Xinfeng Capsule Research Articles

Effects of Xinfeng capsule on the Fas/FasL-mediated apoptotic pathway in patients with rheumatoid arthritis

OBJECTIVETo observe the effects of Xinfeng capsule on the apoptosis of peripheral blood CD4 + T lymphocytes and changes in the Fas/FasL-mediated apoptotic pathway in patients with rheumatoid arthritis (RA). METHODSA total of 28 RA patients were included in the study; they were randomly divided into the Xinfeng capsule (XFC) group (3 capsules, 3 per day) and the leflunomide (LEF) group (1 pellet, once per night). The treatment course in each groups was 12 weeks. The normal control (NC) group consisted of 10 healthy people. The apoptotic rate was examined using flow cytometry. Fas, FasL, caspase 8, caspase 3, bcl-2, and bax mRNA were examined using qRT-PCR. Apoptotic proteins Fas, FasL, caspase 8, and caspase 3 were examined using western blotting. RESULTSAfter treatment, patients in the two groups all showed some trend of improvement. Disease activity indexes, joint morning stiffness time, joint swelling/tenderness number, health assessment questionnaire (HAQ) score, RA quality of life (RAQOL) questionnaire, and self-rating anxiety scale (SAS), as well as all apoptotic related indicators were reduced in both groups after treatment with no significant difference between groups. But the improvement in terms of the self-rating depression scale (SDS) in the XFC group was better than in the LEF group. RA patients showed lower apoptotic rates in CD4+ T cells, lower bax, Fas, caspase 8, and caspase 3 mRNA, and less protein expression of Fas, caspase 8, and caspase 3 than in the NC group. These indicators increased after treatment. However, the level of Bcl-2 mRNA was higher in the XFC group than in the NC group before treatment, and it subsequently decreased. The XFC group expressed lower Bcl-2 mRNA than the LEF group. Negative correlations were found between ESR and the apoptotic rate in CD4+ T cells, Fas, and caspase 3; CRP and Fas; and, swollen joint count and Bax, while positive correlations were found between ESR and Bcl-2. CONCLUSIONXFC can regulate the Fas/FasL system and promote CD4+ T cell apoptosis and thus reduce the abnormal immune response, which can improve symptoms in RA patients.

Drug-containing serum of Xinfeng capsules protect against H9C2 from death by enhancing miRNA-21 and inhibiting toll-like receptor 4/phosphorylated p-38 (p-p38)/p-p65 signaling pathway and proinflammatory cytokines expression

OBJECTIVETo investigate effect of drug-containing serum of Xinfeng capsules on myocardial cell growth. METHODSDrug-containing serum of Xinfeng capsules rat models were established by intragastricly administrated Xinfeng capsules. MTT assay was used to evaluated H9C2 cells viability. H9C2 cells were divided into normal control group, triptolide group, lipopolysaccharide (LPS) group, drug-containing serum group and miRNA-21 inhibitor group. microRNA-21 (miRNA-21) inhibitor was structured and transfected into H9C2 cells. Western blot and immunofluorescence assay were applied to examine toll-like receptor 4 (TLR4), phosphorylated p-38 (p-p38) and p-p65 expression. Quantitative real-time PCR (qRT-PCR) was used to evaluated mRNA levels of miRNA-21. Enzyme linked immunosorbent (ELISA) was used to measure tumor necrosis factor α (TNF-α), IL-6 and IL-17 levels. RESULTSDrug-containing serum treatment significantly increased cell viability compared to LPS treated group. qRT-PCR results indicated that miRNA-21 levels were significantly decreased in drug-containing serum group compared to LPS group. Early and late apoptosis in drug-containing serum group were significantly decreased compared to LPS group. Western blot and immunofluorescence assay results showed that TLR4, p-p38 and p-p65 levels in drug-containing serum group were significantly decreased compared to LPS group. ELISA findings indicated that drug-containing serum significantly decreased inflammatory cytokine levels of TNF-α, IL-6 and IL-17. CONCLUSIONDrug-containing serum of Xinfeng capsules protect against lipopolysaccharide instructed H9C2 cells from death by enhancing miRNA-21 and inhibiting TLR4/p-p38/p-p65 signaling pathway and proinflammatory cytokines expression.

Mechanism studies of Xinfeng capsule on improving cardiovascular function though toll-like receptor 4/nuclear factor kappa B pathway in a rat model of adjuvant arthritis

OBJECTIVETo observe the impact of Xinfeng capsule (XFC) on cardiovascular function in adjuvant arthritis (AA) model rats and investigate the mechanism though toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κβ) signaling pathway. METHODSSeventy rats were randomly divided into seven groups: normal control (NC), model control (MC), tripterygium glycosides tablet (TPT), methotrexate (MTX), high, moderate and low dose XFC group. The administration began from day 19 after modeling for 30 day. Paw swelling, arthritic index (AI), cardiac function indexes and myocardial pathological pattern were detected. The expression of TLR4, myeloid differentiation factor (MyD) 88, interleukin-1 receptor-associated kinase (IRAK) 1, tumor necrosis factor receptor associated factor (TRAF) 6, NF-κβ, tumor necrosis factor-alpha (TNF-α) proteins in myocardial tissue were determined by western blot method. RESULTSPaw swelling and AI in MC group increased in MC group (P < 0.01), and decreased in high and moderate dose XFC groups (P < 0.01 or P > 0.05). Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), heart rate (HR) were elevated in MC group (P < 0.01), and ± dp/dtmax and CI were reduced (P < 0.01); while LVSP, LVEDP and HR declined and ±dp/dtmax, CI improved in high dose XFC group (P < 0.05 or P < 0.01). LVSP in high dose XFC group were reduced more than other treatment groups (P < 0.05 or P < 0.01). The improvements on LVEDP, dp/dt-max were superior to MTX and low dose XFC group, and the improvement on CI was better than low dose XFC group (P < 0.05 or P < 0.01). Myocardial fibers arranged irregular in MC group with intracellular edema and mitochondria damage. The modifications on myocardial structural were shown in each treatment group, but more prominent in TPT, high and moderate dose XFC group. The proteins of TLR4, MyD88, IRAK1, TRAF6, NF-κβ, TNF-α were highly expressed in MC group, and those proteins declined in high and moderate dose XFC group (P < 0.05 or P < 0.01). High dose XFC group was superior to MTX and low dose XFC group on reducing TLR4, NF-κβ, TNF-α (P < 0.05). CONCLUSIONXFC can not only inhibit the excessive activation of TLR4/NF-κB signaling pathway and the increased inflammatory mediators, but also reduce the damage of myocardial tissue and cells.

Effect of Xinfeng capsule on nuclear factor kappa B/tumor necrosis factor alpha and transforming growth factor beta 1/Smads pathways in rats with cardiac injuries induced by adjuvant arthritis

ObjectiveTo investigate effects of Xinfeng capsule (XFC) on cardiac function in rats with adjuvant arthritis (AA) and explore the mechanism of these effects. MethodsForty-eight rats were randomly divided into normal control (NC), model control (MC), methotrexate (MTX) and XFC groups of equal size. In all groups except for the NC group, 0.1 mL Freund's complete adjuvant (FCA) was intracutaneously injected in the right rear vola pedis to induce inflammation. Drugs were applied beginning 19 days after induction of inflammation. Normal saline was administered to the NC and MC groups and 1 mg/100 g MTX (weekly) and 0.12 g/100 g XFC (daily) to the MTX and XFC groups, respectively. Rats were sacrificed after 30 day of treatment. Toe swelling degree (TSD), arthritis index (AI), cardiac function and expression of nuclear factor kappa B (NF-κB)/ tumor necrosis factor alpha (TNF-α) and transforming growth factor beta 1 (TGF-ß1)/Smads pathway proteins were measured. ResultsIn the MC group, TSD and AI were greatly increased, while parameters of cardiac function were decreased and morphological analysis showed myocardial cell damage. Expression of TNF-α, NF-κB, Smad2, P-Smad2, Smad4 and TGF-ß1 proteins were elevated in cardiac tissue, while Smad7 expression was decreased. TSD and AI values closely correlated to parameters of cardiac function and to levels of proteins in the NF-κB/TNF-α and TGF-ß1/Smads pathways. Certain correlations were identified among TGF-ß1 and NF-κB, Smad2, P-Smad2 and Smad4. With XFC intervention, both TSD and AI were decreased and parameters of cardiac function and ultrastructure of myocardial cells improved. Expressions of NF-κB, Smad2, and Smad4 proteins were greatly decreased and Smad7 expression was elevated, as compared with levels in the MC and MTX groups. ConclusionXFC regulates expression of proteins in the NF-κB/TNF-α and TGF-ß1/Smads pathways, decreases immune complex deposition in cardiac tissue and improves cardiac function in AA rats via upregulation of Smad7.

Xinfeng capsule for the treatment of rheumatoid arthritis patients with decreased pulmonary function--a randomized controlled clinical trial.

To determine the effectiveness and safety of Xinfeng Capsules (XFC) for the treatment of rheumatoid arthritis (RA) patients with decreased pulmonary function. 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. 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). 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.

Mechanism of Xinfeng Capsule on Adjuvant-Induced Arthritis via Analysis of Urinary Metabolomic Profiles.

We aimed to explore the potential effects of Xinfeng capsule (XFC) on urine metabolic profiling in adjuvant-induced arthritis (AA) rats by using gas chromatography time-of-flight mass spectrometry (GC-TOF/MS). GC-TOF/MS technology was combined with multivariate statistical approaches, such as principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal projections to latent structures discriminant analysis (OPLS-DA). These methods were used to distinguish the healthy group, untreated group, and XFC treated group and elucidate potential biomarkers. Nine potential biomarkers such as hippuric acid, adenine, and L-dopa were identified as potential biomarkers, indicating that purine metabolism, fat metabolism, amino acid metabolism, and energy metabolism were disturbed in AA rats. This study demonstrated that XFC is efficacious for RA and explained its potential metabolomics mechanism.

Effect of Xinfeng capsule in the treatment of active rheumatoid arthritis: a randomized controlled trial

ObjectiveTo explore the use of Xinfeng capsule (XFC) in the treatment of active rheumatoid arthritis (RA) and its effect on immunoglobulin titer, B cell-activating factor (BAFF) and its receptor (BAFF-R). MethodsA multi-center randomized, double-blind, parallel-controlled study was conducted. 45 RA patients were assigned to two groups: one was treated with XFC plus the placebo for leflunomide (LEF) and the second group was treated with LEF plus XFC placebo, for 12 weeks. The clinical and laboratory parameters were collected at baseline and at 12 weeks. ResultsAfter 12 weeks of treatment, patients in the two groups all showed an therapeutic effect when ACR20, ACR50 and ACR70 were compared, but the differences between two groups were not significant (P < 0.05). The serum levels of IgG1, BAFF and BAFF-R in the XFC group were lower than those in the LEF group (P < 0.05). The level IgG subtypes correlated with clinical parameters; IgG2 levels positively correlated with C-reactive protein (CRP) (P < 0.01); IgG3 levels positively correlated with white blood cell count and CRP (P < 0.01); IgG4 levels positively correlated with Complement 4 (C4) (P < 0.01); the level of BAFF negatively correlated with Lymphocyte (LYMPH#) (P < 0.01); however, BAFF-R positively correlated with Platelet (PLT) and a1-acid glycoprotein (AGP) (P < 0.01). ConclusionXFC can regulate the level of BAFF/BAFF-R in active rheumatoid arthritis and improve the levels of immunoglobulins in RA patients.

Efficacy and safety of Xinfeng capsule in patients with rheumatoid arthritis: a multi-center parallel-group double-blind randomized controlled trial

ObjectiveTo evaluate the efficacy and safety of Xinfeng capsule in patients suffering rheumatoid arthritis (RA). MethodsA multi-center parallel-group designed, double-blind, randomized, controlled trial was conducted. Totally 304 RA patients were assigned to two groups: one group was administered Xinfeng capsule (XFC) plus the placebo of leflunomide and the other given leflunomide (LEF) plus the placebo of XFC for twelve weeks. The clinical and laboratory parameters were compared at baseline and fourth, eighth, and twelfth weeks. ResultsAfter twelve-week treatment, patients in two groups all showed some trend of effectiveness when compared in terms of American Rheumatism Association (ACR) recommended 20%, 50%, 70% improvement criteria, but it was insignificant. The validity in ameliorate modified disease activity score (DAS28) and laboratory indexes as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) were also found no difference. The score of health assessment questionnaire (HAQ), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and quality of life questionnaire with rheumatoid arthritis (RAQOL) both lower than the first week and the changes showed no difference. However, the score of SDS dropped more in XFC group than in the other. A total of 147 adverse reaction cases were reported, which shows no difference between the two groups. The most common adverse reactions were hepatic impairment, anemia, leukocytopenia, epigastric discomfort and phalacrosis. ConclusionXFC demonstrated better improvement in the scores of SDS and compared with those of LEF group.

Quantitative research on toxic component-wilforlide A in Xinfeng capsules before and after compatibility

Objective To study the content changes of wilforlide A in Xinfeng capsules before and after compatibility. Methods The content of wilforlide A was determined in Xinfeng capsules ester content and in Tripterygium wilfordii Hook.f.single solution by TLCS method. Developing solvents: chloroform and methanol(85:1), scanning wavelength:230 nm. Results Wilforlide A showed a good linear relationship in 1.700- 5.100μg, the regression equation is Y= 1 118.766+ 3 253.751X(r= 0.999). The average recovery of the wilforlide A in Xinfeng capsules was 102.84%, and RSD was 3.64%. The average recovery of the wilforlide A in the Tripterygium wilfordii Hook.f.single decoction was 98.14%, and RSD was 2.21%, compatibility levels before and after the change(compatibility with 0. 179mg/g,0.136mg/g after compatibility). Conclusion The established TLCS method was simple, specific and accurately quantitative. The comparative study found that the compatibility of Xinfeng capsules Tripterygium reduced the content of wilforlide A, which may be related to decreasing toxicity. Key words: Xinfeng Capsules; Wilforlide A

Research of Xinfeng Capsule on Pulmonary Function in Adjuvant Arthritis Rats Based on the Effects of B, T Cell Immunity

Objective: to observe the effects of Xinfeng Capsule on adjuvant arthritis rat model of pulmonary function, B, T cell immunity. Methods 40 rats were randomly divided into normal, model, Tripterygium Glycosides tablet and XFC group. Except the normal group, the other rat’s right rear paw intradermal injection of Freund’s complete adjuvant induced arthritis in 0.1 mL. Inflammation induced 19 d after administration, the normal group, the model groups were given physiological saline, rats in the treatment group were given of Xinfeng Capsule (2.4 g/kg), Tripterygium Glycosides tablet (10 mg/kg), once a day, continuous administration of 30D. Joint inflammation in rats was observed performance, flow cytometry detection of peripheral blood B, T lymphocyte attenuator (BTLA), regulatory T cells (Treg) and surface markers of forkhead transcription factor (FoxP3) expression was detected by Western blotting, synovial membrane, lung tissue BTLA, FoxP3. Results compared with the normal group, model group of rat paw swelling degree, arthritis index increased; pulmonary function, reduce the expression levels of peripheral blood BTLA, Tregs and BTLA in pulmonary tissue, synovium, FoxP3 (P <0.05 or P <0.01). While the XFC group rat paw swelling and arthritis index lower than the model group, pulmonary function, BTLA, Tregs and FoxP3 increased (P <0.05 or P <0.01); Xinfeng capsule group is better than control group (P <0.05) medicine Tripterygium wilfordii. Conclusion of Xinfeng capsule may be through upregulation of BTLA, Tregs, and FoxP3 expression, reduce the stimulation of inflammatory mediators in the lung tissue and improve the lung function of rats with adjuvant arthritis.

Xinfeng capsule improves pulmonary function in ankylosing spondylitis patients via NF-κB-iNOS-NO signaling pathway

ObjectiveTo study changes in the nuclear factor-κB p65 (NF-κB p65)-inducible nitric oxide synthase (iNOS)-nitric oxide (NO) signaling pathway and the effects of Xinfeng capsules (XFC) in patients with ankylosing spondylitis (AS) MethodsOne hundred twenty patients with AS were randomly divided into an XFC group and a Salazopyrin group. Sixty health subjects were included as a normal control group. In the two treatment groups, pulmonary functional parameters, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), maximal voluntary ventilation (MVV), peak expiratory flow (PEF), forced expiratory flow at 25% of forced vital capacity (FEF25), forced expiratory flow at 50% of forced vital capacity (FEF50), and forced expiratory flow at 75% of forced vital capacity (FEF75) were determined. Enzyme linked immunosorbent assays were used for detection of the serum oxidative stress indexes, NF-κB p65, iNOS, NO, reactive oxygen species (ROS), reactive nitrogen species (RNS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), total antioxidative capacity (TAOC) and interleukin-4 (IL-4), IL-10, IL-1β, and tumor necrosis factor-α (TNF-α) contents. Westergren's method was used for determination of erythrocyte sedimentation rate (ESR). High-sensitivity C-reactive protein (Hs-CRP) was detected with a 7060 full-automatic biochemical analyzer (Hitachi, Japan). ResultsThe clinical therapeutic effect in the XFC group was significantly superior to that in the Salazopyrin group (P<0.01). Compared with the normal control group, FEV1, MVV, PEF, FEF50, FEF75, SOD, CAT, TAOC, IL-4, IL-10 were significantly lower, and NF-κB p65, iNOS, NO, ROS, RNS, MDA, IL-1β, TNF-α, ESR, and Hs-CRP significantly higher in patients with AS (P<0.01 or P<0.05). Compared with before treatment, FEV1, MVV, PEF, FEF50, FEF75, SOD, CAT, TAOC, IL-4, and IL-10 were significantly increased, and NF-κB p65, iNOS, NO, ROS, RNS, MDA, IL-1β, TNF-α, ESR, CRP, visual analog scales (VAS), Bath ankylosing spondylitis disease active index, Bath ankylosing spondylitis functional index, and Bath ankylosing spondylitis global index significantly decreased in the two treatment groups after treatment (P< 0.01 or P<0.05), with significant differences between the XFC and Salazopyrin groups (P<0.01 or P<0.05). Spearman correlation analysis indicated that FEV1, MVV, PEF, FEF50, and FEF75 were positively correlated with SOD, CAT, TAOC, IL-4, and IL-10, and were negatively correlated with NF-κB p65, iNOS, NO, ROS, RNS, MDA, IL-1β, TNF-α, ESR, and CRP. ConclusionPatients with AS have local pathologic changes in the spinal cord and other joints. They also have decreased pulmonary function, which is negatively correlated with the NF-κB-iNOS-NO signaling pathway, oxidative indexes, and inflammatory factors. XFC improves rigidity and pain in spinal joints and other symptoms, laboratory indexes, and pulmonary function. The mechanism is possibly related to inhibition of the NF-κB-iNOS-NO signaling pathway.

Use of Xinfeng capsule to treat abarticular pathologic changes in patients with rheumatoid arthritis

ObjectiveTo observe the influence of Xinfeng-capsule (XFC) on abarticular pathologic changes (APCs) and other indices of patients with rheumatoid arthritis (RA) and explore the mechanism of action of XFC in improving such changes. MethodsThree-hundred RA patients were divided randomly into a treatment group (n=150) and control group (n=150). A normal control (NC) group (n=90) was also created. Changes in cardiac function, pulmonary function, anemia indices and platelet parameters of RA patients were measured. Curative effects of the two groups were compared, and comparison carried out with the NC group. ResultsIn 300 RA patients, late diastolic peak flow velocity (A peak) was much higher (P<0.01) and early diastolic peak flow velocity (E peak), E/A, and left ventricular fraction shortening much lower (P<0.01) than those in the NC group. Vital capacity (VC), forced vital capacity in one second, forced vital capacity (FVC), maximal voluntary ventilation (MVV), maximal expiratory flow in 50% of VC (FEF50) and FEF75 were lowered remarkably (P< 0.05 or P<0.01). Platelet count (PLT), plateletcrit (PCT) and mean platelet volume (MPV) increased markedly (P<0.05 or P<0.01), and hemoglobin (Hb) level decreased significantly (P<0.05). After XFC treatment, the A peak and PLT and PCT were much lower (P<0.05), and E/A and the number of red blood cells as well as Hb level were much higher (P< 0.05), as were FVC, MVV and FEF50 (P<0.05 or P< 0.01), in the treatment group than those in the NC group. Total score of pain and swelling in joints, uric-acid level and high-sensitivity C-reactive protein level were much lower, and superoxide dismutase level as well as the number of CD4 + CD25 + regulation T cells (Treg) and CD4 + CD25 + CD127-Treg were much higher (P<0.05 or P<0.01) in the treatment group than those in the NC group. ConclusionRA patients with pathologic changes in joints also suffer from lower cardiac and pulmonary functions and from parameters of anemia and platelet factors. XFC can improve the symptoms of RA patients, ameliorate their cardiac and pulmonary functions and reduce the parameters of anemia and platelet factors. XFC lowers the immune inflammatory reaction to improve APCs in RA patients.

Effects of Xinfeng Capsule on the expression of platelet derived growth factor in synovium of adjuvant arthritis rats.

To observe the effects of Xinfeng Capsule (, XFC) on platelet parameters in peripheral blood and expression of platelet derived growth factor (PDGF) in synovium of adjuvant arthritis (AA) rats. A total of 40 male Sprague-Dawley (SD) rats were randomized into 5 groups: normal control (NC), AA model control (MC), methotrexate (MTX) treatment, Tripterygium wilfordii polycoride tablet (TPT) treatment, and XFC treatment. Excluding the NC group, the AA model was induced by intracutaneous injection of 0.1 mL Freund's complete adjuvant in the right hind limb. Induction of AA and the effects of drug treatments were assessed by voix pedis swelling, arthritis index (AI), body mass, and the pathological changes of joints and cartilage with a light microscopy. Platelet parameters in peripheral blood were detected with an automated hematology analyzer. PDGF in synovium was detected with immunohistochemical methods and PDGF mRNA expression in synovium was detected with reverse transcription polymerase chain reaction. Compared with the NC group, the MC group had significantly increased voix pedis swelling, AI, platelet (PLT) and plateletcrit (PCT) in peripheral blood and PDGF as well as PDGF mRNA in synovium (all P<0.01) and the joint cartilage was also highly degenerated. Compared with the MC group, the 3 treated groups had significantly decreased voix pedis swelling, AI, PLT, PCT, PDGF, and PDGF mRNA (P<0.01). The body mass in the XFC group was significantly higher than those in MTX and TPT groups (P <0.05). The levels of PLT, PCT, PDGF, and PDGF mRNA in the XFC group showed a decreasing tendency with no significant difference compared with the MTX and TPT groups (P >0.05). PDGF and PDGF mRNA of AA rats were positively correlated with voix pedis swelling, AI, PLT, and PCT (P <0.05 or P <0.01). The expression and biosynthesis of PDGF increase in the synovium of AA rats and correlate with voix pedis swelling, AI, PLT, and PCT. XFC can decrease the levels of PDGF, PDGF mRNA, PLT, and PCT, thereby mitigating inflammation induced by platelet activation and reducing voix pedis swelling and the AI in AA rats.

Effect of Xinfeng capsule on pulmonary function in a adjuvant arthritis rat model

ObjectiveTo observe the relationship between reduced pulmonary function and regulatory T cells (Tregs) and helper T cells (Th)1/Th2 drift in a rat model of adjuvant arthritis (AA), and to study the impact of Xinfeng capsule (XFC) on pulmonary function and investigate the mechanism of action. MethodsForty rats were randomly divided into normal control group (NC), model control group (MC), Tripterygium glycosides tablet group (TPT), and XFC group, with 10 in each. Except for the NC group, AA was induced in all rats by intracutaneous injection of 0.1 mL Freund's complete adjuvant in the right paw. On the 19th day after modeling, the NC and MC groups were given physiological saline (0.9%), while the TPT and XFC groups were given TPT (10 mg/kg) and XFC (2.4 g/kg), once daily, respectively. Thirty days after administration, changes in paw swelling, arthritis index (AI), pulmonary function, levels of serum γ-interferon (IFN-γ) and interleukin (IL)-4, Tregs in peripheral blood, and IFN-γ, IL-4, Forkhead box transcription factor 3 (FoxP3) in lung tissue were observed by enzyme-linked immunosorbent assay, flow cytometry, polymerase chain reaction, and western blot. ResultsCompared with the NC group, paw swelling, AI, IFN-γ, and Th1/Th2 were increased, and pulmonary function parameters, IL-4, FoxP3 were decreased significantly in the MC group (P<0.05 or P< 0.01). Pulmonary function parameters, Treg, IL-4, FoxP3 (and mRNA) were higher, and paw swelling, AI, and IFN-γ (and mRNA) were lower in the XFC group than those in the MC group. The XFC group was also much better than the TPT group in improving pulmonary function, FoxP3 mRNA, IFN-γ, IL-4, Th1/Th2, and IL-10 (P<0.05 or P<0.01). ConclusionXinfeng capsule can improve pulmonary function by regulating the levels of Tregs, inhibiting the activation of Th1 to Th2 cells, inducing drift, maintaining cell immune suppression, correcting the imbalance of Th1/Th2, and reducing inflammatory mediators.

Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis: study protocol of a multicenter randomized controlled trial

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. 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. The result of this trial will help to evaluate whether Xinfeng Capsule is effective and safe in the treatment of RA. This trial has been registered in ClinicalTrials.gov. The identifier is NCT01774877.

Effect of Xinfeng Capsule on lung function in rats with adjuvant-induced arthritis and its mechanism

To investigate the effects of Xinfeng Capsule (XFC) on pulmonary function and related mechanism in adjuvant-induced arthritis (AA) rats. 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. 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). 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.

Effects of Xinfeng capsule on pulmonary function based on treg-mediated notch pathway in a rat model of adjuvant arthritis

ObjectiveTo observe the impact of xinfeng xapsule (XFC) on pulmonary function in a rat model of adjuvant arthritis (AA) and to investigate the mechanism of action. MethodsForty rats were randomly divided into four groups of ten: normal control (NC); model control (MC); tripterygium glycosides tablet (TPT); and xinfeng capsule (XFC). Except for the NC group, AA was induced in all rats by intracutaneous injection of 0.1 mL Freund's complete adjuvant in the right paw on the 19th day. NC and MC groups were given (0.9%) physiological saline. The TPT and XFC groups were given TPT (10 mg/kg) and XFC (1.2 g/kg), respectively. Thirty days after administration, changes in paw edema (E), the arthritis index (AI), pulmonary function, levels of regulatory T-cells (Treg), ultrastructure of lung tissue, and expression of Notch receptors and ligands in lung tissue were observed. ResultsIn the MC group, E and the AI were increased and pulmonary function significantly decreased; the structure of alveolar type-II cells was damaged; ratios of Treg in peripheral blood were reduced; and expression of Notch receptors such as Notch3 and Notch4 and ligands such as Delta1 in lung tissue were significantly increased whereas expression of Notch1, Jagged1 and Jagged2 were significantly decreased. After intervention with XFC, E and the AI were decreased; pulmonary function was enhanced; the structure of alveolar type-II cells was improved; and expression of Treg, Notch1, Jagged1, Jagged2 was elevated, whereas that of Notch3, Notch4 and Delta1 was reduced. ConclusionXFC can not only inhibit E and the AI and improve joint symptoms, it can also improve pulmonary function and reduce inflammation in lung tissue. These actions could be carried out through increases in the expression of Treg, Notch receptors (Notch1) and ligands (Jagged1, Jagged2), and reductions in the expression of Notch3, Notch4 and Delta1. These phenomena would reduce the deposition of immune complexes and the inflammatory response in lung tissue, thereby improving joint symptoms and pulmonary function.

Effects of xinfeng capsules on expression of platelet granule membrane protein 140 and platelet cluster of differentiation 40 ligand in peripheral blood of adjuvant arthritis rats.

Platelet GMP-140 and CD40L as specific markers of platelet activation play an important role in the morbidity and development of rheumatoid arthritis. The expression of GMP-140, CD40L increases in peripheral blood of AA rats. And they have correlation with voix pedis' swelling, AI. XFC could inhibit the inflammatory response through inhibiting platelet activation of AA rats, which means decreasing the expression of GMP-140, CD40L in peripheral blood. So, the voix pedis' swelling and AI were decreased as the result.

Effects of Chinese herbal medicine Xinfeng Capsule on expressions of platelet-activating factor and interleukins 6 and 17 in peripheral blood of rats with adjuvant arthritis

To observe the levels of platelet-activating factor (PAF), interleukin-6 (IL-6) and IL-17 in peripheral blood of rats with adjuvant arthritis (AA), and the effects of Xinfeng Capsule (XFC), a compound traditional Chinese herbal medicine. A total of 40 male Sprague-Dawley rats were randomized into normal control group, model group, methotrexate (MTX) group, Tripterygium Wilfordii polycoride Tablet (TPT) group, and XFC group, respectively. AA was induced in rats by intracutaneous injection of 0.1 mL Freund's complete adjuvant in the right hindlimb. Contents of PAF, IL-6 and IL-17 in peripheral blood were measured by enzyme-linked immunosorbent assay. Body weight of rats, paw swelling and arthritis index (AI) were also observed. Compared with the normal control group, the levels of PAF, IL-6 and IL-17 in peripheral blood, paw swelling and AI were significantly increased in the model group (P<0.01). Compared with the model group, levels of PAF, IL-6 and IL-17, paw swelling and AI of the three drug-treated groups were significantly decreased (P<0.01). The body weight of the XFC group was significantly higher than those of the MTX- and TPT-treated groups. Compared with the MTX- and TPT-treated groups, level of PAF in the XFC group was significantly increased (P<0.05). The level of PAF in peripheral blood of the AA rats was positively correlated with IL-6 and IL-17 levels in peripheral blood, paw swelling and AI (P<0.01). The expression of PAF increases in peripheral blood of rats with AA, and it correlates with IL-6, IL-17, paw swelling and AI. XFC can decrease the expression of PAF, restrain infection induced by the activation of platelets, decrease the levels of IL-6 and IL-17, and hence decrease the paw swelling of rats with AA.

Effect of Xinfeng Capsule (新风胶囊) on the cardiac function in patients with rheumatoid arthritis

To study the changes in cardiac function of rheumatoid arthritis (RA) patients and: to observe the effect of xinfeng capsule ( XFC) on them. Sixty-eight RA patients were: randomly assigned to two groups by a lottery: 38 patients in the treatment group treated orally with XFC, 3 capsules, thrice a day, and 30 in the control group treated with fengshi gutong capsule (FSGTC), 4 capsules, twice a day, 30 days as one course of treatment, and two courses were given for both groups. A normal control (NC) group including 20 healthy subjects was set up. The clinical efficacy was compared between the two treated groups. The changes in cardiac function, including early diastolic peak flow velocity (E), late diastolic peak flow velocity (A), left ventricular fraction shortening (FS), and E/A, as well as uric acid (UA), erythrocyte sedimentation rate (ESR), α-acid glycoprotein (α-AGP), and hypersensitive C-reaction protein (hs-CRP), were observed. The regulation T cell was determined with flow cytometry. (1) The total effective rate in the treatment group and the control group was 92.1%: (35/38) and 70.0% (21/30), respectively. Significant difference was shown between them (P<0.05). (2) <Compared with those of the NC group, E peak, E/A ratio, and FS of RA patients were lower (P<0.01), while <A peak was higher (P<0.01). Moreover, A peak of the treatment group after treatment was significantly lower <(P<0.05) and E/A ratio was significantly higher (<P<0.05) as compared with those of the control group. (3) The <improvement in the treatment group in reducing UA and hs-CRP was superior to those of the control group (P<0.05). In addition, the improvement in α-AGP, CD4 <CD4(+)CD25 CD25(+) Treg, and CD4 CD4(+)CD25 CD25(+)CD127 CD127(-)Treg of the treatment group was obvious as compared with the control group, although the difference was not statistically significant. The descendent of cardiac function exists in RA patients. XFC could improve cardiac: function of RA patients, which is superior to FSGTC. Its mechanism may be related to its effect on raising CD4 CD4(+)CD25 CD25(+)Treg and CD4 CD4(+)CD25 CD25(+)CD127(-) Treg cells, decreasing UA, α-AGP, and hs-CRP levels, reducing immune inflammation, adjusting the overall balance of immune response, and thus improving the cardiac function of RA patients.