ABSTRACT
This study was aimed to observe the effects of gymnema sylvestre total saponins (GA) on insulin resistance (IR) in adipose tissues of KKay mice,in order to discuss the action mechanism from the PI3K/AKT signal transduction pathway.A total of 27 KKay mice were randomly divided into the model group (DM),Pioglitazone group (BG) and GA group.Nine normal C57BL/6J mice were used as the normal control group (NC).Intragastric administration of drugs was given for eight weeks.The bodyweight and food intake of all mice were tested each week.After the experiment was completed,fasting plasma insulin (Fins) and fasting plasma glucose (FPG) were detected and the insulin sensitive index (ISI) was calculated.Expressions of PDK-1,AKT,P-AKT (Ser473),P-AKT (Thr308) in adipose tissues of epididymis in mice were detected.And expressions of PI3K-p85 mRNA,PTEN mRNA,APN mRNA were also measured.The results showed that compared with DM group,bodyweight of BG and GA groups were decreased (P＜0.05,P＜0.05);FPG and Fins level of BG and GA groups were decreased (P＜0.05,P＜0.05,P＜0.05,P＜0.05),ISI increased (P＜0.05,P＜0.05);APN mRNA increased in BG and GA group (P＜0.01,P＜0.01);PI3K-p85 mRNA increased in GA group (P＜0.05);P-AKT (Thr308) protein expression increased in BG and GA group (P＜0.05,P＜0.01);P-AKT (Ser473) protein expression increased in GA group (P＜0.05);the phosphorylation of AKT (Thr 308) was enhanced in BG and GA group (/9＜0.01,P＜ 0.01);the phosphorylation of AKT (Ser473) was enhanced in GA group (P＜0.01,P＜0.01).PDK-1 protein expression was decreased in BG and GA group (P＜0.05);PTEN mRNA decreased in BG and GA group (P＜0.05,P＜0.01).It was concluded that GA can ameliorate IR by sensitizing PI3κ/AKT signal pathway in adipose tissues of KKAy mice.
ABSTRACT
Objective: To screen the target gene of Buyang Huanwu Decoction (BHD) used for delaying denervated tibial muscle atrophy of rats by genechip technique and to verify the differentially expressed gene PI3K. Methods: After 20 Sprague-Dawley (SD) rats were subjected to common peroneal nerve crush model of 5 mm injury, they were randomly divided into BHD and model groups, for daily ig administration of drugs after operation. The drug administration lasted for 18 d, the genechip analysis was performed to screen the differentially expressed gene. Then, RT-PCR and Western-blotting were used to detect the differential expression of PI3K and protein. Results: Compared with the model group, there was a significant difference of gene expression profile in BHD group. Among them, the expression of 14 genes had up-regulation and 10 genes had down-regulation. In the differential expression genes, Angptl4 and Pik3c2g had the more obvious change (up-regulation for 5-fold). Simultaneously, the validation tests showed: Compared with the model group, the PI3K mRNA and protein expression in the BHD mid- and high-dose (crude drug 12.96 and 25.92 g/kg) groups increased significantly (P < 0.05, 0.01). Conclusion: The preventive and therapeutic effects of BHD on denervated tibial muscle atrophy of rats are relevant with the regulation of many related genes. The mechanism may be as follows: promoting energy synthesis and blood neogenesis, neuroprotection, anti-apoptosis, and inhibition of collage synthesis; BHD could delay the denervated tibial muscle atrophy of rats by increasing the expression of PI3K and protein; The activation of PI3K/Akt signal transduction pathway probably play an important role in delaying the denervated muscle atropy by BHD.
ABSTRACT
Objective: To observe emodin-induced molecular changes in PI3K/AKT signaling pathway in human leukemia K562 cells transplanted into BALB/c nude mice, and to explore whether emodin induces the apoptosis of K562 cells through PI3K/AKT signaling pathway. Methods: The subcutaneously transplanted tumor model of human K562 cells in nude mice was established. After continuously intraperitoneal injection with different doses of emodin for 12 d, the mice were sacrificed. Then the tumor weight and volume were measured, and the tumor inhibition rate was calculated. Emodininduced apoptotic morphological changes of K562 cells were detected by HE stain and scanning electron microscopy. RT-PCR and Western blotting were used to detect the expressions of PI3K, AKT and FoxO 3a mRNAs and proteins, respectively. Results: The relative tumor volumes (V/V0) were significantly smaller in the low-, moderate- and high-dose emodin-treated groups (8.90±0.24, 5.62±0.17 and 2.06± 0.31, respectively) than that in the untreated group (11.83±0.47; P <0.01). Significant apoptosis of K562 cells was found in emodin-treated groups under a light microscope and an electron microscope. RT-PCR revealed down-regulation of PI3K and AKT mRNAs expression and up-regulation of FoxO 3a mRNA expression induced by different concentrations of emodin in a dose-dependent manner. Western blotting analysis showed that the expression levels of PI3K and AKT proteins were markedly decreased and the expression level of FoxO 3a protein was significantly elevated in xenografted tumors treated with emodin. Conclusion: Emodin can significantly inhibit the growth of K562 cell xenografts in nude mice. The underlying mechanism may be associated with inhibition of PI3K/AKT signaling pathway. Copyright© 2011 by TUMOR.