ABSTRACT
Sepsis-induced acute lung injury (ALI) is related to the dysregulation of inflammatory responses. Polydatin supplement was reported to exhibit anti-inflammatory effects in several diseases. The present study aimed to investigate the role of polydatin in sepsis-induced ALI. A cecum ligation and puncture (CLP)-induced mouse ALI model was established first and the pathological changes of lung tissues were assessed using hematoxylin and eosin staining. Meanwhile, to mimic sepsis-induced ALI in vitro, pulmonary microvascular endothelial cells (PMVECs) were treated with lipopolysaccharide (LPS). Pro-inflammatory cytokines levels were measured in lung tissues and PMVECs using ELISA. Reverse transcription-quantitative PCR was used to measure the mRNA levels of Spi-B in lung tissues and PMVECs. Moreover, the expression levels of Spi-B, p-PI3K, p-Akt, and p-NF-κB in lung tissues and PMVECs were determined using western blotting. The data revealed that polydatin attenuated CLP-induced lung injury and inhibited sepsis-induced inflammatory responses in mice. Furthermore, polydatin significantly inhibited the expression of Spi-B, p-PI3K, p-Akt, and p-NF-κB in lung tissues of mice subjected to CLP-induced ALI, while this phenomenon was reversed through Spi-B overexpression. Consistently, the anti-inflammatory effect of polydatin was abolished by Spi-B overexpression. Taken together, the current findings revealed that polydatin alleviated sepsis-induced ALI via the downregulation of Spi-B.
ABSTRACT
PURPOSE: The purpose of this study was to elucidate the role of Baicalein in accelerating invasiveness and inducing apoptosis of glioma cells through the phosphatidilinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. METHODS: U251 glioma cells were treated with different doses of Baicalein (10, 20 or 40 µM) for different time periods (12, 24, 36 or 48 h). Changes in viability, clonality, cell cycle distribution and apoptosis in Baicalein-treated U251 cells were assessed. Meanwhile, relative levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 in U251 cells were detected. Western blot was conducted to examine protein levels of p-Akt and Akt in Baicalein-treated U251 cells. RESULTS: Baicalein treatment attenuated dose-dependently and time-dependently the viability and clonality in U251 cells. It induced cell cycle arrest in G0/G1 phase and cell apoptosis of U251 cells. After Baicalein treatment, the relative levels of MMP-2 and MMP-9 were dose-dependently downregulated. Baicalein treatment activated the PI3K/Akt pathway. Notably, inhibitory effects of Baicalein treatment on MMP levels and invasiveness in glioma were blocked by the application of LY294002 (PI3K/Akt inhibitor), and stimulated by the application of IGF-1 (PI3K/Akt activator). CONCLUSIONS: Baicalein treatment is able to suppress invasiveness and induce apoptosis of glioma cells through inactivating the PI3K/Akt pathway.
