scholarly journals Nerolidol: a potential approach in rheumatoid arthritis through reduction of TNF-α, IL-1β, IL-6, NF-Kβ, COX-2 and anti-oxidant effect in CFA-induced arthritic model

Author(s):  
Shanila Akhter ◽  
Hafiz Muhammad Irfan ◽  
Alamgeer Yuchi ◽  
Shah Jahan ◽  
Muhammad Shahzad ◽  
...  

Abstract Rheumatoid arthritis an autoimmune infectious disorder, is categorized by inflammation and increased level of pro-inflammatory cytokines which are released by immune cells, macrophages or activation of arachidonic acid metabolism. The expression of these cytokines, oxidative free radicals and the activation of COX-2 enzymes are crucial targets for chronic inflammation. On the basis of established anti-inflammatory efficacy of Nerolidol, the primary study was further appraised to determine its efficacy against Freund’s complete adjuvant (CFA) rheumatoid model. Arthritis was persuaded by inoculation of 0.1mL CFA injection into left hind footpad of rats. Anti-arthritic potential of nerolidol (at 200, 400 and 800mg/kg doses) was assessed by measuring the paw volume, body weight, serum analysis, histopathological and radio-graphics of ankle joints. Expressions of cytokine’s panels like IL-10, IL-4, COX-2, NF-Kβ, TNF-α, IL-6, PGE-2 and IL-1β were determined by real time qPCR. Antioxidant enzyme analyses was calculated by measuring the SOD, POD and catalase activity from serum and equated with arthritic control group. Nerolidol prevented the body weight loss, stabilized the biochemical and haematological homeostasis and significantly reduced the paw volume. Furthermore, X-ray and histopathological assessment of ankle joints showed an improvement in the joint structure of rats treated with nerolidol. Besides that, over expression of gene pointers like TNF-α, IL-1β, IL-6, NF-Kβ, PGE-2 and COX-2 in CFA treated control rats were also reversed with nerolidol. This anti-arthritic mechanism was further supported by the increased level of IL-10, IL-4 and serum anti-oxidant activity. The present findings demonstrate that nerolidol reduce the adjuvant arthritis by down-regulating the proinflammatory cytokines and up-regulating the aforementioned anti-inflammatory cytokines and may be used as a therapeutic substance for the management of human rheumatoid arthritis.

2017 ◽  
Vol 43 (2) ◽  
pp. 540-552 ◽  
Author(s):  
Hany H. Arab ◽  
Samir A. Salama ◽  
Tamer M. Abdelghany ◽  
Hany A. Omar ◽  
El-Shaimaa A. Arafa ◽  
...  

Background/Aims: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. Methods: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund’s adjuvant paw inoculation. The levels of TNF-α and IL-10 were measured by ELISA while the protein expression of NF-κBp65, COX-2 and iNOS was detected by immunohistochemistry. The expression of MAPK target proteins was assessed by Western blotting. Results: CM attenuated paw edema, arthritic index and gait score along with dorsal pouch inflammatory cell migration. CM lowered the TNF-α and augmented the anti-inflammatory IL-10 levels in sera and exudates of arthritic rats. It also attenuated the expression of activated NF-κBp65, COX-2 and iNOS in the lining of the dorsal pouch. Notably, CM inhibited the MAPK pathway signal transduction via lowering the phosphorylation of p38 MAPK, ERK1/2 and JNK1/2 in rat hind paws. Additionally, CM administration lowered the lipid peroxide and nitric oxide levels and boosted glutathione and total anti-oxidant capacity in sera and exudates of animals. Conclusion: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.


2021 ◽  
Vol 11 (13) ◽  
pp. 6055
Author(s):  
Akhtar Ali ◽  
En-Hyung Kim ◽  
Jong-Hyun Lee ◽  
Kang-Hyun Leem ◽  
Shin Seong ◽  
...  

Prolonged inflammation results in chronic diseases that can be associated with a range of factors. Medicinal plants and herbs provide synergistic benefits based on the interaction of multiple phytochemicals. The dried root of Scutellaria baicalensis Georgi and its compounds possess anti-inflammatory, anti-oxidative, and anticancer effects. Processing is a traditional method to achieve clinical benefits by improving therapeutic efficacy and lowering toxicity. In this study, we investigated the anti-inflammatory and anti-oxidant effect of processed Scutellaria baicalensis Georgi extract (PSGE) against lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Data using Griess assay and ELISA showed that PSGE decreased nitric oxide and prostaglandin E2 (PGE2) levels against LPS. PSGE treatment up-regulated 15-hydroxyprostaglandin dehydrogenase (PGDH), while cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 expression did not change. Interestingly, PGE2 inhibition was regulated by prostaglandin catabolic enzyme 15-PGDH rather than COX-2/mPGES-1, enzymes essential for PGE2 synthesis. Additionally, PSGE-suppressed LPS-induced IL-6 and TNF-α production through NF-κB signaling. NF-κB release from an inactive complex was inhibited by HO-1 which blocked IκBα phosphorylation. The ROS levels lowered by PSGE were measured with the H2DCFDA probe. PSGE activated NRF2 signaling and increased antioxidant Hmox1, Nqo1, and Txn1 gene expression, while reducing KEAP1 expression. In addition, pharmacological inhibition of HO-1 confirmed that the antioxidant enzyme induction by PSGE was responsible for ROS reduction. In conclusion, PSGE demonstrated anti-inflammatory and anti-oxidant effects due to NRF2/HO-1-mediated NF-κB and ROS inhibition.


2020 ◽  
Vol 48 (08) ◽  
pp. 1875-1893
Author(s):  
Da-Sol Kim ◽  
Kyoung-Eun Park ◽  
Yeon-Ju Kwak ◽  
Moon-Kyoung Bae ◽  
Soo-Kyung Bae ◽  
...  

Inflammation regulation is essential for maintaining healthy functions and normal homeostasis of the body. Porphyromonas gingivalis (P. gingivalis) is a gram-negative anaerobic bacterium and a major pathogen that causes oral inflammation and other systemic inflammations. This study aims to examine the anti-inflammatory effects of Agrimonia pilosa Ledeb root extracts (APL-ME) in Porphyromonas gingivalis LPS-induced RAW 264.7 cells and find anti-inflammatory effect compounds of APL-ME. The anti-inflammatory effects of APL-ME were evaluated anti-oxidant activity, cell viability, nitrite concentration, pro-inflammatory cytokines (interleukin-1[Formula: see text], interleukin-6, tumor necrosis factor (TNF)-[Formula: see text], and anti-inflammatory cytokine (interleukin-10 (IL-10)). Also, Inflammation related genes and proteins, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), expression were decreased by APL-ME and mitogen-activated protein kinase (MAPK) signaling proteins expression was regulated by APL-ME. Liquid chromatography-mass spectrometer (LC/MS)-MS analysis results indicated that several components were detected in APL-ME. Our study indicated that APL-ME suppressed nitrite concentrations, pro-inflammatory cytokines such as IL-1[Formula: see text], IL-6 and TNF-[Formula: see text] in P. gingivalis LPS induced RAW 264.7 cells. However, IL-10 expression was increased by ALP-ME. In addition, protein expressions of COX-2 and iNOS were inhibited APL-ME extracts dose-dependently. According to these results, APL-ME has anti-inflammatory effects in P. gingivalis LPS induced RAW 264.7 cells.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjun Yan ◽  
Dongqing Ren ◽  
Xiaoxue Feng ◽  
Jinwen Huang ◽  
Dabin Wang ◽  
...  

Background: The incidence of cerebral ischemia disease leading cause of death in human population worldwide. Treatment of cerebral ischemia remains a clinical challenge for researchers and mechanisms of cerebral ischemia remain unknown. During the cerebral ischemia, inflammatory reaction and oxidative stress plays an important role. The current investigation scrutinized the neuroprotective and anti-inflammatory role of pterostilbene against cerebral ischemia in middle cerebral artery occlusion (MCAO) rodent model and explore the underlying mechanism.Methods: The rats were divided into following groups viz., normal, sham, MCAO and MCAO + pterostilbene (25 mg/kg) group, respectively. The groups received the oral administration of pterostilbene for 30 days followed by MCAO induction. The neurological score, brain water content, infarct volume and Evan blue leakage were estimated. Hepatic, renal, heart, inflammatory cytokines and inflammatory mediators were estimated.Results: Pterostilbene treatment significantly (p < 0.001) improved the body weight and suppressed the glucose level and brain weight. Pterostilbene significantly (p < 0.001) reduced the hepatic, renal and heart parameters. Pterostilbene significantly (p < 0.001) decreased the level of glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and decreased the level of malonaldehyde (MDA), 8-Hydroxy-2′-deoxyguanosine (8-OHdG). Pterostilbene significantly (p < 0.001) inflammatory cytokines and inflammatory parameters such as cyclooxygenase-2 (COX-2), inducible nitric oxidase synthase (iNOS) and prostaglandin (PGE2). Pterostilbene significantly (p < 0.001) down-regulated the level of metalloproteinases (MMP) such as MMP-2 and MMP-9. Pterostilbene suppressed the cellular swelling, cellular disintegration, macrophage infiltration, monocyte infiltration and polymorphonuclear leucocyte degranulation in the brain.Conclusion: In conclusion, Pterostilbene exhibited the neuroprotective effect against cerebral ischemia in rats via anti-inflammatory mechanism.


2004 ◽  
Vol 107 (3) ◽  
pp. 291-296 ◽  
Author(s):  
Camille CHENEVIER-GOBEAUX ◽  
Séverine MORIN-ROBINET ◽  
Hervé LEMARECHAL ◽  
Serge POIRAUDEAU ◽  
Jean-Charles O. G. EKINDJIAN ◽  
...  

The aim of the present study was to investigate the effects of (i) the pro-inflammatory cytokines IL (interleukin)-1β, TNF-α (tumour necrosis factor-α), IFN-γ (interferon-γ) and anti-inflammatory cytokines IL-4 and IL-13, and (ii) NO (nitric oxide) donors on HA (hyaluronic acid) production by synovial cells from patients with rheumatoid arthritis. Synovial cells obtained from five patients with rheumatoid arthritis were incubated for 24 h without or with IL-1β, TNF-α, IFN-γ, or with this mixture for 24 h plus IL-4 or IL-13 for the last 6 h. The same cells were also incubated for 3–24 h without or with SNP (sodium nitroprusside) or SNAP (S-nitroso-N-acetyl-DL-penicillamine). HA secretion was determined by an immunoenzymic assay based on HA-specific binding by proteoglycan isolated from bovine cartilage. IL-1β, TNF-α and IFN-γ alone or in combination stimulated HA synthesis, whereas IL-4 and IL-13 dose-dependently inhibited HA production induced by Th1 cytokines. HA production was significantly increased by the presence of 1 mM SNP after 6 and 12 h (maximal effect). HA production was significantly increased by the presence of 0.01 and 0.1 mM SNAP after 12 h of incubation, and cells treated with 1 mM SNAP showed a maximal HA production after 24 h of incubation. In conclusion, the present study provides data concerning the regulatory role of pro- and anti-inflammatory cytokines and NO donors on HA metabolism in rheumatoid synovial cells and may help in understanding the pathophysiology of rheumatoid arthritis.


2019 ◽  
Vol 47 (5) ◽  
pp. 393-399
Author(s):  
A. A. Novikov ◽  
Е. N. Aleksandrova ◽  
G. V. Lukina

Background: An important characteristic of immune pathology in rheumatoid arthritis (RA) is a B-cell tolerance defect, associated with autoantibodies production, and antigen-specific activation of Th-1 CD4+ T lymphocytes with an excess production of pro-inflammatory cytokines compared to anti-inflammatory ones. Pro-inflammatory cytokines contribute to the development of local inflammatory effects, induce bone destruction and pannus formation, and contribute to the development of autoimmune abnormalities and systemic manifestations. Anti-inflammatory cytokines are able to reduce the rate of joint destruction. There is evidence of the involvement of Th2 cytokines in the development of early RA. These facts suggest the need for a thorough investigation into the balance between the Th1 and Th2 types of immune response at different stages of the disease.Aim: To assess the importance of сytokine profiling in the evaluation of immune abnormalities in RA.Materials and methods: In this descriptive, controlled, retrospective study, we examined 118 patients with RA and 33 healthy donors as a control group. Serum IgM rheumatoid factor (RF) and C-reactive protein (CRP) levels were measured by immunonephelometry; anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) were determined by an enzyme immunoassay, cytokines levels with "xMAP" technique.Results: Serum cytokine levels vary depending on RA duration. The cytokine profile in early RA, unlike that in established RA with a duration of more than 6 months, is characterized by higher levels of pro-inflammatory (MIP-1α), Th1 (IFN-γ), and Th17 (IL-17) cytokines, colony-stimulating factors (IL-7, G-CSF), and chemokines (IL-8, IP-10) (p < 0.05 for all parameters). In established RA, the levels of pro-inflammatory (IL-1β, -6, -15, TNF-α), anti-inflammatory (IL-1ra, IL-10, IL-13, IL-5), Th1 (IL-2, IL-12), Th2 (IL-9) cytokines and colony-stimulating factors (G-CSF, GM-CSF) correlate with the concentrations of IgM RF and antibodies to citrullinated proteins (antiCCP, anti-MCV) (all p < 0.05). There was also а correlation between CRP and pro-inflammatory (IL-1β, IL-6, TNF-α), Th1 (IL-12), Th2 (IL-5, IL-9) cytokine levels and between DAS28 and pro-inflammatory cytokine (IL-6) and colony-stimulating factor (G-CSF) levels (all p < 0.05). Conclusion: In RA, cytokines, chemokines and colony-stimulating factors mirror the inflammatory activity of the disease. Changes in blood concentrations of cytokines enable to get an insight into the complex interplay of numerous mediators of innate and acquired immunity


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Debabrata Modak ◽  
Subhashis Paul ◽  
Sourav Sarkar ◽  
Subarna Thakur ◽  
Soumen Bhattacharjee

Abstract Background The fronds of Drynaria quercifolia have traditionally been used in rheumatic pain management. The goal of the present study was to validate the potent anti-inflammatory and anti-rheumatoid properties of the methanolic-extract of its rhizome using in vitro, in vivo and in silico strategies. Methods The plant was collected and the methanolic extract was prepared from its rhizome. Protein denaturation test, hypotonicity and heat-induced haemolysis assays were performed in vitro. The in vivo anti-rheumatoid potential was assessed in Freund’s complete adjuvant (FCA)-induced Wistar rat model through inflammatory paw-edema, haematological, biochemical, radiological and histopathological measurements. Moreover, metabolites of methanolic extract were screened by gas chromatography-mass spectrometry (GC-MS) and 3D molecular structures of active components were utilized for in silico docking study using AutoDock. Results In vitro results evinced a significant (p < 0.05) anti-inflammatory activity of the rhizome methanolic extract in a dose-linear response. Further, Drynaria quercifolia rhizome methanolic extract (DME) significantly ameliorated rheumatoid arthritis as indicated by the inhibition of arthritic paw-edema (in millimeter) in the rat rheumatoid arthritis models in both the low (57.71 ± 0.99, p < 0.01) and high dose groups (54.45 ± 1.30, p < 0.001) when compared to arthritic control. Treatment with DME also normalized the haematological (RBC, WBC, platelet counts and hemoglobin contents) and biochemical parameters (total protein, albumin, creatinine and ceruloplasmin) significantly (p < 0.05), which were further supported by histopathological and radiological analyses. Furthermore, GC-MS analysis of DME demonstrated the presence of 47 phytochemical compounds. Compounds like Squalene, Gamma Tocopherol, n-Hexadecanoic acid showed potent inhibition of cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukin (IL-6) in the docking analysis. Conclusion Results from in vivo and in vitro studies indicated that DME possesses a potent anti-inflammatory and anti-arthritic activity. In silico studies delineated the emergent potent inhibitory effects of several bio-active components on the target inflammatory markers (COX-2, TNF-α and IL-6).


Author(s):  
Pelin Arda-Pirincci ◽  
Guliz Aykol-Celik

Ulcerative colitis is an inflammatory bowel disease and many people suffers from this disease across the word. Dextran sulfate sodium (DSS) is a synthetic sulfated polysaccharide that is used to produce ulcerative colitis in rodents. Galectin-1 is a β-galactoside binding animal lectin which plays key roles in many biological events. In this study, we investigated the role of galectin-1 on colon morphology, cell proliferation, oxidative stress, anti-oxidant system, inflammatory and anti-inflammatory mediators in the model of experimental ulcerative colitis induced by DSS in mice. C57BL/6  mice were fed orally 3% DSS in their drinking water for 5 days for acute colitis induction. Animals were injected with 1 mg/kg recombinant human galectin-1 for 7 consecutive days. Oral DSS application resulted in colitis injury by causing histopathological changes; an increase in disease activity index (DAI), lipid peroxidation (MDA), myeloperoxidase (MPO) and TNF-α levels; a decrease in body weight, colon length, cell proliferation index, catalase (CAT), glutahione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, gluathione (GSH) and IL-10 levels. However, treatment with galectin-1 prevented DSS-induced colitis injury through the reduction of DAI, MDA, MPO and TNF-α levels, and the increase of body weight, colon length, cell proliferation, antioxidant enzymes activities, GSH and IL-10 levels. As a result, this study showed that galectin-1 has proliferative, anti-oxidant, anti-inflammatory, and cytoprotective effects against DSS-induced colitis in mice. In addition, galectin-1 reduces the severity of ulcerative colitis via suppressing inflammatory and oxidative mediators.


Author(s):  
Jingshuang Li ◽  
Hui Wang ◽  
Lili Zhang ◽  
Ni An ◽  
Wan Ni ◽  
...  

Abstract. Capsaicin, the main constituent in chili, is an extremely spicy vanillin alkaloid and is found in several Capsicum species in China. Traditionally, it has been used to treat inflammatory diseases such as allergic rhinitis, neuralgia after shingles, refractory female urethral syndrome, spontaneous recalcitrant anal pruritus, and solid tumors. Constant stimulation of the body by inflammatory factors can lead to chronic inflammation. Capsaicin possesses anti-inflammatory activity; however, the underlying mechanism is unknown. We investigated the effect of capsaicin on the secretion of macrophage inflammatory factors in a lipopolysaccharide-induced inflammation model using 56 healthy, SPF grade, BALB/c mice. To this end, mice peritoneal macrophages were isolated and stimulated with lipopolysaccharide (1 μg/mL) and capsaicin (25, 50, 75, or 100 μg/mL) for 24 h. At all concentrations tested, capsaicin significantly promoted the phagocytosis of neutral red dye by macrophages. Furthermore, the gene expression and secretion of inflammatory cytokines significantly increased after induction with lipopolysaccharide (P<0.01); the interleukin (IL)-6 level was 204 μg/mL, tumor necrosis factor (TNF)-α level was 860 μg/mL, and nitric oxide (NO) level was 19.8 μg/mL. However, the treatment with capsaicin reduced their levels (P<0.01) and protein expression of lipopolysaccharide-induced extracellular signal-related kinase 1/2 and p65 (P<0.05). Overall, capsaicin reduced the secretion of inflammatory cytokines (P<0.01), interleukins, TNF-α (P<0.01), and NO by inhibiting the nuclear factor-kappa B and microtubule-associated protein kinase signaling pathways, and thereby reduced lipopolysaccharide-induced inflammatory response in macrophages.


2021 ◽  
Vol 12 ◽  
Author(s):  
Raj Kumar Tiwari ◽  
Silpi Chanda ◽  
Udayabanu M ◽  
Manisha Singh ◽  
Shriya Agarwal

Aims: Scientific biological evaluation of standardized extracts is becoming one of the central needs for the globalization of customary medication in current times. And to validate the presence of active constituents in crude medicinal extracts, analytical techniques like HPLC and HPTLC are the most suitable authentication systems. In the current study we aimed to standardize and evaluate Clerodendrum serratum (L.) Moon (Verbenaceae). For its unique anti-inflammatory and anti-arthritic properties. Evaluation and analysis of the plant, therefore, offers a new platform for the development of the herbal drug and could prove to be a safe and cost effective treatment for arthritis management.Methods: The aqueous extract of C. serratum, a common plant in the Southeastern Asian region, was used for phytochemical investigation and standardization by HPTLC and HPLC. The standardized HPLC method was further validated by using ICH guidelines. The standardized extract was investigated for anti-inflammatory and anti-arthritic activity. Complete Freund’s adjuvant (CFA) model was performed to evaluate the activity. Paw diameter, joint diameter, arthritic score, and body weight was accepted as a parameter for the evaluation of biological activity.Results: HPTLC method revealed the presence of ursolic acid with an Rf value of 0.38 and the amount quantified was 0.03% w/w. The presence of the bioactive phytochemical was further analyzed and confirmed by HPLC for which the validation was done successfully in accordance with ICH guidelines. The assay content for ursolic acid was found to be 0.059% with relative standard deviation (RSD) &lt;2.5% for specificity and precision with spike recovery between 95–110%. The anti-arthritic activity of aqueous extract exhibited COX-2 and TNF-α inhibition as observed in various parameters like paw edema, arthritic index, and joint diameter. Plant extract showed reclamation of arthritis in regard to body weight, arthritic score, paw edema, and joint diameter. The extract showed significant results for TNF-α and COX-2(p &lt; 0.0001). The plant extract also exhibited in-vitro anti-inflammatory activity.Conclusion: The current study established the scientific basis of ethnomedicinal use of the plant for anti-inflammatory purposes and the management of arthritis and can also be used for quality control purposes.


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