scholarly journals Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

2018 ◽  
Vol 51 (6) ◽  
pp. 2575-2590 ◽  
Author(s):  
Gang Zhong ◽  
Ruiming Liang ◽  
Jun Yao ◽  
Jia Li ◽  
Tongmeng Jiang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cruciate Ligament ◽  
Interleukin 1 ◽  
Cartilage Degradation ◽  
Chondrocyte Apoptosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Viability Assay ◽  
Necrosis Factor Alpha ◽  
Anti Inflammatory

Background/Aims: Current drug therapies for osteoarthritis (OA) are not practical because of the cytotoxicity and severe side-effects associated with most of them. Artemisinin (ART), an antimalarial agent, is well known for its safety and selectivity to kill injured cells. Based on its anti-inflammatory activity and role in the inhibition of OA-associated Wnt/β-catenin signaling pathway, which is crucial in the pathogenesis of OA, we hypothesized that ART might have an effect on OA. Methods: The chondro-protective and antiarthritic effects of ART on interleukin-1-beta (IL-1β)-induced and OA patient-derived chondrocytes were investigated in vitro using cell viability assay, glycosaminoglycan secretion, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blotting. We also used OA model rats constructed by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) in the joints to investigate the effects of ART on OA by gross observation, morphological staining, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ART exhibited potent anti-inflammatory effects by inhibiting the expression of proinflammatory chemokines and cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha, and matrix metallopeptidase-13. It also showed favorable chondro-protective effect as evidenced by enhanced cell proliferation and viability, increased glycosaminoglycan deposition, prevention of chondrocyte apoptosis, and degeneration of cartilage. Further, ART inhibited OA progression and cartilage degradation via the Wnt/β-catenin signaling pathway, suggesting that it might serve as a Wnt/β-catenin antagonist to reduce inflammation and prevent cartilage degradation. Conclusion: In conclusion, ART alleviates IL-1β-mediated inflammatory response and OA progression by regulating the Wnt/β-catenin signaling pathway. Thereby, it might be developed as a potential therapeutic agent for OA.

scholarly journals A Novel Synthesized Sulfonamido-Based Gallate-JEZTC Blocks Cartilage Degradation on Rabbit Model of Osteoarthritis: An in Vitro and in Vivo Study

2018 ◽  
Vol 49 (6) ◽  
pp. 2304-2319 ◽  
Author(s):  
Zhenhui Lu ◽  
Qin Liu ◽  
Lei Liu ◽  
Huayu Wu ◽  
Li Zheng ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cruciate Ligament ◽  
Interleukin 1 ◽  
Rabbit Model ◽  
Cartilage Degradation ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Histological Evaluation ◽  
Chondrocyte Apoptosis

Background/Aims: 3, 4, 5-trihydroxy-N-{4-[(5-methylisoxazol-3-yl) sulfamoyl] phenyl} benzamide (JEZTC), synthesized from gallic acid (GA) and sulfamethoxazole (SMZ), was reported with chondroprotective effects. However, the effects of JEZTC on osteoarthritis (OA) are still unclear. The goal of this study was to investigate the anti-osteoarthritic properties of JEZTC on interleukin-1-beta (IL-1β) stimulated chondrocytes in vitro and a rabbit anterior cruciate ligament transaction (ACLT) OA model in vivo. Methods: Changes in matrix metalloproteinases (MMPs) and apoptosis genes (bax, caspase 3 and tnf-α) and OA-specific protein (MMP-1) expression in vitro and in vivo were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. The production of reactive oxygen species (ROS) were investigated upon the treatment of JEZTC in chondrocytes processed with IL-1β in vitro and OA in vivo. Effect of JEZTC on OA was further studied by the macroscopic and histological evaluation and scores. The key proteins in signaling pathways inMAPK/P38, PI3KAkt and NF-κB also determined using western blot (WB) analysis. Results: JEZTC could significantly suppress the expression of MMPs and intracellular ROS, while meaningfully increase the gene expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). Moreover, there was less cartilage degradation in JEZTC group compared with the phosphate-buffered saline (PBS) group in vivo. Results also indicated that JEZTC exerts effect on OA by regulating MAPKs and PI3K/Akt signaling pathways to activate NF-κB pathway, leading to the down-regulation of MMPs. The chondro-protective effect of JEZTC may be related with its ability to inhibit chondrocyte apoptosis by reduction of ROS production. Conclusion: JEZTC may be a possible therapeutic agent in the treatment of OA.

Gigantol Alleviates IL-1β-Induced Inflammation and Catabolism in Mouse Osteoarthritis via PI3K/Akt/NF-κB Pathways In Vivo and In Vitro

2021 ◽  
Author(s):  
Gaosheng Zhu ◽  
Keze Miao ◽  
Mingwei Dong ◽  
Jie Cai ◽  
Zhihao Shen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Therapeutic Option ◽  
Interleukin 1 ◽  
Cartilage Degradation ◽  
Research Society ◽  
Necrosis Factor Alpha ◽  
Persistent Inflammation ◽  
Anti Inflammatory

Abstract Osteoarthritis (OA), a prevalent disabling disease, is characterized by irreversible cartilage degradation and persistent inflammation. The etiology as well as pathogenesis of OA are not completely unclear and need further investigation. Gigantol, is a bibenzyl derivative extracted from Dendrobium plants and has been found exhibit multiple effects such as anti-inflammatory effects. Nevertheless, the biological function of gigantol on osteoarthritis (OA) is still uncertain. This study aimed at examining the anti-inflammatory effects and latent mechanisms of gigantol in IL-1β-mediated OA progression. In vitro, we identified that gigantol treatment suppressed tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) in interleukin-1 beta (IL-1β) mediated mouse OA chondrocytes. Gigantol was also shown to dose dependently downregulate the metalloproteinase 13 (MMP13) as well as thrombospondin motifs 5 (ADAMTS5) levels. Moreover, IL-1β-mediated AKT and PI3K phosphorylation as well as NF-κB activation were inhibited by gigantol. Meanwhile, in vivo, we detected that gigantol treatment inhibited degradation of the cartilage degradation and lowered the Osteoarthritis Research Society International scores (OARSI) in OA mouse. Therefore, gigantol is a promising therapeutic option for OA.

scholarly journals Veronicastrum axillare Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Suppression of Proinflammatory Mediators and Downregulation of the NF-κB Signaling Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Quanxin Ma ◽  
Kai Wang ◽  
Qinqin Yang ◽  
Shun Ping ◽  
Weichun Zhao ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Biological Activities ◽  
Interleukin 1 ◽  
Folk Medicine ◽  
Protective Effects ◽  
Proinflammatory Mediators ◽  
Anti Inflammatory

Veronicastrum axillare is a traditional medical plant in China which is widely used in folk medicine due to its versatile biological activities, especially for its anti-inflammatory effects. However, the detailed mechanism underlying this action is not clear. Here, we studied the protective effects of V. axillare against acute lung injury (ALI), and we further explored the pharmacological mechanisms of this action. We found that pretreatment with V. axillare suppressed the release of proinflammatory cytokines in the serum of ALI mice. Histological analysis of lung tissue demonstrated that V. axillare inhibited LPS-induced lung injury, improved lung morphology, and reduced the activation of nuclear factor-κB (NF-κB) in the lungs. Furthermore, the anti-inflammatory actions of V. axillare were investigated in vitro. We observed that V. axillare suppressed the mRNA expression of interleukin-1β (IL-1β), IL-6, monocyte chemotactic protein-1 (MCP-1), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α) in RAW264.7 cells challenged with LPS. Furthermore, pretreatment of V. axillare in vitro reduced the phosphorylation of p65 and IκB-α which is activated by LPS. In conclusion, our data firstly demonstrated that the anti-inflammatory effects of V. axillare against ALI were achieved through downregulation of the NF-κB signaling pathway, thereby reducing the production of inflammatory mediators.

scholarly journals Antibacterial and Anti-Inflammatory Activities ofPhysalis Alkekengivar.franchetiiand Its Main Constituents

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Zunpeng Shu ◽  
Na Xing ◽  
Qiuhong Wang ◽  
Xinli Li ◽  
Bingqing Xu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Interleukin 1 ◽  
Inflammatory Activity ◽  
Prostaglandin E ◽  
Active Components ◽  
Necrosis Factor Alpha ◽  
Anti Inflammatory

This study was designed to determine whether the 50% EtOH fraction from AB-8 macroporous resin fractionation of a 70% EtOH extract ofP. Alkekengi(50-EFP) has antibacterial and/or anti-inflammatory activity bothin vivoandin vitroand to investigate the mechanism of 50-EFP anti-inflammatory activity. Additionally, this study sought to define the chemical composition of 50-EFP. Results indicated that 50-EFP showed significant antibacterial activityin vitroand efficacyin vivo. Moreover, 50-EFP significantly reduced nitric oxide (NO), prostaglandin E2(PGE2), tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), and interleukin 6 (IL-6) production in lipopolysaccharide- (LPS-) stimulated THP-1 cells. Nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (examined at the protein level) in THP-1 cells were suppressed by 50-EFP, which inhibited nuclear translocation of p65. Consistent with this anti-inflammatory activityin vitro, 50-EFP reduced inflammation in both animal models. Finally, seventeen compounds (8 physalins and 9 flavones) were isolated as major components of 50-EFP. Our data demonstrate that 50-EFP has antibacterial and anti-inflammatory activities bothin vitroandin vivo. The anti-inflammatory effect appears to occur, at least in part, through the inhibition of nuclear translocation of p65. Moreover, physalins and flavones are probably the active components in 50-EFP that exert antibacterial and anti-inflammatory activities.

scholarly journals miR-142-5p as a CXCR4-Targeted MicroRNA Attenuates SDF-1-Induced Chondrocyte Apoptosis and Cartilage Degradation via Inactivating MAPK Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Yaoyv Xiang ◽  
Yanlin Li ◽  
Lingjian Yang ◽  
Yinghong He ◽  
Di Jia ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cartilage Degradation ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Luciferase Reporter ◽  
Chondrocyte Apoptosis ◽  
Bioinformatics Analyses ◽  
Oa Chondrocytes ◽  
Cxcr4 Axis

Osteoarthritis (OA) is a chronic joint function disorder with characteristics of chondrocytes reduction and extracellular matrix (ECM) components destruction. MicroRNAs (miRNAs) and the SDF-1/CXCR4 axis are essential factors of chondrocyte apoptosis and ECM degeneration. However, very few studies have investigated the correlation between miRNAs and the SDF-1/CXCR4 axis in osteoarthritis so far. Here, through miRNAs microarray and bioinformatics analyses, we identified miR-142-5p as a CXCR4-targeted and dramatically downregulated miRNA in cartilage from OA patients, as well as in SDF-1-induced OA chondrocytes in vitro. In SDF-1-treated primary human OA chondrocytes that were transfected with a miR-142-5p mimic or inhibitor, the expression of CXCR4 was found to be inversely correlated with the expression of miR-142-5p. The dual luciferase reporter assay further verified the target relationship between miR-142-5p and CXCR4. Overexpression of miR-142-5p alleviated OA pathology by suppressing chondrocyte apoptosis, even in CXCR4 overexpressed OA chondrocytes. This was associated with decreased cartilage matrix degradation, reduced cartilage inflammation, and inactivated MAPK signaling pathway. Our study suggests that upregulated expression of CXCR4-targeted miR-142-5p can inhibit apoptosis, inflammation, and matrix catabolism and inactivate the MAPK signaling pathway in OA chondrocytes. Our work provides important insight into targeting miR-142-5p and the SDF-1/CXCR4 axis in OA therapy.

scholarly journals Emodin Attenuates LPS-Induced Acute Lung Injury by Inhibiting NLRP3 Inflammasome-Dependent Pyroptosis Signaling Pathway In vitro and In vivo

Inflammation ◽  
2021 ◽  
Author(s):  
Yuhan Liu ◽  
Luorui Shang ◽  
Jiabin Zhou ◽  
Guangtao Pan ◽  
Fangyuan Zhou ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Quantitative Polymerase Chain Reaction ◽  
Interleukin 1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects

Abstract—Emodin, the effective component of the traditional Chinese medicine Dahuang, has anti-inflammatory effects. However, the protective effects and potential mechanisms of emodin are not clear. This study investigated the protective effects and potential mechanisms of emodin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in vitro and in vivo. In vivo, we designed an LPS-induced ALI rat model. In vitro, we chose the J774A.1 cell line to establish an inflammatory cellular model, and knocked down NOD-like receptor family pyrin domain containing 3 (NLRP3) using small interfering RNA. The mRNA and protein expression of NLRP3, a C-terminal caspase recruitment domain (ASC), caspase 1 (CASP1), and gasdermin D (GSDMD) in cells and lung tissues were detected by western blot and real-time quantitative polymerase chain reaction (PCR). The expression levels of interleukin 1 beta (IL-1β) and IL-18 in the serum and supernatant were determined by the enzyme-linked immunosorbent assay. The degree of pathological injury in lung tissue was evaluated by hematoxylin and eosin (H&E) staining. In vitro, we demonstrated that emodin could inhibit NLRP3 and then inhibit the expression of ASC, CASP1, GSDMD, IL-1β, and IL-18. In vivo, we confirmed that emodin had protective effects on LPS-induced ALI and inhibitory effects on NLRP3 inflammasome -dependent pyroptosis. Emodin showed excellent protective effects against LPS-induced ALI by regulating the NLRP3 inflammasome-dependent pyroptosis signaling pathway.

Morin exerts antiosteoarthritic properties: an in vitro and in vivo study

2012 ◽  
Vol 237 (4) ◽  
pp. 380-386 ◽  
Author(s):  
Wei-Ping Chen ◽  
Peng-Fei Hu ◽  
Jia-Peng Bao ◽  
Li-Dong Wu
Keyword(s):  
Rat Model ◽  
Cruciate Ligament ◽  
Interleukin 1 ◽  
Cartilage Degradation ◽  
In Vivo Study ◽  
In Vivo Studies ◽  
Tissue Inhibitors Of Metalloproteinase ◽  
Mitogen Activated Protein

Morin is a flavonoid isolated from members of the Moraceae family. Morin has been reported to possess antioxidative and anticarcinogenic activities. However, the antiosteoarthritic properties of morin have not been investigated. In this study, we evaluate the antiarthritic properties of morin through in vitro and in vivo studies. We examined the effects of morin on the expression levels of matrix metalloproteinase (MMP)-3, MMP-13 and tissue inhibitors of metalloproteinase (TIMP)-1 in interleukin-1 β (IL-1 β)-induced rat chondrocytes by realtime polymerase chain reaction and Western blotting. The effects of morin on the phosphorylation of mitogen-activated protein kinases were also investigated. The in vivo antiosteoarthritic effects of morin were evaluated in the rat model of anterior cruciate ligament transection (ACLT)-induced osteoarthritis (OA). We found that morin inhibited the expression of MMP-3 and MMP-13 and increased the expression of TIMP-1 in IL-1 β-induced rat chondrocytes. In addition, morin inhibited IL-1 β-induced phosphorylation of extracellular signal-regulated kinase and p38. For the in vivo study in a rat model of OA induced by ACLT, in which morin was orally administered to rat, the results show that morin suppressed cartilage degradation. Our results suggest that morin may be considered as a possible therapeutic agent for the treatment of OA.

scholarly journals Tert-butylhydroquinone attenuates osteoarthritis by protecting chondrocytes and inhibiting macrophage polarization

2021 ◽  
Vol 10 (11) ◽  
pp. 704-713
Author(s):  
Hua Zhang ◽  
Jie Li ◽  
Xiaobing Xiang ◽  
Bengen Zhou ◽  
Changqing Zhao ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Interleukin 1 ◽  
Mitogen Activated Protein Kinase ◽  
Chondrocyte Apoptosis ◽  
Necrosis Factor Alpha ◽  
Expression Levels ◽  
Mapk Signalling

Aims Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA. Methods OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1β) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 μM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1β, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot. Results Tert-butylhydroquinone significantly attenuated cartilage destruction in DMM-induced mice in vivo. It demonstrated clear evidence of inhibiting IL-1β-induced chondrocyte apoptosis, inflammation, and differentiation defect in vitro. Meanwhile, tBHQ inhibited LPS-induced activation of NF-κB and MAPK signalling pathways, and also inhibited LPS-induced reactive oxygen species production and macrophages repolarization in vitro. Conclusion Taken together, tBHQ might be a potential therapeutic strategy for protecting against OA development. Cite this article: Bone Joint Res 2021;10(11):704–713.

scholarly journals Chyawanprash, An Ancient Indian Ayurvedic Medicinal Food, Regulates Immune Response in Zebrafish Model of Inflammation by Moderating Inflammatory Biomarkers

2021 ◽  
Vol 12 ◽  
Author(s):  
Acharya Balkrishna ◽  
Meenu Tomer ◽  
Moumita Manik ◽  
Jyotish Srivastava ◽  
Rishabh Dev ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Dependent Manner ◽  
Zebrafish Model ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Medicinal Food ◽  
Anti Inflammatory ◽  
Oxidative Effects

The time-tested Ayurvedic medicinal food, Chyawanprash, has been a part of the Indian diet since ancient times. It is an extremely concentrated mixture of extracts from medicinal herbs and processed minerals, known for its immunity boosting, rejuvenating, and anti-oxidative effects. In this study, we have evaluated the anti-inflammatory potential of Patanjali Special Chyawanprash (PSCP) using the zebrafish model of inflammation. Zebrafish were fed on PSCP-infused pellets at stipulated doses for 13 days before inducing inflammation through lipopolysaccharide (LPS) injection. The test subjects were monitored for inflammatory pathologies like behavioral fever, hyperventilation, skin hemorrhage, locomotory agility, and morphological anomaly. PSCP exerted a strong prophylactic effect on the zebrafish that efficiently protected them from inflammatory manifestations at a human equivalent dose. Expression levels of pro-inflammatory cytokines, like interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β), were also reduced in the LPS-stimulated zebrafish fed on PSCP-infused pellets. Skin hemorrhage, hyperventilation, and loss of caudal fins are characteristics of LPS-induced inflammation in zebrafish. PSCP prophylactically ameliorated skin hemorrhage, restored normal respiration, and prevented loss of caudal fin in inflamed zebrafish. Under in vitro conditions, PSCP reduced IL-6 and TNF-α secretion by THP-1 macrophages in a dose-dependent manner by targeting NF-κB signaling, as evident from the secreted embryonic alkaline phosphatase (SEAP) reporter assay. These medicinal benefits of PSCP can be attributed to its constitutional bioactive components. Taken together, these observations provide in vivo validation of the anti-inflammatory property and in vitro insight into the mode-of-action of Chyawanprash, a traditionally described medicinal food.

scholarly journals Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Morphological Changes ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

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