Hypoglycemic effect of whole grain diet in C57BL/KsJ-db/db mice by activating PI3K/Akt and AMPK pathways

Food Science and Biotechnology - Type II diabetes mellitus (T2DM), characterized by abnormal blood glucose level, is a metabolic disease caused by pancreatic β-cell dysfunction and insulin...     

Regulation of lipid and glucose homeostasis by mango tree leaf extract is mediated by AMPK and PI3K/AKT signaling pathways

Ethanolic extract of Mangifera indica (mango) dose-dependently decreased serum glucose and triglyceride in KK-A^y mice. Our in vitro and in vivo investigations revealed that the effect of mango leave extract (ME) on glucose and lipid homeostasis is mediated, at least in part, through the PI3 K/AKT and AMPK signaling pathway. ME up-regulated the expression of PI3 K, AKT and GYS genes by 2.0-fold, 3.2-fold, and 2.7-fold, respectively, leading to a decrease in glucose level. On the other hand, ME up-regulated AMPK and altered lipid metabolism. ME also down-regulated ACC (2.8-fold), HSL (1.6-fold), FAS (1.8-fold) and PPAR-γ (4.0-fold). Finally, we determined that active metabolites of benzophenone C-glucosides, Iriflophenone 3-C-β-glucoside and Foliamangiferoside A from ME, may play a dominant role in this integrated regulation of sugar and lipid homeostasis.     

基于抗氧化研究三七提取物对6-OHDA损伤PC12细胞的保护作用

为探究电子束辐照灭菌对三七粉品质的影响,以三七粉为实验对象,研究不同辐照剂量（0、2、4、6、8、13 kGy）对其微生物数量、水分、灰分、醇溶性浸出物、主要活性成分、抗氧化能力及指纹图谱的影响。结果表明：电子束辐照能有效杀灭三七粉中的微生物,需氧菌总数的杀菌剂量的D₁₀为2.04 kGy,当辐照剂量为4 kGy时微生物数量降至检测标准限度以下,抗氧化能力显著提高（P<0.05）,水分、灰分、醇溶性浸出物、色泽、三七皂苷R₁、人参皂苷Rb₁、人参皂苷Rg₁、指纹图谱等无明显变化（P>0.05）。因此,电子束辐照是一种有效的三七粉灭菌方式,13 kGy以内剂量的电子束辐照不会对其质量显著影响,且能提高其抗氧化活性。本研究为电子束辐照技术在三七粉及以三七粉为原料的其他加工产品中的质量控制提供理论参考。     

Citrus-derived auraptene stimulates angiogenesis by activating the Erk- and PI3K/Akt/eNOS-dependent signaling pathways in human umbilical vein endothelial cells

Auraptene is a citrus-derived natural monoterpene that has been shown to exert anti-cancer, anti-bacterial, anti-inflammatory, and antioxidant roles. Since little is known about other biological functions of auraptene, we examined the efficacy of auraptene for stimulating angiogenesis in human umbilical vein endothelial cells (HUVECs). Treatment with low concentrations of auraptene stimulated endothelial cell proliferation, migration, and tube formation. Furthermore, auraptene activated Erk, Akt, and endothelial nitric oxide synthase (eNOS), and increased NO production. Auraptene also partially induced the phosphorylation of VEGFR2. Furthermore, auraptene-induced activation of Erk, Akt, and eNOS were significantly inhibited by the inhibitors PD98059, LY294002, and l-NIO dihydrochloride. These results suggest that auraptene stimulates angiogenesis by regulating the VEGFR2, Erk, and PI3K/Akt-eNOS signaling pathways.     

Whole grain cereal attenuates obesity-induced muscle atrophy by activating the PI3K/Akt pathway in obese C57BL/6N mice

Whole grain comprises starchy endosperm, germ, and bran tissues, which contain fibers, minerals, vitamins, and several phytochemicals. Whole grain cereal (WGC)-based food products supply beneficial nutrients (essential for health care) and macronutrients (essential for body maintenance and support). The present study investigated the inhibitory effect of WGC on obesity-induced muscle atrophy in obese C57BL/6N mice. WGC attenuated the body weight gain, fat pad mass, adipocyte size, food efficiency ratio, serum lipid profile, and non-alcoholic fatty liver. Furthermore, WGC increased muscle mass and muscle strength by activating the phosphatidylinositol 3-kinase/protein kinase B pathway. Accordingly, WGC up-regulated the expression of factors that regulate muscle hypertrophy and myogenesis, whereas it down-regulated the atrophy-related factors. Overall, these results demonstrate that WGC effectively attenuates obesity-induced muscle atrophy as well as overall obesity, suggesting that WGC can be used as a functional food.     

Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice

We investigated the effect of curcumin on insulin resistance and glucose homeostasis in male C57BL/KsJ-db/db mice and their age-matched lean non-diabetic db/+ mice. Both db/+ and db/db mice were fed with or without curcumin (0.02%, wt/wt) for 6 wks. Curcumin significantly lowered blood glucose and HbA 1c levels, and it suppressed body weight loss in db/db mice. Curcumin improved homeostasis model assessment of insulin resistance and glucose tolerance, and elevated the plasma insulin level in db/db mice. Hepatic glucokinase activity was significantly higher in the curcumin-supplemented db/db group than in the db/db group, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were significantly lower. In db/db mice, curcumin significantly lowered the hepatic activities of fatty acid synthase, beta-oxidation, 3-hydroxy-3-methylglutaryl coenzyme reductase, and acyl-CoA: cholesterol acyltransferase. Curcumin significantly lowered plasma free fatty acid, cholesterol, and triglyceride concentrations and increased the hepatic glycogen and skeletal muscle lipoprotein lipase in db/db mice. Curcumin normalized erythrocyte and hepatic antioxidant enzyme activities (superoxide dismutase, catalase, gluthathione peroxidase) in db/db mice that resulted in a significant reduction in lipid peroxidation. However, curcumin showed no effect on the blood glucose, plasma insulin, and glucose regulating enzyme activities in db/+ mice. These results suggest that curcumin seemed to be a potential glucose-lowering agent and antioxidant in type 2 diabetic db/db mice, but had no affect in non-diabetic db/+ mice.     

人参皂苷F2通过PI3K/Akt途径改善3T3-L1脂肪细胞胰岛素抵抗

该研究探讨了人参皂苷F2对3T3-L1脂肪细胞胰岛素抵抗的影响及其机制。将3T3-L1前脂肪细胞诱导分化成熟后,用1 μmol/L地塞米松处理48 h,建立胰岛素抵抗模型。用10 μmol/L的罗格列酮（阳性对照）和25、50、100 μmol/L人参皂苷F2处理胰岛素抵抗细胞12 h,检测细胞对2-NBDG的摄取。实验结束后用RT-qPCR检测各组细胞中葡萄糖转运蛋白4（GLUT-4）和胰岛素底物受体1（IRS-1）mRNA相对表达量,并利用Western blot检测PI3K/Akt信号通路中蛋白表达及其磷酸化水平。结果表明：与模型组相比,25、50、100 μmol/L人参皂苷F2均能促进胰岛素抵抗3T3-L1脂肪细胞对2-NBDG的摄取,分别增加了12.58%、29.07%和34.62%（p<0.05）;人参皂苷F2作用12 h后,GLUT-4和IRS-1 mRNA相对表达量以及PI3K、Akt的磷酸化水平显著提高（p<0.01）。该研究表明人参皂苷F2可通过促进胰岛素抵抗3T3-L1脂肪细胞中GLUT-4和IRS-1mRNA相对表达,增加PI3K和Akt蛋白磷酸化,从而激活PI3K/Akt信号通路,改善其糖代谢和胰岛素抵抗。     

四氢姜黄素经PI3K/Akt信号通路对人血小板活化和聚集的调控作用

目的：探讨姜黄素的主要肠道代谢物四氢姜黄素（tetrahydrocurcumin,THC）对血小板活化和聚集的影响及其可能的分子机制。方法：在体外实验中,用不同浓度的THC（0、0.5、1、10 μmol/L）提前与健康人纯化血小板共同孵育40 min,然后加入凝血酶激活血小板2 min,用流式细胞术测定血小板表面CD62P和CD63的表达量,用酶联免疫吸附法测定血小板释放血小板因子-4（platelet factor-4,PF4）和趋化因子配体-5（chemokine ligand 5,CCL5）水平,用血小板聚集仪检测血小板释放ATP水平和血小板最大聚集率,用Western blot蛋白免疫印迹法检测血小板磷酸肌醇-3-激酶（phosphoinositide 3-kinase,PI3K）和Akt蛋白的磷酸化水平。结果：与模型组（血小板悬液中加入0.05%二甲基亚砜）相比,THC能抑制凝血酶诱导的血小板表面CD62P和CD63的表达,抑制PF4、CCL5和ATP的释放,降低血小板最大聚集率,下调PI3K和Akt蛋白的磷酸化水平,且呈浓度依赖效应,其中10 μmol/L的浓度下作用效果显著（P＜0.01、P＜0.001）。PI3K的特异性激动剂740 Y-P可部分逆转THC对PF4和CCL5释放和血小板聚集的抑制作用（P＜0.05、P＜0.01）。结论：THC具有显著抑制血小板活化和聚集的作用,其机制可能是THC可下调PI3K/Akt介导的信号通路。     

Taurine protects murine hepatocytes against oxidative stress-induced apoptosis by tert-butyl hydroperoxide via PI3K/Akt and mitochondrial-dependent pathways

The present study aims to investigate the beneficial role of taurine in tert-butyl hydroperoxide (TBHP)-induced oxidative stress, cytotoxicity and cell death using murine hepatocytes as the working model. TBHP caused a time-dependent increase in alkaline phosphatase leakage, extensive ROS formation and alteration in antioxidant machineries. Moreover, TBHP upregulated NF-κB phosphorylation, caused injury to cellular mitochondria by reciprocal regulation of Bcl2 family proteins; incapacitated cellular respiration, accelerated cytochrome c release from mitochondria and induced apoptotic death in hepatocytes. Taurine treatment prevented TBHP-induced oxidative insult and decreased the activation of NF-κB as well as apoptotic signalling pathways. Signal transduction studies with specific inhibitors PS1145 (IκB inhibitor) and LY294002 (PI3K inhibitor) showed that the mechanism of the protective action of taurine involves the upregulation of Akt and inhibition of NF-κB. Combining, our result suggest that taurine supplementation in regular diet may provide a potential therapeutic choice against TBHP-induced hepatic oxidative injury.     

Tetrahydrocurcumin, a major metabolite of curcumin, induced autophagic cell death through coordinative modulation of PI3K/Akt-mTOR and MAPK signaling pathways in human leukemia HL-60 cells

Scope: Autophagy (type II programmed cell death) is crucial for maintaining cellular homeostasis. Several autophagy‐deficient or knockout studies indicate that autophagy is a tumor suppressor. Tetrahydrocurcumin (THC), a major metabolite of curcumin, has been demonstrated with anti‐colon carcinogenesis and antioxidation in vivo. Methods and results: In the present study, we found that treatment with THC induced autophagic cell death in human HL‐60 promyelocytic leukemia cells by increasing autophage marker acidic vascular organelle (AVO) formation. Flow cytometry also confirmed that THC treatment did not increase sub‐G1 cell population whereas curcumin did with strong apoptosis‐inducing activity. At the molecular levels, the results from Western blot analysis showed that THC significantly down‐regulated phosphatidylinositol 3‐kinase/protein kinase B and mitogen‐activated protein kinase signalings including decreasing the phosphorylation of mammalian target of rapamycin, glycogen synthase kinase 3β and p70 ribosomal protein S6 kinase. Further molecular analysis exhibited that the pretreatment of 3‐methyladenine (an autophagy inhibitor) also significantly reduced acidic vascular organelle production in THC‐treated cells. Conclusion: Taken together, these results demonstrated the anticancer efficacy of THC by inducing autophagy as well as provided a potential application for the prevention of human leukemia.     

D-松醇对二型糖尿病大鼠PI3K及下游糖原合成基因的调控

主要探究D-松醇对2型糖尿病大鼠PI3K及下游糖原合成基因的调控作用,选用雄性SD大鼠进行实验。高脂高糖饲料喂养配合注射链脲佐菌素(STZ)诱导建立2型糖尿病模型。将实验动物分为正常对照组(N)、模型对照组(C)、D-松醇低剂量组(L,30mg/(kg BW·d))、D-松醇高剂量组(H,60mg/(kg BW·d))和正常高剂量组(NH,60mg/(kg BW·d))。N组和NH组饲喂正常饲料,其余3组饲喂高脂高糖饲料,灌胃治疗期间定期进行体重和空腹血糖(FBG)测定,5周后大鼠处死并对其糖化血清蛋白(GSP)、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)以及肝糖原等生化指标进行测定,并从肝脏中提取m RNA,利用PCR技术对大鼠肝脏中的PI3K、Akt、GSK-3β和GS的表达进行检测。结果表明:经灌胃治疗5周后,H组与C组相比FBG、GSP、AST和ALT水平均极显著性降低(p0.01),肝糖原含量极显著性增加(p0.01),L组和H组PI3K、Akt和GS的表达上调,GSK-3β表达下调,说明D-松醇可以通过调控大鼠肝脏PI3K及下游糖原合成基因来调节患糖尿病大鼠的血糖,起到降血糖的作用。     

Neferine from Nelumbo nucifera induces autophagy through the inhibition of PI3K/Akt/mTOR pathway and ROS hyper generation in A549 cells

Previously we have reported that neferine from the medicinal plant Nelumbo nucifera, inhibited cancer cell proliferation by inducing apoptosis. The present study was focused on the action mechanism of neferine in inducing autophagy in lung cancer cells. Neferine markedly inhibited A549 cell proliferation in a dose dependent manner. Acidic vesicular accumulation was observed in neferine treated cells as an indication of autophagy. Neferine could induce the conversion of LC3B-I to LC3B-II without affecting the expression levels of PI3KCIII and Beclin1. It has been observed that neferine mediated autophagy is dependent on inhibition of PI3K/Akt/mTOR signaling by neferine. Neferine treatment could also lead to the ROS hypergeneration and depletion of cellular antioxidant, GSH. The results demonstrate that neferine-induced autophagy is mediated through ROS hypergeneration and mTOR inhibition. Taken together, the present study unveils a novel mechanism of action of neferine on lung cancer cells in the induction of autophagy.