Anti-arthritic Potential Research Articles

Assessment of anti-arthritic potential of traditionally fermented ayurvedic polyherbal product chandanasava by molecular modelling, docking and dynamics approaches

Rheumatoid arthritis is triggerred by proteus mirabilis and its virulence factor, urease. We have used molecular modelling, docking, dynamics simulations and experimental approaches to assess the anti-arthritic potential of phytochemicals of Ayurvedic polyherbal formulation Chandanasava by targeting urease subunits of Proteus mirabilis. Chandanasava exhibited antibacterial activity against Proteus mirabilis and Gas Chromatography-Mass Spectroscopy analysis indicated the presence of 42 bioactive phytochemicals. The three dimensional structures of urease subunits (ureA, ureB and ureC) were not available and hence these structures were predicted using homology modelling approach and validated using Ramachandran plot. Molecular docking and dynamics simulations of phytochemicals of Chandanasava against urease subunits showed efficient binding of almost all the compounds. Significantly, lactose, isosorbide, 1,2,3-Benzenetriol, 1,2-Cyclopentanedione and 2-Furancarboxaldehyde, 5-(hydroxymethyl) binds efficiently among other compounds. Thus Chandanasava formulation and some of its bioactive compounds give insights about its therapeutic property against arthritis and further investigations on it can bring out promising therapeutics.

Antiarthritic potential of aqueous and ethanolic fruit extracts of “Momordica charantia” using different screening models

Background: Momordica charantia (Cucurbitaceae) is a plant, reported for its variety of ethnic medicinal uses and widely grown in Asia, Africa, and the Caribbean for its edible fruit. Objective: The present work has been planned to screen antiarthritic activity of fruit of the plant with the ethanolic and aqueous extracts. Materials and Methods: Fruit powder was successively extracted with ethanol (95%) and water using soxhlet extraction and subjected to phytochemical screening to identify different phytoconstituents. Ld50studies for both (ethanolic and aqueous) extracts were conducted up to the dose level of 2 g/kg by following OECD up and down method of guidelines No. 425. Antiarthritic activity was performed using formaldehyde, Freund's adjuvant-induced arthritis in rats, and Collagen-induced arthritis model in mice. Statistical analysis was performed using one-way analysis of variance followed by Dunnett's t-test. P Abbreviations Used: LD50: Lethal dose 50%, OECD: Organization for Economic and Co-operation Development, CMC: Carboxy Methyl Cellulose.

Bergenin loaded gum xanthan stabilized silver nanoparticles suppress synovial inflammation through modulation of the immune response and oxidative stress in adjuvant induced arthritic rats.

Bergenin (BG) is a naturally occurring C-glycoside with demonstrated anti-arthritic potential. Its therapeutic efficacy is compromised due to its lower absorption and instability at neutral-basic pH. The present study reports fabrication of gum xanthan (GX) stabilized silver nanoparticles (AgNPs) with BG for anti-arthritic activity in a CFA-induced arthritis model targeting ROS, cytokines and TLR expression. NPs were characterized through UV-vis, zetasizer, FT-IR and AFM. Oral administration of BG loaded NPs (1 mg kg-1) exhibited potent anti-arthritic activity with a minimal arthritic score, mild to moderate paw tissue swelling, reduced degenerative changes along with mild articular changes and less influx of inflammatory cells in macroscopic X-ray and histological examination. Administration of BG and its NPs suppressed the levels of reactive oxygen species (ROS) significantly as compared to the arthritic control group. Moreover, increased production of O2˙- in human neutrophils, stimulated by opsonized zymosan (OZ) and phorbol-12-myristate-13-acetate (PMA) was also suppressed. BG and its loaded NPs were revealed to antagonize the oxidative stress via interference with the NADPH oxidase metabolic pathway. Their anti-oxidant activity was further assessed by their inhibitory effect against TLR (TRL-2 & -4) and cytokine (IL-1β, IL-6 and TNF-α) production. The current investigation validates GX stabilized AgNPs as stable and promising multi-targeted therapeutic nano-cargo for BG delivery with efficient treatment of RA.

Anti-arthritic Potential of Ardisia crispa Root (Myrsinaceae) in vitro and in vivo

Event Abstract Back to Event Anti-arthritic potential of Ardisia crispa root (Myrsinaceae) in vitro and in vivo Joan A. Blin1, Roslida Abd Hamid1*, Yoke Kqueen Cheah1 and Razana Mohd Ali2 1 Department of Biomedical Sciences, Faculty of Medicine and Health sciences, University of Putra Malaysia, Malaysia 2 Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia Background Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disease characterised by excessive angiogenesis. Anti-angiogenesis could be a promising therapeutic strategy against RA. Ardisia crispa or “Mata Itik” is a local plant traditionally used for treating various illnesses. Its properties like anti-tumour, anti-inflammatory and anti-angiogenic have been reported in previous studies. However, its anti-angiogenic role against RA has yet to be investigated. Thus, the present study investigated the anti-angiogenic potential of hexane extract (ACRH), quinone rich fraction (QRF), and benzoquinone (BQ) isolated from the roots of the plant using cell-based assays in vitro. ACRH was also tested against in vivo model. Methods Cytotoxicity, tube formation, cell invasion, and cell apoptosis assays were performed using human umbilical vein endothelial cells (HUVEC) and human fibroblast-like synoviocytes for rheumatoid arthritis cells (HFLS-RA). In vivo study was performed using collagen-induced arthritis (CIA) in rats. Results ACRH, QRF and BQ were highly cytotoxic against HUVEC (IC50 at 1.9 ± 0.2, 2.5 ± 0.8 and 1.7 ± 0.2 µg/mL, respectively). Nevertheless, ACRH and QRF were found to be less cytotoxic against HFLS-RA cell (4.0 ± 2.3 and 5.7 ± 0.9 µg/mL, respectively) after 24 hours of exposure. Interestingly, BQ remained highly cytotoxic against HFLS-RA cells with IC50 at 1.6 ± 0.5 µg/mL. All samples (0.05, 0.5 and 5 µg/mL) significantly (P<0.05) inhibited VEGF-induced HUVEC tube formation and IL-1β-induced HFLS-RA cell invasion in a concentration-dependent manner. Both ACRH and BQ exhibited late apoptotic activity in IL-1β-induced HFLS-RA cells at highest concentration (5 µg/mL). For CIA in rats, all doses of ACRH (10, 30, 100 mg/kg) showed significance reduction of ankle joint diameter, paw volume, and arthritic scoring. Conclusion This study had uncovered the anti-angiogenic effect of Ardisia crispa root in suppressing angiogenesis against both HUVEC and HFLS-RA cells, even though its role in modulating angiogenic biomarkers in RA animal model has yet to be determined. Acknowledgements The present work were financially supported by Fundamental Research Grant Scheme (FRGS/2/2014/SKK10/UPM/02/1) and Geran Putra IPS (GPIPS9576500). Keywords: Ardisia crispa root, Human Umbilical Vein Endothelial Cells (HUVEC), human fibroblast-like synoviocytes for rheumatoid arthritis cells (HFLS-RA), Rheumatoid arthritis, Angiogenesis, Collagen-induced arthritis rat Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Oral Presentation Topic: Inflammatory diseases Citation: Blin JA, Abd Hamid R, Cheah Y and Mohd Ali R (2019). Anti-arthritic potential of Ardisia crispa root (Myrsinaceae) in vitro and in vivo. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00011 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 03 Oct 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. Roslida Abd Hamid, Department of Biomedical Sciences, Faculty of Medicine and Health sciences, University of Putra Malaysia, Kuala Lumpur, Malaysia, roslida@upm.edu.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Joan A Blin Roslida Abd Hamid Yoke Kqueen Cheah Razana Mohd Ali Google Joan A Blin Roslida Abd Hamid Yoke Kqueen Cheah Razana Mohd Ali Google Scholar Joan A Blin Roslida Abd Hamid Yoke Kqueen Cheah Razana Mohd Ali PubMed Joan A Blin Roslida Abd Hamid Yoke Kqueen Cheah Razana Mohd Ali Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Stachytarpheta jamaicensis leaf extract: Chemical composition, antioxidant, anti-arthritic, anti-inflammatory and bactericidal potentials

Stachytarpheta jamaicensis is an important plant with multi therapeutic properties. Hence, this study seeks to screen the leaf extract of S. jamaicensis for its chemical composition and pharmacological activities in order to find possible sources for novel phytochemicals in food and pharmaceutical formulations. The chemical composition, pH, TPC, TFC, TTC, TAA, carotenoid, antioxidant, anti-arthritic, anti-inflammatory and bactericidal potential were measured using GC-MS, pH meter, Folin-Ciocalteu’s, AlCl3, FeCl3/gelatine, 2,4- DNPH, acetone-hexane, DPPH, PTAC, BSA and agar-well diffusion methods respectively. The pH of the aqueous solution was 6.02. The GC and GC-MS analyses revealed the presence of 30 organic compounds. The most abundant components were 3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one (13.7%), D-arabinitol (13.5%), 2-benzylidenemalonic acid (11.9%), 1,3-cyclopentadione (8.9%), α-5-ethyl-2-furylglycine (6.8%), 4,5-dihydro-5-methoxy-4-(2,3-dimethyl-2-buten-4-yl)-2(3H)-furanone (6.4%) and 3-methyl-2H-indazol-2-ol (5.8%). The TPC, TFC, TTC, TAA, β-carotene and lycopene values were 31,882.80 ±0.00 µgmg-1 GAE, 29.29±0.00 µgmg-1 QE, 126.47 µgmg-1 TAE, 53.75±0.01 µgmg-1 AAE, 0.17 mgg-1 and 0.14 mgg-1 , respectively. The antioxidant IC50 and AAI values of the leaf extract were 5.0 µgml-1 and 8.0. The extract was capable of scavenging free radicals in a range between 51.30-78.99%. The PTAC value was 396.15±0.00 µgmg-1 AAE. The extract also gave high egg albumin and BSA anti-arthritic/anti-inflammatory values between 22-80% with IC50 values of 0.04 and 0.15 mgml-1 , respectively. The extract was active against all the tested bacteria with high zones of inhibition (14.0-25.0 mm). These results showed that the leaf extract of S. jamaicensis could be used for the formulation of active compounds with broad activities for food and pharmaceutical industries.

Anti-inflammatory effects of 4-o-methyl-benzenesulfonyl benzoxazolone (MBB) in vivo and in vitro as a novel NSAIDs lead compound.

Great attention has been paid to the development of novel anti-inflammatory drugs to overcome the adverse reactions of traditional drugs. Recently, a new compound 4-o-methyl-benzenesulfonyl benzoxazolone (MBB) we have prepared attracted our attention for its promising anti-inflammatory activity and low toxicity. The present study aimed to further investigate the anti-inflammatory effects of MBB both in vivo and in vitro in order to determine its potential as a novel NSAIDs lead compound. The anti-inflammatory effects in vivo were evaluated using acetic acid-induced mice writhing, xylene-induced mice ear edema and collagen-induced rat arthritis. NO, TNF-α, IL-6, IL-1β and iNOS productions by LPS-stimulated RAW264.7 cells were determined to investigate the basis of anti-inflammatory effects. Finally, the COX inhibition effect was tested in vitro using COX inhibitor screening assay kit. MBB could significantly decrease the writhing and ear swelling in a dose-dependent manner, and it also had a moderate anti-arthritic potential associated with an attenuation of arthritis index score, arthritis swelling, and inhibition of TNF-α and IL-1β. MBB could inhibit the activity of NO, TNF-α, IL-6, IL-1β and iNOS to perform its activity in vitro, but it had no effect against COX-1 and COX-2. The anti-inflammation effect may be mediated via the inhibition of iNOS to reduce the production of inflammatory mediators which should be further confirmed. The compound MBB displayed anti-inflammatory and anti-arthritic effect, and it could be considered as a new NSAIDs lead compound for the further structure modification to develop novel anti-inflammatory drugs.

Assessment of anti-arthritic potential of Ephedra gerardiana by in vitro and in vivo methods

&lt;p class="Abstract"&gt;The present study determines the anti-arthritic potential of Ephedra gerardiana ethanolic extract and its ethyl acetate, n-butanol and aqueous fractions adopting in vitro and in vivo tests. In vitro tests included thermally induced bovine serum albumin denaturation and egg albumin denaturation, also membrane stabilizing assay at concentration of 50-6400 µg/mL, whereas in vivo study comprised formaldehyde-induced arthritis at 50, 100 and 200 mg/kg doses. The crude extract and fractions inhibited protein denaturation and stabilized red blood cells membrane in concentration-dependent fashion, with maximal effect achieved at 6,400 µg/mL (p&amp;lt;0.001). Similarly, in formaldehyde model, the extract and fractions dose-dependently reduced injected paw volume and diameter, with maximum reduction at 200 mg/kg (p&amp;lt;0.001). However, results of aqueous fraction were on a par with hydroalcoholic extract in each test. These results suggest that E. gerardiana provides protection against arthritis that might be owing to the existence of phytoconstituents thus, supporting folkloric claim.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Video Clip of Methodology&lt;/strong&gt;:&lt;/p&gt;&lt;p&gt;23 min 48 sec: &lt;a href="https://youtube.com/v/Pr4sgq3sBUY"&gt;Full Screen&lt;/a&gt; &lt;a href="https://youtube.com/watch?v=Pr4sgq3sBUY"&gt;Alternate&lt;/a&gt;&lt;/p&gt;

Targeting IL-17 AND IL-17D receptors of rheumatoid arthritis using phytocompounds: A Molecular Docking study

Rheumatoid arthritis (RA) is a chronic autoimmune condition of the connective tissue in synovial joints, characterized by inflammation which can lead to bone and cartilage destruction. IL-17 and IL-17D cytokines produced by a number of cell types, primarily promote pro-inflammatory immune responses and negative regulator in fibroblast growth factor signalling. Thus, the promising therapeutic strategies focus on targeting these cytokines, which has led to the identification of effective inhibitors. However, several studies focused on identifying the anti-arthritic potential of natural compounds. Therefore, in the present study we undertook in silico investigations to decipher the anti-inflammatory prospective of phytocompounds by targeting IL-17 and IL-17D cytokines using Patch Dock algorithm. Additionally, IL-17 and IL-17D proteins structure were modelled and validated for molecular docking study. Further, phytocompounds based on anti-inflammatory property were subjected to Lipinski filter and ADMET properties indicated that all of these compounds showed desirable drug-like criteria. The outcome of this investigation sheds light on the anti-inflammatory mechanism of phytocompounds by targeting IL-17 and IL-D for effective treatment of RA.

Evaluation of anti-arthritic potential of Leonotis nepetifolia (L.)R.Br. against Freund’s adjuvant induced arthritis

Background: Leonotis nepetifolia (L.)R.Br. (LN) belonging to Lamiaceae family is a tall erect annual weed native to Southern India and tropical Africa used by tribals and folklore traditions in India for cough, fever, stomach ache, skin ailments, kidney diseases, rheumatism and dysmenorrhoea. The purpose of the study is to evaluate the anti-arthritic activity of the traditional dosage form( decoction) as used by the tribals in comparison to a modified dosage form(dry aqueous extract ) of whole plant of LN in experimental animal models. Materials and Methods: Thirty wistar strain albino rats were selected and randomly divided into five groups. Arthritis was induced by Freund’s complete adjuvant (FCA) and then treated with either the decoction of whole plant of LN or the dry aqueous extract for 30 days.The various parameters like paw volume, ponderal changes, serum biochemical parameters and histopathological changes were assessed. The data was analyzed by employing one-way ANOVA followed by Dunnet’s multiple‘t’ test for unpaired data to determine significant difference between groups at P&gt;0.05. Results: In the present study it was observed that dry aqueous extract form of the test drug is having weak activity against primary oedema whereas decoction form did not show any effect on primary oedema. Both forms of test drug have comparable values as standard drug on 25th day in secondary oedema. Conclusion: The findings suggest the beneficial effect of the drug against chronic inflammation and inhibition of periarthritis and osteogenic activity.

Heterocyclic homoprostanoid derivative attenuates monoarthritis in rats: An in vitro and in vivo preclinical paradigm

From our lab, among the nineteen heterocyclic homoprostanoids (HHPs), three derivatives (compounds 3, 3b and 3c) exerted antioxidant and anti-inflammatory activity. Present study is an extension of the earlier work, and, is designed to establish their therapeutic potential in monoarthritis in rats. In addition, their possible mechanism of action would be investigated. A battery of in vitro tests such as lipopolysaccharide (LPS)-induced nitrite (NO)/reactive oxygen species (ROS) and NO/interleukin (IL)-6 generation in murine macrophages and whole blood (WhB), respectively were conducted. Later, in vitro cyclooxygenase (COX) enzyme inhibitory activity was also evaluated. All the tested compounds showed comparable efficacy against ROS and NO in LPS-stimulated murine macrophages. However, compound 3 did not exert inhibitory effect on LPS-induced NO/IL-6 generation in WhB assay. Compounds (3b and 3c) inhibited the NO generation in LPS-stimulated WhB. However, only compound 3b reversed the raised IL-6 levels in this assay. None of the test compounds inhibited COX iso-enzymes in the in vitro assay. All three HHPs showed comparable efficacy against carrageenan-induced paw inflammation. However, none of them exhibited any dose-dependent effect in this model. Based upon previous reports, compound 3c was explored against adjuvant-induced monoarthritis (AIA) in male Sprague-Dawley rats, where it exerted promising therapeutic effect. In addition to radiological and histological examinations of tibio-tarsal joint, various parameters such as chronic inflammation/pain, clinical score, interleukin (IL)-6 levels and complete blood cell profile were evaluated in AIA rats. Chronic treatment with 3c halted the disease progression in rats, improved the overall health of animals, as demonstrated by haematological, clinical scoring and joint examinations (radiological and histopathological). Inhibitory effect on elevated IL-6 in AIA rats suggested the possible mechanism of 3c on cytokine signalling. Overall, the study supports the anti-arthritic potential of compound 3c.

Clitoria ternatea flower petals: Effect on TNFR1 neutralization via downregulation of synovial matrix metalloproteases

Ethnopharmacological relevanceClitoria ternatea Linn. (C. ternatea) is a traditionally used herb in arthritis, and its anti-arthritic activity has been attributed to polyphenols (e.g. quercetins) from its flower petal. Aim of the studyThe present study was designed to investigate whether C. ternatea or quercetin-3ß-D-glucoside (QG) support the antibody mediated TNFα-receptor 1 (TNFR1) neutralization to ameliorate arthritis in mice. Materials and methodsDevelopment of collagen-induced arthritis (CIA) in male Swiss mice (20–22g, 3–4 weeks of age) was followed by estimation of synovial polymorphonuclear cell (PMN) accumulation (in terms of myeloperoxidase activity), synovial and systemic release of cytokines, chemokines and C-reactive protein (CRP) by enzyme-linked immunosorbent assay (ELISA), biochemical estimation of synovial free radical generation and antioxidant status, as well as immunoblot assessment of synovial TNFR1, toll-like receptor 2(TLR2), cyclooxygenase-2(COX-2) and inducible nitric oxide synthase (iNOS) expression; and zymographic analysis of synovial matrix-metalloprotease-2 (MMP-2) activity. ResultsCIA was induced from day 2 post-secondary immunizations as evidenced from arthritic scores and joint swelling in parallel to increased inflammatory and oxidative stress parameters in synovial joints. Long term supplementation with extract from Clitoria ternatea flower petals CTE (50mg/kg) and QG (2.5mg/kg) upto 24 days post booster immunization augmented anti-arthritic potential of TNFR1 neutralization with anti-TNFR1 antibody (10μg per mice) in terms of reduced MPO activity, decrease in release of pro-inflammatory cytokines, chemokines, reactive oxygen species (ROS)/ reactive nitrogen species (RNS) production in parallel to significant (p<0.05) reduction in TNFR1, TLR2, iNOS, COX-2 and MMP-2 expression. ConclusionCTE and QG possess potential anti-arthritic activity which targets synovial MMP-2 in arthritic joints and TNFR1 targeting followed by CTE or QG treatment might become a combinatorial approach in future therapeutic research in treatment of arthritis.

Investigation of anti-arthritic potential of Acacia torta (roxb.) craib

Background: Acacia torta (Roxb.) Craib, traditionally used in respiratory, circulatory, digestive, musculo-skeletal, skin diseases etc., Numerous plants of this genus have been used in folk medicine to treat stomach pain, cough, diarrhoea, piles, sore-throat; as astringent, antipyretic, antimicrobial, antimalarial, antiviral, anti-oxidant and as anti-hypertensive. Hence, the present study was aimed to investigate the anti‐arthritic potential of Acacia Torta (Roxb.) Craib, since, systematic study of this plant has not been carried out.Methods: Ethanol and water were used to prepare stem extract by soxhlet extraction method. The extract is evaluated by using Freund’s complete adjuvant induced arthritis in albino wistar rats at the dose of 100mg/kg/p.o. and 400mg/kg/p.o. and indomethacin at 10mg/kg were used for the study.Results: The hydro alcoholic extract of the stem Acacia torta (Roxb.) Craib in crude form contains phytoconstituents like saponins, tannins, steroids, and triterpenes. The reference standard, Indomethacin at the dose of 10 mg/kg showed significant inhibition of paw edema by 71.61% (P &lt;0.001), as compared to the vehicle control. Treatment with the hydro alcoholic extract of stem Acacia Torta at doses of 100 and 400 mg/kg caused significant inhibition of paw edema by 59.26% (P &lt;0.001) and 69.14% (P &lt;0.001) respectively, was observed on 21st day, as compared to the vehicle control.Conclusions: The data obtained from the present study indicated that several factors may contribute to the anti-inflammatory and anti-arthritic activity of hydro alcohol extract of the stem Acacia torta (Roxb.) Craib. adjuvant induced arthritis showed inhibition of prostaglandin synthesis might be the major mechanism by which the hydro alcoholic extract of the stem Acacia torta (Roxb.) Craib exerts anti-inflammatory and arthritic activity.

Anti-arthritic potential of marine macroalgae Turbinaria ornata in Complete Freund’s Adjuvant induced rats

T. ornata a macroalgae rich in bioactive molecules possess various biological activities. Herein, the aim of the study is to evaluate the aqueous extract and the sulphated polysaccharide isolated from T. ornata for its anti-arthritic potential in Complete Freund’s Adjuvant (CFA) induced arthritis in rats. Anti-arthritic potential of aqueous T. ornata (ATO) and T. ornata sulphated polysaccharide (TSP) was evidenced by the significant reduction in paw volume and arthritic score. Inflammatory and antioxidant markers were found to be restored in the drug treated groups which was found to be in line with dexamethasone a standard anti-inflammatory drug. The histopathological and radiological examination adds on the support to the above findings confirming the anti-arthritic potential of ATO and TSP. It is interesting to note that the sulphated polysaccharide inhibits inflammation and bone damage at very low dose itself. Hence, TSP could be considered as a better candidate in the management of chronic inflammatory diseases like rheumatoid arthritis.

Enhanced Anti Arthritic Potential of Tacrolimus by Transdermal Nanocarrier System

Current work entails the development and assessment of a well-tolerated colloidal carrier system containing immunosuppressant drug tacrolimus (TL) for transdermal delivery to study its efficacy against arthritis. TL-NEs of different composition from phase diagram were prepared by high sheer homogenization and a comprehensive physico-chemical characterization of the novel NEs were performed using different techniques in order to get most optimum NE. Optimized NE was incorporated in to carbopol-934 gel and subjected to ex vivo skin permeation studies, droplet size analysis, zeta potential measurement, TEM examination, Rheology, and stability study. Moreover, we have evaluated the in vivo anti arthritic potential of same formulation and compared it with a marketed ointment (Protopic®, 0.03%) for the first time. Optimized TL-NG formulation composed of Capryol 90 (5.0% w/w), tween-20 (15.0% w/w), Transcutol HP (7.5% w/w), water (72.5%) w/w, carbopol-934 (1.0%) and found to have permeation flux (68.88 μg/cm2/h), release (1621.46 μg/24 h), small droplet size (12.72 nm), and viscosity of 1.07 Pa-s. The results of ZP indicated that formulation was stable and shelf life at room temperature was calculated as 1.59 years. The in vivo investigation demonstrated direct evidence on significant reduction (41.80%) in inflammation over a period of 24 h. On the basis of these preliminary finding, we conclude that developed TL-NG has good anti-inflammatory action and may provide promising perspective for treatment of Arthritis.

Anti-inflammatory and anti-arthritic properties of naringenin via attenuation of NF-κB and activation of the heme oxygenase ﴾HO﴿-1/related factor 2 pathway.

Naringenin, a bioflavonoid present in various species of citrus fruit, tomatoes and grapes, has been shown to have various pharmacological effects. We evaluated the anti-arthritic potential of naringenin in formaldehyde-induced inflammation and complete Freund's adjuvant (CFA)-induced arthritis. For both evaluations, rats were divided into groups of six. Different doses of naringenin (5, 10 and 20mg/kg) were used in the models. Body weight and the arthritic index were assessed. Biochemical and antioxidant parameters were determined. Naringenin dose-dependently reduced joint inflammation, decreasing the joint diameter and inflammatory cell infiltration. Naringenin-treated rats showed an improvement in the synovium redox status (down-regulation of malondialdehyde and glutathione and up-regulation of Catalase (CAT) and superoxide dismutase levels). Naringenin significantly reduced the level of the inflammatory marker TNF-α. Naringenin increased Nrf-2/HO-1 and reduced NF-κB mRNA levels in CFA-treated animal joints. Additionally, naringenin treatment decreased the expression of extracellular matrix degrading enzymes, such as matrix metalloproteinase (MMP-3 and MMP-9), in CFA-induced arthritic rats. We conclude that naringenin exerts anti-arthritic effects by downregulating NF-κB and activating the Nrf-2/HO-1 pathway.

Appraisal of anti-arthritic and nephroprotective potential of Cuscuta reflexa

Context: Cuscuta reflexa Roxb. (Cuscutaceae) has been used traditionally for treating sore knees and kidney problems, but its efficacy has not been scientifically examined in treating arthritis and nephrotoxicity.Objective: Present study determines antiarthritic and nephroprotective potential of the aqueous methanolic extract of Cuscuta reflexa (AMECR).Materials and methods: Antiarthritic activity of Cuscuta reflexa in formaldehyde and turpentine oil-induced rat arthritis models was appraised at 200, 400 and 600 mg/kg doses for 10 days and 6 h period, respectively, and in vitro protein denaturation (bovine serum albumin, egg albumin) inhibition was studied at 25–800 μg/mL concentration. The nephroprotective effect involved gentamicin-induced nephrotoxicity in rats at 200, 400 and 600 mg/kg doses.Results: Plant extract at 600 mg/kg significantly reduced paw oedema and joint swelling with maximal inhibition of 71.22% at the 6th hour for turpentine oil and 76.74% on 10th day for formaldehyde. Likewise, in vitro results corroborated significant concentration-dependent increase in percentage protection at 800 μg/mL against both bovine serum albumin (89.30%) and egg albumin (93.51%) denaturation. Similarly, 600 mg/kg dose showed maximum nephroprotection by reducing serum urea (41.400 ± 0.510 mg/dL), uric acid (0.740 ± 0.032 mg/dL), blood urea nitrogen (18.370 ± 0.328), creatinine (3.267 ± 0.076) and minimizing kidney weight gain (0.586 ± 0.005) and histopathological alterations on 8th day. Furthermore, phytochemical and HPLC analysis revealed the presence of important phytoconstituents.Discussion and conclusions: These results suggest that AMECR provides protection against arthritis and nephrotoxicity that might be due to the existence of phytoconstituents, thus supporting folkloric claim.

Ethyl Caffeate Ameliorates Collagen-Induced Arthritis by Suppressing Th1 Immune Response.

The present study was designed to assess the antiarthritic potential of ECF in collagen-induced arthritis (CIA) and explore its underlying mechanism. Methods. In vitro, lymphocyte proliferation assay was measured by CCK-8 kit. In vivo, the therapeutic potential of ECF on CIA was investigated; surface marker, Treg cell, and intracellular cytokines (IL-17A and IFN-γ) were detected by flow cytometry. Th1 cell differentiation assay was performed, and mRNA expression in interferon-γ-related signaling was examined by q-PCR analysis. Results. In vitro, ECF markedly inhibited the proliferation of splenocytes in response to ConA and anti-CD3. In vivo, ECF treatment reduced the severity of CIA, inhibited IFN-γ and IL-6 secretion, and decreased the proportion of CD11b+Gr-1+ splenic neutrophil. Meanwhile, ECF treatment significantly inhibited the IFN-γ expression in CD4+T cell without obviously influencing the development of Th17 cells and T regulatory cells. In vitro, ECF suppressed the differentiation of naive CD4+ T cells into Th1. Furthermore, ECF intensely blocked the transcriptional expression in interferon-γ-related signaling, including IFN-γ, T-bet, STAT1, and STAT4. Conclusion. Our results indicated that ECF exerted antiarthritic potential in collagen-induced arthritis by suppressing Th1 immune response and interferon-γ-related signaling.

Plants having Anti-arthritic and Immunomodulator Potentials: An Review

Many allopathic drugs reported to be used for the treatment of inflammatory disorders are of least interest now a days due to their potential side effects and serious adverse effects and as they are found to be highly unsafe for human assistance. Herbals containing anti-inflammatory activity (AIA) are topics of immense interest due to the absence of several problems in them, which are associated with synthetic preparations. The primary objective of this review is to provide a deep overview of the recently explored anti-inflammatory agents belonging to various classes of phytoconstituents like alkaloids, glycosides, terpenoids, steroids, polyphenolic compounds, and also the compounds isolated from plants of marine origin, algae and fungi. Also, it enlists a distended view on potential interactions between herbals and synthetic preparations, related adverse effects and clinical trials done on herbals for exploring their AIA.

Nyctanthes arbor-tristis Ameliorated FCA-Induced Experimental Arthritis: A Comparative Study among Different Extracts.

Nyctanthes arbor-tristis (NAT) is commonly used traditionally for the treatment of rheumatism and inflammatory diseases. Current study evaluates the antiarthritic potential of NAT using Freund's adjuvant-induced arthritic rat model. Treatments with methanolic, ethyl acetate, and n-hexane extracts were continued for consecutive 20 days. Macroscopic arthritic scoring and water displacement plethysmometry were used to evaluate arthritic development. Hematological and biochemical parameters were investigated and ankle joints were processed for histopathological evaluation. Qualitative phytochemical analysis and GC-MS analysis were conducted for identification of constituents. NAT extracts suppressed arthritic scoring, paw edema, infiltration of inflammatory cells, pannus formation, and bone erosion. The plant extracts ameliorated total leukocytes and platelet counts and nearly normalized red blood cells (RBC) counts and hemoglobin (Hb) content. The extracts were found safe in terms of hepatotoxicity and nephrotoxicity as determined by aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea levels. Comparative analysis showed that ethyl acetate extract produced the highest inhibition of paw edema. The major constituents found in ethyl acetate extract can be classified into three major classes, that is, terpenes, terpenoids, fatty acids, and iridoid glycosides. Current study showed that Nyctanthes arbor-tristis ameliorated experimental rheumatoid arthritis and ethyl acetate extract possessed the highest inhibitory activity.

Discovery of New Benzothiazine Derivative as Modulator of Pro- and Anti-inflammatory Cytokines in Rheumatoid Arthritis.

The anti-inflammatory activities of benzothiazine and pyrazole derivatives are well documented. A series of novel N'-arylmethylidene-2-(3,4-dimethyl-5,5-dioxidopyrazolo(4,3 c)(1,2) benzothiazin-2(4H)yl) acetohydrazide compounds were previously synthesized by combining benzothiazine and pyrazole moieties into a single nucleus. The current study investigates the anti-arthritic potential of 3-ethoxy-4-hydroxyphenyl derivative (EHP) and its possible mechanism in arthritic rat model. Sprague-Dawley rats were induced rheumatoid arthritis with Freund's complete adjuvant and treated with EHP and piroxicam. At the end of the study, arthritic score was calculated, and ankle joint histopathology was performed using hematoxylin and eosin staining. Real-time reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to determine mRNA expression and protein levels of various inflammatory markers, respectively. In vitro concanavalin A (ConA)-stimulated splenocyte proliferation was measured. Serum levels of C-reactive protein (CRP), urea, creatinine, aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were also determined. EHP significantly attenuated macroscopic arthritic score, joint histopathological lesions, and CRP levels. Treatment with EHP significantly reduced pro-inflammatory tissue necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-кB), interleukin-17 (IL-17), and prostaglandin-E2 (PGE2) levels and increased the levels of anti-inflammatory interleukin-4 (IL-4) and interleukin-10 (IL-10). ConA-stimulated splenocyte proliferation was also significantly suppressed by treatment with EHP. Normalizing all hematological markers and ALP levels, EHP did not display any sign of nephrotoxicity and hepatotoxicity as determined by urea, creatinine, ALT, and AST levels. In conclusion, EHP possesses significant anti-arthritic property which may be attributed to its anti-inflammatory and immunomodulatory effects.