Suppression of inflammation and cartilage destruction by steroid-rich methanolic extract of Withania Somnifera: A study on collagen induced arthritic rats

2017 ◽  
Vol 2 (2) ◽  
pp. 172
Author(s):  
Mahmood Ahmad Khan ◽  
Mythily Subramaneyaan ◽  
Vinod Kumar Arora ◽  
Rafat Sultana Ahmed
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Withania Somnifera ◽  
Methanolic Extract ◽  
Bone Erosion ◽  
Cartilage Destruction ◽  
Normal Serum ◽  
Inflammatory Disorder ◽  
Tnf Α ◽  
And Cartilage

Rheumatoid arthritis (RA) is an inflammatory disorder characterized by oxidative stress, inflammation and cartilage destruction. Withania somnifera (WS) is used in Indian folk medicine for the treatment of various musculoskeletal disorders. WS is considered to possess potent antioxidant and anti-inflammatory activities. The aim of the present study was to evaluate the possible mechanism of action of methanolic extract of Withania somnifera roots (WSMe) against collagen induced arthritic (CIA) rats. Arthritis in rats was induced by subcutaneous injection of bovine type II collagen and was treated with WSMe at the dose of 200 mg/kg BW for 20 days after arthritis was induced. Number of biochemical, molecular and histological changes was observed in CIA rats. In CIA rats we found an imbalance in antioxidant and oxidant status as level of MDA was increased while GST, GSH and FRAP was found to be decreased. Administration of WSMe200 significantly ameliorates the level of antioxidant and oxidant to near normal. Serum concentration of transcription factor NF-kB, inflammatory cytokines like TNF-α, IL-1β, IL-6 and IL-10 were altered in CIA rats. In consistent to this mRNA expression of NF-kB, TNF-α and MMP-8 were also found to be Up-regulated, which were significantly inhibited by WSMe200 treatment. These findings are positively correlated with the results of histological examinations of joints, which showed reduced inflammation and bone erosion in the treated group. The ability to inhibit the production of oxidative stress and subsequent modulation of the inflammatory cytokines shows the protective effect of WSMe and its potential use for the treatment of arthritis.

scholarly journals Kinetics and Interplay of Mediators of Inflammation-Induced Bone Damage in the Course of Adjuvant Arthritis

2013 ◽  
Vol 26 (1) ◽  
pp. 37-48 ◽  
Author(s):  
S.M. Nanjundaiah ◽  
J.P. Stains ◽  
K.D. Moudgil
Keyword(s):  
Bone Remodeling ◽  
Inflammatory Cytokines ◽  
Adjuvant Arthritis ◽  
Bone Erosion ◽  
Experimental Conditions ◽  
Mediators Of Inflammation ◽  
Bone Damage ◽  
Tnf Α ◽  
Kinetics Of ◽  
Pro Inflammatory Cytokines

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation, bone erosion, and cartilage destruction in the joints. It is increasingly being realized that inflammation might play an important role in inducing bone damage in arthritis. However, there is limited validation of this concept in vivo in well-controlled experimental conditions. We addressed this issue using the adjuvant arthritis (AA) model of RA. In AA, the draining lymph nodes are the main sites of activation of pathogenic leukocytes, which then migrate into the joints leading to the induction of arthritis. We tested the temporal kinetics of mediators of bone damage [e.g., receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and osteopontin (OPN)] and inflammation (pro-inflammatory cytokines and chemokines) in the draining lymph node cells (LNC) at different phases of AA, and then examined their inter-relationships. Our study revealed that, together with cytokines/chemokines, some of the mediators of bone remodeling are also produced in LNC. Various cytokines/chemokines showed distinct kinetics of expression as well as patterns of correlation with mediators of bone remodeling at different phases of the disease. Pro-inflammatory cytokines such as TNF-α are known to play an important role in bone damage. Interestingly, there was a positive correlation between TNF-α and RANKL, between RANKL and each of the 3 chemokines tested (RANTES, MIP-1α, and GRO/KC), and between TNF-α and RANTES. Our results in the AA model lend support to the concept of osteo-immune crosstalk during the course of autoimmune arthritis.

Mitigation of IL-1β, IL-6, TNF-α, and markers of apoptosis by ursolic acid against cisplatin-induced oxidative stress and nephrotoxicity in rats

2021 ◽  
Vol 40 (12_suppl) ◽  
pp. S397-S405
Author(s):  
Pankaj Tripathi ◽  
Saeed Alshahrani
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Uric Acid ◽  
Inflammatory Cytokines ◽  
Caspase 3 ◽  
Caspase 9 ◽  
Histological Damage ◽  
Tnf Α ◽  
Mda Content ◽  
Pro Inflammatory Cytokines

Background: Ursolic acid (UA) is a natural pentacyclic triterpenoid that is known for its benefits under several pathological conditions. Cisplatin (CP) is among the most preferred chemotherapeutic agents; however, its nephrotoxicity limits its clinical utility. Purpose: This study was aimed to determine the role of UA in the reduction of CP-induced nephrotoxicity and mitigation of pro-inflammatory cytokines and apoptosis in a rat model. Methodology: Male Wistar rats were randomized into vehicle control, CP (7.5 mg/kg), UA 10 mg/kg, and CP with UA 5 and 10 mg/kg groups. Kidney and blood samples were collected for assessment of renal function, measurement of pro-inflammatory cytokines, apoptosis markers, antioxidant activity, and tissue histology. Results: CP significantly increased the levels of serum Cr, BUN, and uric acid; it also induced histological damage reflecting the pathophysiology observed during nephrotoxicity. CP has also shown its pro-oxidant activity in kidney tissue because CP decreased the levels of GSH, SOD, and CAT; it increased the lipid peroxidation as measured by MDA content. In addition, CP significantly upregulated the activity of pro-inflammatory cytokines and expression of apoptotic markers, that is, there were increased levels of IL-1β, IL-6, TNF-α, caspase-3, and caspase-9. Two weeks of continuous treatment of UA showed significant recovery against CP-induced nephrotoxicity; UA decreased the levels of Cr, BUN, and uric acid and ameliorated histological damage. UA also downregulated the activities of IL-1β, IL-6, and TNF-α as well as expression of caspase-3 and caspase-9. Furthermore, CP-induced oxidative stress that was antagonized by UA—the levels of GSH, SOD, and CAT were significantly increased while MDA content was decreased. Conclusions: UA has a protective effect against CP-induced nephrotoxicity, which may be due to its antioxidant activity and mitigation of ILβ-1, ILβ-6, TNF-α, and markers of apoptosis.

scholarly journals Effects of Portabella mushrooms on collagen-induced arthritis, inflammatory cytokines, and body composition in dilute brown non-agouti (DBA1) mice

2011 ◽  
Vol 1 (9) ◽  
pp. 279
Author(s):  
Sandra Peterson ◽  
Edralin A. Lucas ◽  
Djibril Traore ◽  
Lawrance Christopher ◽  
Christine French ◽  
...  
Keyword(s):  
Body Composition ◽  
Mass Loss ◽  
Inflammatory Cytokines ◽  
Fat Mass ◽  
Lean Mass ◽  
Cell Function ◽  
Bone Erosion ◽  
Collagen Induced Arthritis ◽  
Tnf Α

Background: Exotic mushrooms have long been used in Asia for treatment and/or prevention of chronic diseases due to their immunomodulatory properties. However, the health benefits of portabella mushrooms (PM) (brown Agaricus bisporous), on collagen-induced arthritis (CIA) and associated complications, (i.e. loss of lean mass, increased fat mass and inflammatory cytokines), have not been previously investigated.Methods: We investigated CIA pathogenesis, body composition and plasma levels of IL- 6, TNF-α and sICAM1 in DBA1 female mice fed either the AIN76 diet or the same diet fortified with 5% lyophilized PM (n=19-20/group). Ten mice/group were immunized with 100 µg bovine collagen type II on day 42 of the protocol, followed by 50 µg lipopolysaccharides on day 62, and euthanized on day 73-74. Cytokines were measured by ELISA.Results: Compared to baseline diet, PM had: no protective effect from CIA since all collagen-immunized mice developed severe edema, bone erosion, and mononuclear cell infiltration in paws. In mice with and those without CIA, feeding a PM-fortified diet resulted in higher percent of body fat than feeding the baseline diet (p<0.05). After CIA induction, PM provided the following beneficial effects: (a) a smaller reduction in lean mass and absolute thymus weight; (b) a higher fat mass loss; and (c) lower plasma TNF-α levels (p <0.05). PM-fortification did not alter plasma IL-6 and sICAM1 regardless of CIA status; but it increased in vitro IL-6 secretion by mitogen-treated spleen cells.Conclusion: Our data suggest that PM may reduce plasma TNF-α, attenuate lean mass loss and thymus atrophy associated with arthritis, and protect spleen cell function assessed by IL-6 secretion. However, PM-fortification did not attenuate overall CIA pathogenesis which may be due to lack of effect on plasma IL-6. Decreased TNF-α without alterations in IL-6 may reduce the risk of other conditions associated with chronic inflammation such as cardiovascular disease.Key words: portabella mushrooms, inflammatory cytokines, collagen-induced arthritis, body composition, TNF-α, IL-6, thymus, DBA1 mice.

scholarly journals Super Critical Fluid Extracted Fatty Acids from Withania somnifera Seeds Repair Psoriasis-Like Skin Lesions and Attenuate Pro-Inflammatory Cytokines (TNF-α and IL-6) Release

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 185 ◽  
Author(s):  
Acharya Balkrishna ◽  
Pradeep Nain ◽  
Anshul Chauhan ◽  
Niti Sharma ◽  
Abhishek Gupta ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Inflammatory Cytokines ◽  
Withania Somnifera ◽  
Therapeutic Potential ◽  
Skin Lesions ◽  
Luciferase Reporter ◽  
Plant Parts ◽  
Tnf Α ◽  
Psoriatic Lesions ◽  
Pro Inflammatory Cytokines

(1) Background: Withania somnifera Dunal (Ashwagandha) is a widely used medicinal herb in traditional medicinal systems with extensive research on various plant parts. Surprisingly, seeds of W. somnifera have never been investigated for their therapeutic potential. (2) Methods: W. somnifera seeds were extracted for fatty acids (WSSO) using super critical fluid extraction, and was analyzed by gas chromatography. Its therapeutic potential in psoriasis-like skin etiologies was investigated using a 12-O tetradecanoyl phorbol 13-acetate (TPA)-induced psoriatic mouse model. Psoriatic inflammation along with psoriatic lesions and histopathological scores were recorded. WSSO was also tested on murine macrophage (RAW264.7), human epidermoid (A431), and monocytic (THP-1) cells, stimulated with TPA or lipo poly-saccharide (LPS) to induce pro-inflammatory cytokine (IL-6 and TNF-α) release. NFκB promoter activity was also measured by luciferase reporter assay. (3) Results: Topical application of WSSO with concurrent oral doses significantly reduced inflammation-induced edema, and repaired psoriatic lesions and associated histopathological scores. Inhibition of pro-inflammatory cytokines release was observed in WSSO-treated A431 and THP-1 cells, along with reduced NFκB expression. WSSO also inhibited reactive nitrogen species (RNS) in LPS-stimulated RAW264.7 cells. (4) Conclusion: Here we show that the fatty acids from W. somnifera seeds have strong anti-inflammatory properties, along with remarkable therapeutic potential on psoriasis-like skin etiologies.

scholarly journals Effect of caraway on gentamicin-induced oxidative stress, inflammation and nephrotoxicity in rats

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Hoda Erjaee ◽  
Fatemeh Azma ◽  
Saeed Nazifi
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Group Treatment ◽  
Structural Damage ◽  
Seed Oil ◽  
Treated Group ◽  
Control Group ◽  
Protective Effects ◽  
Simultaneous Treatment ◽  
Tnf Α

Different potentially therapeutic approaches to prevent or attenuate gentamicin (GEM) induced nephrotoxicity have been proposed. The aim of the present study was to investigate the possible protective effects of caraway seed oil against GEM-induced nephrotoxicity in rats. Rats (24) were randomly assigned into four equal groups: i) normal control group, ii) treated with GEM, iii) pretreated with orally caraway seed oil 10 (mg kg−1) plus GEM and iv) treated with GEM and caraway seed oil 10 mg kg−1. Biochemical examinations were utilized for evaluation of the oxidative stress and renal nephrotoxicity. Creatinine, blood urea nitrogen (BUN), plasma malondialdehyde (MDA) levels, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined. Administration of gentamicin to rats induced a marked renal failure, characterized by a significant increase in plasma creatinine and BUN concentrations. The animals treated with gentamicin alone showed a significantly higher plasma MDA level andlower SOD, GSH-Px and CAT activities when compared with the control group. Treatment and simultaneous treatment with caraway seed oil produced amelioration in MDA and increased the activity of antioxidant enzymes SOD, GSH-Px and CAT when compared with the gentamicin treated group. In addition, GEM nephrotoxicity increased renal inflammatory cytokines (TNF-α, IL-6 and IFN-γ). Pro-inflammatory cytokines were significantly decreased (P&lt;0.05) in the test groups administered caraway seed oil. These findings suggest that caraway seed oil treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress and inflammation in rats.

Spinal and general anesthesia produces differential effects on oxidative stress and inflammatory cytokines in orthopedic patients

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Peter A. Aremu ◽  
Abayomi M. Ajayi ◽  
Benneth Ben-Azu ◽  
Olayinka T. Orewole ◽  
Solomon Umukoro
Keyword(s):  
Oxidative Stress ◽  
General Anesthesia ◽  
Inflammatory Cytokines ◽  
Orthopedic Surgery ◽  
Interleukin 6 ◽  
Surgical Stress ◽  
Oxidative Stress Biomarkers ◽  
Differential Effects ◽  
Stress Biomarkers ◽  
Tnf Α

AbstractObjectivesThe contribution of anesthetic procedure to surgical stress and postoperative complications has been attributed to increased oxidative stress and release of inflammatory cytokines. Thus, the levels of oxidative stress biomarkers and inflammatory cytokines in patients with general anesthesia (GA) and spinal anesthesia (SA) that underwent open reduction and internal fixation (ORIF) in orthopedic surgery at Federal Teaching Hospital, Ido-Ekiti, Ekiti state, Nigeria were investigated.MethodsForty patients were randomly distributed into two groups (n = 20) namely GA and SA. Blood samples were collected before and after surgery for estimation of glucose, oxidative stress biomarkers (malondialdehyde [MDA], glutathione, catalase and nitrile) and inflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6) levels.ResultsThe post-operative blood glucose level was higher than the pre-operative value (p<0.5) in the two groups. There were significant (p<0.05) changes in MDA concentration and catalase activity in patients with GA in the post-operative stage relative to preoperative phase. There were no significant differences in glutathione, nitrite and interleukin-6 contents between the two groups. The patients with SA had higher levels of TNF-α in the post-operative stage.ConclusionsThese findings suggest that anesthesia has differential effects on oxidative stress and inflammatory cytokines in patients with ORIF orthopedic surgery.

scholarly journals Curcumin Ameliorates Chronic Mild Stress-Induced Depressive-Like Behavior via HMGB1/TLR4/NF-κB Signaling Pathway

2021 ◽  
Author(s):  
Li Miao ◽  
Fei Huang ◽  
Wei Jiang ◽  
Ying-ying Sun ◽  
Yong-jin Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Immunofluorescent Staining ◽  
Antidepressant Effect ◽  
Therapeutic Drug ◽  
Inflammatory Disorder ◽  
Mild Stress ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

Abstract BackgroundDepression, one of the most frequently-occurring psychiatric disorders worldwide, is a significant inflammatory disorder. The polyphenol curcumin (Cur), which is extracted from Curcuma longa, has marked anti-inflammatory and anti‑oxidative effects against inflammatory diseases. However, whether Cur has antidepressant effects and the possible mechanisms, are unclear. The present study aimed to assess Cur’s beneficial effects on depressive-like behaviors using a chronic unpredictable mild stress (CUMS) model and its possible molecular mechanisms. MethodsWe performed CUMS treated Sprague Dawley (SD) rats as a model of depression. Behavioral observations were performed by sucrose preference test (SPT), force swimming test (FST) and tail suspension test (TST). Hippocampal expression of oxidative stress markers and inflammatory cytokines were measured with ELISA. Hippocampal expression of high-mobility group box 1 (HMGB1), IL-1β, TNF-α and IL-6 were determined with quantitative PCR analyses and immunofluorescent staining. Hippocampal Toll-like receptor 4 (TLR4) and NF-κB activation were examined with Western blotting analysis.ResultsRats subjected to CUMS demonstrated marked depressive-like behavior (decreased locomotor activity and sucrose intake, and prolonged immobility). Their levels of oxidative stress and inflammatory cytokines increased significantly, and their levels of phosphorylated nuclear factor kappa-B (NF-κB), toll-like receptor 4 (TLR4), and HMGB1, also increased in the hippocampus. The changes were ameliorated significantly by treatment with Cur (50, 100 mg/kg) to varying degrees.Conclusion This study demonstrated that Cur has a potent antidepressant effect via the HMGB1/TLR4/NF-κB pathway, suggesting that Cur might be a promising therapeutic drug for depression.

scholarly journals The Influence of Sevelamer Hydrochloride and Calcium Carbonate on Markers of Inflammation and Oxidative Stress in Hemodialysis at Six Months of Follow-Up

2021 ◽  
Vol 8 ◽  
Author(s):  
Elodia Nataly Díaz-De la Cruz ◽  
José Ignacio Cerrillos-Gutiérrez ◽  
Andrés García-Sánchez ◽  
Carlos Gerardo Prado-Nevárez ◽  
Jorge Andrade-Sierra ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Calcium Carbonate ◽  
Inflammatory Cytokines ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Sevelamer Hydrochloride ◽  
Tnf Α ◽  
Compensatory Effect ◽  
Pro Inflammatory Cytokines

Patients with end-stage renal disease (ESRD) present alterations in mineral and bone metabolism. Hyperphosphatemia in ESRD is considered an independent risk factor for cardiovascular disease (CVD), increasing morbidity, and mortality. Sevelamer hydrochloride is a calcium-free, non-absorbable phosphate-chelating polymer. Calcium carbonate chelator is helpful in controlling serum phosphate levels. There is insufficient information on the influence of sevelamer hydrochloride and calcium carbonate on the behavior of oxidative stress (OS) markers and inflammation in patients on hemodialysis (HD). A randomized open clinical trial was carried out on patients to evaluate sevelamer hydrochloride and calcium carbonate influence at 6 months of study follow-up. Levels of oxidants (LPO, NO, and 8-isoprostanes), antioxidants (SOD and TAC), oxidative DNA damage (8-OHdG and hOGG1), pro-inflammatory cytokines (IL-6 and TNF-α), and inflammation markers (ferritin and C-reactive protein) were measured with colorimetric and ELISA methods. We found a significant increase in oxidants LPO and NO, and antioxidants SOD and TAC, and downregulation of IL-6 and TNF-α. Ferritin decrease at 6 months follow-up in the sevelamer hydrochloride group. Increase in C-reactive protein was found in the group of patients treated with calcium carbonate. In conclusion, we found an oxidative state imbalance with increase in LPO and NO oxidants. The activity of the antioxidant enzymes (SOD and TAC) was also found to increase, suggesting a compensatory effect in the face of increase in oxidants. The same phenomenon was observed with increase in the oxidative damage marker to DNA and the increase in the DNA repair enzyme, suggesting a compensatory effect. Pro-inflammatory cytokines were predominantly downregulated by TNF-α in the group that ingested sevelamer hydrochloride in the final determination at 6 months of follow-up. Serum ferritin levels decreased significantly at the end of follow-up in patients on HD in the sevelamer hydrochloride group. The management of hyperphosphatemia with sevelamer hydrochloride appears to have obvious anti-inflammatory and antioxidant benefits.

scholarly journals Susceptibility of Cyclin-dependent Kinase Inhibitor-1–deficient Mice to Rheumatoid Arthritis From IL-1β–induced Inflammation

2020 ◽  
Author(s):  
Yoshinori Takashima ◽  
Shinya Hayashi ◽  
Koji Fukuda ◽  
Toshihisa Maeda ◽  
Masanori Tsubosaka ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Monoclonal Antibodies ◽  
Kinase Inhibitor ◽  
Joint Inflammation ◽  
Type Ii Collagen ◽  
Cartilage Destruction ◽  
Knee Joints ◽  
Inflammatory Disorder ◽  
Cyclin Dependent Kinase ◽  
And Cartilage

Abstract Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disorder whose progression is modulated by fibroblast-like synoviocytes (FLSs). Cyclin-dependent kinase (CDK) inhibitor 1 (p21) regulates the activation of other CDKs, and we recently reported that p21 deficiency induces susceptibility to osteoarthritis. Here, we focused on joint inflammation to determine the mechanisms associated with p21 function in synovial and cartilage tissues in RA.Methods: p21-knockout (p21-/-) mice and wild-type C57BL/6 (WT p21+/+) mice were used to establish a collagen antibody-induced arthritis (CAIA) model. The severity of arthritis was evaluated visually, and histological and immunohistological analyses performed 7, 14, and 28 days after injection with a cocktail of five monoclonal antibodies that recognize conserved epitopes on various species of type II collagen. The response of p21 siRNA-treated human RA FLSs to IL-1β stimulation was also determined.Results: Arthritis scores were higher in p21-/- mice than those in p21+/+ mice. More severe and prolonged synovitis of the knee joints and earlier loss of staining and cartilage destruction were observed in p21-/- mice than in p21+/+ mice. p21-/- mice expressed higher levels of IL-1β, F4/80, p-IKKα/β, and MMPs in cartilage and synovial tissues at each time point, except for before injection of the monoclonal antibodies, via IL-1β-induced NF-kB signaling. IL-1β stimulation significantly increased MMP expression and enhanced IKKα/β phosphorylation in human FLSs.Conclusion: p21-deficient CAIA mice are susceptible to alterations in the RA phenotype, including joint cartilage destruction and severe synovitis, via IL-1β-induced inflammation. Therefore, p21 regulation may constitute a possible strategy for RA treatment.

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