| Lipid metabolism is the process by which fats/fatty acids are digested and absorbed in the digestive tract, as well as broken down for energy, or stored in the human body for later energy use. Therefore fats (lipids) are an important source of energy for the body. Fatty acid is the components of triglyceride, which make up the bulk of foods like vegetable oils and animal products. Disorders of lipid metabolism such as elevated cholesterol or triglyceride level, metabolic syndrome and hypertension are known risk factors for serious conditions like coronary heart diseases and stroke.Wuweizi (WWZ), the fruit of Schisandra, includes bei-Wuweizi (BWWZ) and nan-Wuweizi (NWWZ) in China. It is an herb that has long been used in traditional Chinese medicine as a tonic, stimulant, astringent, antiseptic for treating several health problems including cough, wheezing, diarrhea, and many other things. Since1970’s, Chinese physicians have begun to apply WWZ as a remedy for hepatitis. Currently, it has been found that the ethanol extracts of WWZ, and the related compound schisandrin B, bifendate, bicyclol regulated lipid metabolism, including elevated blood and liver triglyceride level, reduced liver cholesterol level. Here, the effects of BWWZ and NWWZ aqueous extract, ethanol extract and petroleum ether extract on lipid metabolism are investigated in normal and hypercholesterolemic mice.Part1Effects of aqueous extract of Wuweizi (Aq-WWZ) on lipid metabolism in mice.1.1Extraction procedure of Aq-WWZ.Objective:Preparation of Aq-BWWZ and Aq-NWWZMethod:For the preparation of the Aq-WWZ. Powdered BWWZ or NWWZ was boiled in ten volumes of distilled water for1h. The procedure was repeated twice with8volumes of water. The pre-Aq-WWZ was then precipitated twice with95%ethanol for12h at5℃.89g of Aq-BWWZ and124g of Aq-NWWZ was finally obtained and stored at4℃until use.1.2Effect of dietary Aq-WWZ on lipid metabolism in normal mice.Objective:To study the effect of both Aq-BWWZ and Aq-NWWZ on lipid metabolism in normal mice.Method:Mice were fed ND or ND supplemented with Aq-BWWZ/Aq-NWWZ or fenofibate for13days.At the day13, the blood and liver tissue samples were obtained. Hepatic index was estimated from the ratio of total liver weight to body weight. Hepatic TG and TC levels were measured according to the manufacture’s instructions.Results:Supplementation with Aq-BWWZ at a dose of1or4%did not affect serum and hepatic lipid levels and body weight. However, Aq-NWWZ significantly increased serum TC, TG, and LDL levels, as well as hepatic TG in normal mice. In addition, Aq-NWWZ reduced body weight.Conclusion:Aq-NWWZ reduced serum and hepatic lipid levels and the body gain, but not Aq-BWWZ, in normal mice.1.3Effect of dietary Aq-WWZ on lipid metabolism in hypercholesterolemia mice.Objective:To study the effect of both Aq-BWWZ and Aq-NWWZ on lipid metabolism in hypercholesterolemic mice.Method:Mice fed with HFCBD to form hypercholesterolemic mice. Mice were fed ND or HFCBD supplemented with Aq-BWWZ/Aq-NWWZ or fenofibate for13days. Other experimental details were described in "1.2Effect of dietary Aq-WWZ on lipid metabolism in normal mice".Results:HFCBD markedly increased serum TC, HDL, LDL and ALT in mice. While the serum HDL and LDL levels were elevated, hepatic TC and TG levels were reducedin mice fed HFCBD/Aq-BWZ/Aq-NWWZ-supplemented diet, when compared with those fed with HFCBD only.Conclusion:Aq-BWWZ and Aq-NWWZ reduced hepatic lipid levels in hypercholesterolemic mice.Part2Effects of dietary ethanolic extract of Wuweizi (Et-WWZ) on lipid metabolism in mice.2.1Extraction procedure of Et-WWZ.Objective:Preparation of Et-BWWZ and Et-NWWZ.Method:For the preparation of the Et-WWZ, WWZ was crushed into small pieces and extracted twice with five volumes of80%ethanol under reflux. The pooled extract was filtered by filter paper and concentrated under reduced pressure by rota-evaporation to obtain EtFSC, and stored at4℃until use.2.2Effect of dietary Et-WWZ on lipid metabolism in normal mice.Objective:To study the effect of Et-BWWZ and Et-NWWZ on lipid metabolism in normal mice.Method:Mice were fed ND or ND supplemented with Et-BWWZ/Et-NWWZ or fenofibate for13days.Other experimental details were described in "1.2Effect of dietary Aq-WWZ on lipid metabolism in normal mice".Results:The serum and hepatic TG level was elevated in mice fed with4%Et-NWWZ and Et-BWWZ, compared with the control. Both Et-BWWZ and Et-NWWZ reduced serum ALT activity. In addition,1and4%Et-NWWZ increased HI, and decreased body weight gain.Conclusion:Et-WWZ reduced the serum ALT activity and Et-NWWZ inhibited weight gain in normal mice.2.3Effect of dietary Et-WWZ on lipid metabolism in hypercholesterolemic mice.Objective:To study the effect of both Et-BWWZ and Et-NWWZ on lipid metabolism in hypercholesterolemic mice.Method:Mice fed with HFCBD to form hypercholesterolemic mice. Mice were fed ND or HFCBD supplemented with Et-BWWZ/Et-NWWZ or fenofibate for13days. Other experimental details were described in "1.2. Effect of dietary Aq-WWZ on lipid metabolism in normal mice".Results:The serum TC, HDL, LDL levels and ALT active, hepatic lipids and HI were markedly increased in the mice fed with HFCBD, compared with the normal mice. However, the serum TG level was decreased. Et-BWWZ and Et-NWWZ significantly increased serum HDL and LDL levels and decreased serum ALT activity in hypercholesterolemic mice. While the serum HDL and LDL levels were elevated, hepatic TC and TG levels were reduced in mice fed HFCBD/Aq-BWWZ/Aq-NWWZ-supplemented diet, when compared with those fed with HFCBD only.Conclusion:Et-BWWZ and Et-NWWZ elevated serum lipid levels, but reduced hepatic lipid levels in hypercholesterolemia mice. Et-WWZ has hepatoprotective effect in hypercholesterolemia mice.Part3Effect of Wuweizi fatty oil (WWZFO) on lipid metabolism in normal mice.3.1Extraction procedure of WWZFO.Objective. Preparation of BWWZFO and NWWZFO.Method:BWWZ/NWWZ was soaked with five volumes of petroleum ether (v/w) for30min. Then they were extracted twice.The final150ml and135ml fatty oil was obtained from BWWZ and NWWZ, respectively, and stored at4CC until use.3.2Effect of oral administration of WWZFO on lipid metabolism in normal mice.Objective:To study the effect of WWZFO on lipid metabolism in normal mice.Method:Single dose and Six doses experiment were adopted. Other experimental details were described in "1.2Effect of dietary Aq-WWZ on lipid metabolism in normal mice".Results:Treatment with single dose WWZFO increased serum TG, TC, and LDL levels in mice. At the same time, WWZFO reduced serum ALT activity and increased HI, compared with the control. When mice were treated with WWZFO daily for6days, serum TG, TC, HDL, and LDL and HI were increased24h after the last treatment. However, BWWZFO increase hepatic TG, and NWWZ lowered serum ALT activity.Conclusion:WWZFO increased serum lipids and liver weight and NWWZFO reduced ALT activity in normal mice.3.3Effect of dietary WWZFO on lipid metabolism in normal mice.Objective:To study the effect of dietary WWZFO on lipid metabolism in normal mice.Method:Mice were fed diet supplemented drugs for13days. Then serum and liver tissues simples were obtained. Other experimental details were described in "1.2. Effect of dietary Aq-WWZ on lipid metabolism in normal mice"Results:Supplementation with1%BWWZFO significantly increased serum TC, TG, HDL and LDL levels. But NWWZFO only elevated serum TG. Both BWWZFO and NWWZFO increased hepatic TC contents and HI, compared with the control.Conclusion:Feeding the mice with BWWZFO and NWWZFO elevated serum or hepatic lipid levels and caused hepatomegaly.Part4Effect of Wuweizi fatty oil (WWZFO) on lipid metabolism in hypercholesterolemic mice.4.1Effect of oral administration of WWZFO on lipid metabolism in hypercholesterolemic mice.Objective:To study the effect of oral administration of BWWZFO and NWWZFO on lipid metabolism in hypercholesterolemia mice.Method:Three studies were designed.1) Mice were fed with HFCBD for7days and orally administrated with WWZFO2and5g/kg at day6. Twenty-four h later, the serum and liver tissue simples were obtained.2) Mice were fed with HFCBD and treated with daily dose of WWZFO2g/kg for6days. The serum and hepatic lipids were determined at7days.3) Mice were fed with HFCBD for13days and treated with WWZFO from day6to day12. Then the serum liver tissues simples were obtained24h after the last dose. Other experimental details were described in "1.2Effect of dietary Aq-WWZ on lipid metabolism in normal mice".Results:Feeding mice with HFCBD for7or13days significantly increased serum TC, TG, LDL, and ALT levels, as well HI. Both BWWZFO and NWWZFO treatment increased serum lipids and HI, but decreased hepatic lipid levels and serum ALT activity, in hypercholesterolemic mice.Conclusion:Oral administration of BWWZFO and NWWZFO elevated serum lipid levels and showed hepatoprotective effect in hypercholesterolemic mice.4.2Effects of dietary WWZFO on lipid metabolism in hypercholesterolemic mice.Objective:To study the effect of diet supplement with BWWZFO and NWWZFO on lipid metabolism in hypercholesterolemic mice. Method:In this study three mouse model of hypercholesterolemia were used. They included CB diet, HFC diet and HFCB diet. BWWZFO and NWWZFO were added to these diets for feeding mice. Bicyclol and fenofibrate was also used as a positive control for comparison. Other experimental details were described in "1.2Effect of dietary Aq-WWZ on lipid metabolism in normal mice".Results:Feeding mice with CB diet, HFC diet and HFCB diet significantly increased serum TC and LDL levels and ALT activity. Supplementation with WWZFO at concentration of0.25or1%decreased serum ALT activity, but increased serum HDL and LDL levels in mouse model of hypercholesterolemia. Hepatic TC, TG, and HI were increased in the hypercholesterolemic mice. However, WWZFO supplement further elevated hepatic lipid contents and HI.Conclusion:Dietary WWZFO have significant effect on indicators in hypercholesterolemic mice.Part5Action mechanism of Wuweizi fatty oil (WWZFO)-induced hypertriglyceridemia and hepatomegaly.5.1Hypertriglyceridema and high blood VLDL and Apo-B48caused by WWZFO in mice.Objective:To study the mechanism of WWZFO-induced hypertriglyceridemia.Method:Mice were orally administrated with a single does of either BWWZFO or NWWZFO (dose range0.3-5g/kg). Serum TG was measured with a photoelectric colorimetry at6,12,24,48,72, and96h post-dosing. The serum triglyceride transfer protein (TTP), Apo-B48, and VLDL levels were determined by using ELISA method at24h after WWZ fatty oil treatment. Other experimental details were described in "1.2Effect of dietary Aq-WWZ on lipid metabolism in normal mice"Results:BWWZFO and NWWZFO treatment caused a time-/does-dependent increase in serum TG levels, reaching a maximum height, associated with elevation of serum TTP, Apo-B48, and VLDL levels, compared with the control animals at24h post-dosing.Conclusion:Hypertriglyceridemia generated by WWZFO involved endogenous and exogenous pathways of TG synthesis.5.2Hepatomegaly and high blood hepatocyte growth factor caused by WWZFO in mice.Objective:To study the mechanism of WWZFO-induced hepatomegaly.Method:Mice were orally administrated with a single does of either BWWZFO or NWWZFO.Hepatic TG was measured with a photoelectric colorimetry at6,12,24,48,72, and96h post-dosing. The serum hepatocyte growth factor (HGF) was determined by using ELISA method at48h after WWZ fatty oil treatment. Other experimental details were described in "1.2Effect of dietary Aq-WWZ on lipid metabolism in normal mice"Results:BWWZFO and NWWZFO treatment caused a time-/does-dependent increase in hepatic weight, reaching a maximum height, associated with elevation of serum HGF levels, compared with the control animals at48h post-dosing.Conclusion:WWZFO increase the hepatic weight associated with the elevation of serum HGF. |
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