scholarly journals Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-κB/STAT3 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Runan Yang ◽  
Zijing Li ◽  
Yuting Zou ◽  
Jingjian Yang ◽  
Lin Li ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Gallic Acid ◽  
Signaling Pathway ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
P2x7 Receptor ◽  
Pain Behaviors ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tnf Α

Neuropathic pain is a complex disease with high incidence. Adenosine triphosphate (ATP) and its activated P2X7 receptor are involved in the signal transmission of neuropathic pain. Gallic acid (3,4,5-trihydroxybenzoic acid) is a traditional Chinese medicine obtained from natural plants that exhibit anti-inflammatory, analgesic, and antitumor effects. However, the underlying mechanism for gallic acid in analgesia remains unknown. This study aims to reveal how gallic acid alleviates neuropathic pain behaviors in a rat model with chronic constriction injury (CCI). Real-time PCR, western blotting, double-label immunofluorescence, molecular docking, and whole-cell patch clamp technology were used to explore the therapeutic action of gallic acid on neuropathic pain. The results showed that after CCI rats were treated with gallic acid for 1 week, the mechanical withdrawal threshold and thermal withdrawal latency were increased, accompanied by inhibition of the upregulated expression of P2X7 and TNF-α at both mRNA and protein levels, and reduced NF-κB and phosphorylated-STAT3 in the dorsal root ganglia. At the same time, gallic acid significantly decreased the coexpression of P2X7 and glial fibrillary acidic protein in the dorsal root ganglia. In addition, gallic acid could suppress ATP-activated current in human embryonic kidney 293 (HEK293) cells transfected with the plasmid expressing P2X7 but had no effect on ATP activation current of P2X7-mutant plasmid (with the point mutation sequence of the key site where gallic acid binds to the P2X7 receptor). Therefore, our work suggests that gallic acid may alleviate neuropathic pain in CCI rats by inhibiting the P2X7 receptor and subsequent activation of the TNF-α/STAT3 signaling pathway.

scholarly journals MiR-223 improves intestinal inflammation through inhibiting the IL-6/STAT3 signaling pathway in dextran sodium sulfate-induced experimental colitis

2020 ◽  
Author(s):  
Juanjuan Zhang ◽  
Chenyang Wang ◽  
Zhen Guo ◽  
Binlin Da ◽  
Weiming Zhu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Sodium Sulfate ◽  
Quantitative Polymerase Chain Reaction ◽  
Negative Control ◽  
Dextran Sodium Sulfate ◽  
Enzyme Linked Immunosorbent Assay ◽  
Colonic Inflammation ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tnf Α

Abstract Background: The pathogenesis of inflammatory bowel disease (IBD) has not yet been clarified and is closely related to several proinflammatory factors. MicroRNA-233 (miR-223) might be involved in the development of IBD; however, the mechanism underlying its pathogenesis is unclear. In this study, we attempted to determine the role of miR-223 in dextran sodium sulfate (DSS)-induced colitis and explore the involvement of the IL-6/STAT3 pathway in the development of intestinal mucosal inflammation.Methods: Male C57BL/6 mice were divided into six groups: control (WT) group, DSS group, DSS+miR-223 agomir (DSS+A) group, DSS+miR-223 agomir negative control (DSS+A+NC) group, DSS+miR-223 antagomir (DSS+AN) group and DSS+miR-223 antagomir negative control (DSS+AN+NC) group. Body weight, stool consistency, fecal blood and the disease activity index (DAI) score were recorded daily. The length of each colon was measured, and colonic inflammation was evaluated with hematoxylin and eosin (H&E) staining and histopathological scoring. The expression of myeloperoxidase (MPO), TNF-α, IL-6, IL-10 and IL-17 in the colonic tissues was measured by Enzyme-linked Immunosorbent Assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR). The mRNA expression of gp130, Bcl-2 and Bcl-xl in the colon was measured using RT-qPCR. The colonic levels of STAT3 and p-STAT3 were determined by Western blotting.Results: MiR-223 expression in the terminal ileum and colon was increased in the DSS group compared with the WT group. Colitis symptoms were significantly alleviated in the DSS+A group and exacerbated in the DSS+AN group after administration of the miR-223 agomir and antagomir, respectively. MPO, TNF-α, IL-6 and IL-17 were decreased and IL-10 was increased in the DSS+A group, but these changes were reversed in the DSS+AN group. Gp130 mRNA, p-STAT3, Bcl-2 and Bcl-xl in the colon declined in the DSS+A group, but these levels increased in the DSS+AN group.Conclusion: The upregulation of miR-223 by agomir administration alleviated colonic inflammation in a DSS-induced colitis model, which was likely mediated by inhibiting the production of proinflammatory cytokines via the IL-6/STAT3 signaling pathway. These findings provide evidence that miR-223 might have potential therapeutic implications in IBD.

Inhibition of Stat3 signaling pathway decreases TNF-α-induced autophagy in cementoblasts

2018 ◽  
Vol 374 (3) ◽  
pp. 567-575 ◽  
Author(s):  
Leilei Wang ◽  
Yunlong Wang ◽  
Mingyuan Du ◽  
Zhijian Liu ◽  
Zhengguo Cao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tnf Α

scholarly journals YQWY Decoction Improves Myocardial Remodeling via Activating the IL-10/Stat3 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
He Li ◽  
Zhi-Jun Gong ◽  
Yun He ◽  
Jing-Jing Huang ◽  
Yu-Ning Jiang ◽  
...  
Keyword(s):  
Left Ventricular Function ◽  
Ventricular Function ◽  
Signaling Pathway ◽  
Myocardial Fibrosis ◽  
Caspase 3 ◽  
Left Ventricular ◽  
Collagen I ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tnf Α

Heart failure (HF) has been known as a global health problem, and cardiac remodeling plays an essential role in the development of HF. We hypothesized that YQWY decoction might exert a cardioprotective effect against myocardium inflammation, fibrosis, and apoptosis via activating the interleukin-10 (IL-10)/Stat3 signaling pathway. To test this hypothesis, the HF model in rats was established by pressure overload through the minimally invasive transverse aortic constriction (MTAC). Echocardiography was performed to assess the left ventricular function of rats. Myocardial fibrosis in rats was observed by Masson and Picrosirius red staining, and the degree of myocardial apoptosis was detected via TUNEL staining. In addition, expression levels of IL-10, tumor necrosis factor-α (TNF-α), Stat3 (P-Stat3), P65 (P-P65), CD68, collagen I, TGF-β, CTGF, Bax, Bcl-2, cleaved caspase-3, and PARP in rat serum and myocardium samples were examined by ELISA, western blot, and immunohistochemistry, respectively. YQWY decoction treatment significantly improved left ventricular function in HF rats, especially in those of the high-dose group (LVEF%: 51.29 ± 5.876 vs. 66.02 ± 1.264, P < 0.01 ;, LVFS%: 27.75 ± 3.757 vs. 37.76 ± 1.137, P < 0.01 ). Furthermore, YQWY decoction markedly inhibited MTAC-induced myocardial fibrosis as evidenced by downregulated collagen I, TGF-β, and CTGF in myocardium and alleviated apoptosis (downregulated caspase-3 and PARP and increased Bcl-2/Bax ratio in cardiomyocytes). In addition, YQWY decoction decreased the level of the proinflammatory cytokine TNF-α in both circulating blood and myocardium and attenuated infiltration of inflammatory cells in heart tissue from HF rats. Most importantly, YQWY decoction suppressed MTAC-induced NF-κB activation and phosphorylated Stat3 by upregulating IL-10 in rat heart tissues. Our study showed that YQWY decoction could attenuate MTAC-induced myocardial inflammation, fibrosis, apoptosis, and reverse the impairment of cardiac function in rats by activating the IL-10/Stat3 signaling pathway and improving myocardium remodeling. Our findings suggested a therapeutic potential of YQWY decoction in HF.

scholarly journals Pentoxifylline Ameliorates Mechanical Hyperalgesia in a Rat Model of ChemotherapyInduced Neuropathic Pain

2016 ◽  
Vol 4;19 (4;5) ◽  
pp. E589-E600
Author(s):  
Salahadin Abdi
Keyword(s):  
Neuropathic Pain ◽  
Continuous Infusion ◽  
Inflammatory Cytokines ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Pain Treatment ◽  
Phosphodiesterase Inhibitor ◽  
Pain Behavior ◽  
Sprague Dawley ◽  
Tnf Α

Background: Chemotherapy-induced neuropathic pain is difficult to treat. Pentoxifylline inhibits the production of inflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Objective: The aims of our study were to investigate the analgesic and preventive effects of pentoxifylline on paclitaxel-induced neuropathic pain in rats and to identify its mechanisms of action. Study Design: Controlled animal study. Methods: Neuropathic pain was induced with intraperitoneally injected paclitaxel on 4 alternate days in male Sprague-Dawley rats. Pentoxifylline was administered systemically as a single injection and a continuous infusion before or after the injection of paclitaxel. The mechanical threshold for allodynia was measured by using von Frey filaments. Protein levels and localization of inflammatory cytokines were performed by using Western blotting and immunohistochemistry, respectively. Results: After the rats developed neuropathic pain behavior, a single intraperitoneal injection and continuous infusion of pentoxifylline ameliorated paclitaxel-induced mechanical allodynia. In addition, systemic infusion of pentoxifylline in the early phase of the development of pain behavior delayed the onset of paclitaxel-induced pain behavior. Paclitaxel increased the levels of the catalytic subunit α of protein kinase A, phosphorylated nuclear factor κB, TNF-α, and IL-1β in the lumbar dorsal root ganglia. Pentoxifylline decreased the paclitaxel-induced TNF-α and IL1β levels. In addition, IL-1β was expressed in neurons and satellite cells in the lumbar dorsal root ganglia after paclitaxel. Limitations: Although this study was performed in the animal model by well-designed manner, clinical study will be needed to confirm the analgesic effect of pentoxifylline. Conclusion: Pentoxifylline alleviated chemotherapy-induced neuropathic pain in rats by reducing the levels of inflammatory cytokines in dorsal root ganglia and may be effective chemotherapyinduced neuropathic pain in patients. Key words: Chemotherapy, chronic pain, inflammatory cytokines, neuropathic pain, paclitaxel, pain behavior, pain treatment, pentoxifylline, phosphodiesterase inhibitor

Sign in / Sign up

Export Citation Format

Share Document