RESUMO
Ginsenoside Rg1, one of the most notable active components of Panax ginseng, has been widely reported to exert anti-inflammatory actions. This study aimed to reveal whether ginsenoside Rg1 also exhibits beneficial roles against lipopolysaccharide (LPS)-induced apoptosis and inflammation in human renal tubular epithelial cells, and to evaluate the potential role of the component on tubulointerstitial nephritis treatment. HK-2 cells were treated with various doses of ginsenoside Rg1 (0, 50, 100, 150, and 200 μM) in the absence or presence of 5 μg/mL LPS. Thereafter, CCK-8 assay, flow cytometry, western blot, migration assay, reactive oxygen species (ROS) assay, and ELISA were carried out to respectively assess cell viability, apoptosis, migration, ROS activity, and the release of inflammatory cytokines. As a result, ginsenoside Rg1 protected HK-2 cells from LPS-induced injury, as cell viability was increased, cell apoptosis was decreased, and the release of MCP-1, IL-1β, IL-6, and TNF-α was reduced. Ginsenoside Rg1 functioned to HK-2 cells in a dose-dependent manner, and the 150 μM dose exhibited the most protective functions. Ginsenoside Rg1 had no significant impact on cell migration and ROS activity, while it alleviated LPS-induced ROS release and migration impairment. Furthermore, the down-regulations of p-PI3K, p-AKT, and up-regulations of PTEN, p-IκBα, p-p65, Bcl-3 induced by LPS were recovered to some extent after ginsenoside Rg1 treatment. In conclusion, ginsenoside Rg1 protects HK-2 cells against LPS-induced inflammation and apoptosis via activation of the PI3K/AKT pathway and suppression of NF-κB pathway.
Assuntos
Humanos , Lipopolissacarídeos , Apoptose/efeitos dos fármacos , Ginsenosídeos/farmacologia , Células Epiteliais/efeitos dos fármacos , Túbulos Renais/citologia , Anti-Inflamatórios/farmacologia , Ensaio de Imunoadsorção Enzimática , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Western Blotting , Reprodutibilidade dos Testes , Análise de Variância , Citocinas/análise , Citocinas/efeitos dos fármacos , Ensaios de Migração CelularRESUMO
Ginsenoside Rg1, one of the most notable active components of Panax ginseng, has been widely reported to exert anti-inflammatory actions. This study aimed to reveal whether ginsenoside Rg1 also exhibits beneficial roles against lipopolysaccharide (LPS)-induced apoptosis and inflammation in human renal tubular epithelial cells, and to evaluate the potential role of the component on tubulointerstitial nephritis treatment. HK-2 cells were treated with various doses of ginsenoside Rg1 (0, 50, 100, 150, and 200 µM) in the absence or presence of 5 µg/mL LPS. Thereafter, CCK-8 assay, flow cytometry, western blot, migration assay, reactive oxygen species (ROS) assay, and ELISA were carried out to respectively assess cell viability, apoptosis, migration, ROS activity, and the release of inflammatory cytokines. As a result, ginsenoside Rg1 protected HK-2 cells from LPS-induced injury, as cell viability was increased, cell apoptosis was decreased, and the release of MCP-1, IL-1ß, IL-6, and TNF-α was reduced. Ginsenoside Rg1 functioned to HK-2 cells in a dose-dependent manner, and the 150 µM dose exhibited the most protective functions. Ginsenoside Rg1 had no significant impact on cell migration and ROS activity, while it alleviated LPS-induced ROS release and migration impairment. Furthermore, the down-regulations of p-PI3K, p-AKT, and up-regulations of PTEN, p-IκBα, p-p65, Bcl-3 induced by LPS were recovered to some extent after ginsenoside Rg1 treatment. In conclusion, ginsenoside Rg1 protects HK-2 cells against LPS-induced inflammation and apoptosis via activation of the PI3K/AKT pathway and suppression of NF-κB pathway.
Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Ginsenosídeos/farmacologia , Túbulos Renais/citologia , Lipopolissacarídeos , Nefrite/prevenção & controle , Análise de Variância , Western Blotting , Linhagem Celular , Ensaios de Migração Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/análise , Citocinas/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Humanos , Túbulos Renais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/análise , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/análise , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Espécies Reativas de Oxigênio/análise , Reprodutibilidade dos TestesRESUMO
Clopidogrel hydrogen sulfate (CHS) is a thienopyridine, which can be used to prevent cardiovascular complications alone or in combination with acetyl salicylic acid as an important antiplatelet agent. Clopidogrel benzene sulfonate (CB) is a special clopidogrel salt that can be used as a conventional drug for antiplatelet effects, but the mechanism is still unknown. This study aimed to compare the antiplatelet effects of CHS and CB in stable coronary artery disease patients. Stable coronary artery disease patients (N = 119) were randomly divided into two groups receiving CHS (N = 67) or CB (N = 52). The patients were administered the drugs (600 mg dosage) and monitored for 12 to 14 h to detect antiplatelet effects. Antiplatelet response was evaluated by the P2Y12 response unit (PRU) and P2Y12 suppression percentage. In addition, all patients' CYP2C19*2, CYP2C19*3, and CYP3A5 polymorphisms were studied. Similar clinical manifestations were observed in the two groups. No obvious difference was detected in the platelet levels of patients given CHS or CB. The antiplatelet response (PRU and P2Y12 evaluation) of the patients using CHS and CB was not significantly different. In the two groups, the CYP2C19*2 polymorphic heterozygote number and antiplatelet response were similar. CB and CHS presented similar antiplatelet effects in stable coronary artery disease patients, and there was no difference in the CYP2C19*2 heterozygous polymorphism.