RESUMO
Tetrahydroxystilbene glucoside (THSG) is one of the active ingredients of Polygonum multiflorum. It has been shown to exert a variety of pharmacological effects, including antioxidant, anti-aging, and anti-atherosclerosis. Because of its prominent anti-inflammatory effect, we explored whether THSG had analgesic effect. In this study, we used a model of chronic inflammatory pain caused by injecting complete Freund's adjuvant into the hind paw of mice. We found THSG relieved swelling and pain in the hind paw of mice on a dose-dependent manner. In the anterior cingulate cortex, THSG suppressed the upregulation of GluN2B-containing N-methyl-D-aspartate receptors and the downregulation of GluN2A-containing N-methyl-D-aspartate receptors caused by chronic inflammation. In addition, THSG increased Bcl-2 and decreased Bax and Caspase-3 expression by protecting neuronal survival. Furthermore, THSG inhibited the phosphorylation of p38 and the increase of nuclear factor κB (NF-κB) and tumor necrosis factor α (TNF-α). Immunohistochemical staining revealed that THSG blocked the activation of microglia and reduced the release of proinflammatory cytokines TNF-α, interleukin 1ß (IL-1ß), and interleukin 6 (IL-6). In conclusion, this study demonstrated that THSG had a certain effect on alleviating complete Freund's adjuvant-induced chronic inflammatory pain.
Assuntos
Apoptose , Dor Crônica/tratamento farmacológico , Glucosídeos/uso terapêutico , Giro do Cíngulo/metabolismo , Giro do Cíngulo/patologia , Inflamação/tratamento farmacológico , Microglia/patologia , Receptores de N-Metil-D-Aspartato/metabolismo , Estilbenos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dor Crônica/complicações , Dor Crônica/patologia , Citocinas/metabolismo , Edema/tratamento farmacológico , Adjuvante de Freund/administração & dosagem , Glucosídeos/química , Glucosídeos/farmacologia , Giro do Cíngulo/efeitos dos fármacos , Hiperalgesia/complicações , Hiperalgesia/tratamento farmacológico , Inflamação/complicações , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Estilbenos/química , Estilbenos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Background: In the past, multiple studies have offered incremental evidence that indicates that competitive endogenous RNA (ceRNA) regulatory networks are involved in tumor growth and present novel therapeutic targets. Herein, we investigated the impact of thymidine kinase 1 (TK1)-related ceRNA networks on the prognosis of non-small cell lung cancer (NSCLC). Methods: TK1 expression data in NSCLC and normal tissue samples were retrieved from the Cancer Genome Atlas (TCGA) database and were then compared. Thereafter, the findings of the immunohistochemical staining experiments and clinical follow-up data derived from patients with NSCLC were used for conducting prognostic analysis. The starBase database was searched to determine TK1-targeted microRNAs and long non-coding RNAs, and clinical data from TCGA were used for survival analysis to construct a ceRNA network associated with TK1 expression and prognosis. Finally, the roles played by methylation and immunity in the prognosis and treatment of NSCLC were analyzed. Results: Our findings revealed that the cancer tissues expressed significantly higher TK1 levels than normal tissues, and the follow-up clinical data revealed that the prognosis was generally worse in the high-expression patients than in the low-expression patients. In addition, clinical data collected from the starBase and TCGA databases showed that the LINC00665/has-let-7b-5p/TK1 network could influence the growth and prognosis of NSCLC. It was also noted that the TK1 methylation site was correlated with the prognosis of NSCLC, and immunoprognostic analysis further indicated that patients with higher TK1 expression levels displayed a worse prognosis. Conclusion: When the regulatory network of LINC00665/has-let-7b-5p/TK1 was assessed, it was observed that elevated TK1 levels may affect the prognosis of NSCLC. Therefore, it could be considered a prognostic biomarker and a probable therapeutic target for predicting NSCLC prognosis.