Adjuvant Arthritis Model Research Articles

A Novel Chinese Medicine, Xinfeng Capsule, Modulates Proinflammatory Cytokines via Regulating the Toll-Like Receptor 4 (TLR4)/Mitogen-Activated Protein Kinase (MAPK)/Nuclear Kappa B (NF-κB) Signaling Pathway in an Adjuvant Arthritis Rat Model.

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease targeting joints. This research aimed to explore the effects of Xinfeng capsules (XFC) on cardiac injury in adjuvant arthritis (AA) model rats and assessed the associated mechanism.Material/MethodsAn adjuvant arthritis (AA) rat model was established by intracutaneously injection with Freund’s complete adjuvant (FCA). Model rats were divided into 4 groups: an AA model group, an astragalus polysaccharides (APS) group, a methotrexate (MTX) group, and an XFC and triptolide (TPT) group. Hematoxylin-eosin (HE) staining was used to observe histopathologic changes. TUNEL assay was utilized to evaluate the apoptosis of cardiomyocytes. ELISA was utilized to evaluate levels of tumor necrosis factor α (TNF-α), interleukin 17 (IL-17), and interleukin 6 (IL-6) in myocardial tissues. Quantitative RT-PCR (qRT-PCR) was used to detect microRNA-21 (miRNA21) levels. Mitogen-activated protein kinase (MAPK)/p38, Toll-like receptor 4 (TLR4), and nuclear kappa B (NF-κB)/p65 levels were evaluated using Western blot.ResultsXFC significantly improved proinflammatory response compared to the AA model group (p<0.05). XFC treatment significantly decreased the number of cells staining TUNEL-positive compared with the model group (p<0.05). XFC treatment significantly reduced TNF-α, IL-17, and IL-6 levels in myocardial tissues compared to the model group (p<0.05). Levels of miRNA21 were significantly lower in the XFC group compared to the AA model group (p<0.05). TLR4, MAPK/p38, and NF-κB/p65 expression levels were significantly lower in the XFC group than in the model group (p<0.05).ConclusionsXinfeng capsule, a traditional Chinese medicine preparation, protects against cardiac injury in AA rats by modulating proinflammatory cytokines expression via the TLR4/MAPK/NF-κB signaling pathway.

Assessing the development and treatment of rheumatoid arthritis using multiparametric photoacoustic and ultrasound imaging.

Rheumatoid arthritis (RA), characterized by polyarthritis, is a chronic, systemic and inflammatory autoimmune disease. In this study, we developed a dual-modality multiparametric photoacoustic and ultrasound imaging technique, and successfully derived multiple parameters such as relative concentration of total hemoglobin (CHbT ), ratio of angiogenesis, joint size and area of synovia to assess the development and treatment of RA. We established a model of adjuvant arthritis using a total number of 15 rats and randomly divided them into three groups: (a) targeted group in which the rats received targeted antirheumatic drugs; (b) nontargeted group in which the rats were treated with nontargeted antirheumatic drugs; (c) control group. We longitudinally monitored the joints of the rats in all three groups for up to 20 days and carried out quantitative analysis to evaluate the development and treatment of RA based on the derived parameters. The results suggest that the proposed dual-modality imaging technique is able to assess the effectiveness of the RA treatment using quantitative hemodynamic and morphological parameters. To show the clinical feasibility of this technique, we performed in vivo joint studies of health volunteers to visualize both structures and inside hemodynamics of the distal interphalangeal joint.

Electroacupuncture on ST36 and GB39 Acupoints Inhibits Synovial Angiogenesis via Downregulating HIF-1α/VEGF Expression in a Rat Model of Adjuvant Arthritis.

Introduction. The hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) play a key role in synovial angiogenesis in rheumatoid arthritis (RA). Therefore, this study aimed to test the hypothesis that electroacupuncture (EA) may inhibit RA synovial angiogenesis via HIF-1α/VEGF expression. Methods. Sprague-Dawley rats were randomly distributed to 4 groups: control, adjuvant arthritis (AA), AA+electroacupuncture (AA+EA), and AA+sham EA groups. AA model was induced by injection of Freund's complete adjuvant in bilateral hind footpad. 3 days after injection, EA was delivered to the acupoints Zusanli (ST 36) and Xuanzhong (GB 39) once every two days for a total of 8 times in the AA+EA group, while sham EA treatment was applied in the AA+sham EA group. The arthritis score, paw volume, and H&E staining for each animal were measured. CD34 expression in synovial tissue of ankle joint was observed by immunohistochemistry. HIF-1α and VEGF mRNA and protein levels in synovial tissue were determined by real-time quantitative PCR and Western blot, respectively. Results. Compared with rats in AA group, EA stimulation significantly decreased arthritis scores, paw volume, and pathological damage of synovial tissues. Moreover, EA markedly suppressed the synovial angiogenesis of AA rats, as evidenced by reduced CD34 positive expression. Furthermore, EA significantly reduced HIF-1α and VEGF mRNA and protein levels in synovial of AA rats. Finally, the CD34 expression in synovial tissue was positively correlated with HIF-1α and VEGF protein levels. Conclusion. EA on ST36 and GB39 acupoints can effectively inhibit synovial angiogenesis in the AA rat model via downregulating HIF-1α/VEGF expression.

Leaves and stems of Capparis erythrocarpos, more sustainable than roots, show antiarthritic effects

Ethnopharmacological relevanceCapparis erythrocarpos is a medicinal plant used widely in many parts of Africa for the management of pain and inflammatory conditions such as rheumatoid arthritis. Its wide range of use, popularity and high value, make C. erythrocarpos containing products a target for economically driven adulteration. This is made worse, by the use of roots, which are unsustainable plant parts. In addition, the mechanism of anti-inflammation is not clearly understood. Aim of the studyTherefore, this study comparatively evaluated the anti-arthritic and analgesic effects of the leaves, stems and roots of C. erythrocarpos, while elucidating the mechanism of anti-inflammation. Materials and methodsUsing the complete Freund's adjuvant arthritis model, the antiathritic effects were evaluated. The analgesic effects were determined by measuring responses to Von Frey filament number 9. Effects of C. erythrocarpos extracts on the levels of Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α) were determined using ELISA. Haematological and serum biochemical assays were also carried out. ResultsThe leaf, stem and root extracts significantly reduced paw volumes with ED50 values (mg/kg) of 182.5, 181.5 and 36.4 respectively. The leaf extract at a dose of 100 mg/kg showed substantial analgesic activity with a decrease in the percentage response to Von Frey filament 9. However, there was no significant difference in activities of the leaf, stem and root extracts. Results from ELISA assays show that lower doses of the stem extracts reduce levels of IL-6. Lower doses of all extracts also reduce TNF-α levels. Haematological analysis showed extracts reversed elevated WBC and platelet levels. Toxicity evaluation with kidney and liver function tests indicated no significant differences between the treatment and control groups. ConclusionsThe leaves and stems, just as the roots, have antiarthritic and analgesic effects and can be used as more sustainable alternatives to the roots. This will support the continuous growth of the industry that has developed around C. erythrocarpos.

Investigation of gene expression profiles in a rat adjuvant arthritis model suggests an effective role of triptolide via PI3K-AKT signaling.

Rheumatoid arthritis (RA) is a common systemic autoimmune disease mainly involving the formation of a synovial pannus, for which no effective treatment is available. In order to study the molecular biological mechanisms underlying the inhibition of RA synovial pannus by triptolide, differentially expressed genes in synovial tissues from an adjuvant arthritis (AA) rat model with and without triptolide treatment were detected in an mRNA microarray profile produced by Agilent Technologies and verified by reverse transcription-quantitative polymerase chain reaction analysis (RT-qPCR). An AA model was established by subcutaneously injecting 0.1 ml Freund's complete adjuvant daily for 18 days and scored by arthritis index assessment. Subsequently, triptolide (0.4 mg/kg) or an equivalent amount of saline was administered daily for 14 days. At the end of the experiment, synovial tissues were obtained from the ankle joints of the rats' hind legs. Total RNA was extracted and purified, and microarray hybridization was used to obtain the gene expression profile for RA with and without triptolide treatment. A total of 48 genes were identified to be differentially expressed between the treatment and model groups, including 32 upregulated and 16 downregulated genes. The possible signaling pathways associated with the effect of triptolide were investigated by Gene Ontology and pathway analysis, revealing that the phosphoinositide-3 kinase (PI3K)/AKT signaling pathway has a key role in the proliferation and apoptosis of synovial cells in RA joints. Reverse transcription-quantitative polymerase chain reaction analysis was applied to confirm the aberrant expression of key mRNAs and revealed that vascular endothelial growth factor (VEGF) A and C1q and tumor necrosis factor related protein 3 (C1QTNF3) were downregulated in the treatment group compared with the model group (P<0.05). In conclusion, triptolide may exert its effects against RA via the PI3K/AKT pathway and has an inhibitory effect on the expression of VEGFA and C1QTNF3, thus are potentially associated with the occurrence and development of RA.

Identification of Imidazo[1,2-b]pyridazine Derivatives as Potent, Selective, and Orally Active Tyk2 JH2 Inhibitors.

In sharp contrast to a previously reported series of 6-anilino imidazopyridazine based Tyk2 JH2 ligands, 6-((2-oxo-N1-substituted-1,2-dihydropyridin-3-yl)amino)imidazo[1,2-b]pyridazine analogs were found to display dramatically improved metabolic stability. The N1-substituent on 2-oxo-1,2-dihydropyridine ring can be a variety of alkyl, aryl, and heteroaryl groups, but among them, 2-pyridyl provided much enhanced Caco-2 permeability, attributed to its ability to form intramolecular hydrogen bonds. Further structure-activity relationship studies at the C3 position led to the identification of highly potent and selective Tyk2 JH2 inhibitor 6, which proved to be highly effective in inhibiting IFNγ production in a rat pharmacodynamics model and fully efficacious in a rat adjuvant arthritis model.

Cubic and hexagonal liquid crystals as drug carriers for the transdermal delivery of triptolide

The purpose of this study was to develop and evaluate triptolide-loaded cubic and hexagonal liquid crystals for transdermal drug delivery systems (TDDSs). We prepared and characterized triptolide-loaded lyotropic liquid crystals and evaluated for their percutaneous permeation properties in vitro and in vivo. We then used the adjuvant arthritic rat model and HaCaT cells to analyze the pharmacodynamics and conduct cell-stimulating studies of these liquid crystals. The optimized preparations were identified as cubic and hexagonal phase structures, respectively. Moreover, the in vitro percutaneous penetration studies demonstrated that compared to the homemade triptolide gel, cubic and hexagonal liquid crystals could significantly increase the percutaneous cumulative penetration of drugs within 48 h. Besides, the results of skin-blood synchronous microdialysis showed that the triptolide concentration in skin was higher than that in blood, and the cubic and hexagonal liquid crystals significantly increased the bioavailability of triptolide. Triptolide-loaded cubic and hexagonal liquid crystals presented excellent anti-arthritic effects, alleviating paw swelling and inhibiting inflammation by downregulating the levels of TNF-α and IL-1β. In vitro cell-stimulating studies displayed that triptolide-loaded cubic and hexagonal liquid crystals exhibited no obvious toxicity, which exhibited that triptolide-loaded cubic and hexagonal liquid crystals were remarkable biocompatibility. Collectively, triptolide-loaded cubic and hexagonal liquid crystals represented a promising candidate for rheumatoid arthritis therapy.

A DOSE RESPONSE STUDY FOR THE ANTI ARTHRITIC EFFECT OF RESVERATROL IN A MODEL OF ADJUVANT ARTHRITIS IN RATS

The aim of this study was to investigate the effects of resveratrol (Res) on the clinical symptoms of rheumatoid arthritis in rats with adjuvant arthritis (AA). An AA model was established by injection of complete Freund’s adjuvant (CFA). Ankle diameter, paw volume, arthritic index, gait score as well as paw histopathological examination were assessed to determine the anti-arthritic effect of Res. Resveratrol, at dose 50 mg/kg, was able to significantly alleviate rheumatoid related paw swelling and ankle diameter and decrease both arthritic and gait scores. Besides, a significant reduction of inflammatory cell infiltration in the ankle joint tissue was shown by histopathological examination. These findings confirm the anti-rheumatic activity of Res which can be correlated to its anti-inflammatory activity.

Development of a daphnetin transdermal patch using chemical enhancer strategy: insights of the enhancement effect of Transcutol P and the assessment of pharmacodynamics

Objective: The aim of this study was to develop a drug-in-adhesive patch for transdermal delivery of daphnetin (DA), which is a coumarin derivative in Girald Daphne, and to investigate the role of Transcutol P (TP) in the release and percutaneous permeation processes of DA.Methods: Backing films, permeation enhancers and enhancer content in the transdermal patch were investigated through in vitro experiments using rat skin. Anti-inflammatory and analgesic effects of the optimized formulation were evaluated using the adjuvant arthritis model and the pain model induced by acetic acid, respectively. In addition, the enhancement effect of TP was investigated using differential scanning calorimetry (DSC), FTIR, and molecular dynamic simulation.Results: The optimal formulation, composed of DURO-TAK® 87-2852, CoTranTM 9680, 1% DA, and 10% TP showed anti-inflammatory and analgesic effects. It was found that TP only promoted the release process of DA from its transdermal patch. Furthermore, the decrease of interaction between drug and pressure sensitive adhesive (PSA) as well as the improvement of PSA mobility due to TP addition were the main factors that enhanced the release of DA from patch.Conclusions: This study successfully used TP to develop a DA patch with good anti-inflammatory and analgesic effects, proving that TP promotes the release of DA by reducing the interaction between DA and PSA and increasing the mobility of PSA.

Assessment of anti-arthritic potential of ethanolic extract and its fractions of aerial parts of Alhagi pseudalhagi (Bieb.) Desv. in animal models

The plant Alhagi pseudalhagi (Bieb.) Desv. (family: Fabaceae) have long been used traditionally mainly for the treating rheumatism and gout in Indian system of medicine. The present work explores the phytochemical screening and effect of the crude extract of the aerial parts of A. pseudalhagi and its fractions in different experimental models of arthritis. The dried pulverized aerial parts of the plant were extracted using 95% ethanol and water. The 95% ethanolic extract (APEE) was fractionated in four fractions including chloroform fraction (APC), ethyl acetate fraction (APEA), methanolic fraction (APM) and aqueous fraction (APA). Both extracts and all the four fractions were subjected to preliminary phytochemical screening and TLC. Hematological and biochemical parameters viz. measurement of paw volume, joint diameter, body weight, RBC, WBC, Platelets, CRP, RF, Hb, ALT, AST, ALP and Total protein were determined on APEE and APEA and justified by histopathological and radiological analysis. The anti-arthritic activity was evaluated using Formaldehyde induced arthritic model, Turpentine induced arthritic model and complete freund’s adjuvant arthritic model in wistar albino rats. The plant exhibited dose dependent anti arthritic effect in Formaldehyde, Turpentine induced and complete freund’s adjuvant arthritic model. The ethyl acetate fraction showed more significant effect as compared to the 95% ethanolic extract at 400 mg/kg body weight dose. A. pseudalhagi remarkably ameliorated altered hematological parameters, body weight and positively modified radiographic and histopathological changes.

Effect of Electroacupuncture in “Zusanli” and “Kunlun” Acupoints on TLR4 Signaling Pathway of Adjuvant Arthritis Rats

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Previous study suggested that toll-like receptor (TLR) signaling pathway contributes to the development and progression of RA. In recent years, acupuncture has become one of the most vital treatments of arthralgia. But little is known about the mechanisms of improving RA by acupuncture. The study studied the effect of electroacupuncture in "Zusanli" and "Kunlun" acupoints on the expression of TLR4, myeloid differentiation factor 88 (MYD88), and NF-κB in adjuvant arthritis rats to clarify the molecular mechanism of acupuncture of RA. A rat model of adjuvant arthritis was established with injection of 0.1 mL Freund complete adjuvant in the right hindlimb footpad. We next punctured the Zusanli and Kunlun acupoints with 0.25 × 40-mm acupuncture needles to 5-mm depth. Then, we performed electroacupuncture treatment for 28 days with frequency of 2 Hz and intensity of 2 mA, once a day and 30 minutes each time. Arthritis index and paw swelling were measured every week. FQ-PCR and western blot were used to detect the expression of TLR4, MYD88, and NF-κB. Paw swelling of rats injected with Freund complete adjuvant was more serious than that of the normal rats, which illustrated the successful establishment of adjuvant arthritis rat model. After treatment for 14 days, the paw swelling and joint symptoms score decreased, paw tissue inflammation eased in the rats of treatment group compared with the model group during the same period. After treatment for 28 days, the expression of TLR4, MYD88, and NF-κB in the ankle bone tissues decreased at both mRNA and protein levels. Stimulation with electric needle in Zusanli and Kunlun acupoints can reduce the expression of TLR4, MYD88, and NF-κB, which play an important role in treatment of adjuvant arthritis.

Micellar solubilisation enhances the antiinflammatory activities of curcumin and boswellic acids in rats with adjuvant-induced arthritis.

Native extracts of curcumin and boswellia are known to exert antiinflammatory properties but have poor bioavailability when given orally. Using advanced micellation technology, it has been possible to produce stable solubilisates of these extracts with markedly enhanced bioavailability. In the present study, we compared the chronic antiinflammatory activities of native and micellar curcumin in the rat adjuvant arthritis model, using diclofenac as a reference drug. Adjuvant arthritis was induced by injecting Freund's complete adjuvant (FCA) into the right hind paw of rats and monitoring paw volume over 3 wk. The drugs were given daily for 3 wk, starting from the day of adjuvant inoculation. The serum was collected at end of the experiment for the assay of inflammatory and oxidative stress parameters. Statistical comparisons between different groups were carried out by one-way analysis of variance followed by Tukey-Kramer multiple comparison test. Solubilized curcumin showed better antiinflammatory activity than its native form. The reduction in paw volume was reflected in corresponding changes in relevant mediators of inflammation like tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), myeloperoxidase (MPO), and lipid peroxidation markers. The combination of curcumin and boswellia solubilisates synergistically produced an even more potent therapeutic effect. The findings confirm that micellar solubilisation of curcumin and boswellia not only increases their bioavailability, but also enhances their biological activity. Micellar curcumin, in particular in combination with micellar boswellia, may thus represent a promising concomitant tool for antiinflammatory treatment and a potential antiinflammatory alternative to synthetic drugs.

The evaluation of the effectiveness of the application of bischofite-modified yellow clay (an experimental studi)

The topical problems in balneotherapeutics and health resort activities in general are the development of the yellow clay-based preparations enriched in the natural mineral bischofite and the investigation of their therapeutic effects with the purpose of improvement of their curative potential. The objective of the present study was to evaluate the effectiveness of the course of the experimental therapeutic applications of the yellow clay obtained by the open pit mining of its deposits located in the vicinity of Pyatigorsk and modified by the addition of bischofite. The experiments were carried out with the use of 57 eugamic Wistar male rats with adjuvant arthritis. The yellow clay supplemented with bischofite in various concentrations was applied in 12 procedures each 15 minutes in duration every other or every two days beginning from the 38th day of experimentally-induced arthritis. The animals were allocated to five groups as follows: group 1 included the healthy animals that served as controls (n=5), groups 2-5 were comprised of the animals with adjuvant arthritis. The animals included in group 2 served as the experimental model of adjuvant arthritis (n=8), those comprising group 3 were treated by the applications of yellow clay without additives (n=14), group 4 was composed of the animals with adjuvant arthritis treated by the applications of yellow clay containing 10% of bischofite (n=15), the animals in group 5 having adjuvant arthritis were treated by the applications of yellow clay containing 20% of bischofite (n=15). The study has demonstrated the reduction of the reactively enhanced relative abundance of, activated T-cells, and B-lymphocytes down to the respective control values in the animals with adjuvant arthritis after the course of applications of the yellow clay preparations. Simultaneously, normalization of the immunoregulatory index, IRI, (the T-helpers to cytotoxic T-lymphocytes ratio) was documented. The treatment was associated with the strong dependence of the interleukin (IL-1β) contents on the cortisol level and the well apparent relationship between the levels of interleukins and IRI. Specifically, the relation between IL-1β and IRI following the application of non-modified yellow clay was characterized as (r=+0.8, p=0.03) in comparison with the relation between IL 6 and IRI (r=+0.8, p=0.03) after the treatment with yellow clay containing 10% of bischofite or between IL 6 and IRI (r=+0.8, p=0.004) after the application of yellow clay containing 20% of bischofite. The results of the study give evidence of the immunomodulatory action of yellow clay modified by the addition of bischofite. They suggest the promising opportunities for the application of these preparations for the management and rehabilitation of the patients presenting with the diseases of the musculoskeletal system in the future.

Effect of Qianghuo Erhuang Decoction on T Regulatory and T Helper 17 Cells in Treatment of Adjuvant-induced Arthritis in Rats

QianghuoErhuang Decoction (QED) is an effective recipe in treating rheumatoid arthritis. The present study aimed to explore the effects of QED on Treg and Th17 in adjuvant arthritis (AA) model. The study included 6 group rats: normal control group, AA group, AA + methotrexate (MTX) group, AA + high, moderate, and low dose QED groups. The arthritis score was significantly decreased in the MTX and high-dose QED groups compared with the AA group on days 24 and 28 (P < 0.01), respectively. The synovial tissue inflammation was attenuated by histological observation, and the proliferation of splenocytes was significantly inhibited in MTX and high-dose QED groups (P < 0.01). High-dose QED can up-regulated the percentage of Treg cells (P < 0.01) and down-regulated the percentage of Th17 cells (P < 0.05). Notably, the serum levels of IL-6, IL-17 and TNF-α were significantly decreased, while TGF-β levels were apparently elevated compared with AA group (P < 0.05, P < 0.01). Interestingly, moderate and low-dose QED had no such similar effects. In summary, high-dose QED had a therapeutic effect against adjuvant arthritis and regulated the related cytokine levels in serum. The underlying mechanism might be mediated via restoration of the imbalance in CD4+ T lymphocyte subsets, Treg/Th17.

English

The present study seeks to evaluate the immunoregulatory effects of extracts of the root bark of Cassia sieberiana, a plant used in Ghana for various painful inflammatory conditions, in a modified adjuvant arthritis model induced by administration of very low dose of Mycobacterium tuberculosis (MT) – carrageenan mixture in the rat. A volume of 0.1 mg kg-1 heat killed MT in paraffin oil was mixed with equal volume of 0.05% (w/v, normal saline) carrageenan. A single intraplantar dose of 0.1 ml of the MT - carrageenan mixture was administered to experimental animals. Groups were administered extracts (20 to 200 mg kg-1, p.o.), dexamethasone (0.3 mg kg-1, p.o.) or vehicle an hour prior to the test and daily from test day till the 6th day. Paw volume (ml) of the injected hind limbs were measured using a plethysmometer, while paw withdrawal thresholds were determined using an analgesy meter. Serum levels of IL-1α, IL-6, IL-10 and TNF-α were determined via enzyme linked immunosorbent assay (ELISA). Results showed that the extracts attenuated the inflammation and hyperalgesia caused by the intraplantar injection of MT-carrageenan mixture in the rats in a dose-dependent fashion. Similarly, the extracts reduced the serum levels of IL-1α, IL-6 and TNF- α while increasing the levels of IL-10. It can be concluded that the anti-inflammatory activity of extracts of root bark of C. sieberiana may be attributable to their immunomodulatory effects via suppression of pro-inflammatory cytokines, TNF-α, IL-1α and IL-6; and elevation of the anti-inflammatory cytokine, IL-10 levels, in serum. Key words: Immunoregulatory, pro-inflammatory cytokines, TNF-α, adjuvant, C. sieberiana, IL-10.

Effects of Prunus tomentosa total flavone on adjuvant-induced arthritis

ABSTRACTTo investigate the effect and mechanism of Prunus tomentosa total flavone (PTTF) treatment on adjuvant arthritis (AA), the rat AA model was induced by a single intradermal injection of complete Freund's adjuvant (CFA) into the left ankle. The degree of lateral ankle swelling was measured by the foot volume method. The rats were sacrificed, the thymus and spleen were taken out and the organ index was calculated. Paraffin sections of the left ankle specimens were fabricated and the organization forms of the articular cartilage and synovium were observed. Kits were used to measure the serum nitric oxide (NO), NO synthase (NOS) and prostaglandin E2 (PGE2) content. After 18 days, the swelling degree of ankle joints in the dexamethasone group, the PTTTF 7.0 and 14 mg/kg groups were significantly lower than that in the model group (P < 0.05). The organ index in the dexamethasone group and the PTTF group were not statistically significantly different from that in the normal group (P > 0.05). Compared to the CFA model control group, the dexamethasone group and the PTTF each group had significantly less synovial proliferation and congestion. In these groups, the joint surface was smooth, with no obvious structural damage; the serum NO, NOS and PGE2 were significantly lower than in the control group (P < 0.01). The results indicated that PTTF at 7 and 14 mg/kg can effectively alleviate the secondary inflammatory response to AA in rats’ lateral ankle. The mechanism may be related to inhibition of the secretion of NO, PGE2 and NOS.

A Novel Brucine Gel Transdermal Delivery System Designed for Anti-Inflammatory and Analgesic Activities.

The seeds of Strychnos nux-vomica L., as a traditional Chinese medicine, have good anti-inflammatory and analgesic activities. However, it usually leads to gastrointestinal irritation and systemic toxicity via oral administration. In the study, it was discovered that a novel gel transdermal delivery system contained brucine, the main effective component extracted from Strychnos nux-vomica. Results showed that the brucine gel system inhibited arthritis symptoms and the proliferation of the synoviocytes in the rat adjuvant arthritis model, which indicated its curative effect for rheumatoid arthritis. Meanwhile, it significantly relieved the xylene-induced ear edema in the mouse ear swelling test, which manifested its anti-inflammatory property. Moreover, the brucine gel eased the pain of paw formalin injection in the formalin test, which demonstrated its analgesic effects. In addition, the brucine significantly inhibited lipopolysaccharide (LPS)-induced Prostaglandin E2 (PGE2) production without affecting the viability of cell in vitro anti-inflammatory test, which proved that its anti-inflammatory and analgesic actions were related to inhibition of prostaglandin synthesis. It is suggested that the brucine gel is a promising vehicle for transdermal delivery on the treatment of inflammatory disease.

Pharmacodynamic mechanism of modified Ganlu Yaoyu San intreatment of rheumatoid arthritis based on MAPK signaling pathway

According to the findings, modified Ganlu Yaoyu San has a good anti-inflammatory activity, and can significantly alleviate the degree of arthritis. Its therapeutic effect for rheumatoid arthritis may be related to the regulation of MAPK pathway of synovial cells. In the study, the rat adjuvant arthritis(AA) model was established to further investigate the pharmacodynamic mechanism for regulating MAPK pathway of synovial cells. Enzyme-linked immune assay was used to determine the serum TNF-α level of AA rats administered with drug for two weeks, synovial tissue protein kinases ERK1/2 and p38 content were determined by immunohistochemistry, synovial tissue JNK1, ERK1, p38 gene(mRNA) expression were detected with fluorescence quantitative PCR(RT-PCR) method. According to the results, after administration for two weeks, the levels of serum TNF-α of AA rat was significantly decreased(P<0.05). After administration for four weeks, the protein expressions of p38 and ERK1/2 in synovial tissue were reduced(P<0.05 or P<0.01), the gene expressions of JNK1, p38 and ERK1 in knee joint synovial tissue were reduced(P<0.05 or P<0.01). In conclusion, modified Ganlu Yaoyu San can effectively treat rheumatoid arthritis. Its mechanism might be related to the reduction of TNF-α levels in serum, protein expression of p38 and ERK1/2 in synovial tissue, and JNK1, p38 and ERK1 gene expressions, and regulation of MAPK pathway.

Anti-inflammatory activity of two varieties of pumpkin seed oil in an adjuvant arthritis model in rats

The aim of the present research was to evaluate the anti-inflammatory activity of pumpkin seed oils (PSOs) of an Egyptian and European variety, in a rat model of adjuvant arthritis. Edema thickness, plasma tumor necrosis factor-α (TNF-α) and erythrocyte sedimentation rate (ESR) were determined as inflammatory biomarkers while malondialdehyde (MDA) and total antioxidant capacity (TAC) were assessed as indicative of oxidative stress. Chromosomal aberration, sperm shape abnormalities, and DNA fragmentations are cytogenetic parameters which aid in tracing inflammatory and oxidative activity. Phenolic contents and β-carotene were determined in PSOs. The results showed elevated ESR, plasma TNF-α, plasma MDA, liver cellular DNA fragmentation, bone marrow chromosomal aberration, sperm shape abnormalities with a reduction in plasma TAC and body weight gain in an adjuvant arthritis control compared to a healthy control. Administration of low and high doses of either Egyptian or European PSO improved all the aforementioned parameters with variable degrees.

Effects of Tibetan medicine Manu-Xitang granules on the expression of prostaglandin E2 and TNF-α on adjuvant arthritis rats

Objective To study the effect of Tibetan Medicine Manu-Xitang granules on the expression of prostaglandin E2 and TNF-α on adjuvant arthritis (AA) rats. Methods A total of 60 rats were randomly divided into the control group, the model group, the Aspirin group, the low-, medium- and high- dose Manu-Xitang granules groups (each group with 10). Complete Freund's adjuvant method was used for the adjuvant arthritis model except the control group. All the groups started treatment at 8th day, and the treatment last 20 days. The low-, middle- high-dosage groups were treated with 2.0, 1.0, 0.5g/(kg body weight) Manu-Xitang granules, while the the Aspirin group with ASP (0.27 g/kg), control and medol groups with the equal volumn saline. The body weight, the swelling of primary side of arthritis index were observed. The levels of PGE2 and TNF-α were measured by ELISA. Results At 6th, 12th, 18th day, compared with the model group, the body weights in Aspirin group, the low-, middle-, high-dosage groups significantly increased (P<0.05 or P<0.01); at the 6th day, the foot swelling (0.40% ± 0.18%, 0.50% ± 0.25%, 0.55% ± 0.35% vs. 0.85% ± 0.15%) in the Aspirin group, middle-, and high-dosage groups significantly decreased (P<0.05 or P<0.01). And the PGE2 (0.66 ± 0.31 vs. 0.39 ± 0.11) and TNF-α (0.72 ± 0.24 vs. 0.50 ± 0.15) in the high- dose group were significantly lower than the model group (P<0.05). Conclusions The Tibetan medicine Manu-Xitang granules could treat AA through the changes of PGE2 and TNF-α. Key words: Tibetan drugs; Manu-Xitang granules; Adjuvant arthritis; Prostaglandin E2; Rats