The Protective Effect of Kirenol in Osteoarthritis: an in Vitro and in Vivo Study

2022 ◽  
Author(s):  
Wei Hu ◽  
Chao Mao ◽  
Weibin Sheng
Keyword(s):  
Cartilage Degradation ◽  
Cartilage Destruction ◽  
In Vivo Study ◽  
Griess Reaction ◽  
Tnf Α ◽  
Collagen Ii ◽  
Cox 2 ◽  
Product Compound

Abstract Background: Osteoarthritis (OA) is a chronic degenerative disease, its main characteristic involves articular cartilage destruction and inflammation response, absent of effective medical treatment. Our current research aimed to explore anti-inflammatory effect of kirenol, a diterpenoid natural product compound, in the development of OA and its potential molecular mechanism through in vitro and in vivo study.Methods: In vitro, chondrocytes were pretreated with kirenol for 2 h before IL-1β stimulation. Production of NO, PGE2, TNF-α, IL-6, aggrecan, collagen-II, MMP13and ADAMTS5 were evaluated by the Griess reaction and ELISAs. The mRNA (aggrecan and collagen-II) and protein expression (COX-2, iNOS, P65, IκB, PI3K, AKT) were measured by qRT-PCR and Western blot respectively. Immunofluorescence was used to assess the expression of collagen-II and P65. The in vivo effect of kirenol was evaluated in mice OA models induced by destabilization of the medial meniscus (DMM).Results: We found that kirenol inhibited IL-1β-induced expression of NO, PGE2, TNF-α, IL-6, COX-2, iNOS, ADAMTS-5. Besides, kirenol remarkably decreased IL-1β-induced degradation of aggrecan and collagen-II. Furthermore, kirenol significantly inhibited IL-1β-induced phosphorylation of PI3K/Akt and NF-κB signaling. In vivo, the cartilage in kirenol-treated mice exhibited less cartilage degradation and lower OARSI scores.Conclusions: Taken together, the results of this study provide potent evidence that kirenol could be utilized as a potentially therapeutic agent in prevention and treatment of OA.

scholarly journals The Protective Effect of Ligustilide in Osteoarthritis: An in Vitro and in Vivo Study

2018 ◽  
Vol 48 (6) ◽  
pp. 2583-2595 ◽  
Author(s):  
Xiaobin Li ◽  
Dengying Wu ◽  
Zhichao Hu ◽  
Jiangwei Xuan ◽  
Xiaoxia Ding ◽  
...  
Keyword(s):  
Western Blotting ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Ecm Degradation ◽  
Collagen Ii ◽  
Cox 2 ◽  
Vitro Effect

Background/Aims: Osteoarthritis is a degenerative joint disease characterized by cartilage degeneration and a chondrocyte inflammatory response that induces an inflammatory environment closely linked to extracellular matrix (ECM) degradation. Ligustilide (LIG) is a major component of the herb Radix Angelicae Sinensis, with demonstrated anti-inflammatory effects. To confirm whether LIG has an equally inhibitory effect on inflammation in human osteoarthritis chondrocytes, we performed in vivo and in vitro experiments to validate the above conjectures and determine the relevant mechanisms. Methods: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-3, MMP-13, ADAMTS-5, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of other inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT and nuclear factor kappa B (NF-κB) signaling pathways were also analyzed by western blotting, whereas immunofluorescence was used to assess the expression of collagen II and aggrecan. The in vitro effect of LIG was evaluated by intraperitoneal injection into a mouse osteoarthritis model induced by destabilization of the medial meniscus. Results: LIG lowered the phosphorylation levels of p65, IκBα, and IKKα/β and suppressed the IL-1β-induced expression of MMP-3, ADAMTS-5, iNOS, and COX-2 and the inflammatory factors PGE2, TNF-α, and IL-6. LIG markedly decreased IL-1β-induced degradation of collagen II and aggrecan. In vivo results showed that LIG-treated mouse cartilage showed less damage than the control group; the Osteoarthritis Research Society International (OARSI) score was also lower. LIG further reduced the thickness of the subchondral bone plate and alleviated the synovitis. Conclusion: LIG may act as a promising therapeutic agent for osteoarthritis by attenuating IL-1β-induced inflammation in chondrocytes and ECM degradation via suppression of NF-κB activation by the PI3K/AKT pathway.

scholarly journals Bakuchiol Suppresses Inflammatory Responses Via the Downregulation of the p38 MAPK/ERK Signaling Pathway

2019 ◽  
Vol 20 (14) ◽  
pp. 3574 ◽  
Author(s):  
Hye-Sun Lim ◽  
Yu Jin Kim ◽  
Bu-Yeo Kim ◽  
Soo-Jin Jeong
Keyword(s):  
Mrna Expression ◽  
P38 Mapk ◽  
Inflammatory Responses ◽  
Mitogen Activated Protein Kinase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mice Model ◽  
Tnf Α ◽  
Cox 2

The purpose of the present study was to evaluate the effects of bakuchiol on the inflammatory response and to identify the molecular mechanism of the inflammatory effects in a lipopolysaccharide (LPS)-stimulated BV-2 mouse microglial cell line and mice model. The production of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay. The mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 was measured using reverse transcription–polymerase chain reaction analysis. Mitogen-activated protein kinase (MAPK) phosphorylation was determined by western blot analysis. In vitro experiments, bakuchiol significantly suppressed the production of PGE2 and IL-6 in LPS-stimulated BV-2 cells, without causing cytotoxicity. In parallel, bakuchiol significantly inhibited the LPS-stimulated expression of iNOS, COX-2, and IL-6 in BV-2 cells. However, bakuchiol had no effect on the LPS-stimulated production and mRNA expression of TNF-α or on LPS-stimulated c-Jun NH2-terminal kinase phosphorylation. In contrast, p38 MAPK and extracellular signal-regulated kinase (ERK) phosphorylation were inhibited by bakuchiol. In vivo experiments, Bakuchiol reduced microglial activation in the hippocampus and cortex tissue of LPS-injected mice. Bakuchiol significantly suppressed LPS-injected production of TNF-α and IL-6 in serum. These results indicate that the anti-neuroinflammatory effects of bakuchiol in activated microglia are mainly regulated by the inhibition of the p38 MAPK and ERK pathways. We suggest that bakuchiol may be beneficial for various neuroinflammatory diseases.

scholarly journals Nerolidol Mitigates Colonic Inflammation: An Experimental Study Using both In Vivo and In Vitro Models

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2032
Author(s):  
Vishnu Raj ◽  
Balaji Venkataraman ◽  
Saeeda Almarzooqi ◽  
Sanjana Chandran ◽  
Shreesh K. Ojha ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
In Vitro Models ◽  
Mrna Levels ◽  
Colonic Inflammation ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Ht 29

Nerolidol (NED) is a naturally occurring sesquiterpene alcohol present in various plants with potent anti-inflammatory effects. In the current study, we investigated NED as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were administered 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. Six groups received either vehicle alone or DSS alone or DSS with oral NED (50, 100, and 150 mg/kg body weight/day by oral gavage) or DSS with sulfasalazine. Disease activity index (DAI), colonic histology, and biochemical parameters were measured. TNF-α-treated HT-29 cells were used as in vitro model of colonic inflammation to study NED (25 µM and 50 µM). NED significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue Myeloperoxidase (MPO) concentrations, neutrophil and macrophage mRNA expression (CXCL2 and CCL2), and proinflammatory cytokine content (IL-1β, IL-6, and TNF-α) both at the protein and mRNA level were significantly reduced by NED. The increase in content of the proinflammatory enzymes, COX-2 and iNOS induced by DSS were also significantly inhibited by NED along with tissue nitrate levels. NED promoted Nrf2 nuclear translocation dose dependently. NED significantly increased antioxidant enzymes activity (Superoxide dismutase (SOD) and Catalase (CAT)), Hemeoxygenase-1 (HO-1), and SOD3 mRNA levels. NED treatment in TNF-α-challenged HT-29 cells significantly decreased proinflammatory chemokines (CXCL1, IL-8, CCL2) and COX-2 mRNA levels. NED supplementation attenuates colon inflammation through its potent antioxidant and anti-inflammatory activity both in in vivo and in vitro models of colonic inflammation.

Anti-Oxidative and Anti-Inflammatory Effects of Lobelia chinensis In Vitro and In Vivo

2015 ◽  
Vol 43 (02) ◽  
pp. 269-287 ◽  
Author(s):  
Kun-Cheng Li ◽  
Yu-Ling Ho ◽  
Guan-Jhong Huang ◽  
Yuan-Shiun Chang
Keyword(s):  
Nitric Oxide ◽  
Folk Medicine ◽  
Ethyl Acetate Fraction ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Factor Α

Lobelia chinensis Lour (LcL) is a popular herb that has been widely used as folk medicine in China for the treatment of fever, lung cancer, and inflammation for hundreds of years. Recently, several studies have shown that the anti-inflammatory properties were correlated with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) from the NF-κB pathway. The aim of this study was to evaluate the anti-oxidative and anti-inflammatory activities of L. chinensis. Both suppressive activities on LPS-induced nitric oxide production in RAW264.7 macrophages in vitro and the acute rat lung injury model in vivo were studied. The results showed that the methanol extract of LcL and its fractions within the range of 62.5–250 μg/mL did not induce cytotoxicity (p < 0.001). The ethyl acetate fraction of LcL showed better NO inhibition activity than other fractions. On the other hand, the Lc-EA (62.5, 125, 250 mg/kg) pretreated rats showed a decrease in the pro-inflammatory cytokines (TNF-α, IL-β, IL-6) and inhibited iNOS, COX-2 expression through the NF-κB pathway. These results suggested that L. chinensis exhibited an anti-inflammatory effect through the NF-κB pathways.

scholarly journals Pro-inflammatory properties of cadmium.

2012 ◽  
Vol 59 (4) ◽  
Author(s):  
Tomasz Olszowski ◽  
Irena Baranowska-Bosiacka ◽  
Izabela Gutowska ◽  
Dariusz Chlubek
Keyword(s):  
Research Strategy ◽  
Inflammatory Factor ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Research Findings ◽  
Cox 2 ◽  
Environmental Health Problem ◽  
Different Doses

Cadmium is a toxic and carcinogenic heavy metal that nowadays constitutes a serious environmental health problem. The aim of this study is to review the effects of cadmium on selected inflammatory mediators and markers, such as NF-κB and AP-1 transcription factors, IL-6, TNF-α, IL-1β cytokines, IL-8 or MIP-2 chemokine, MPO, iNOS, MMPs and COX-2 enzymes, PGE(2) (product of COX-2 enzyme), ICAM-1, VCAM-1 and PECAM-1 adhesion molecules, and CRP. The research strategy identified articles available in Medline, published between 1998 and 2012; we included both in vivo and in vitro studies carried out on humans and rodents. Most of the reviewed research findings suggest that cadmium in micromolar concentrations (especially in the 1-10 μM range) causes up-regulation of the mediators and markers of inflammation, and appears to have pro-inflammatory properties. However, it is worth mentioning that a contradictory or even opposite hypothesis exists, which suggests cadmium to be an anti-inflammatory factor. Further research including detailed histological analyses should solve this discrepancy. Nevertheless, it appears that the main reason for these contradictory findings is the experimental setup: different biological systems analyzed and different doses of cadmium applied.

An In Vitro and In Vivo Study on the Intensity of Adhesion and Colonization by Staphylococcus epidermidis and Pseudomonas aeruginosa on Originally Synthesized Biomaterials With Different Chemical Composition and Modified Surfaces and Their Effect on Expression of TNF-α, β-Defensin 2 and IL-10 in Tissues

Medicina ◽  
2011 ◽  
Vol 47 (10) ◽  
pp. 80 ◽  
Author(s):  
Aigars Reinis ◽  
Māra Pilmane ◽  
Agnese Stunda ◽  
Jānis Vētra ◽  
Juta Kroiča ◽  
...  
Keyword(s):  
Bacterial Adhesion ◽  
Bacterial Colonization ◽  
Cell Activity ◽  
In Vivo Study ◽  
Plate Count ◽  
Nonspecific Resistance ◽  
Colony Forming Units ◽  
Tnf Α

The aim of this study was to determine adhesion and colonization of bacteria on the surface of originally synthesized glass-ceramic biomaterials and their effect on inflammation reactions in tissues surrounding the implant. Materials and Methods. Biomaterial discs were contaminated with bacterial suspensions of 10, 102, and 103 colony forming units (CFU)/mL (P. aeruginosa ATCC 27853 and S. epidermidis ATCC 12228), and after 2 hours of cultivation, the intensity of bacterial adhesion was determined. For in vivo tests, the samples were contaminated with 102 and 103 CFU/mL cultivated at 37oC for 2 h to ensure bacterial adhesion. Contaminated biomaterial samples were implanted in the interscapular area of chinchilla rabbits for 2 and 4 weeks. The biomaterials were removed, and using plate count and sonification methods, bacterial colonization on the surface of biomaterials was determined. Moreover, the expression of TNF-α, β-defensin 2, and IL-10 in the surrounding tissues was assessed by using immunohistochemistry methods. Results. P. aeruginosa more intensively colonized biomaterials in the in vivo study as compared with S. epidermidis. Il-10 is a regulatory cytokine, which reduces the intensity of inflammatory cell activity, thus reducing nonspecific resistance of the organism. Conclusions. The expression of TNF-α and IL-10 was not affected by short (2 and 4 weeks) biomaterial implantation. Pronounced cytokine expression in tissues around implanted biomaterials contaminated with P. aeruginosa was observed.

scholarly journals Fucoxanthin-Containing Cream Prevents Epidermal Hyperplasia and UVB-Induced Skin Erythema in Mice

Marine Drugs ◽  
2018 ◽  
Vol 16 (10) ◽  
pp. 378 ◽  
Author(s):  
Azahara Rodríguez-Luna ◽  
Javier Ávila-Román ◽  
María González-Rodríguez ◽  
María Cózar ◽  
Antonio Rabasco ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Antioxidant Properties ◽  
Epidermal Hyperplasia ◽  
Topical Formulation ◽  
Tnf Α ◽  
Skin Erythema ◽  
Cox 2 ◽  
Anti Inflammatory

Microalgae represent a source of bio-active compounds such as carotenoids with potent anti-inflammatory and antioxidant properties. We aimed to investigate the effects of fucoxanthin (FX) in both in vitro and in vivo skin models. Firstly, its anti-inflammatory activity was evaluated in LPS-stimulated THP-1 macrophages and TNF-α-stimulated HaCaT keratinocytes, and its antioxidant activity in UVB-irradiated HaCaT cells. Next, in vitro and ex vivo permeation studies were developed to determine the most suitable formulation for in vivo FX topical application. Then, we evaluated the effects of a FX-containing cream on TPA-induced epidermal hyperplasia in mice, as well as on UVB-induced acute erythema in hairless mice. Our results confirmed the in vitro reduction of TNF-α, IL-6, ROS and LDH production. Since the permeation results showed that cream was the most favourable vehicle, FX-cream was elaborated. This formulation effectively ameliorated TPA-induced hyperplasia, by reducing skin edema, epidermal thickness, MPO activity and COX-2 expression. Moreover, FX-cream reduced UVB-induced erythema through down-regulation of COX-2 and iNOS as well as up-regulation of HO-1 protein via Nrf-2 pathway. In conclusion, FX, administered in a topical formulation, could be a novel natural adjuvant for preventing exacerbations associated with skin inflammatory pathologies as well as protecting skin against UV radiation.

scholarly journals Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Hongsik Cho ◽  
Andrew Walker ◽  
Jeb Williams ◽  
Karen A. Hasty
Keyword(s):  
Gene Expression ◽  
Type Ii Collagen ◽  
Cartilage Degradation ◽  
Cyclooxygenase 2 ◽  
Cox Inhibitor ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory

Patients with osteoarthritis (OA), a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs) and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM). To compare the effects of these treatments on chondrocyte metabolism, TNF-αwas incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2). The chondrocytes were then treated with either a steroid (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxibin vivowas investigated using a posttraumatic OA (PTOA) mouse model.In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 productionin vitroand that celecoxib may demonstrate beneficial effects on anabolic metabolismin vivo.

scholarly journals Anti-Arthritic and Anti-Inflammatory Potential of Spondias mangifera Extract Fractions: An In Silico, In Vitro and In Vivo Approach

Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 825
Author(s):  
Mohammad Khalid ◽  
Mohammed H. Alqarni ◽  
Ambreen Shoaib ◽  
Muhammad Arif ◽  
Ahmed I. Foudah ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Arthritis Score ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

The fruits of Spondias mangifera (S. mangifera) have traditionally been used for the management of rheumatism in the northeast region of India. The present study explores the probable anti-arthritis and anti-inflammatory potential of S. mangifera fruit extract’s ethanolic fraction (EtoH-F). To support this study, we first approached the parameters in silico by means of the active constituents of the plant (beta amyrin, beta sitosterol, oleonolic acid and co-crystallised ligands, i.e., SPD-304) via molecular docking on COX-1, COX-2 and TNF-α. Thereafter, the absorption, distribution, metabolism, excretion and toxicity properties were also determined, and finally experimental activity was performed in vitro and in vivo. The in vitro activities of the plant extract fractions were evaluated by means of parameters like 1,1-Diphenyl-2- picrylhydrazyl (DPPH), free radical-reducing potential, albumin denaturation, and protease inhibitory activity. The in vivo activity was evaluated using parameters like COX, TNF-α and IL-6 inhibition assay and arthritis score in Freund Adjuvant (CFA) models at a dose of 400 mg/kg b.w. per day of different fractions (hexane, chloroform, alcoholic). The molecular docking assay was performed on COX-1, COX-2 and TNF-α. The results of in vitro studies showed concentration-dependent reduction in albumin denaturation, protease inhibitors and scavenging activity at 500 µg/mL. Administration of the S. mangifera alcoholic fraction at the abovementioned dose resulted in a significant reduction (p < 0.01) in arthritis score, paw diameters, TNF-α, IL-6 as compared to diseased animals. The docking results showed that residues show a critical binding affinity with TNF-α and act as the TNF-α antagonist. The alcoholic fraction of S. mangifera extract possesses beneficial effects on rheumatoid arthritis as well as anti-inflammatory potential, and can further can be used as a possible agent for novel target-based therapies for the management of arthritis.

scholarly journals Antibacterial, Immunomodulatory, and Lung Protective Effects of Boswelliadalzielii Oleoresin Ethanol Extract in Pulmonary Diseases: In Vitro and In Vivo Studies

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1444
Author(s):  
Badriyah Alotaibi ◽  
Walaa A. Negm ◽  
Engy Elekhnawy ◽  
Thanaa A. El-Masry ◽  
Walaa S. Elseady ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Ethanol Extract ◽  
Lung Damage ◽  
Pulmonary Diseases ◽  
Human Skin Fibroblast ◽  
Tnf Α ◽  
Cox 2

Lung diseases such as asthma, chronic obstructive pulmonary diseases, and pneumonia are causing many global health problems. The COVID-19 pandemic has directed the scientific community’s attention toward performing more research to explore novel therapeutic drugs for pulmonary diseases. Herein, gas chromatography coupled with mass spectrometry tentatively identified 44 compounds in frankincense ethanol extract (FEE). We investigated the antibacterial and antibiofilm effects of FEE against Pseudomonas aeruginosa bacteria, isolated from patients with respiratory infections. In addition, its in vitro immunomodulatory activity was explored by the detection of the gene expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide synthase (iNOS), cycloxygenase-2 (COX-2), and nuclear factor kappa-B (NF-κB) in lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells (PBMC). In addition, its anticancer activity against the A549 lung cancer cell line and human skin fibroblast (HSF) normal cell line was studied. Moreover, the in vivo lung protective potential of FEE was explored histologically and immunohistochemically in mice using a benzo(a)pyrene induced lung damage model. FEE exhibited antibacterial and antibiofilm activities besides the significant inhibition of gene expression of TNFα, IL-6, and NF-κB. FEE also exerted a cytotoxic effect against A549 cell line. Histological and immunohistochemical investigations with morphometric analysis of the mean area percentage and color intensity of positive TNF-α, COX-2, and NF-κB and Bcl-2 reactions revealed the lung protective activity of FEE. This study outlined the promising therapeutic activity of oleoresin obtained from B. dalzielii in the treatment of different pulmonary diseases.

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