scholarly journals Rhoifolin Ameliorates Osteoarthritis via Regulating Autophagy

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiyuan Yan ◽  
Bowei Ni ◽  
Gaohong Sheng ◽  
Yingchi Zhang ◽  
Yifan Xiao ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Cartilage Damage ◽  
Cartilage Degradation ◽  
Joint Disease ◽  
Signal Pathways ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Age Related ◽  
Anti Inflammatory

Osteoarthritis (OA) is a common age-related joint disease. Its development has been generally thought to be associated with inflammation and autophagy. Rhoifolin (ROF), a flavanone extracted from Rhus succedanea, has exhibited prominent anti-oxidative and anti-inflammatory properties in several diseases. However the exact role of ROF in OA remains unclear. Here, we investigated the therapeutic effects as well as the underlying mechanism of ROF on rat OA. Our results indicated that ROF could significantly alleviate the IL-1β–induced inflammatory responses, cartilage degradation, and autophagy downregulation in rat chondrocytes. Moreover, administration of autophagy inhibitor 3-methyladenine (3-MA) could reverse the anti-inflammatory and anti-cartilage degradation effects of ROF. Furthermore, P38/JNK and PI3K/AKT/mTOR signal pathways were involved in the protective effects of ROF. In vivo, intra-articular injection of ROF could notably ameliorate the cartilage damage in rat OA model. In conclusion, our work elucidated that ROF ameliorated rat OA via regulating autophagy, indicating the potential role of ROF in OA therapy.

scholarly journals Selonsertib Alleviates the Progression of Rat Osteoarthritis: An in vitro and in vivo Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiyuan Yan ◽  
Yingchi Zhang ◽  
Gaohong Sheng ◽  
Bowei Ni ◽  
Yifan Xiao ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Cartilage Damage ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Therapeutic Effects ◽  
Exact Role

Osteoarthritis (OA) is a prevalent degenerative joint disease. Its development is highly associated with inflammatory response and apoptosis in chondrocytes. Selonsertib (Ser), the inhibitor of Apoptosis Signal-regulated kinase-1 (ASK1), has exhibited multiple therapeutic effects in several diseases. However, the exact role of Ser in OA remains unclear. Herein, we investigated the anti-arthritic effects as well as the potential mechanism of Ser on rat OA. Our results showed that Ser could markedly prevent the IL-1β-induced inflammatory reaction, cartilage degradation and cell apoptosis in rat chondrocytes. Meanwhile, the ASK1/P38/JNK and NFκB pathways were involved in the protective roles of Ser. Furthermore, intra-articular injection of Ser could significantly alleviate the surgery induced cartilage damage in rat OA model. In conclusion, our work provided insights into the therapeutic potential of Ser in OA, indicating that Ser might serve as a new avenue in OA treatment.

scholarly journals The Role of Chondrocyte Hypertrophy and Senescence in Osteoarthritis Initiation and Progression

2020 ◽  
Vol 21 (7) ◽  
pp. 2358 ◽  
Author(s):  
Yeri Alice Rim ◽  
Yoojun Nam ◽  
Ji Hyeon Ju
Keyword(s):  
Adult Population ◽  
Cartilage Damage ◽  
Natural Process ◽  
Joint Disease ◽  
Endochondral Bone Formation ◽  
Potential Therapeutic Target ◽  
Endochondral Bone ◽  
Chondrocyte Hypertrophy ◽  
Age Related

Osteoarthritis (OA) is the most common joint disease that causes pain and disability in the adult population. OA is primarily caused by trauma induced by an external force or by age-related cartilage damage. Chondrocyte hypertrophy or chondrocyte senescence is thought to play a role in the initiation and progression of OA. Although chondrocyte hypertrophy and cell death are both crucial steps during the natural process of endochondral bone formation, the abnormal activation of these two processes after injury or during aging seems to accelerate the progression of OA. However, the exact mechanisms of OA progression and these two processes remain poorly understood. Chondrocyte senescence and hypertrophy during OA share various markers and processes. In this study, we reviewed the changes that occur during chondrocyte hypertrophy or senescence in OA and the attempts that were made to regulate them. Regulation of hypertrophic or senescent chondrocytes might be a potential therapeutic target to slow down or stop OA progression; thus, a better understanding of the processes is required for management.

scholarly journals Undenatured Type II Collagen Ameliorates Inflammatory Responses and Articular Cartilage Damage in the Rat Model of Osteoarthritis

2021 ◽  
Vol 8 ◽  
Author(s):  
Cemal Orhan ◽  
Vijaya Juturu ◽  
Emre Sahin ◽  
Mehmet Tuzcu ◽  
Ibrahim Hanifi Ozercan ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Responses ◽  
Cartilage Damage ◽  
Joint Inflammation ◽  
Type Ii Collagen ◽  
Serum Levels ◽  
Joint Disease ◽  
Type Ii ◽  
Age Related ◽  
Undenatured Type Ii Collagen

Osteoarthritis (OA) is an age-related joint disease that includes gradual disruption of the articular cartilage and the resulting pain. The present study was designed to test the effects of undenatured type II collagen (UC-II®) on joint inflammation in the monoiodoacetate (MIA) OA model. We also investigated possible mechanisms underlying these effects. Female Wistar rats were divided into three groups: (i) Control; (ii) MIA-induced rats treated with vehicle; (iii) MIA-induced rats treated with UC-II (4 mg/kg BW). OA was induced in rats by intra-articular injection of MIA (1 mg) after seven days of UC-II treatment. UC-II reduced MIA-induced Kellgren-Lawrence scoring (53.3%, P < 0.05). The serum levels of inflammatory cytokines [IL-1β (7.8%), IL-6 (18.0%), TNF-α (25.9%), COMP (16.4%), CRP (32.4%)] were reduced in UC-II supplemented group (P < 0.0001). In the articular cartilage, UC-II inhibited the production of PGE2 (19.6%) and the expression of IL-1β, IL-6, TNF-a, COX-2, MCP-1, NF-κB, MMP-3, RANKL (P < 0.001). The COL-1 and OPG levels were increased, and MDA decreased in UC-II supplemented rats (P < 0.001). UC-II could be useful to alleviate joint inflammation and pain in OA joints by reducing the expression of inflammatory mediators.

Ezetimibe prevents IL-1β-induced inflammatory reaction in mouse chondrocytes via modulating NF-κB and Nrf2/HO-1 signaling crosstalk

2022 ◽  
Vol 23 ◽  
Author(s):  
Qiuyan Weng ◽  
Tongzhou Hu ◽  
Xiaohan Shen ◽  
Jinming Han ◽  
Yong Zhang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Inflammatory Reaction ◽  
Cholesterol Absorption ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Protective Effects ◽  
Signaling Crosstalk ◽  
Age Related ◽  
Cholesterol Absorption Inhibitor ◽  
Anti Inflammatory

Background: Osteoarthritis, a type of age-related, chronic, degenerative joint disease. Ezetimibe, a cholesterol absorption inhibitor, is widely used for the treatment of various diseases. The role of ezetimibe in osteoarthritis remains unclear. Objective: This study aimed to explored the anti-inflammation effect of ezetimibe on mouse chondrocytes. Method: In the present study, ELISA, qPCR and western blot analysis were performed to evaluate the anti-inflammatory effects of ezetimibe. In addition, enzymes that are highly associated with the anabolism and catabolism of the extracellular matrix of the articular cartilage were also evaluated. Results: Treatment with ezetimibe attenuated the IL-1β-induced degradation of the extracellular matrix, including aggrecan and collagen II. Ezetimibe also attenuated the IL-1β-induced expression levels of MMP3, MMP13 and ADAMTS5, thus exerting protective effects against IL-1β-induced extracellular matrix degradation. The complex mechanism of the anti-inflammatory reaction contributed to the activation of the Nrf2/HO-1 pathway and the suppression of the NF-κB pathway. Conclusion: On the whole, the present study demonstrates that ezetimibe may be a promising agent for further osteoarthritis therapy

scholarly journals Protective effects of Schisandrin C on chondrocyte damage by inhibiting MAPK and NF-κB signal pathways

2020 ◽  
Author(s):  
Ruipeng Li
Keyword(s):  
Inflammatory Response ◽  
Cartilage Damage ◽  
The Elderly ◽  
Cartilage Degradation ◽  
Mitogen Activated Protein Kinase ◽  
Signal Pathways ◽  
Protective Effects ◽  
Amino Terminal

Abstract Background: Osteoarthritis (OA) is a common joint disorder that affects the elderly population. The pathogenesis of OA is related to cartilage degradation and inflammatory response. Schisandrin C (Sch C), a dibenzocyclooctadiene derivative of Schisandra chinensis, has been demonstrated to exert anti-inflammatory effect in various inflammation diseases. However, the effect of Sch C on OA remains unclear. Thus, we aimed to investigate its action on chondrocytes and explore the mechanism associated with the inflammatory response. Methods: In this study, we chose rabbits and SW1353 cells as in vivo/in vitro models. Matrix metalloproteinase (MMP3), Nitric oxide (NO), IL-1β and TNF-α were detected by ELISA kits. The expression of MAPK/NF-κB related signaling molecules were determined by western blot. Results: In vitro, Sch C suppressed the IL-1β-induced production of NO and PGE2. Additionally, Sch C significantly decreased IL-1β-induced p65 phosphorylation and mitogen-activated protein kinase (MAPK) activation, as evidenced by the reduced phosphorylation of p38, extracellular signal-regulated kinase (ERK), and c-Jun amino-terminal kinase (JNK). Moreover, Sch C prevented cartilage damage in rabbit OA model with lower Mankin’s score than the model group. Sch C also inhibited the level of inflammatory cytokines in the articular cavity flushing fluid in rabbit OA model. Conclusions: Our study suggested that Sch C inhibited the IL-1β-induced inflammation and cartilage degradation through suppressing the MAPK and NF-κB signal pathways, indicating a potential in OA treatment.

scholarly journals Icariin inhibits the inflammation through down-regulating NF-κB/HIF-2α signal pathways in chondrocytes

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Pengzhen Wang ◽  
Qingqi Meng ◽  
Wen Wang ◽  
Shaoheng Zhang ◽  
Xifeng Xiong ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Degradation ◽  
Cartilage Injury ◽  
Flavonoid Compound ◽  
Common Disease ◽  
Signal Pathways ◽  
Protective Effects ◽  
Chondrocyte Phenotype ◽  
Articular Cartilage Injury ◽  
Anti Inflammatory

Abstract Articular cartilage injury or defect is a common disease and is mainly characterized by cartilage degradation because of chondrocyte inflammation. By now, there are no effective drugs and methods to protect articular cartilage from degradation. Icariin (ICA) is a typical flavonoid compound extracted from Epimedii Folium with anti-inflammatory and bone-protective effects. Our previous studies demonstrate that ICA up-regulates HIF-1α expression and glycolysis in chondrocytes and maintains chondrocyte phenotype. As another member of HIFs family, HIF-2α always plays a key role in inflammation. The effect of ICA on HIF-2α is unclear by now. In the present study, we confirmed the findings in our previous study that ICA promoted not only chondrocyte vitality and extracellular matrix (ECM) synthesis, but also the anti-inflammatory effect of ICA. In bone defect mice, ICA inhibited the expressions of NF-κB and HIF-2α. In TNF-α-treated ADTC5 chondrocytes, ICA neutralized the activation of IKK (IKK phosphorylation), the phosphorylation of IkB and NF-κB and the expression of HIF-2α. Furthermore, ICA inhibited the nucleus transfer of NF-κB and the expressions of MMP9 and ADAMTS5, two key targets of NF-κB/HIF-2α signal pathway. Taken together, the present study demonstrated that ICA may increase the vitality of chondrocytes by suppressing the inflammatory injury through the inhibition on NF-κB/HIF-2α signaling pathway. ICA is one effective candidate drug for the treatment of articular cartilage injury.

scholarly journals Aqueous extract of Kan-Lu-Hsiao-Tu-Tan ameliorates collagen-induced arthritis in mice by regulating immune and inflammatory responses

2020 ◽  
Author(s):  
Chih-Chao Chiang ◽  
Yi‐Rong Li ◽  
Kuei-Hung Lai ◽  
Wei-Jen Cheng ◽  
Shih-Chao Lin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hydrogen Peroxide ◽  
Th17 Cells ◽  
Inflammatory Responses ◽  
Bone Erosion ◽  
Cartilage Damage ◽  
Radical Scavenging ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis ◽  
Anti Inflammatory

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease featured by joint inflammation and systemic comorbidities. Kan-Lu-Hsiao-Tu-Tan (KLHTT), a Chinese medicine formulation, has free radical scavenging capacity and anti-inflammatory activity in vitro. However, its anti-arthritic effect remains unknown. Herein, we aimed to explore the anti-arthritic effects of KLHTT on collagen-induced arthritis (CIA) in mice and investigate the underlying mechanisms. Methods KLHTT was extracted using boiling water. KLHTT (50 and 100 mg/kg) was fed orally for 21 days once a day on CIA in DBA/1J mice. The severity of CIA was evaluated by histological assessments. Levels of inflammatory cytokines, malondialdehyde (MDA), and hydrogen peroxide (H2O2) were measured using ELISA, thiobarbituric acid reactive substances, and hydrogen peroxide assay kits, respectively. Anti-collagen type II (CII) antibody was assayed by ELISA. Proliferation of splenocytes was tested using radioactive thymidine incorporation assay. Levels of Th1 and Th17 cells were obtained using flow cytometry. Results KLHTT significantly ameliorated paw edema and restored body weight in CIA mice. The synovitis, cartilage damage, and bone erosion were reduced by KLHTT. KLHTT exhibited anti-inflammatory effects by decreasing the levels of interleukin (IL)-1β, IL-6, IL-17A, and tumour necrosis factor-α in the paw homogenates and serum. KLHTT also showed antioxidant activity by reducing the concentrations of MDA and H2O2 in paw tissues. Moreover, KLHTT reduced anti-CII antibody formation, suppressed splenocyte proliferation, and mitigated the levels of splenic Th1 and Th17 cells in CIA mice. Conclusion The therapeutic effects of KLHTT in CIA mice were through regulating immune and inflammatory responses. Our results suggest that KLHTT has potential to treat rheumatoid arthritis.

scholarly journals Analgesic and Anti-Inflammatory Effects of Aucklandia lappa Root Extracts on Acetic Acid-Induced Writhing in Mice and Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Plants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 42
Author(s):  
Hee-Geun Jo ◽  
Geon-Yeong Lee ◽  
Chae Yun Baek ◽  
Ho Sueb Song ◽  
Donghun Lee
Keyword(s):  
Acetic Acid ◽  
Weight Bearing ◽  
Bone Diseases ◽  
Joint Disease ◽  
Root Extracts ◽  
Raw264.7 Macrophages ◽  
Age Related ◽  
Monosodium Iodoacetate ◽  
Anti Inflammatory

Osteoarthritis (OA) is an age-related joint disease and one of the most common degenerative bone diseases among elderly people. The currently used therapeutic strategies relying on nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids for OA are often associated with gastrointestinal, cardiovascular, and kidney disorders, despite being proven effective. Aucklandia lappa is a well-known traditional medicine. The root of A. lappa root has several bioactive compounds and has been in use as a natural remedy for bone diseases and other health conditions. We evaluated the A. lappa root extracts on OA progression as a natural therapeutic agent. A. lappa substantially reduced writhing numbers in mice induced with acetic acid. Monosodium iodoacetate (MIA) was injected into the rats through their knee joints of rats to induce experimental OA, which shows similar pathological characteristics to OA in human. A. lappa substantially reduced the MIA-induced weight-bearing of hind limb and reversed the cartilage erosion in MIA rats. IL-1β, a representative inflammatory mediator in OA, was also markedly decreased by A. lappa in the serum of MIA rats. In vitro, A. lappa lowered the secretion of NO and suppressed the IL-1β, COX-2, IL-6, and iNOS production in RAW264.7 macrophages activated with LPS. Based on its analgesic and anti-inflammatory effects, A. lappa could be a potential remedial agent against OA.

Immunomodulatory role of paliperidone in the poly(I:C) model of schizophrenia

2016 ◽  
Vol 33 (S1) ◽  
pp. s220-s221
Author(s):  
K. MacDowell ◽  
E. Munarriz-Cuezva ◽  
D. Martín-Hernández ◽  
A. Sayd ◽  
B. García-Bueno ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Inflammatory Responses ◽  
Poly I:C ◽  
Mrna Levels ◽  
Behavioral Test ◽  
Inflammatory Pathways ◽  
Anti Inflammatory ◽  
Cellular Markers ◽  
Endogenous Antioxidant

IntroductionAlterations on the innate inflammatory response may underlie the pathophysiology of psychiatric diseases, but the mechanisms implicated remain elusive. Current antipsychotics modulate pro/anti-inflammatory pathways, but the specific mechanisms involved remain elusive. One attractive possibility is the regulation of the intracellular signalling pathways of the innate immune receptors Toll-like 3 (TLR3), which triggers antiviral and inflammatory responses.AimsTo elucidate the regulatory role of paliperidone on maternal immune activation (MIA) induced alterations on TLR3 pathway and on the two emerging endogenous antiinflammatory/antioxidant mechanisms NRF2/antioxidant enzymes pathway and the cytokine milieu regulating M1/M2 polarization in microglia.MethodsPregnant mice were treated with the synthetic Toll-like Receptor 3 (TLR3) agonist Poly(I:C) in gestational day 9 and chronically treated with paliperidone (0,05 mg/kg i.p.) in adult offspring. Animals were sacrificed one day after treatment and behavioral test. Inflammation oxidative stress-related mediators were analysed at mRNA and protein level in prefrontal cortex samples. In addition, behavioral test t-maze was conducted.ResultsPaliperidone prevented TLR3 pathway activation and the subsequent MIA-induced neuroinflammatory response. Also, paliperidone induced an increment in the activity and protein expression of nuclear NRF2, as well as increased mRNA levels of the antioxidant enzymes HO1, SOD and catalase in the MIA model. Otherwise, paliperidone increases the antiinflammatory cytokines levels TGFβ and IL-10 in favour of a M2 microglia profile and increased the levels of the M2 cellular markers ArgI and FOLR2.ConclusionsThe modulation of neuroinflammation and enhancement of endogenous antioxidant/anti-inflammatory pathways by current and new antipsychotics could represent an interesting therapeutic strategy for the future.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Therapeutically Targeting Neuroinflammation and Microglia after Acute Ischemic Stroke

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Youngjeon Lee ◽  
Sang-Rae Lee ◽  
Sung S. Choi ◽  
Hyeon-Gu Yeo ◽  
Kyu-Tae Chang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Inflammatory Responses ◽  
Secondary Injury ◽  
Initial Event ◽  
Stroke Models ◽  
Anti Inflammatory ◽  
Preclinical And Clinical Studies ◽  
Multiple Receptor

Inflammation has a pivotal role in the pathogenesis of ischemic stroke, and recent studies posit that inflammation acts as a double-edged sword, not only detrimentally augmenting secondary injury, but also potentially promoting recovery. An initial event of inflammation in ischemic stroke is the activation of microglia, leading to production of both pro- and anti-inflammatory mediators acting through multiple receptor signaling pathways. In this review, we discuss the role of microglial mediators in acute ischemic stroke and elaborate on preclinical and clinical studies focused on microglia in stroke models. Understanding how microglia can lead to both pro- and anti-inflammatory responses may be essential to implement therapeutic strategies using immunomodulatory interventions in ischemic stroke.

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