Mechanism of Xinfeng Capsules improving rheumatoid arthritis based on CD19~+B cells regulating FAK/CAPN/PI3K pathway / 中国中药杂志

To observe the effect of Xinfeng Capsules on rheumatoid arthritis (RA) B lymphocytes,inflammatory mediators,FAK/CAPN/PI3K pathway,in order to explore the mechanism of Xinfeng Capsules in improving clinical symptoms of RA.Joint and systemic symptoms of RA patients were observed,and laboratory indicators[hemoglobin (HGB),platelet count (PLT),erythrocyte sedimentation (ESR),immunoglobulin (Ig) G,Ig A,Ig M,rheumatoid factor (RF),anti-cyclic citrulline antibody (CCP-AB),C-reactive protein (CRP)]were detected.ELISA was used to detect serum interleukin (IL)-1β，IL-10,IL-33,chemokine 5 (CCL5),and vascular endothelial growth factor (VEGF).CD3~-CD19~+B cells were measured by flow cytometry.Western blot was used to detect FAK,p-FAK,CAPN,PI3K protein.The results showed that Xinfeng Capsules could significantly alleviate RA joint and systemic symptoms and improve clinical efficacy.And Xinfeng Capsules could increase HGB,decrease PLT,CCP-AB,CRP,ESR index,upregulate IL-10 expression,and down-regulate IL-1β，IL-33,CCL5,VEGF,CD3~-CD19~+B cells,FAK,p-FAK,CAPN,PI3K expressions (P<0.01).Based on the above results,Xinfeng Capsules may reduce the expression of CD3~-CD19~+,regulate the balance of inflammatory cytokines and chemokines,inhibit abnormal activation of FAK/CAPN/PI3K pathway,and improve clinical symptoms of RA.

Xinfeng capsule for the treatment of rheumatoid arthritis patients with decreased pulmonary function--a randomized controlled clinical trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the effectiveness and safety of Xinfeng Capsules (XFC) for the treatment of rheumatoid arthritis (RA) patients with decreased pulmonary function.</p><p><b>METHODS</b>This was a randomized controlled clinical trial of 80 RA patients. Participants were assigned to the trial group (40 cases) and the control group (40 cases) by block randomization. The trial group was treated with XFC, three pills each time three times daily for 2 months. The control group was treated with tripterygium glycoside (TPT), two pills each time three times daily for 2 months. Both groups were followed up after 2 months. The clinical effects, changes in joint and pulmonary function, and quality of life before and after treatment were observed; safety indices were also evaluated.</p><p><b>RESULTS</b>Pain, swelling, tenderness, and duration of morning stiffness of joints were obviously decreased after treatment in both the trial and the control groups compared with baseline (P<0.01). Compared with before treatment, hand grip strength increased significantly after treatment in the trial group (P=0.0000); pulmonary function parameters such as forced expiratory volume in the first second of expiration/forced vital capacity (FEV1/FVC), 50% of the expiratory flow of forced vital capacity (FEF50), carbon monoxide diffusing capacity (DLco) were increased (P<0.01 or P<0.05); measures of quality of life such as role-physical, body pain, vitality and mental health were also improved after treatment in the trial group (all P<0.05). Joint swelling in the trial group decreased compared with the control group (P=0.0043), while hand grip strength was increased after treatment (P=0.0000). The increase in FEF50, DLco, and the dimensions of quality of life such as vitality and mental health were all significantly greater in the trial group than the control group (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>XFC not only relieved joint pain in RA patients, but also significantly improved the ventilation and diffusion function of the lungs. Therefore, XFC could improve the whole body function and enhance the quality of life of RA patients.</p>

Relations of synovial angiogenesis and PTEN/PI3K/AKT signaling pathway in rats with adjuvant arthritis / 中国骨伤

<p><b>OBJECTIVE</b>To observe the change of PTEN/PI3K/AKT pathway hypoxia-inducible factor (HIF-1α), vascular endothelial growth factor (VEGF) in rats with adjuvant arthritis and to explore the mechanism of neovasculization in rheumatoid arthritis.</p><p><b>METHODS</b>Thirty rats were randomly divided into normal control group and model control group. The model control group were established the model of adjuvant arthritis using Freund's complete adjuvant. At 19 days after modeling, the expression of microvascular density (MVD), HIF-1α, VEGF were detected by ELISA assay and PTEN, PI3K, AKT were detected by Werstern Blotting.</p><p><b>RESULTS</b>Compared with the normal control group, paw swelling, arthritic index were increased, and the expression of MVD, VEGF, HIF-1α of serum, PI3K, AKT of synovial tissue were significantly increased, PTEN was significantly decreased in model control group. PI3K, HIF-1α were positively correlated with MVD; VEGF, AKT were positively correlated with paw swelling; PTEN was negatively correlated with the arthritis index; HIF-1α was positively correlated with VEGF; PI3K was positively correlated with AKT, PTEN was negatively correlated with PI3K, AKT, VEGF.</p><p><b>CONCLUSION</b>Imbalance of PTEN/PI3K/AKT pathway in rats with adjuvant arthritis is one of the mechanisms of synovial neovasculization.</p>

Effect of triptolide on expressions of Notch receptors and ligands in rats with adjuvant- induced arthritis and reduced pulmonary function / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of triptolide on Notch receptor and ligand expressions in rats with adjuvant-induced arthritis (AA).</p><p><b>METHODS</b>Forty rats were randomly divided into normal control (NC) group, model (MC) group, methotrexate group and triptolide groups. Rat models of AA were established by an intradermal injection of 0.1 mL Freund's complete adjuvant into the right paw. Twelve days after the injection, the rats were treated with corresponding drugs for 30 days; the rats in NC group and MC group were given saline only. Paw edema volume (E), arthritis index (AI), pulmonary function, histomorphologies, and Notch receptor/ ligand expression in the lung tissue were analyzed after the treatments.</p><p><b>RESULTS</b>Compared with the NC group, E, AI, Notch3, Notch4, and Delta1 expressions in the lung tissues significantly increased while pulmonary function and pulmonary expressions of Notch1, Jagged1, and Jagged2 significantly decreased the model rats (P<0.01). Compared with the MC group, triptolide-treated rats showed significantly improved pulmonary functions, increased expressions of Notch1, Jagged1, and Jagged2 and decreased expressions of Notch3, Notch4, and Delta1 in the lungs (P<0.05, P<0.01); the therapeutic effect of triptolide was better than that of methotrexate.</p><p><b>CONCLUSION</b>Triptolide can reduce inflammatory reaction and immune complex deposition to improve joint and pulmonary symptoms in rats with AA possibly by up-regulating the expressions of Notch3, Notch4, and Delta1 and down-regulating the expressions of Jagged1, Jagged2, and Notch1.</p>

Effect of Xinfeng Capsule on Lipoprotein Metabolism of Rheumatoid Arthritis Patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of Xinfeng Capsule (XC) on lipoprotein metabolism of rheumatoid arthritis (RA) patients.</p><p><b>METHODS</b>Totally 180 RA patients were assigned to the experimental group and the control group by random digit table, 90 in each group. Patients in the experimental group took XC (three pills each time, three times daily), while those in the control group took Methotrexate Tablet (four tablets each time, once per week). One month consisted of one therapeutic course and all patients were treated for two therapeutic courses. A healthy control group consisting of 60 patients was also set up. Changes of lipoprotein indices, clinical efficacy, lipid metabolism, joint symptoms and signs, activity indicators were observed, and correlation analyses were performed.</p><p><b>RESULTS</b>Compared with the healthy control group, expression levels of prealbumin (PA), globulin (GLO), high-density lipoprotein (HDL), apolipoprotein Al (Apo-A1) were lowered in RA patients (P <0. 05, P <0. 01). Correlation analyses showed that PA was negatively correlated with joint tenderness, morning stiffness time, disease activity score (DAS-28), C-reactive protein (CRP), interleukin (IL)-6, respectively. Total protein (TP) was negatively correlated with joint tenderness. GLO was negatively correlated with joint tenderness and DAS-28. HDL was negatively correlated with erythrocyte sedimentation rate (ESR) and endothelin (ET)-1. Apo-Al was negatively correlated with joint pain; Apo-B was negatively correlated with CRP; LDL was negatively correlated with morning stiffness time (P <0. 05, P <0. 01). Compared with before treatment, expression levels of PA, HDL, Apo-A1 , Apo-B, and serum IL-10 contents increased, and expression levels of ESR, CRP, IL-6, ET-1 , joint pain, joint swelling, morning stiffness time, and DAS-28 decreased in the experimental group (P <0. 05, P <0. 01). PA increased more after treatment than before treatment in the control group (P <0. 01). There was statistical difference in joint symptoms (except joint tenderness) and activity indices (except ET-1) in the control group (P <0. 05, P <0. 01). Compared with the control group after treatment, PA and HDL increased, ET-1 and duration of morning stiffness decreased in the experimental group (all P <0. 05).</p><p><b>CONCLUSIONS</b>Lipoprotein metabolic disorder exists in RA patients, and it is associated with disease activity. XC could obviously improve lipoprotein metabolism and joint symptoms.</p>

Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis: study protocol of a multicenter randomized controlled trial / 中西医结合学报

<p><b>BACKGROUND</b>Rheumatoid arthritis (RA), as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA.</p><p><b>METHODS AND DESIGN</b>This is a 12-week, randomized, placebo-controlled, double-blind, multicenter trial on the treatment of RA. The participants will be randomly assigned to the experimental group and the control group at a ratio of 1:1. Participants in the experimental group will receive Xinfeng Capsule and a pharmaceutical placebo (imitation leflunomide). The control group will receive leflunomide and an herbal placebo (imitation Xinfeng Capsule). The American College of Rheumatology (ACR) Criteria for RA will be used to measure the efficacy of the Xinfeng Capsule. The primary outcome measure will be the percentage of study participants who achieve an ACR 20% response rate (ACR20), which will be measured every 4 weeks after randomization. Secondary outcomes will include the ACR50 and ACR70 responses, the side effects of the medications, the Disease Activity Score 28, RA biomarkers, quality of life, and X-rays of the hands and wrists. The first four of the secondary outcomes will be measured every 4 weeks and the others will be measured at baseline and after 12 weeks of treatment.</p><p><b>DISCUSSION</b>The result of this trial will help to evaluate whether Xinfeng Capsule is effective and safe in the treatment of RA.</p><p><b>TRIAL REGISTRATION</b>This trial has been registered in ClinicalTrials.gov. The identifier is NCT01774877.</p>

Effect of Xinfeng Capsule on lung function in rats with adjuvant-induced arthritis and its mechanism / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of Xinfeng Capsule (XFC) on pulmonary function and related mechanism in adjuvant-induced arthritis (AA) rats.</p><p><b>METHODS</b>The rats were randomly divided into five groups: normal control (NC), model control (MC) groups, methotrexate (MTX), tripterygium glycosides tablet (TPT) and Xinfeng capsule (XFC) treatment groups. The adjuvant-induced arthritis model was established by intracutaneous injection of 0.1 mL Freund ' s complete adjuvant in the right paw of rats; the drugs were given 19 d after model establishment. The toe swelling degree (E), arthritis index (AI), pulmonary function, peripheral blood Treg levels, pathological changes of lung tissue and expression of Foxp3, TGF-β1, Smad3, Smad7 proteins in lung tissue were measured 30 d after drug administration.</p><p><b>RESULTS</b>Compared to NC group, the levels of E, AI, alveolitis score, TGF-β1 and Smad3 were significantly increased (P <0.05 or P <0.01); maximum expiratory flow 25% of vital capacity (FEF25),50% maximal expiratory vital capacity flow (FEF50), maximum expiratory flow at 75% of vital capacity (FEF75), maximum mid-expiratory flow (MMF), force peak expiratory flow (PEF), CD4+ CD25+ Treg, Foxp3 and Smad7 were significantly decreased in MC group (P <0.05 or P < 0.01). Compared to MC group,the expression of E, AI, TGF-β1 and Smad3 were reduced, while FEF50, FEF75, MMF, PEF, Treg, Foxp3 and Smad7 were elevated in XFC group (P <0.05 or P <0.01). Compared to XFC group, the level of body mass,FEF25,FEF50, FEF75, MMF and Treg were lower in MTX and TPT groups (P <0.05 or P <0.01).</p><p><b>CONCLUSION</b>There are inflamed joints and reduced pulmonary function in rats of adjuvant-induced arthritis. XFC can inhibit paw edema degrees, reduce arthritis response, and improve pulmonary function, which is associated with up-regulating expression of Treg and Foxp3, down-regulating the expression of TGF-β1 and adjusting TGF-β1/Smads signal pathway.</p>

Treatment of rheumatoid arthritis by xinfeng capsule: an efficacy observation / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the curative effect of Xinfeng Capsule (XC) in treatment of rheumatoid arthritis (RA).</p><p><b>METHODS</b>Recruited were 80 active RA patients, who were randomly assigned to the normal control group and the treatment group, 40 in each group. All patients received the same routine anti-rheumatic treatment: Methotrexate 10 mg per week; Diclofenac 50 mg when pain was obvious, twice daily. Patients in the treatment group took XC 3 tablets each time, thrice daily. All treatment lasted for 12 consecutive weeks. Serum iron (SI), serum ferritin (SF), transferrin (TRF); and RA disease activity index (DAS-28) were detected in all patients.</p><p><b>RESULTS</b>XC could improve HAQ, DAS-28, hypersensitive C reactive protein (hs-CRP), prostaglandins A (PGA), erythrocyte sedimentation rate (ESR), number of swelling joints, number of tender joints, and morning stiffness time in acute RA patients, showing statistical difference when compared with those of the control group (P < 0.01, P < 0.05). Compared with the control group, SI, SF, DAS-28, and TRF significantly decreased in the treatment group (P < 0.05).</p><p><b>CONCLUSION</b>XC could improve DAS-28, and SI reserve in patients with active RA, and lower DAS-28 related indicators.</p>