scholarly journals Efficacy of Mitochondrial Antioxidant Plastoquinonyl-decyl-triphenylphosphonium Bromide (SkQ1) in the Rat Model of Autoimmune Arthritis

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Alexander A. Andreev-Andrievskiy ◽  
Nataliya G. Kolosova ◽  
Natalia A. Stefanova ◽  
Maxim V. Lovat ◽  
Maxim V. Egorov ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Wistar Rats ◽  
Clinical Signs ◽  
Therapeutic Window ◽  
Autoimmune Arthritis ◽  
Dependent Manner ◽  
Specific Pathogen ◽  
Triphenylphosphonium Bromide

Rheumatoid arthritis is one of the most common autoimmune diseases. Many antioxidants have been tested in arthritis, but their efficacy was, at best, marginal. In this study, a novel mitochondria-targeted antioxidant, plastoquinonyl-decyl-triphenylphosphonium bromide (SkQ1), was testedin vivoto prevent and cure experimental autoimmune arthritis. In conventional Wistar rats, SkQ1 completely prevented the development of clinical signs of arthritis if administered with food before induction. Further, SkQ1 significantly reduced the fraction of animals that developed clinical signs of arthritis and severity of pathological lesions if administration began immediately after induction of arthritis or at the onset of first symptoms (day 14 after induction). In specific pathogen-free Wistar rats, SkQ1 administered via gavage after induction of arthritis did not reduce the fraction of animals with arthritis but decreased the severity of lesions upon pathology examination in a dose-dependent manner. Efficacious doses of SkQ1 were in the range of 0.25–1.25 nmol/kg/day (0.13–0.7 μg/kg/day), which is much lower than doses commonly used for conventional antioxidants. SkQ1 promoted apoptosis of neutrophilsin vitro, which may be one of the mechanisms underlying its pharmacological activity. Considering its low toxicity and the wide therapeutic window, SkQ1 may be a valuable additional therapy for rheumatoid arthritis.

scholarly journals Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Intracellular Degradation ◽  
Main Pathway ◽  
First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

scholarly journals Effect of Massoia (Massoia aromatica Becc.) Bark on the Phagocytic Activity of Wistar Rat Macrophages

2018 ◽  
Author(s):  
Triana Hertiani ◽  
Agustinus Yuswanto ◽  
Sylvia Utami Tunjung Pratiwi ◽  
Harlyanti Mashar
Keyword(s):  
Phagocytic Activity ◽  
Wistar Rats ◽  
In Vitro Assay ◽  
Phagocytic Index ◽  
Dependent Manner ◽  
Vitro Assay ◽  
Macrophage Cells ◽  
In Vivo Assay

Massoia (Massoia aromatica Becc., Lauraceae) bark has been widely used as a component of traditional Indonesian medicine. The indigenous people boil or steam the bark for traditional applications. Our preliminary research revealed the potency of Massoia essential oil and its major compound, C-10 Massoialactone as potential immunomodulator in vitro. However, no scientific evidence regarding its in vivo effects is available. Therefore, this study evaluated the potential immunomodulatory effects of Massoia bark infusion on the nonspecific immune response (phagocytosis) of Wistar rats. The aqueous extract of Massoia bark was obtained by boiling pulverized bark in water, and the C-10 massoialactone content of the extract was determined through Thin Layer Chromatography (TLC) densitometry. For the in vitro assay, macrophages were treated with the freeze-dried infusion at the concentrations of 2.5, 5, 10, 20, or 40 &mu;g/mL media. For the in vivo assay, 2-month-old male Wistar rats were divided into 5 groups. The baseline group received distilled water at the dose of 1 mL/100 g BW with the immunostimulant herbal product &ldquo;X&rdquo; administered as the positive control at the dose of 0.54 mL/rat. The treatment groups received the infusion at a dose of 100, 300, or 500 mg/100 g BW. Treatments were given orally every day for 14 days. The ability of macrophage cells to phagocyte latex was determined as phagocytic index (PI) and was observed under microscopy with 300 macrophages. The in vitro study revealed that the phagocytic activity of the infusion-treated macrophages significantly increased in comparison with that of the control macrophages in a concentration-dependent manner. Among all treatment concentrations, the concentration of 40 &mu;g/ml provided the highest activity with a PI value of 70.51% &plusmn; 1.11%. The results of the in vivo assay confirmed those of the in vitro assay. The results of the present study indicate that Massoia bark can increase the phagocytic activity of rat macrophage cells. Its potential as a naturally derived immunomodulatory agent requires further study.

scholarly journals Inhibitory Effect ofChrysanthemum zawadskiiHerbich var.latilobumKitamura Extract on RANKL-Induced Osteoclast Differentiation

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Dong Ryun Gu ◽  
Jin-Ki Hwang ◽  
Munkhsoyol Erkhembaatar ◽  
Kang-Beom Kwon ◽  
Min Seuk Kim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Osteoclast Differentiation ◽  
Ethanol Extract ◽  
Inhibitory Effect ◽  
Bone Diseases ◽  
Dependent Manner ◽  
Erk Activation

Chrysanthemum zawadskii Herbichvar.latilobum Kitamura, known as “Gujulcho” in Korea, has been used in traditional medicine to treat various inflammatory diseases, including rheumatoid arthritis. However, these effects have not been tested on osteoclasts, the bone resorbing cells that regulate bone metabolism. Here, we investigated the effects ofC. zawadskiiHerbich var.latilobumKitamura ethanol extract (CZE) on osteoclast differentiation induced by treatment with the receptor activator of NF-κB ligand (RANKL). CZE inhibited osteoclast differentiation and formation in a dose-dependent manner. The inhibitory effect of CZE on osteoclastogenesis was due to the suppression of ERK activation and the ablation of RANKL-stimulated Ca2+-oscillation via the inactivation of PLCγ2, followed by the inhibition of CREB activation. These inhibitory effects of CZE resulted in a significant repression of c-Fos expression and a subsequent reduction of NFATc1, a key transcription factor for osteoclast differentiation, fusion, and activationin vitroandin vivo. These results indicate that CZE negatively regulates osteoclast differentiation and may be a therapeutic candidate for the treatment of various bone diseases, such as postmenopausal osteoporosis, rheumatoid arthritis, and periodontitis.

scholarly journals AttenuatedSalmonella typhimuriumSV4089 as a Potential Carrier of Oral DNA Vaccine in Chickens

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Seyed Davoud Jazayeri ◽  
Aini Ideris ◽  
Zunita Zakaria ◽  
Abdul Rahman Omar
Keyword(s):  
Dna Vaccine ◽  
Oral Vaccine ◽  
Serum Antibody ◽  
Clinical Signs ◽  
Eukaryotic Expression ◽  
Specific Pathogen ◽  
Viable Bacteria

AttenuatedSalmonellahas been used as a carrier for DNA vaccine. However,in vitroandin vivostudies on the bacteria following transfection of plasmid DNA were poorly studied. In this paper, eukaryotic expression plasmids encoding avian influenza virus (AIV) subtype H5N1 genes, pcDNA3.1/HA, NA, and NP, were transfected into an attenuatedSalmonella enteric typhimuriumSV4089.In vitrostability of the transfected plasmids intoSalmonellawere over 90% after 100 generations. The attenuatedSalmonellawere able to invade MCF-7 (1.2%) and MCF-10A (0.5%) human breast cancer cells. Newly hatched specific-pathogen-free (SPF) chicks were inoculated once by oral gavage with 109colony-forming unit (CFU) of the attenuatedSalmonella. No abnormal clinical signs or deaths were recorded after inoculation. Viable bacteria were detected 3 days after inoculation by plating from spleen, liver, and cecum. Fluorescentin situhybridization (FISH) and polymerase chain reaction (PCR) were carried out for confirmation.Salmonellawas not detected in blood cultures although serum antibody immune responses toSalmonellaO antiserum group D1 factor 1, 9, and 12 antigens were observed in all the inoculated chickens after 7 days up to 35 days. Our results showed that live attenuatedS. typhimuriumSV4089 harboring pcDNA3.1/HA, NA, and NP may provide a unique alternative as a carrier for DNA oral vaccine in chickens.

scholarly journals Myeloid skewing in murine autoimmune arthritis occurs in hematopoietic stem and primitive progenitor cells

Blood ◽  
2012 ◽  
Vol 120 (11) ◽  
pp. 2203-2213 ◽  
Author(s):  
Kwadwo A. Oduro ◽  
Fang Liu ◽  
Qing Tan ◽  
Chan-Kyu Kim ◽  
Olga Lubman ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Myeloid Cell ◽  
Autoimmune Arthritis ◽  
Dependent Manner ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Arthritis Model ◽  
Pathologic State

Abstract Skewing toward myeloid cell production is often observed in chronic inflammation and autoimmune diseases. Herein, we determined whether persistent myeloid activation and proinflammatory output occurring in pathologic conditions is at the level of hematopoietic stem and primitive progenitor cells (HSPPCs). By using a mouse arthritis model, we found that even though HSPPCs in arthritis still retained the capacity to differentiate into different lineages, they acquired enhanced in vitro and in vivo propensity in a disease-dependent manner to generate myeloid cells, the key perpetrators of tissue damage in arthritis. This myeloid skewing was cell intrinsic, as arthritic HSPPCs up-regulate myeloid-specific transcripts including S100a8. Exogenous S100a8 promoted myeloid cell output from wild-type HSPPCs, suggesting mechanistic involvement of this gene in the myeloid priming that occurs in arthritic HSPPCs. Therefore, our results indicate that in arthritic mice, HSPPCs adopt a pathologic state that favors disease persistence.

Side-effects of drugs used in the treatment of rheumatoid arthritis

1995 ◽  
Vol 61 ◽  
pp. 195-207 ◽  
Author(s):  
P.J. Evans ◽  
B. Halliwell
Keyword(s):  
Rheumatoid Arthritis ◽  
Arachidonic Acid ◽  
Side Effects ◽  
Oxidative Damage ◽  
Biological Fluids ◽  
Flufenamic Acid ◽  
Dependent Manner ◽  
Haem Proteins

A number of anti-inflammatory and other drugs used in the treatment of rheumatoid arthritis have been screened for their ability to cause oxidative damage to lipids and proteins in vitro. Although many drugs exhibited an antioxidant profile, a few drugs tested were pro-oxidant, increasing peroxidation of arachidonic acid by mixtures of haem proteins and H2O2. This system may be an appropriate model to use in the inflammatory situation, since microbleeding to release haemoglobin occurs in the inflamed rheumatoid joint, where H2O2 is produced by invading neutrophils. The damaging effects of the pro-oxidant drugs phenylbutazone, meclofenamic acid and flufenamic acid were investigated in some detail using this system. Arachidonic acid peroxidation was accentuated in a dose-dependent manner and in the presence of haem proteins and H2O2, phenylbutazone also causes inactivation of α1-antiproteinase, a major serine proteinase inhibitor in biological fluids. The above drugs may interact with ferryl haemoglobin, produced by the reaction of H2O2 with haemoglobin, to generate drug-derived radicals causing oxidative damage in these systems. If such reactions occur in vivo, they could contribute to the side-effects induced by these drugs on administration to certain rheumatoid arthritis patients.

scholarly journals Haemostatic property of Chromolaena odorata leaf extracts: in vitro and in vivo evaluation in wistar rats

2016 ◽  
Vol 89 (2) ◽  
Author(s):  
Henshaw Uchechi Okoroiwu ◽  
Item Justin Atangwho ◽  
Emmanuel Kufre Uko ◽  
Okafor Ifeyinwa Maryann
Keyword(s):  
Wistar Rats ◽  
Ethanol Extract ◽  
Dependent Manner ◽  
Chromolaena Odorata ◽  
Sample Collection ◽  
Leaf Extracts ◽  
In Vivo Evaluation ◽  
Coagulation Study

This study was designed to investigate the effects of aqueous, ethanol and crude extracts of <em>Chromolaena odorata</em> leaf on haemostatic mechanism of wistar rats and its possible <em>in vitro</em> use in coagulation study. Fifty wistar rats of both sexes weighing between 140-180 g were sorted into 10 groups each fed via oral gavage once daily for 21 days. Sample collection was done by cardiac puncture. Bleeding and clotting times were performed using Duke’s and Ivy’s methods, respectively. The prothrombin time was performed using the Quick’s one stage method, while the partial thromboplastin time using kaolin was done using Macpherson and Hardity method using Giess diagnosis reagent. Significant results were observed in the bleeding and clotting times of the three extracts in a dose-dependent manner. The 300-mg/kg ethanol extract decreased the bleeding time more than the other two extracts. Only the ethanol 150 and 300 mg/mL showed <em>in vitro</em> activity. The study showed the <em>in vivo</em> haemostatic properties of <em>Chromolaena odorata</em> leaf extracts and its possible use in <em>in vitro</em> coagulation study.

scholarly journals In vitro and In vivo Anti-inflammatory Activities of Mesua ferrea Linn

2018 ◽  
Vol 10 (03) ◽  
Author(s):  
Krishna Chaithanya K ◽  
Gopalakrishnan V K ◽  
ZenebeHagos . ◽  
Nagaraju B ◽  
Kamalakararao K ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Wistar Rats ◽  
Inflammatory Activity ◽  
Raw 264.7 Cells ◽  
Bark Extract ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Anti Inflammatory

Objective: Mesuaferrea L is a medicinal plant belongs to the family Clusiace, it is extensively used in folk medicine for treatment of chronic inflammatory diseases.The present study was aimed to evaluate in vitro and in vivo anti-inflammatory activity of M. ferrea L. Methods: The in vitro anti-inflammatory activities such as nitric oxide, PGE2, pro-inflammatory cytokines (TNF-α and IL-1β) were studied in RAW 264.7 cells and in vivo studies were carried out on carrageenan -induced inflammation in Wistar rats. The sequentially extracted M. ferreaL bark extracts (MFBHE, MFBEE, and MFBME) exhibited inhibitory effects on pro-inflammatory mediators such as nitric oxide, prostaglandin E2, tumour necrosis factorαandinterleukin-1βproduction in concentration dependent manner in LPS induced RAW 264.7 cells andCarrageenan induced paw oedema in Wistar rats. Conclusion: The result of the present study indicated that M. ferrea L ethyl acetate bark extract exhibited significant in vitroand in vivoanti-inflammatory activity.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  
Keyword(s):  
Biological Effects ◽  
Exchange Chromatography ◽  
Health Concern ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

Comparison of In Vitro and In Vivo Effects of Infliximab on Cytokine Production in Proliferating CD4+ T Cells in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 1 (2) ◽  
pp. 122-128
Author(s):  
Syuichi Koarada ◽  
Yuri Sadanaga ◽  
Natsumi Nagao ◽  
Satoko Tashiro ◽  
Rie Suematsu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production
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