Five electronic databases were searched for umbrella reviews, meta-analyses, and systematic reviews of randomised controlled trials on acupuncture, diet, exercise, herbal medicine, nutrient supplements, and mind-body therapies for rheumatoid arthritis, spondyloarthritis, and gout published from January 2012 to December 2022. The primary outcomes were functional status and quality of life. Quality assessment was performed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) tool, and the certainty of evidence for our primary outcomes was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach where possible. Results We included 52 reviews. Exercise was beneficial for functional status in both rheumatoid arthritis and spondyloarthritis, with moderate certainty of evidence. Chinese herbal medicine in combination with disease-modifying anti-rheumatic drugs may improve functional status in rheumatoid arthritis (very low certainty evidence). Acupuncture may improve functional status in rheumatoid arthritis and pain in both rheumatoid arthritis and gout; however, the evidence is of very low certainty. Evidence for other therapies was not clinically significant; however, it suggests possible benefits from quercetin and polyunsaturated fatty acids. Yoga may result in a moderate improvement in functional status when used as an adjunct to medication; however, the certainty of evidence is very low. Diet interventions offered inconsistent improvements to functional status in rheumatoid arthritis, spondyloarthritis, and gout with low to very low certainty. Conclusion Exercise should be prescribed for people with rheumatoid arthritis and spondyloarthritis. More research is needed to confirm or refute evidence for Chinese herbal medicine, acupuncture, yoga, and anti-inflammatory diets.
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Affiliation(s)
- Joshua Lin
- School of Medicine, Western Sydney University, Sydney, NSW, Australia
| | - Jing Liu
- NICM Health Research Institute, Western Sydney University, Sydney, NSW, Australia
| | - Allana O’Fee
- NICM Health Research Institute, Western Sydney University, Sydney, NSW, Australia
| | - Chhiti Pandey
- NICM Health Research Institute, Western Sydney University, Sydney, NSW, Australia
| | - Sarah Benna-Doyle
- NICM Health Research Institute, Western Sydney University, Sydney, NSW, Australia
| | - Alison Maunder
- NICM Health Research Institute, Western Sydney University, Sydney, NSW, Australia
| | - Vibhuti Rao
- NICM Health Research Institute, Western Sydney University, Sydney, NSW, Australia
| | - Simon Alesi
- NICM Health Research Institute, Western Sydney University, Sydney, NSW, Australia
- Monash Centre for Health Research and Implementation, Monash University, Melbourne, VIC, Australia
| | - Beverly Ng
- Department of Rheumatology, Westmead Hospital, Sydney, NSW, Australia
| | - Carolyn Ee
- NICM Health Research Institute, Western Sydney University, Sydney, NSW, Australia
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Wei P, Wang M, Lin M, Wang Z. Tripterine Serves a Dual Role in Palmitate-Induced Pancreatic Beta-Cell Lipotoxicity. DOKL BIOCHEM BIOPHYS 2023; 511:156-161. [PMID: 37833599 DOI: 10.1134/s1607672923600057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2023]
Abstract
Tripterine (TP, also called celastrol), a pentacyclic triterpene extracted from Tripterygium wilfordii, has beneficial effects on multiple diseases, including obesity and diabetes. However, the effects of TP on β‑cell lipotoxicity have not been fully explored. Here, we found that TP modulated β-cell lipotoxicity in a concentration-dependent and bidirectional manner. At low concentrations, TP potentially protected MIN6 β-cells from palmitate (PA)-induced lipotoxicity. At high concentrations, TP significantly promoted β-cell lipotoxicity, further reinforcing PA-induced cell apoptosis. Furthermore, low-concentration TP inhibited the PA-induced increase in reactive oxygen species (ROS) levels, and its protective effects were abolished by the ROS inducer tert-butyl hydroperoxide. Conversely, high-concentration TP significantly exacerbated the PA-triggered ROS generation, and its enhanced cytotoxicity was partially reversed by the ROS inhibitor N-acetyl-L-cysteine. Thus, TP plays a dual role in β-cell lipotoxicity, suggesting that care should be taken when it is used for obesity and diabetes treatment.
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Affiliation(s)
- Pei Wei
- Department of Immunology, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
| | - Min Wang
- Department of Pharmacy, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Mao Lin
- Department of Physiology, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
| | - Zhiyong Wang
- Department of Immunology, Zhuhai Campus of Zunyi Medical University, Zhuhai, China.
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Moudgil KD, Venkatesha SH. The Anti-Inflammatory and Immunomodulatory Activities of Natural Products to Control Autoimmune Inflammation. Int J Mol Sci 2022; 24:95. [PMID: 36613560 PMCID: PMC9820125 DOI: 10.3390/ijms24010095] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/04/2022] [Accepted: 12/05/2022] [Indexed: 12/24/2022] Open
Abstract
Inflammation is an integral part of autoimmune diseases, which are caused by dysregulation of the immune system. This dysregulation involves an imbalance between pro-inflammatory versus anti-inflammatory mediators. These mediators include various cytokines and chemokines; defined subsets of T helper/T regulatory cells, M1/M2 macrophages, activating/tolerogenic dendritic cells, and antibody-producing/regulatory B cells. Despite the availability of many anti-inflammatory/immunomodulatory drugs, the severe adverse reactions associated with their long-term use and often their high costs are impediments in effectively controlling the disease process. Accordingly, suitable alternatives are being sought for these conventional drugs. Natural products offer promising adjuncts/alternatives in this regard. The availability of specific compounds isolated from dietary/medicinal plant extracts have permitted rigorous studies on their disease-modulating activities and the mechanisms involved therein. Here, we describe the basic characteristics, mechanisms of action, and preventive/therapeutic applications of 5 well-characterized natural product compounds (Resveratrol, Curcumin, Boswellic acids, Epigallocatechin-3-gallate, and Triptolide). These compounds have been tested extensively in animal models of autoimmunity as well as in limited clinical trials in patients having the corresponding diseases. We have focused our description on predominantly T cell-mediated diseases, such as rheumatoid arthritis, multiple sclerosis, Type 1 diabetes, ulcerative colitis, and psoriasis.
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Affiliation(s)
- Kamal D. Moudgil
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Baltimore VA Medical Center, Baltimore, MD 21201, USA
| | - Shivaprasad H. Venkatesha
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Vita Therapeutics, Baltimore, MD 21201, USA
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Jo HG, Seo J, Lee D. Clinical evidence construction of East Asian herbal medicine for inflammatory pain in rheumatoid arthritis based on integrative data mining approach. Pharmacol Res 2022; 185:106460. [PMID: 36152738 DOI: 10.1016/j.phrs.2022.106460] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/15/2022] [Accepted: 09/19/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to a significant social burden. East Asian herbal medicine (EAHM) has long been used to treat RA. Therefore, a systematic study of how EAHM treatments can be developed into new drugs using specific materials is needed. METHODS Eleven databases containing literature in English, Korean, Chinese, and Japanese were searched for randomized controlled trials comparing EAHM with conventional medicine (CM). A meta-analysis was performed on the variable data to assess their effects on inflammatory pain. Subsequently, we searched for core materials and combinations of core material-based data mining methods. RESULTS A total of 186 trials involving 19,716 patients with RA met the inclusion criteria. According to the meta-analysis, EAHM had a significantly superior effect on continuous pain intensity, tender joint count, and response rate. Patients treated with EAHM had a significantly reduced incidence of adverse events compared with those treated with CM. Based on additional analysis of the EAHM formula data included in this meta-analysis, 21 core materials and five core herbal combinations were identified. CONCLUSION EAHM remedies for RA have the adequate potential for use as candidate materials for treating inflammatory pain in RA. The candidate core herbs evaluated in this study act on multiple pathways and are expected to provide pain relief, sustained inflammation suppression, immune regulation, and prevention of joint destruction. It seems worthwhile to conduct follow-up research on drug development using the core materials derived from this review.
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Affiliation(s)
- Hee-Geun Jo
- BS Healthcare Co., Ltd., 11 Teheran-ro 33-gil, Gangnam-gu, Seoul 06141, Republic of Korea; Allbarun Kyunghee Korean Medicine Clinic, 18, Pungmu-ro 146-gil, Gimpo, Gyeonggi-do, Republic of Korea; Department of Herbal Pharmacology, College of Korean Medicine, Gachon University, 1342 Seongnamdae-ro, Sujeong-gu, Seongnam 13120, Republic of Korea.
| | - Jihye Seo
- BS Healthcare Co., Ltd., 11 Teheran-ro 33-gil, Gangnam-gu, Seoul 06141, Republic of Korea; Allbarun Kyunghee Korean Medicine Clinic, 18, Pungmu-ro 146-gil, Gimpo, Gyeonggi-do, Republic of Korea; Department of Herbal Pharmacology, College of Korean Medicine, Gachon University, 1342 Seongnamdae-ro, Sujeong-gu, Seongnam 13120, Republic of Korea
| | - Donghun Lee
- BS Healthcare Co., Ltd., 11 Teheran-ro 33-gil, Gangnam-gu, Seoul 06141, Republic of Korea; Allbarun Kyunghee Korean Medicine Clinic, 18, Pungmu-ro 146-gil, Gimpo, Gyeonggi-do, Republic of Korea; Department of Herbal Pharmacology, College of Korean Medicine, Gachon University, 1342 Seongnamdae-ro, Sujeong-gu, Seongnam 13120, Republic of Korea.
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Feng Z, Fu L, Wang J, Zhu Y, He X, Zhou L, Zhou X. Efficacy of tripterygium glycosides (TG) in rheumatoid arthritis as a disease-modifying anti-rheumatic drug (DMARD) in combination with conventional DMARDs: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 2022; 184:106405. [PMID: 36028187 DOI: 10.1016/j.phrs.2022.106405] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 08/16/2022] [Accepted: 08/16/2022] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To explore efficacy and safety, as well as efficacy mechanisms, main efficacy characteristics, and efficacy influencing factors of TG, in combination with one conventional DMARD, to provide guidance for the clinical application of TG in treating RA. METHODS We searched the databases of PubMed, Embase, Web of Science, Cochrane Library, Ovid, Scopus, Clinicaltrials.gov, CNKI, Wanfang, SinoMed, VIP, Chinese Clinical Trial Registry, KTKP, and J-STAGE to August 12, 2022. All included studies were analyzed with Stata 16.0 software and Review Manager 5.4 software according to the PRISMA Statement. RESULTS Thirty-eight randomized controlled trials (RCTs) were included. Combined TG was superior in 28-joint count Disease Activity Score (DAS28) and American College of Rheumatology 50 response (ACR50) and did not increase adverse events (AEs). Combined TG significantly suppressed interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). And combined TG showed significant advantages in improving tender joint count (TJC), swollen joint count (SJC), pain score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and physician's and patient's global assessments of disease activity. However, the average age of the intervention population, treatment course, the combined DMARDs category, and the risk of bias were important factors influencing the above effects. CONCLUSIONS The combination of TG is superior to conventional DMARD monotherapy in improving RA conditions with a good safety profile. This effect is closely related to the mechanism of TG reducing IL-1, IL-6 and TNF-α. And the combination of TG shows better effect in all aspects such as improving joint signs, symptoms, inflammatory indicators, and overall health. But for those under 45 years of age, with short-term intermittent dosing, in combination with MTX may be more beneficial for TG to show better efficacy.
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Affiliation(s)
- Zhe Feng
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Ling Fu
- Department of Diabetes and Cancer Metabolism, City of Hope National Medical Center, Duarte, CA 91010, USA
| | - Junqin Wang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yamei Zhu
- Department of Rheumatology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, China
| | - Xiaojin He
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Lingling Zhou
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Xueping Zhou
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
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Chen GY, Luo J, Liu Y, Yu XB, Liu XY, Tao QW. Network Pharmacology Analysis and Experimental Validation to Investigate the Mechanism of Total Flavonoids of Rhizoma Drynariae in Treating Rheumatoid Arthritis. Drug Des Devel Ther 2022; 16:1743-1766. [PMID: 35702063 PMCID: PMC9188779 DOI: 10.2147/dddt.s354946] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 05/26/2022] [Indexed: 12/16/2022] Open
Abstract
Objective The study aimed to explore the mechanism of total flavonoids of Rhizoma Drynariae (TFRD) in the treatment of rheumatoid arthritis (RA) based on network pharmacology and experimental validation. Methods The active components of TFRD were identified from TCMSP and TCMID databases. Relevant targets of the active compounds of TFRD and RA-related targets were predicted by public databases online. A component-target (C-T) regulatory network was constructed by Cytoscape. The genes of TFRD regulating RA were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. KEGG enrichment analysis was performed to predict the crucial mechanism of TFRD against RA. The active components of TFRD underwent molecular docking with the key proteins. Collagen-induced arthritis (CIA) model of rats and inflammatory factors-stimulated fibroblast-like synoviocytes were used in vivo and in vitro to validate the efficacy and predicted critical mechanisms of TFRD. Results Network Pharmacology analysis revealed that TFRD had 14 active compounds, corresponding to 213 targets, and RA related to 2814 genes. There were 137 intersection genes between TFRD and RA. KEGG indicated that therapeutic effects of TFRD on RA involves T cell receptor signaling pathway, Th17 cell differentiation, IL-17 signaling pathway, TNF signaling pathway, MAPK signaling pathway and PI3K/AKT signaling pathway. In vivo experiments suggested TFRD can alleviate the inflammatory response, joint swelling and synovial abnormality of CIA rats. TFRD contributed to the decrease of Th17 cells and the down-regulated secretion of IL-17A and TNF-α of activated lymphocyte in CIA model. In vitro experiments confirmed TFRD can effectively inhibit the inflammatory response of fibroblast-like synoviocytes and suppress the abnormal activation of MAPK, PI3K/AKT and NFκB signaling pathways. Conclusion The treatment of RA with TFRD is closely related to inhibiting Th17 differentiation and inflammatory response of synoviocytes.
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Affiliation(s)
- Guang-yao Chen
- Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China
| | - Jing Luo
- Department of TCM Rheumatology, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China
| | - Yi Liu
- Humanities School, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China
| | - Xin-bo Yu
- Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China
| | - Xiao-yu Liu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China
| | - Qing-wen Tao
- Department of TCM Rheumatology, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China
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Li D, Hong X, Chen T. Association Between Rheumatoid Arthritis and Risk of Parkinson's Disease: A Meta-Analysis and Systematic Review. Front Neurol 2022; 13:885179. [PMID: 35645965 PMCID: PMC9130734 DOI: 10.3389/fneur.2022.885179] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 04/11/2022] [Indexed: 12/24/2022] Open
Abstract
Background Rheumatoid arthritis (RA) and Parkinson's disease (PD) are two common chronic diseases worldwide, and any potential link between the two would significantly impact public health practice. Considering the current inconsistent evidence, we conducted a meta-analysis and systematic review to examine the risk of PD in patients with RA. Methods Two investigators (DL and XH) conducted a comprehensive search of PubMed, Embase, and Web of Science using medical subject headings terms combined with free words to identify relevant papers published from inception through December 31, 2021. All studies that explored the relationship between RA and PD were included for quantitative analysis and qualitative review. Random- and fixed-effects models were used to pool the risk ratios (RRs) of PD in patients with RA. The Newcastle-Ottawa scale was used to assess the quality of included studies. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guideline. Results Four population-based studies involving 353,246 patients and one Mendelian randomized study were included in our study. The pooled result showed a significantly reduced risk of PD in patients with RA than in the general population (RR = 0.74, 95% CI: 0.56-0.98, P = 0.034). No apparent effects of gender, age, region, follow-up time, or study design on PD risk were observed. Sensitivity analysis showed that pooled results were relatively stable, and no publication bias was detected. The Mendelian randomization study indicated a significant inverse association between RA and PD (genetic correlation: −0.10, P = 0.0033) and that each one standard deviation increase in the risk of RA was significantly associated with a lower risk of PD. Of note, the current study is limited by the relatively small number of included studies and unmeasured confounding factors, especially for RA-related anti-inflammatory agents. Conclusions This study supports that people with RA had a lower PD risk than those without RA. Further studies are needed to explore the underlying molecular mechanisms of the interaction between the two diseases.
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Tripterygium wilfordii Hook. f. Preparations for Rheumatoid Arthritis: An Overview of Systematic Reviews. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:3151936. [PMID: 35463070 PMCID: PMC9019410 DOI: 10.1155/2022/3151936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 02/07/2022] [Indexed: 12/03/2022]
Abstract
Objectives To summarize the quantity and quality of evidence for using Tripterygium wilfordii Hook. f. (TwHF) preparations in patients with rheumatoid arthritis (RA) and to find the reasons of the disparity by comprehensively appraising the related systematic reviews (SRs). Methods We performed an overview of evidence for the effectiveness and safety of TwHF preparations for patients with RA. We searched seven literature databases from inception to July 15, 2021. We included SRs of TwHF preparations in the treatment of RA. Four tools were used to evaluate the reporting quality, methodological quality, risk of bias, and the certainty of evidence for the included SRs, which are the PRISMA, the AMSTAR-2, the ROBIS, and the GRADE approach. Results We included 27 SRs (with 385 studies and 33,888 participants) for this overview. The AMSTAR-2 showed that 19 SRs had critically low methodological quality and the remaining 8 had low methodological quality. The rate of overlaps was 68.31% (263/385), and the CCA (corrected covered area) was 0.53, which indicated the degree of overlap is slight. Based on the assessment of ROBIS, all 27 SRs were rated as low risk in phase 1; one SR was rated as low risk in domain 1, 9 SRs were in low risk in domain 2, 16 SRs were in low risk in domain 3, and 16 SRs were in low risk in domain 4 in phase 2; 7 SRs were rated as low risk in phase 3. Among 27 items of PRISMA, 15 items were reported over 70% of compliance, the reporting quality of 16 SRs was rated as “fair,” and 11 were “good.” Using GRADE assessment, moderate quality of evidence was found in 5 outcomes, and 5 outcomes were low quality. Conclusion The use of TwHF preparations for the treatment of RA may be clinically effective according to the moderate-quality evidence. There are methodological issues, risk of bias, and reporting deficiencies still needed to be improved. SRs with good quality and further randomized clinical trials that focus on clinical important outcomes are needed.
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Effects and Safety of the Tripterygium Glycoside Adjuvant Methotrexate Therapy in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:1251478. [PMID: 35368750 PMCID: PMC8970871 DOI: 10.1155/2022/1251478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 12/15/2021] [Accepted: 02/23/2022] [Indexed: 11/17/2022]
Abstract
Objective This study aimed to systematically review the efficacy and clinical safety of different courses and doses of tripterygium glycoside (TG) adjuvant methotrexate (MTX) therapy in the treatment of rheumatoid arthritis (RA). Methods Randomized controlled trials (RCTs) of TG adjuvant MTX therapy in patients with RA were retrieved from SinoMed, China Network Knowledge Infrastructure, WanFang Data, PubMed, Cochrane Library, and Embase from inception to September 30, 2021. The effects and clinical safety evaluations were conducted using RevMan 5.3 software. Results A total of 9 RCTs and 892 patients with RA were included in this study. In the meta-analysis, a total of 463 and 429 patients were enrolled into the TG adjuvant MTX therapy group and MTX monotherapy group, respectively. In comparison with MTX monotherapy, the results of the analyzed effects showed that the TG adjuvant MTX therapy can achieve 20%, 50%, and 70% improvements in American College of Rheumatology (ACR) criteria ACR20, ACR50, and ACR70 at P = 0.005, P = 0.0001, and P = 0.004, respectively. Simultaneously, the efficacy of the TG adjuvant MTX therapy was improved at either 30 or 60 mg/day over a six-month course compared to MTX monotherapy (P < 0.0001). There was no statistical difference in the effects between the doses of 30 and 60 mg/day after three months (P = 0.82). TG adjuvant MTX also reduced the expression rate of the swollen joint count, tender joint count, erythrocyte sedimentation rate, rheumatoid factor, and C-reactive protein in subgroup analyses with different courses and doses. In terms of hepatic adverse effects (P = 0.28), leukopenia (P = 0.78), gastrointestinal adverse effects (P = 0.17), cutaneous adverse effects (P = 0.94), and irregular menstruation adverse effects (P = 0.29), there was no statistically significant difference with TG adjuvant MTX therapy and MTX monotherapy with different courses and doses. Conclusions TG adjuvant MTX therapy is more effective than MTX monotherapy and is a safe strategy for RA treatment in doses of 30 or 60 mg/day over a treatment course of six months. However, high-quality multicenter RCT studies with large sample sizes are still needed to confirm the effects and clinical safety of different courses and doses of TG adjuvant MTX therapy.
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Jo HG, Song HS, Lee D. Oral administration of East Asian herbal medicine for rheumatoid arthritis: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2022; 101:e28819. [PMID: 35147122 PMCID: PMC8830828 DOI: 10.1097/md.0000000000028819] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 01/26/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Rheumatoid arthritis (RA) is a chronic, inflammatory, and painful joint disease. The aim of this review is to systematically evaluate the efficacy and safety of oral administration East Asian herbal medicine monotherapy for inflammatory pain of RA, and to explore core herb material information based on collected data. METHODS A comprehensive literature search will be conducted in 11 electronic databases including PubMed, Cochrane Library, Cumulative Index to Nursing & Allied Health Literature, Excerpta Medica database, Korean Studies Information Service System, Research Information Service System Oriental Medicine Advanced Searching Integrated System, Korea Citation Index, Chinese National Knowledge Infrastructure Database, Wanfang data, citation information by NII for randomized controlled trials from their inception until October 13, 2021. Statistical analysis will be performed in the software R version 4.1.1. and R studio program using the default settings of the "meta" and "metafor" package. When heterogeneity in studies is detected, the cause will be identified through subgroup analysis. Methodological quality will be assessed independently using the revised tool for risk of bias in randomized trials (Rob 2.0). RESULTS This study will provide more comprehensive and specific evidence of East Asian herbal medicine monotherapy for RA pain management. CONCLUSIONS Based on the results of this review, it is expected that the efficacy and safety of East Asian herbal medicine for inflammatory pain of RA may be confirmed. In addition, it will be possible to derivation of a core herb material information related to this research topic through additional data mining. ETHICS AND DISSEMINATION There are no ethical issues as there are no primary data collected by directly recruiting subjects. The results of this review will be reported in a peer-reviewed scientific journal. PROSPERO REGISTRATION NUMBER CRD42021273643.
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Affiliation(s)
- Hee-Geun Jo
- Department of Bioinformatics and Statistics, Graduate School of Korea National Open University, 86 Daehak-ro, Jongro-gu, Seoul, Republic of Korea
| | - Ho-Sueb Song
- Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Gachon University 1342 Seongnamdae-ro, Sujeong-gu, Seongnam, Republic of Korea
| | - Donghun Lee
- Department of Herbal Pharmacology, College of Korean Medicine, Gachon University, 1342 Seongnamdae-ro, Sujeong-gu, Seongnam, Republic of Korea
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Beneficial Modulation of Lipid Mediator Biosynthesis in Innate Immune Cells by Antirheumatic Tripterygium wilfordii Glycosides. Biomolecules 2021; 11:biom11050746. [PMID: 34067705 PMCID: PMC8155965 DOI: 10.3390/biom11050746] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 05/06/2021] [Accepted: 05/10/2021] [Indexed: 12/31/2022] Open
Abstract
Tripterygium wilfordii glycosides (TWG) is a traditional Chinese medicine with effectiveness against rheumatoid arthritis (RA), supported by numerous clinical trials. Lipid mediators (LM) are biomolecules produced from polyunsaturated fatty acids mainly by cyclooxygenases (COX) and lipoxygenases (LOX) in complex networks which regulate inflammation and immune responses and are strongly linked to RA. The mechanism by which TWG affects LM networks in RA treatment remains elusive. Employing LM metabololipidomics using ultra-performance liquid chromatography-tandem mass spectrometry revealed striking modulation of LM pathways by TWG in human monocyte-derived macrophage (MDM) phenotypes. In inflammatory M1-MDM, TWG (30 µg/mL) potently suppressed agonist-induced formation of 5-LOX products which was confirmed in human PMNL and traced back to direct inhibition of 5-LOX (IC50 = 2.9 µg/mL). TWG also efficiently blocked thromboxane formation in M1-MDM without inhibiting other prostanoids and COX enzymes. Importantly, in anti-inflammatory M2-MDM, TWG (30 µg/mL) induced pronounced formation of specialized pro-resolving mediators (SPM) and related 12/15-LOX-derived SPM precursors, without COX and 5-LOX activation. During MDM polarization, TWG (1 µg/mL) decreased the capacity to generate pro-inflammatory 5-LOX and COX products, cytokines and markers for M1 phenotypes. Together, suppression of pro-inflammatory LM but SPM induction may contribute to the antirheumatic properties of TWG.
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Zeng L, Li C, Jiang H, Chen Y, Li Z, Xu F, Liu R. Total Saponins from Nigella glandulifera Seeds Ameliorate Adjuvant-Induced Rheumatoid Arthritis in Rats by Inhibition of an Inflammatory Response and Bone Erosion. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6613527. [PMID: 33575330 PMCID: PMC7864740 DOI: 10.1155/2021/6613527] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 01/09/2021] [Accepted: 01/13/2021] [Indexed: 12/14/2022]
Abstract
Rheumatoid arthritis (RA) is a widespread inflammatory disease whose clinical manifestations are joint swelling, pain, and disability, affecting approximately 1% of individuals worldwide. Conventional anti-RA drugs currently used in clinic have severe side effects. The present study is aimed at investigating the antiarthritic effects of total saponins from Nigella glandulifera seeds (TSNGS) in rats with adjuvant-induced rheumatoid arthritis (AIA). Arthritis score, paw swelling, and body weight were monitored throughout the period of TSNGS treatment. The histopathological features and levels of cytokines, including IFN-γ, TNF-α, IL-1β, IL-4, IL-6, IL-10, and IL-17A, and OPG/RANKL signaling, were measured to determine the amelioration by TSNGS and its potential mechanisms on the inflammatory response and bone erosion. The differentiation of regulatory T cells (Tregs) in serum was assessed by flow cytometry. The results demonstrate that TSNGS at 10 mg/kg, 50 mg/kg, and 250 mg/kg inhibited AIA-induced clinical score, paw swelling, and histological changes. TSNGS reduced the immune-inflammatory reaction by restoring the secretion and expression of inflammatory cytokines and elevating the proportion of CD4+ CD25+ Tregs, accompanied by an increase in transcription factor Foxp3 levels. TSNGS also displayed bone protection by upregulation of the OPG/RANKL pathway. Collectively, TSNGS inhibited arthritis in AIA rats and so represents a potential novel treatment for RA.
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Affiliation(s)
- Li Zeng
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Chenyang Li
- Key Laboratory of Uighur Medicine of Xinjiang Uygur Autonomous Region, Xinjiang Institute of Materia Medica, Urumqi 830004, China
| | - Hailun Jiang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Yan Chen
- Key Laboratory of Uighur Medicine of Xinjiang Uygur Autonomous Region, Xinjiang Institute of Materia Medica, Urumqi 830004, China
| | - Zhuorong Li
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Fang Xu
- Key Laboratory of Uighur Medicine of Xinjiang Uygur Autonomous Region, Xinjiang Institute of Materia Medica, Urumqi 830004, China
| | - Rui Liu
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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