CFA-induced Arthritic Rats Research Articles

Protective effect of Tecoma stans (L.) Juss.ex Kunth in CFA-induced arthritic rats

Ethnopharmacological relevanceTecoma stans (L.) Juss.ex Kunth (Bignoniaceae) is mainly found in tropical and subtropical regions of Africa and Asia. The leaves, flowers, roots, and bark are used to treat various aliments includes, skin infections, kidney problems, intestinal disorders, jaundice, toothaches, joint pain and repair cracked bones, antidotes for snake, scorpion, and rat bites. Aim of the studyThe objective of the study is to assess the anti-arthritic properties of T. stans leaf using Complete Freund's adjuvant (CFA)-induced rat. Materials and methodThe ethanol extract of T. stans leaf (ETSL) was subjected toGas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis for the identification of potential bioactive. The anti-arthritic activity was carried out by administering CFA (0.1 ml) into the sub-plantar surface of the right hind paw. The experimental animals were treated with indomethacin (10 mg/kg) and ETSL (250, 500 mg/kg) once a day orally for fourteen days. The arthritic parameters and hematological and biochemical parameters were evaluated using standard kit reagents. The levels of pro-inflammatory cytokines and inflammatory mediators were measured in blood serum. Antioxidant parameters were assessed in homogenized liver and joint tissues. Radiological and histopathological analysis of joint was performed. A computational molecular docking investigation of the phytoconstituents was conducted against COX-2, IL-1β, IL-6, and TNF-α receptors. ResultsThe ETSL at 500 mg/kg demonstrated significant (p < 0.01) restoration of arthritic parameters, hematological and biochemical indices and oxidative stress in CFA-induced rats which was further supported by radiological histological examination. In addition, there was significant (p < 0.05) reduction observed in pro-inflammatory cytokines, inflammatory mediators and up-regulation of anti-inflammatory cytokines in the treated group. Verbascoside was found to exhibit better biding affinities −10.4, −7.4, −7 and −6.2 kcal/mol against COX-2, IL-1β, TNF-α, and IL-6 respectively, confirmed through in silico study. ConclusionsThe observed outcome suggests that ETSL at a dosage of 500 mg/kg demonstrated notable anti-arthritic effects by suppressing pro-inflammatory cytokines and oxidative stress biomarkers. This effect could potentially be attributed to the presence of bioactive verbascoside identified in the LC-MS analysis.

Analgesic effect of Keishinieppiittokajutsubu on low barometric pressure-induced pain response in arthritic model rats

Rheumatoid arthritis (RA) is a disease that causes inflammation of joints, resulting in pain and swelling. Reduced barometric pressure induces painful symptom of RA, but there is no appropriate animal model and pharmacological evaluation. Keishinieppiittokajutsubu (KNEIJB), a Kampo medicine used to treat RA; however, its mechanism of action is not clear. Here, we found that KNEIJB suppressed the low barometric pressure (LP)-induced pain response in CFA-induced arthritic model rats. Furthermore, we found that KNEIJB reduced plasma IL-6 levels. These results suggest that KNEIJB might be beneficial in the treatment of RA or some other arthralgia induced by LP.

Anti-Arthritic and Antioxidant Efficacy of Ethanol and Aqueous Root Extracts of Olax subscorpioidea in CFA-Induced Arthritic Rats

Anti-Arthritic and Antioxidant Efficacy of Ethanol and Aqueous Root Extracts of Olax subscorpioidea in CFA-Induced Arthritic Rats

Mechanistic Evaluation of Antiarthritic Effects of Eupatilin in CFA-Induced Arthritic Rats: An in Vivo and in Silico Study

Objectives In the present study, we explored the antiarthritic potential of Eupatilin on complete Freund's adjuvant (CFA)-induced arthritis rats. Materials and Methods In order to induce arthritis in the Sprague-Dawley rats, CFA vaccination was used, and Eupatilin was given to the rats at dose of 5, 10, and 20 mg/kg. Various biochemical and other parameters were studied to define the pharmacological benefit of Eupatilin. Results The study's findings revealed that Eupatilin increases rats’ body weight and significantly reduces hind paw volume. It also improves the antioxidant status of CFA rats by lowering malondialdehyde levels and increasing the concentration of endogenous antioxidants superoxide dismutase and GPx. Eupatilin also improved hematological markers, which were demonstrated to be altered in CFA rats as compared to the control. In the Eupatilin-treated group, the level of pro-inflammatory cytokines was found to be reduced as compared to CFA rats. In a molecular docking analysis, it showed favorable interaction with the active site of cyclooxygenase-2 (COX-2) by the formation of numerous nonbonded interactions by interacting with Cys32, Leu138, Pro 139, Val141, Ala142, and Cys145. It also showed a Vina score of −9.4 and interacts with the cavity volume of 4435 Å3. Conclusion Eupatilin showed favorable antiarthritic benefits in the CFA-induced arthritis model, as evidenced by reductions in paw volume, significant weight loss prevention, and maintenance of the healthy hematological and biochemical profile may be through inhibiting COX-2.

Mechanistic Evaluation of Antiarthritic Effects of Citronellol in CFA-Induced Arthritic Rats.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation, joint tissue damage, pain, and synovitis. It leads to deformity of joints, disability, and even premature death. Markers of inflammation are highly expressed in synovium fluid and serum of arthritic patients and play an important role in the pathophysiology of RA. These transcription factors promote the fabrication of type I interferons and inflammatory cytokines. In RA, degradation of synovial cartilage and bone results from stimulation of proinflammatory cytokines. Citronellol (Ct), a monoterpene alcohol, is found in citrus fruits and essential oils of many aromatic plants. It possesses numerous pharmacological properties such as antioxidant activity and potential antinociceptive and anti-inflammatory effects. Keeping in view the significant anti-inflammatory role of Ct, a trial of 28 days was conducted. Ct was administered orally at three different doses (25, 50, and 100) mg/kg in Freund's adjuvant-induced arthritic rats, and the results were compared with piroxicam, chosen as the standard drug. The antiarthritic activity of the compound was evaluated through measurements of arthritic scoring and plethysmometry before and after treatment. The blood biochemical and hematological parameters and histopathological analyses were performed. Additionally, qPCR was conducted to analyze the mRNA expression levels of TNF-α, IL-1β, NF-κB, MMP3, IL-6, and IL-4 in the blood. ELISA was performed to evaluate the levels of PGE2. The results demonstrated that Ct showed significant results at all doses, but the highest dose proved to be most significant in terms of decreasing arthritic scoring and paw edema, indicating the antiarthritic potential of Ct. Furthermore, the compound was found to downregulate all the proinflammatory cytokines (TNF-α, IL-1β, NF-κB, MMP3, and IL-6) and upregulate the anti-inflammatory cytokine (IL-4). The levels of PGE2 were also reduced which further supported the antiarthritic effects of Ct and validated it as a potential antiarthritic candidate.

Anti-arthritic and Antioxidant Effects of Trehalose in an Experimental Model of Arthritis.

The purpose of the present study was to study the potential anti-arthritic and antioxidant effects of trehalose in an experimental model of complete Freund's adjuvant (CFA)-induced arthritis. Arthritis was induced via subcutaneous injection of CFA (0.1) into the right footpad of each rat. Trehalose (10 mg/kg per day) and indomethacin (5 mg/kg) as a reference drug were intraperitoneally injected into CFA-induced arthritic rats from days 0 to 21. Changes in paw volume, pain responses, arthritic score, and oxidative/antioxidative parameters were determined. Trehalose administration could significantly decrease arthritis scores (p <0.01) and paw edema (p <0.001), and significantly increase the nociceptive threshold (p <0.05) in CFA-induced arthritic rats. Trehalose also significantly reduced the pro-oxidant-antioxidant balance values when compared to CFA treatment alone. In addition, no significant difference was found between the trehalose group and indomethacin as a positive control group. The current study suggests that trehalose has a protective effect against arthritis, which may be mediated by antioxidative effects of this disaccharide.

Bioactive fraction of Tragia involucrata Linn leaves attenuates inflammation in Freund’s complete adjuvant-induced arthritis in Wistar albino rats via inhibiting NF-κB

Tragia involucrata Linn. (T. involucrata) belongs to the family of Euphorbiaceae found in the subtropical regions. Traditionally, the plant parts are used to treat inflammation, wounds and skin infection by people of the Western Ghats, India. Few studies on the acute anti-inflammatory activity of T. involucrata extracts were reported earlier. The present study aims to identify the bioactive fraction of T. involucrata and to evaluate its mechanism in Complete Freund's Adjuvant-induced arthritic rat model. The leaf extract was highly effective among the methanolic leaf and root extracts. The hexane (HF) and a methanolic fraction (MF) of the leaf extract of T involucrata were further identified as a bioactive fraction evaluated through protein denaturation assay. The HF and MF were further studied for their anti-inflammatory potential in a chronic inflammatory model, and their mechanism of action was explored further. Arthritis was induced by administering 0.1ml of CFA intradermally. The treatment was started the next day with HF (100 and 250mg/kg/day) and MF (100 and 250mg/kg/day), while the HF and MF alone group served as the drug control, Indomethacin-treated group served as the positive control. On the 25th day, the animals were euthanized, and their body weight, paw thickness, arthritic score, spleen and thymus weight, haematological parameters, biochemical parameters, radiographs and histopathology were analyzed. Results showed that the MF-treated animals maintained dry weight, reduced paw thickness, arthritic scores, and haematological and biological parameters compared to the HF-treated and CFA-induced arthritic rats. Both radiological and histopathological analyses of the joints revealed that the MF-treated groups restored bone architecture without any erosion and normal tissue architecture with nil signs of active inflammation. Western blot analysis revealed that MF has effectively inhibited the protein expression levels of MMP-3, MMP-9, and NF-κB in the synovial tissues compared to that of CFA-induced arthritic rats. Besides, HPLC analysis revealed the presence of flavonoids, including gallic acid, rutin and Quercetin, in the MF of T. involucrata, which had shown to have potent anti-inflammatory potential. Thus, it can be emphasized that T. involucrata could be a potential therapeutic candidate for treating inflammatory diseases, which needs further experimental studies to confirm its safety and efficacy.

Diosmin and Trolox Have Anti-Arthritic, Anti-Inflammatory and Antioxidant Potencies in Complete Freund's Adjuvant-Induced Arthritic Male Wistar Rats: Roles of NF-κB, iNOS, Nrf2 and MMPs.

Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease caused by a malfunction of the immune system. The aim of this study was to examine the anti-arthritic effects and suggest the mechanisms of actions of diosmin and trolox in male Wistar rats. Complete Freund’s adjuvant (CFA) was used to establish RA in the animals by subcutaneous injection of 100 µL CFA/rat into plantar region of right hind leg in two consecutive days. Diosmin and/or trolox were administered orally at a dosage of 20 mg/kg/day to CFA-induced arthritic rats for 2 weeks. The normal and arthritic control groups were orally given the same equivalent volume of a vehicle (1% carboxymethyl cellulose) in which treatment agents were dissolved. At the end of the experiment, blood samples were collected from the jugular vein for the detection of the total leukocyte count (TLC) and differential leukocyte count (DLC) in blood and the detection of rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), tumor necrosis factor-α (TNF-α), interleukin-13 (IL-13), and interleukin-17 (IL-17) levels by enzyme-linked immunosorbent assay (ELISA), as well as markers of oxidative stress and the antioxidant defense system in serum. The right hind ankle regions of three rats from each group were dissected out and fixed in 10% neutral-buffered formalin for histological examination and the other three were kept at −30 °C for Western blot analysis of nuclear factor-kappa B (NF-κB) protein 50 (NF-κB p50), NF-κB p65, inducible nitric oxide synthase (iNOS), nuclear factor erythroid-2-related factor 2 (Nrf2), and matrix metalloproteinase (MMP)-1 (MMP-1), MMP-3, and MMP-9. The CFA injection was deleterious to the ankle joint’s histological architecture, manifesting as infiltration of inflammatory cells into the articular cartilage, hyperplasia of the synovium, and erosion of the cartilage. All these effects were ameliorated by diosmin and/or trolox, with the combined dose being the most effective. The two compounds significantly lowered the elevated serum levels of RF, ACPA, TNF-α, and IL-17, as well as other pro-inflammatory mediators, such as NF-κB p50, NF-κB p65, iNOS, MMP-1, MMP-3 and MMP-9. They also increased the levels of the anti-inflammatory cytokine, IL-13, and the cytoprotective transcription factor Nrf2. The compounds stimulated higher activities of antioxidants, such as glutathione, glutathione-S-transferase, catalase, and superoxide dismutase, and reduced lipid peroxidation in the serum of arthritic rats. In conclusion, diosmin, trolox, and their combination, which was the most potent, exerted anti-arthritic, anti-inflammatory and antioxidant effects by suppressing NF-κB signaling, inhibiting matrix metalloproteinases, and activating Nrf2.

In vivo Anti-Inflammatory and Anti-Arthritic Potential of Ethanolic Acacia modesta Extract on CFA-Induced Adjuvant Arthritic Rats

In vivo Anti-Inflammatory and Anti-Arthritic Potential of Ethanolic Acacia modesta Extract on CFA-Induced Adjuvant Arthritic Rats

Amelioration of complete Freund\u2019s adjuvant-induced arthritis by Calotropis procera latex in rats

BackgroundRheumatoid arthritis is the most common cause of disability, affecting 0.3–1% of the adult population worldwide. The latex of Calotropis procera possesses potent anti-inflammatory as well as analgesic properties. In light above facts, the present study was designed to evaluate anti-arthritic activity of Calotropis procera latex in complete Freund's adjuvant (CFA)-induced arthritis in Wistar albino rats. Complete Freund's adjuvant was injected into the left hind paw on day 0, and treatment of prednisolone and Calotropis procera latex was given from day 0 to 28. Various biochemical, hematological and functional parameters as well as radiological and histopathological changes of joint along with body weight and paw volume were measured.ResultsCalotropis procera treatment significantly lowered paw volume in CFA-induced arthritic rats. Significant improvement was observed in functional, biochemical and hematological parameters in Calotropis procera-treated rats. However, the body weight remained unaffected. Histological and radiographical examination of synovial joints in Calotropis procera-treated animals exhibited less synovial hyperplasia, infiltration and accumulation of inflammatory cell in synovial fluid, cartilage and bone erosion and joint space narrowing.ConclusionCalotropis procera latex possesses anti-arthritic activity, which is facilitated by modulation in the level of inflammatory mediators and oxidative stress. The improvement in hematological as well as biochemical parameters might be reflected on functional, histopathological, radiological changes and thereby disease progression.

Anti-inflammatory activity of different isolated sites of Chloranthus serratus in complete Freund's adjuvant-induced arthritic rats.

Chloranthus serratus is a traditional Chinese medicine for treating arthritis and bruises. The aim of the present study was to investigate the anti-arthritic activities and possible associated mechanisms of different isolated sites of Chloranthus serratus (DISC) in adjuvant-induced arthritis (AA) rats. The therapeutic effects of the extracts were assessed through changes in body weights, swelling rates, arthritis indexes (AI) and organ indexes. The levels of nitric oxide (NO), malondialdehyde and superoxide dismutase were determined using one-step method, TBA method and hydroxylamine method, respectively; the levels of TNF-α, IL-1β, IL-6, prostaglandin E2, macrophage inhibitor factor-1, VEGF, immunoglobulin (Ig) G, IgM and IFN-γ in serum were determined using ELISA. Pathological changes and positive expression of VEGF in the ankle joints were investigated using hematoxylin-eosin staining and immunohistochemical staining, respectively. DISC treatment increased the weight gains and thymus indexes, and decreased the swelling rates, spleen indexes and AI in AA rats. The water isolated site (WA) and ethyl acetate isolated site (EA) significantly reversed complete Freund's adjuvant (CFA)-induced changes in the levels of NO, IL-6, TNF-α, IgG and IFN-γ, while the n-butanol isolated site (NB) only reversed the changes in IL-6 and IgG contents. Some changes in the chloroform isolated site group showed the same trend as those in the model group. The extracts relieved synovial hyperplasia, inflammatory cell infiltration and articular surface defects, and reduced the positive expression rate of VEGF in the synovial tissues of the AA rats to varying degrees. The WA exhibited the most marked effects, followed by the EA and NB, indicating that WA had optimal therapeutic effects on CFA-induced arthritic rats, which may be mediated by the oxidative stress and inhibition of inflammatory factors. C. serratus may serve as a potential candidate for the treatment of rheumatoid arthritis.

Farrerol ameliorate adjuvant‐induced ankle injury via alteration of PPAR‐γ signal pathway

This study evaluated the anti-inflammatory activity against lipopolysaccharide (LPS)-mediated mouse macrophages (in vitro) and assessed the protective effect of farrerol on arthritis caused by complete freund adjuvant (CFA) in rats. For the evaluation of the pharmacological effect of farrerol on the activity of nitric oxide (NO) and cyclooxygenase, pro-inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β, RAW 264.7 cells were used. A 0.1ml CFA was injected subcutaneously for the induction of arthritis. The paw volume, body weight and arthritic score were estimated at regular intervals. Pro-inflammatory cytokines, inflammatory mediators, and antioxidant parameters were also estimated. Farrerol suppressed NO production and COX-catalyzed prostaglandin (PGE2 ) in RAW 264.7. Farrerol also downregulated the p-p65, p-IκBα expression and upregulated the PPAR-γ expression in RAW 264.7 cells. Treatment of farrerol increased body weight substantially, and reduced paw edema and arthritic score. Farrerol treatment also significantly improved the level of hemoglobin (Hb), count of red blood cells (RBC), and decreased the rate of erythrocyte sedimentation (ESR), white blood cell (WBC) parameters, while the generation of pro-inflammatory cytokines inhibited. Together, farrerol also suppressed the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. Obtained results directed that the farrerol exerted its therapeutic effect against CFA-induced arthritic rats through anti-inflammatory mechanism by regulation of the PPAR-γ. PRACTICAL APPLICATIONS: Increase the arthritis disease worldwide day-by-day. The current research study showed the anti-arthritic effect of farrerol (flavonoid phytoconstituent) of Rhododendron dauricum Linn. In this study, farrerol considerably inhibited the NF-κB to show the anti-arthritic effect. The finding showed the potential effect against acute and chronic inflammation via inhibition of inflammatory mediators and oxidative stress. The result suggests the anti-inflammatory and antioxidant effect of farrerol. On the basis of result, we can say that farrerol can be the beneficial drug to treat the arthritis.

Potency of Bone Marrow-Derived Mesenchymal Stem Cells and Indomethacin in Complete Freund's Adjuvant-Induced Arthritic Rats: Roles of TNF-α, IL-10, iNOS, MMP-9, and TGF-β1.

Rheumatoid arthritis (RA) is an autoimmune syndrome affecting joint spaces, leading to the disabled state. Currently, there is no optimal therapy for RA except for systemic immunosuppressants that have variable undesirable effects after long-term use. Hence, the need for other treatment modalities has emerged in an attempt to develop a treating agent that is effective but without bad effects. Bone marrow-derived mesenchymal stem cells (BM-MSCs) may be an alternative medicine since they may differentiate into a variety of mesenchymal tissues including bone and cartilage. Indomethacin (IMC) could be suggested as an analgesic, anti-inflammatory, and antirheumatic potential agent against the course of RA since it possesses significant palliative effects and antipyretic properties. Therefore, our target of this study was to explore and compare the effect of BM-MSCs (1 × 106 cells/rat at the 1st, 6th, 12th, and 18th days) and IMC (2 mg/kg b.w./day for 3 weeks) either alone or in combination on arthritic rats. The model of rheumatoid arthritis in rats was induced by subcutaneous injection of 0.1 mL/rat CFA into the footpad of the right hind paw. The BM-MSC intravenous injection and IMC oral administration significantly reduced the elevated right hind leg paw diameter and circumference, serum anti-CCP, and ankle joint articular tissue expressions of TNF-α, iNOS, MMP-9, and TGF-β1 while they significantly increased the lowered articular IL-10 expression in CFA-induced arthritic rats. The combinatory effect of the two treatments was the most potent. In conclusion, the treatment of RA with BM-MSCs and IMC together is more effective than the treatment with either BM-MSCs or IMC. The Th1 cytokine (TNF-α), Th2 cytokine (IL-10), iNOS, MMP-9, and TGF-β1 are important targets for mediating the antiarthritic effects of BM-MSCs and IMC in CFA-induced arthritis in rats.

Brassica juncea (L.) Czern. leaves alleviate adjuvant-induced rheumatoid arthritis in rats via modulating the finest disease targets - IL2RA, IL18 and VEGFA

Brassica juncea (BJ) is a familiar edible crop, which has been used as a dietary ingredient and to prepare anti-inflammatory/anti-arthritic formulations in Ayurveda. But, the scientific validation or confirmation of its therapeutic properties is very limited. This study was performed to determine the efficiency of BJ leaves for the treatment of Rheumatoid arthritis using in vivo and in silico systems. Standard in vitro procedures was followed to study the total phenolic, flavonoid contents and free radical scavenging ability of the extracts of BJ. The effective extract was screened and the presence of bioactive chemicals was studied using HPLC. Further, the possible therapeutic actions of the BJ active principles against the disease targets were studied using PPI networking and docking analysis. IL2RA, IL18 and VEGFA are found to be the potential RA target and the compounds detected from BJ extract have shown great binding efficiency towards the target from molecular docking study. The resulting complexes were then subject to 100 ns molecular dynamics simulation studies with the GROMACS package to analyze the stability of docked protein-ligand complexes and to assess the fluctuation and conformational changes during protein-ligand interactions. To confirm the anti-arthritic activity of BJ, the extract was tested in CFA-induced arthritic Wistar rats. The test groups administered with BJ extract showed retrieval of altered hematological parameters and substantial recovery from inflammation and degeneration of rat hind paw. Communicated by Ramaswamy H. Sarma

Combinatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells and Indomethacin on Adjuvant-Induced Arthritis in Wistar Rats: Roles of IL-1β, IL-4, Nrf-2, and Oxidative Stress.

Rheumatoid arthritis (RA) is a disorder triggered by autoimmune reactions and related with chronic inflammation and severe disability. Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs) have shown a hopeful immunomodulatory effect towards repairing cartilage and restoring joint function. Additionally, indomethacin (IMC), a nonsteroidal compound, has been considered as a potent therapeutic agent that exhibits significant antipyretic properties and analgesic effects. The target of the current research is to assess the antiarthritic efficacy of BM-MSCs (106 cells/rat at 1, 6, 12 and 18 days) and IMC (2 mg/kg body weight/day for 3 weeks) either alone or concurrently administered against complete Freund's adjuvant-induced arthritic rats. Changes in paw volume, body weight, gross lesions, and antioxidant defense system, as well as oxidative stress, were assessed. The Th1 cytokine (IL-1β) serum level and Th2 cytokine (IL-4) and Nrf-2 ankle joint expression were detected. In comparison to normal rats, it was found that the CFA-induced arthritic rats exhibited significant leukocytosis and increase in paw volume, LPO level, RF, and IL-1β serum levels. In parallel, arthritic rats that received BM-MSCs and/or IMC efficiently exhibited decrease in paw edema, leukocytosis, and enhancement in the antioxidant enzymatic levels of SOD, GPx, GST, and GSH in serum besides upregulation of Nrf-2 and anti-inflammatory IL-4 expression levels in the ankle articular joint. Likewise, these analyses were more evidenced by the histopathological sections and histological score. The data also revealed that the combined administration of BM-MSC and IMC was more potent in suppressing inflammation and enhancing the anti-inflammatory pathway than each agent alone. Thus, it can be concluded that the combined therapy with BM-MSC and IMC may be used as a promising therapeutic choice after assessing their efficacy and safety in human beings with RA, and the antiarthritic effects may be mediated via modulatory effects on Th1/Th2 cytokines, ozidative stress, and Nrf-2.

Metabolomic and transcriptomic analyses of the anti-rheumatoid arthritis potential of xylopic acid in a bioinspired lipoprotein nanoformulation

Xylopic acid (XA), a diterpene kaurene and the major active ingredient of the African spice Xylopia aethiopica (Annonaceae), is reported to possess anti-inflammatory and analgesic properties. Here, we investigated the therapeutic potential of XA for rheumatoid arthritis (RA), a debilitating autoimmune inflammatory disease characterized by joint damage, in the complete Freund's adjuvant (CFA)-induced arthritis model in rats. We synthesized bioinspired reconstituted high-density lipoprotein (rHDL) nanoparticles loaded with purified XA crystals (rHDL/XA) that passively accumulate in inflamed joints of CFA-induced arthritic rats. Treatment with rHDL/XA minimized mononuclear cell infiltration of CFA-induced arthritic sites and ameliorated disease burden. Metabolomic and transcriptomic analyses revealed that the major molecular pathways perturbed following CFA-induced arthritis correlated with amino acid and lipid metabolism, which were restored to normal states by rHDL/XA treatment. This work demonstrates the anti-RA potential of XA in a nanoformulation and uncovers its underlying therapeutic mechanisms at the transcript and metabolite levels.

Ameliorative and anti-arthritic potential of arjunolic acid against complete Freund’s adjuvant-induced arthritis in rats

Purpose: To determine the anti-arthritic effect of arjunolic acid against complete Freund’s adjuvant (CFA)-induced arthritis in rats.Methods: Arthritis was induced in male Sprague Dawley rats by intradermal injection of 0.1 mL of CFA at the right footpad. Upon induction of osteoarthritis, arjunolic acid was administered via oral gavage at doses of 40 and 80 mg/kg once daily for 25 successive days. Indomethacin was used as reference drug at a dose of 3 mg/kg via gavage twice weekly for 25 days. Changes in paw swelling, serum hematology, antioxidant enzymes, serum inflammatory mediators, and histopathology were determined using standard procedures.Results: Paw swelling and weight loss in CFA-induced arthritic rats were significantly reversed (p &lt; 0.01) by arjunolic acid. Malondialdehyde (MDA) levels, spleen index and thymus index were significantly reduced in CFA-induced arthritic rats (p &lt; 0.01). Moreover, arjunolic significantly increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, while downregulating the expressions of TNF-α, IL-1β and IL-6 in serum (p &lt; 0.01). The hematological and histopathological changes due to CFA-induced arthritis were ameliorated by arjunolic acid.Conclusion: The results obtained in this study indicate that arjunolic acid may possess therapeutic potentials for the management of arthritis.&#x0D; Keywords: Arjunolic acid, Triterpenoid; Oxidative stress, osteoarthritis, Inflammation

Anti-arthritic activity of D-carvone against complete Freund’s adjuvant-induced arthritis in rats through modulation of inflammatory cytokines

Chronic joint pain due to loss of cartilage function, degradation of subchondral bone, and related conditions are common plights of an arthritis patient. Antioxidant compounds could solve the problems in arthritic condition. The objective of this study was to evaluate the anti-arthritic activity of D-carvone against complete Freund’s adjuvant (CFA)-induced arthritis in rats. D-carvone was orally administered for 25 days at the doses of 30 and 60 mg/kg against CFA-induced arthritic rats. Changes in body weight, paw swelling, organ index, hematological parameters, oxidative stress markers, inflammatory cytokines, and histopathology were recorded. Oral treatment of D-carvone significantly improved the body weight, reduced the paw swelling, edema formation, and organ index in arthritic rats. The levels of white blood cells were reduced, red blood cells and hemoglobin levels were improved in D-carvone treated arthritic rats. Lipid peroxidation levels were lowered whereas enzymatic and non-enzymatic antioxidants were significantly elevated by D-carvone administration against arthritic rats. D-carvone significantly modulated inflammatory cytokine levels and improved the ankle joint pathology against CFA-induced arthritic inflammation. In conclusion, D-carvone proved significant anti-arthritic activity against CFA-induced arthritis in rats.

Iridoid glycosides from Morinda officinalis How. exert anti-inflammatory and anti-arthritic effects through inactivating MAPK and NF-\u03baB signaling pathways

BackgroundThe root of Morinda officinalis How. (MO, the family of Rubiaceae) has long been used to treat inflammatory diseases in China and other eastern Asian countries, and iridoid glycosides extracted from MO (MOIG) are believed to contribute to this anti-inflammatory effect. However, the mechanism underlying the anti-inflammatory and anti-arthritic activities of MOIG has not been elucidated. The aim of the present study was to determine how MOIG exerted anti-inflammatory and anti-arthritic effects in vivo and in RAW 264.7 macrophages.MethodsMOIG were enriched by XDA-1 macroporous resin. The maximum feasible dose method was adopted to evaluate its acute toxicity. The analgesic effect of MOIG was evaluated by acetic acid writhing test and the anti-inflammatory effect was evaluated by cotton-pellet granuloma test in rats and air pouch granuloma test in mice. The anti-arthritic effect was evaluated by establishing an adjuvant arthritis model induced by Complete Freund’s Adjuvant (CFA). The viability of the cultured RAW 264.7 macrophages was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The anti-inflammatory activity was evaluated by measuring NO, IL-1β, IL-6 and TNF-α levels in LPS-stimulated RAW 264.7 cells. The protein level of inflammatory responsive genes was evaluated by Western blot analysis.ResultsMOIG had no significant toxicity at maximum feasible dose of 22.5 g/kg. MO extracts and MOIG (50,100 and 200 mg/kg) all evoked a significantly inhibitory effects on the frequency of twisting induced by acetic acid in mice compared with the model control group. Administration of MO extracts and MOIG markedly decreased the dry and wet weight of cotton pellet granuloma in rats and air pouch granuloma in mice. MOIG significantly attenuated the paw swelling and decreased the arthritic score, weight loss, spleen index, and the serum level of inflammatory factors IL-1β, IL-6 and IL-17a in CFA-induced arthritic rats. MOIG inhibited the production of inflammatory cytokines in LPS-stimulated RAW264.7 cells, and the expressions of iNOS, COX-2 and proteins related to MAPK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 macrophages.ConclusionMOIG exerted anti-inflammatory and anti-arthritic activities through inactivating MAPK and NF-κB signaling pathways, and this finding may provide a sound experimental basis for the clinical treatment of rheumatoid arthritis with MOIG.

Polysaccharide from Angelica Sinensis Suppresses Inflammation and Reverses Anemia in Complete Freund's Adjuvant-induced Rats.

The anti-inflammatory and antianemic activities of Angelica sinensis polysaccharide (ASP) isolated from roots of Angelica sinensis (AS) was investigated in a complete Freund's adjuvant (CFA)-induced arthritic rat model. It was observed that serum iron (SI) and total iron binding capacity (TIBC) levels were elevated after 4-week oral administration of ASP. Red blood cell (RBC) count and hemoglobin (Hb) concentrations were ameliorated as well. Moreover, inflammatory cytokines IL-6 and TNF-a were decreased strikingly in CFA-induced arthritic rats after treatment of ASP. Evidence also showed that ASP strongly inhibited hepcidin expression through the Janus kinase/signal transducers and activators of transcription (JAK2/STAT3) pathway. Furthermore, ASP exhibited reduced primary and secondary lesions in adjuvant arthritis, attenuating synovitis and inflammatory joint damage. Data presented in this article collectively indicated that ASP significantly decreased proinflammatory cytokines (TNF-a, IL-6), which might play a crucial role in the CFA-induced arthritic rats, and had a therapeutic effect on adjuvant arthritis in rats. Results of Western blot analysis indicated that ASP inhibited the activation of IL-6/JAK2/STAT3 signaling pathway in the CFA-induced arthritic rats.