scholarly journals Acteoside inhibits inflammatory response via JAK/STAT signaling pathway in osteoarthritic rats

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhiguang Qiao ◽  
Jiaxin Tang ◽  
Wen Wu ◽  
Jian Tang ◽  
Ming Liu
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Rat Model ◽  
Inflammatory Responses ◽  
Annexin V ◽  
Chondrocyte Apoptosis ◽  
Articular Chondrocyte ◽  
Joint Protection ◽  
Stat Signaling

Abstract Background Osteoarthritis (OA) is a common degenerative disease of synovial joints caused by inflammation. Acteoside (ACT), a major component and lipase inhibitor from the Chinese tea Ligustrum purpurascens kudingcha, has been reported to regulate the inflammation and immune response. The study aims to investigate the effects of ACT on inflammatory responses and joint protection in OA rats. Methods Cell proliferation was examined by MTT and colony formation assay. Apoptosis was analyzed using flow cytometry with Annexin V/PI staining. ELISA was employed to examine the concentration of inflammatory cytokines. OA rat model was established by surgery stimulation. Results ACT treatment significantly inhibited the upregulation of inflammatory cytokines induced by IL-1β in primary chondrocytes, including IL-6, IL-12, TNF-α and IFN-γ. ACT stimulation also enhanced the cell proliferation, while inhibited cell apoptosis in IL-1β-treated chondrocytes. Consistently, ACT treatment led to downregulation of cleaved-caspase-3 and apoptosis regulator Bax, and upregulation of Bcl-2. Furthermore, ACT treatment inhibited IL-1β-induced activation of JAK/STAT pathway. The results were confirmed in surgery-induced OA rat model. Moreover, ACT treatment significantly inhibited synovial inflammation and articular chondrocyte apoptosis in OA rats. Conclusion Our findings indicate that ACT has the potential therapeutic effect on OA through inhibiting the inflammatory responses via inactivating JAK/STAT signaling pathway.

miR-34 Promotes Autophagy and Apoptosis of Spinal Chondrocytes by Mammalian Target of Rapamycin/Phosphatidylinositol-3-Kinase/Protein Kinase B Signaling

2020 ◽  
Vol 10 (12) ◽  
pp. 1877-1883
Author(s):  
Jun Wu ◽  
Fenfen Zhao ◽  
Feng Tian ◽  
Feng Ma ◽  
Tao Guan
Keyword(s):  
Cell Proliferation ◽  
Real Time ◽  
Signaling Pathway ◽  
Real Time Pcr ◽  
Caspase 3 ◽  
Akt Signaling ◽  
Chondrocyte Apoptosis ◽  
Control Group ◽  
Akt Signaling Pathway ◽  
Articular Chondrocyte

Autophagy and apoptosis of chondrocytes participate in spondyloarthritis (SpA). miR-34 involves in various diseases. However, miR-34’s role in autophagy and apoptosis of spine chondrocytes remains unclear. SpA patients and normal bone and articular cartilage tissues were collected, and miR-34 level was detected by Real-time PCR. The chondrocytes of SpA patients were isolated and divided into control group, miR-34 siRNA group and miR-34 group followed by analysis of Caspase 3 activity, cell proliferation by MTT assay, expression of Bax, Bcl-2, ATG5 and Beclin1 by Real time PCR, mTOR/PI3K/AKT signaling pathway protein expression by western blot, as well as TNF-α and IL-6 secretion by ELISA. miR-34 was significantly upregulated in SpA patients compared to normal (P <0.05). miR-34 siRNA transfection into SpA chondrocytes significantly down-regulated miR-34 expression, promoted cell proliferation, decreased Caspase 3 activity and Bax expression, increased Bcl-2, ATG5 and Beclin1 expression, decreased TNF-α and IL- 6 secretion as well as increased pmTOR and pAKT expression (P <0.05). miR-34 mimics was transfected into SpA chondrocytes, which up-regulated miR-34 expression and significantly reversed the above changes (P <0.05). miR-34 is upregulated in SpA patients. Down-regulation of miR-34 inhibits articular chondrocyte apoptosis and promotes autophagy by down-regulatingmTOR/PI3K/AKT signaling pathway, thereby promoting articular chondrocyte proliferation and inhibiting joint inflammation.

scholarly journals Lipopolysaccharide Pre-conditioning Attenuates Pro-inflammatory Responses and Promotes Cytoprotective Effect in Differentiated PC12 Cell Lines via Pre-activation of Toll-Like Receptor-4 Signaling Pathway Leading to the Inhibition of Caspase-3/Nuclear Factor-κappa B Pathway

2021 ◽  
Vol 14 ◽  
Author(s):  
Pushpa Gandi Sangaran ◽  
Zaridatul Aini Ibrahim ◽  
Zamri Chik ◽  
Zahurin Mohamed ◽  
Abolhassan Ahmadiani
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Caspase 3 ◽  
Inflammatory Responses ◽  
Annexin V ◽  
Future Research ◽  
Protective Effects ◽  
Destructive Effect ◽  
Effector Caspase ◽  
Gene And Protein Expression

Lipopolysacharide (LPS) pre-conditioning (PC), has been shown to exert protective effects against cytotoxic effects. Therefore, we hypothesized, the tolerance produced by LPS PC will be resulted by the alterations and modifications in gene and protein expression. With reference to the results of MTT assays, AO/PI staining, and Annexin V-FITC analyses of LPS concentration (0.7815–50 μg/mL) and time-dependent (12–72 h) experiments, the pre-exposure to 3 μg/mL LPS for 12 h protected the differentiated PC12 cells against 0.75 mg/mL LPS apoptotic concentration. LPS-treated cells secreted more inflammatory cytokines like IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-17, IFN-γ, and TNF-α than LPS-PC cells. The production of inflammatory mediators ROS and NO was also higher in the LPS-induced cells compared to LPS-PC cells. Conversely, anti-inflammatory cytokines (like IL-10, IL-13, CNTF, and IL-1Ra) were upregulated in the LPS-PC cells but not in the LPS-induced cells. Meanwhile, the LPS initiated caspase-8 which in turn activates effector caspase 3/7. When the activities of caspases in the LPS-induced cells were inhibited using z-VADfmk and z-DEVDfmk, the expressions of c-MYC and Hsp70 were increased, but p53 was reduced. The potential molecules associated with protective and destructive effect was measured by RT2 Profiler PCR array to elucidate the signaling pathways and suggested inhibition NF-κB/caspase-3 signaling pathway regulates the cytoprotective genes and proto-oncogenes. In conclusion, this study provides a basis for future research to better understand the molecular mechanism underlying LPS pre-conditioning /TLR4 pre-activation and its functional role in offering cytoprotective response in neuronal environment.

scholarly journals Protective role of Dihydromyricetin in Alzheimer’s disease rat model associated with activating AMPK/SIRT1 signaling pathway

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Ping Sun ◽  
Jun-Bo Yin ◽  
Li-Hua Liu ◽  
Jian Guo ◽  
Sheng-Hai Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Rat Model ◽  
Inflammatory Responses ◽  
Protective Role ◽  
Spatial Learning And Memory ◽  
Related Proteins

Abstract The aim of the present study was to understand the possible role of the Dihydromyricetin (DHM) in Alzheimer’s disease (AD) rat model through regulation of the AMPK/SIRT1 signaling pathway. Rats were divided into Sham group, AD group, AD + DHM (100 mg/kg) group and AD + DHM (200 mg/kg) group. The spatial learning and memory abilities of rats were assessed by Morris Water Maze. Then, the inflammatory cytokines expressions were determined by radioimmunoassay while expressions of AMPK/SIRT1 pathway-related proteins by Western blot; and the apoptosis of hippocampal cells was detected by TdT-mediated dUTP nick end labeling assay. AD rats had an extended escape latency with decreases in the number of platform crossings, the target quadrant residence time, as well as swimming speed, and the inflammatory cytokines in serum and hippocampus were significantly elevated but AMPK/SIRT1 pathway-related proteins were reduced. Meanwhile, the apoptosis of hippocampal cells was significantly up-regulated with decreased Bcl-2 and increased Bax, as compared with Sham rats (all P<0.05). After AD rats treated with 100 or 200 mg/kg of DHM, the above effects were significantly reversed, resulting in a completely opposite tendency, and especially with 200 mg/kg DHM treatment, the improvement of AD rats was more obvious. DHM exerts protective role in AD via up-regulation of AMPK/SIRT1 pathway to inhibit inflammatory responses and hippocampal cell apoptosis and ameliorate cognitive function.

scholarly journals Punicalagin Prevents Inflammation in LPS-Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Inflammatory Responses ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Autophagy Inhibition ◽  
Pro Inflammatory Cytokines

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

scholarly journals Kyungheechunggan-Tang-01, a New Herbal Medication, Suppresses LPS-Induced Inflammatory Responses through JAK/STAT Signaling Pathway in RAW 264.7 Macrophages

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Hee-Soo Han ◽  
Eungyeong Jang ◽  
Ji-Sun Shin ◽  
Kyung-Soo Inn ◽  
Jang-Hoon Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Molecular Data ◽  
Mrna Levels ◽  
Protein Levels ◽  
Stat3 Phosphorylation ◽  
Stat Signaling ◽  
Cox 2 ◽  
Anti Inflammatory

Medicinal plants have been used as alternative therapeutic tools to alleviate inflammatory diseases. The objective of this study was to evaluate anti-inflammatory properties of Kyungheechunggan-tang- (KCT-) 01, KCT-02, and Injinchunggan-tang (IJCGT) as newly developed decoctions containing 3–11 herbs in LPS-induced macrophages. KCT-01 showed the most potent inhibitory effects on LPS-induced NO, PGE2, TNF-α, and IL-6 production among those three herbal formulas. In addition, KCT-01 significantly inhibited LPS-induced iNOS and COX-2 at protein levels and expression of iNOS, COX-2, TNF-α, and IL-6 at mRNA levels. Molecular data revealed that KCT-01 attenuated the activation of JAK/STAT signaling cascade without affecting NF-κB or AP-1 activation. In ear inflammation induced by croton oil, KCT-01 significantly reduced edema, MPO activity, expression levels of iNOS and COX-2, and STAT3 phosphorylation in ear tissues. Taken together, our findings suggest that KCT-01 can downregulate the expression of proinflammatory genes by inhibiting JAK/STAT signaling pathway under inflammatory conditions. This study provides useful data for further exploration and application of KCT-01 as a potential anti-inflammatory medicine.

scholarly journals The Anti-Inflammatory Effects of Angiogenin in an Endotoxin Induced Uveitis in Rats

2020 ◽  
Vol 21 (2) ◽  
pp. 413
Author(s):  
Jihae Park ◽  
Jee Taek Kim ◽  
Soo Jin Lee ◽  
Jae Chan Kim
Keyword(s):  
Western Blot ◽  
Inflammatory Cytokines ◽  
Aqueous Humor ◽  
Rat Model ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Ocular Tissue ◽  
Tnf Α ◽  
Anti Inflammatory

Angiogenin (ANG) is involved in the innate immune system and inflammatory disease. The aim of this study is to evaluate the anti-inflammatory effects of ANG in an endotoxin induced uveitis (EIU) rat model and the pathways involved. EIU rats were treated with balanced salt solution (BSS), a non-functional mutant ANG (mANG), or wild-type ANG (ANG). The integrity of the blood-aqueous barrier was evaluated by the infiltrating cell and protein concentrations in aqueous humor. Histopathology, Western blot, and real-time qRT-PCR of aqueous humor and ocular tissue were performed to analyze inflammatory cytokines and transcription factors. EIU treated with ANG had decreased inflammatory cells and protein concentrations in the anterior chamber. Compared to BSS and mANG, ANG treatment showed reduced expression of IL-1β, IL-8, TNF-α, and Myd88, while the expression of IL-4 and IL-10 was increased. Western blot of ANG treatment showed decreased expression of IL-6, inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and phosphorylated NF-κB and increased expression of IL-10. In conclusion, ANG seems to reduce effectively immune mediated inflammation in the EIU rat model by reducing the expression of proinflammatory cytokines, while increasing the expression of anti-inflammatory cytokines through pathways related to NF-κB. Therefore, ANG shows potential for effectively suppressing immune-inflammatory responses in vivo.

scholarly journals Mechanism of Action of Acupotomy in Inhibiting Chondrocyte Apoptosis in Rabbits with KOA through the PI3K/Akt Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiao-shuang Huang ◽  
Kai Geng ◽  
Shi-yu Luo ◽  
Cun-bin Liu ◽  
Kai-ning Yang ◽  
...  
Keyword(s):  
Placebo Group ◽  
Knee Joint ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Drug Group ◽  
Chondrocyte Apoptosis ◽  
Akt Signaling Pathway ◽  
Articular Chondrocyte ◽  
Expression Levels ◽  
Mrna And Protein Expression

Objective. We examined the effects of acupotomy on the PI3K/Akt signaling pathway to elucidate the mechanism of action of acupotomy on articular chondrocyte apoptosis among rabbits with knee osteoarthritis (KOA). Methods. New Zealand rabbits were randomly assigned to a healthy control group, placebo group, acupotomy group, and drug group, with 10 rabbits in each group. Changes in chondrocytes were examined by hematoxylin and eosin staining, and articular chondrocyte apoptosis was measured by electron microscopy and immunofluorescence. The mRNA and protein expression levels of PI3K and Akt were measured by real-time quantitative PCR and Western blot. Results. In contrast, less chromatin margination and clear and smooth nuclear envelope boundary were visible in the acupotomy group and drug group. The number of apoptotic chondrocytes in the knee joint of rabbits was significantly higher in the placebo group than that in the acupotomy group and drug group ( P < 0.05 ). The acupotomy group had a nonsignificantly lower number of apoptotic chondrocytes than the drug group ( P > 0.05 ). Furthermore, the mRNA and protein expression levels of PI3K and Akt were significantly higher in the acupotomy group and drug group than those in the placebo group ( P < 0.05 ) and were closer to normal levels in the acupotomy group than those in the drug group ( P < 0.05 ). PI3K and Akt expression levels were negatively correlated with chondrocyte apoptosis in the knee joint of rabbits in all groups. Conclusion. Inhibiting chondrocyte apoptosis in the knee joint of KOA rabbits by upregulating the PI3K/Akt signaling pathway may be a possible mechanism of acupotomy in treating KOA.

scholarly journals Long non-coding RNA RP11-468E2.5 curtails colorectal cancer cell proliferation and stimulates apoptosis via the JAK/STAT signaling pathway by targeting STAT5 and STAT6

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Li Jiang ◽  
Xu-Hai Zhao ◽  
Yin-Ling Mao ◽  
Jun-Feng Wang ◽  
Hui-Jun Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Target Genes ◽  
Biological Activities ◽  
Janus Kinase ◽  
Normal Tissues ◽  
Stat Signaling

Abstract Background Long non-coding RNAs (lncRNAs) are tumor-associated biological molecules and have been found to be implicated in the progression of colorectal cancer (CRC). This study aims to examine the effects of lncRNA RP11-468E2.5 and its target genes (STAT5 and STAT6) on the biological activities of CRC cells via the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway. Methods We initially screened the GEO database for differentially expressed lncRNAs related to CRC and then made a prediction of the implicated target genes. Then we collected CRC tissues and adjacent normal tissues from 169 CRC patients. Human CRC HCT116 and SW480 cells were treated with small interference RNA (siRNA) against RP11-468E2.5, AG490 (an inhibitor of the JAK/STAT signaling pathway), or both in combination. Next, we measured the effects of RP11-468E2.5 treatment on cellular activities such as cell viability, cycle distribution and cell apoptosis, and studied interactions among RP11-468E2.5, STAT5/STAT6, and the JAK/STAT signaling pathway. Finally, an in vivo tumor formation assay was performed to observe the effect of RP11-468E2.5 on tumor growth. Results The CRC-related gene microarray data showed low expression of RP11-468E2.5 in CRC surgical specimens. However, RP11-468E2.5 was confirmed to target STAT5 and STAT6, which participate in the JAK/STAT signaling pathway. CRC tissues showed lower expression of RP11-468E2.5, higher expression of STAT5, STAT6 and of the cell cycle marker Cyclin D1 (CCND1), compared to the findings in adjacent normal tissues. The treatment of siRNA against RP11-468E2.5 increased expression of JAK2, STAT3, STAT5, STAT6, CCND1 and Bcl-2 along with the extent of STAT3, STAT5 and STAT6 phosphorylation, while lowering expression of P21 and P27. Treatment with AG490 exhibited approximately opposite effects, whereas siRNA against RP11-468E2.5 treatment stimulated CRC cell proliferation and reduced cell apoptosis, while promoting cell cycle entry; AG490 treatment reversed these results. Conclusions Altogether, we conclude that up-regulation of RP11-468E2.5 inhibits the JAK/STAT signaling pathway by targeting STAT5 and STAT6, thereby suppressing cell proliferation and promoting cell apoptosis in CRC.

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