Effects Of Phloridzin On Experimental Hypertriglyceridemia By Activating Lipoprotein Lipase

Aim: To study the effect of Phloridzin on hypertriglyceridemia and its possible mechanism inhypertriglyceridemic mice induced by Triton WR1339.Methods:(1) Male KM mice were randomly divided into6groups, including normal controlgroup, Triton WR1339model group, three Phloridzin groups and fenofibrate group. Phloridzingroups and fenofibrate group received oral administration of Phloridzin and fenofibraterespectively while normal control and model mice received distilled water for consecutively7days. On the6thday of administration, all mice were fasted for12h. Treatment of Triton WR1339by the tail vein was performed to all mice, except for normal control group,1h after finaladministration on the7thday. Twenty hours after Triton WR1339treatment, all mice wereanesthetized by ether and blood was drawn by heart puncture to determine serum TG, TC andLDL-C levels. Gene expressions of ANGPTL4of liver was determined by RT-PCR, and Geneexpressions of LPL and GPIHBP1of skeletal muscle were also determined by RT-PCR. Theeffect of Phloridzin on lipid peroxidation was measured by commercial kit.(2) Male KM micewere randomly divided into3groups, including normal control group, Phloridzin group andfenofibrate group. All mice were injected with fat emulsion through the tail vein. Certain time (5,10,20,30,40and60min) after injection, all mice were anesthetized by ether and blood wasdrawn from eye and placed in the tubes containing2%sodium heparin. Plasma were determinedtriglyceride levels.(3) Male KM mice were randomly divided into6groups, including normalcontrol group, Phloridzin group, fenofibrate group, Triton WR1339group, Phloridzin+TritonWR1339group, and fenofibrate+Triton WR1339group. All other groups were treatedaccording the the above mentioned in section (1). Twenty hours after Triton WR1339treatment,all mice were injected with heparin by the tail vein. Ten mins later, all mice were anesthetized byether and blood was drawn by heart puncture to determine lipoprotein lipase activity.(4)Macrophages were incubated with50and100μM of Phloridzin for24h. Lipoprotein lipaseactivity was measured by commercial kit.Results:(1) Compared with the control group, plasma TG, TC and LDL-C levels of model micewere significantly elevated. middle dose group and high dose group of Phloridzin could significantly reduced TG level, but had no effect on lowering TC and LDL-C levels. The resultsdemostrated that Phloridzin has a potent effect on decreasing endogenously generatedtriglycerides.(2) In fat emulsion loading mice model, Phloridzin has a certain degree ofimprovement on hypertriglyceridemia induced by exogenous fat.(3) Phloridzin couldsignificantly increase LPL activity regardless of the effect of Triton WR1339. It was found that100μM Phloridzin could significantly enhance lipoprotein lipase activity in RAW264.7macrophages.(4) Phloridzin could down-regulate ANGPTL4of liver mRNA expression whileLPL and GPIHBP1mRNA expression has little changes in skeletal muscles.(5) high dose groupof Phloridzin could significantly decrease MDA level in plasma.Conclusion：Phloridzin has a potent hypotriglyceridemic effect on endogenously generatedtriglycerides induced by Triton WR1339on endogenously hyperlipidemia mouse model, and insome extent, Phlorizin can also increase the rate of elimination of triglycerides on exogenousload model. The mechanism may be,(1) enhanced LPL activity by Phloridzin in vivo and invitro, thereby promoting the hydrolysis of TG into glycerol and free fatty acids.(2)Down-regulation of ANGPTL4(LPL inhibitor) expression, thereby preventing the inactivationof LPL.(3) Phloridzin had reduced plasma MDA level and improved vascular lipid peroxidationinduced by Triton WR1339, and improved the LPL anchor in the vessel wall.