The effects of schisandrin B (Sch B) on liver and serum lipid contents were investigated in mice with experimentally-induced hypercholesterolaemia. Hypercholesterolaemia was induced either by oral administration of a cholesterol/bile salts mixture (2/0.5 g kg(-1)) for four days or by feeding a high fat/cholesterol/bile salts (10/1/0.3%, w/w) diet for seven days. Daily co-administration of Sch B (50-200 mg kg(-1), i.g.) for four or six days, respectively, decreased hepatic total cholesterol (TC) and triglyceride (TG) levels (by up to 50% and 52%, respectively) in hypercholesterolaemic mice. Sch B treatment also increased hepatic indices (14-84%) in hypercholesterolaemic mice. The results indicated that Sch B treatment could decrease hepatic TC and TG levels, and increase liver weight, in mouse models of hypercholesterolaemia. Fenofibrate treatment (100 mg kg(-1)) produced effects similar to those of Sch B on the hepatic index and lipid levels of hypercholesterolaemic mice.
Bicyclol is used for the treatment of chronic hepatitis B in China. In this study, the effects of bicyclol (100 or 300 mg kg(-1), p.o.) on serum and liver lipid contents were investigated in both normal and experimentally induced hypercholesterolaemic mice. Hypercholesterolaemia was induced by either oral administration of cholesterol/bile salt or feeding a diet containing lard/cholesterol. Daily administration of bicyclol for 7 days dose-dependently increased the serum triglyceride level (29-80%) but slightly decreased the hepatic total cholesterol level (12-17%) in normal mice. Co-administration of bicyclol with cholesterol/bile salt decreased the hepatic triglyceride and total cholesterol levels (7-15% and 25-31%, respectively), when compared with the drug-untreated and cholesterol/bile salt-treated group. Bicyclol treatment for 7 days decreased hepatic triglyceride (5-76%) and total cholesterol (5-48%) levels in mice fed with high-fat/cholesterol diet. In contrast, bicyclol treatment increased the serum triglyceride level (18-77%) in mice treated with cholesterol/bile salt or fed with high-fat/cholesterol diet. Bicyclol treatment also caused an increase in hepatic index of normal and hypercholesterolaemic mice (3-32%). The results indicate that bicyclol treatment can invariably decrease hepatic lipid levels and increase serum triglyceride levels in normal and hypercholesterolaemic mice.
Effects of the ethanol extract of Fructus Schisandrae (EtFSC) on serum and liver lipid contents were investigated in mice fed with high fat/cholesterol (HFC) diet for 8 or 15 days. The induction of hypercholesterolemia by HFC diet caused significant increases in serum and hepatic total cholesterol (TC) levels (up to 62% and 165%, resp.) and hepatic triglyceride (TG) levels (up to 528%) in mice. EtFSC treatment (1 or 5 g/kg/day for 7 days; from Day 1 to 7 or from Day 8 to 14, i.g.) significantly decreased the hepatic TG level (down to 35%) and slightly increased the hepatic index (by 8%) in hypercholesterolemic mice. Whereas fenofibrate treatment (0.1 g/kg/day for 7 days, i.g.) significantly lowered the hepatic TG level (by 61%), it elevated the hepatic index (by 77%) in hypercholesterolemic mice. Acute toxicity test showed that EtFSC was relatively non-toxic, with an LD50 value of 35.63 ± 6.46 g/kg in mice. The results indicate that EtFSC treatment can invariably decrease hepatic TG in hypercholesterolemic mice, as assessed by both preventive and therapeutic protocols, suggesting its potential use for fatty liver treatment.
Effects of the cholinesterase inhibitors tacrine and bis(7)- tacrine (0.25–20 μmol/kg, s.c.) on locomotor activity and passive-avoidance response were investigated in mice treated with scopolamine (SCP, 1 or 5 μmol/kg, i.p.), using an open-field test and step-through task with a 24-hour retention interval. Drugs were given 30 min prior to the first session. During the acquisition session, SCP treatment increased the locomotor activity (10–16%). Tacrine, but not bis(7)-tacrine, cotreatment significantly reduced the locomotor activity by 23 or 27%, when compared with the SCP-treated control mice. In the step-through task, tacrine or bis(7)-tacrine coadministration dose-dependently attenuated the increase in the number of footshocks (by 50 or 58%) in SCP-treated mice. The lowest dose of tacrine and bis(7)-tacrine for prolonging the retention latency (up to 500%) in SCP-treated mice was 5 and 1 μmol/kg, respectively. Tacrine and bis(7)-tacrine inhibited brain acetylcholinesterase (AChE) activity 15 min (but not 30 min) after the drug administration in mice. At the same dose of 20 μmol/kg, the bis(7)-tacrine-induced AChE inhibition in serum was 14-fold higher than that of tacrine. The results indicated that bis(7)-tacrine was less potent than tacrine in causing motor dysfunction. However, bis(7)-tacrine was more potent than tacrine in the cognitive enhancement of SCP-induced memory loss and in AChE inhibition.
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