Fenofibrate for patients with asymptomatic primary biliary cirrhosis

AIM:Primary biliary cirrhosis (PBC) is a chronic, cholestatic disease of autoimmune etiology,the histology of which shows a destruction of the intrahepatic bile duct and portal inflammation. Ursodeoxycholic acid (UDCA) is now used as a first-line drug for asymptomatic PBC (aPBC) because it is reported that UDCA decreases mortality and prolongs the time of liver transplantation.However, only 20-30% of patients respond fully to UDCA.Recently,lipoprotein-lowering agents have been found to be effective for PBC.The aim of this study was to examine the safety and efficacy of fenofibrate, a member of the fibrate class of hypolipidemic and anti-inflammatory agent via peroxysome proliferatory-activated receptor α,in patients with aPBC.METHODS:Fenofibrate was administered for twelve weeks in nine patients with aPBC who failed to respond to UDCA.UDCA was used along with fenofibrate during the study.The data from aPBC patients were analyzed to assess the biochemical effect of fenofibrate during the study.RESULTS: The serum levels of alkaline phosphatase (ALP)(285±114.8IU/L) and immunoglobulin M (IgM) (255.8±85.9mg/dl) significantly decreased to 186.9±76.2IU/L and 192.9±67.5mg/dL respectively, after fenofibrate treatment in patients with aPBC (P<0.05). Moreover,the titer of antimitochondrial antibody (AMA) also decreased in 4 of 9 patients with aPBC. No adverse reactions were observed in any patients.CONCLUSION:Fenofibrate appears to be significantly effective in treating patients with aPBC who respond incompletely to UDCA alone.Although the mechanism of fenofibrate on aPBC has not yet been fully clarified,combination therapy using fenofibrate and UDCA might be related to the anti-immunological effects, such as the suppression of AMA production as well as its antiinflammatory effect.

THE EFFECTS OF RADIX SALVIAE MILTIORRHIZAE ON LIPID ACCUMULATION OF PEROXIDIZED LOW DENSITY LIPOPROTEIN IN MOUSE PERITONEAL MACROPHAGES ?LIPID ANALYSIS AND MORPHOLOGICAL STUDIES

Mouse peritoneal macrophages were incubated in DMEM with pox-LDL and Rradlx Salviae Miltiorrhizae (RSM) to investigate the effects of RSM on the internalization of peroxidized low density lipoprotein (pox-LDL) by using lipid analysis and electron microscopy. Lipid peroxide (LPO) concentrations were increased slightly in the medium after incubation of macrophages with normal LDL (n-LDL), while decreased significantly in the media after incubation of macrophages with pox-LDL. In the three groups with pox-LDL, it could be found that there was a dose-dependent decrease of concentrations of LPO and total cholesterol (TCH) in the two RSM groups, and the decrease in the two RSM groups was much greater than in the group without RSM. RSM accelerated a more decrease of LPO than cholesterol contents in the media containing pox-LDL. The ultrastructural studies also showed that RSM induced the accumulation of lipid droplets in the cytoplasm of mouse peritoneal macrophages. The results suggested that RSM could accelerate the phagocytosis and degradation of pox-LDL by macrophages.

Atorvastatin Reduces the Expression of COX-2 mRNA in Peripheral Blood Monocytes from Patients With Acute Myocardial Infarction in Vitro

Objectives To examine effect of atorvastatin on the expression of COX-2 in peripheral blood monocytes from patients with early stage of acute myocardial infarction (AMI) in vitro, and the IL-6 concentration in supernatant was also examined. Methods Patients with AMI (n=40) and with stable coronary heart disease (CHD) (n=18) were registered. Peripheral blood monocytes from all participants were isolated and cultured for 24 hrs, but those from patients with AMI were randomly exposed to various concentration of atorvastatin (0, 0.1, 1, 10 μmol/L) during the cultivation. COX-2 mRNA expression in monocytes was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Concentration of IL-6 in supernatant was measured by enzyme-linked immunosorbent assay (ELISA). Results COX-2 expression and IL-6 secretion by peripheral blood monocytes from patients with AMI (0.92±0.13, 205±46 pg/ml) were higher than that from controls (0.19±0.08, 41±8 pg/ml) (both P<0.05), and COX-2 expression was dramatically reduced up to 52% by atorvastatin (P<0.05), in a concentration-dependent manner respectively. The expression of COX-2 from patients with AMI was obviously correlated with the secretion of IL-6 (r=0.636, P<0.05). COX-2 expression in the monocytes after intervention of atorvastatin was also positively correlated with IL-6 secretion by these cells (r=0.783, P<0.05). Conclusions COX-2 involves inflammatory respond in early-stage of AMI. Atorvastatin may decrease COX-2 expression in peripheral blood monocytes from patients with AMI and cyclooxygenase-dependent pathway might be correlated with the anti-inflammation mechanism of statin.

Change in cholesterol absorption and synthesis markers in patients with coronary heart disease after combination therapy with simvastatin plus ezetimibe

Bad, round Statins and ezetimibe have been reported to change the balance of cholesterol metabolism, but few studies have been performed on Chinese patients. The aim of this study was to evaluate changes in cholesterol metabolism markers in patients with coronary heart disease. Methods Forty-five patients with coronary heart disease were treated with 20 mg/d of simvastatin for four weeks. Subjects were then divided into two different therapy groups according to whether they reached the target values for total cholesterol and low density lipoprotein cholesterol level. Patients who reached the target values remained on simvastatin and those who did not reach the target values took a combination of simvastatin plus 10 mg/d ezetimibe until the 12th week. The concentrations of cholesterol synthesis markers （lathosterol and desmosterol） and absorption markers （campesterol and sitosterol） were measured on the 1st, 4th, and 12th week of the study by gas chromatography. Results After treatment with simvastatin for four weeks, the levels of total cholesterol and low density lipoprotein cholesterol decreased significantly compared to levels measured during the 1st week （P 〈0.05）. On the 12th week the levels of total cholesterol and low density lipoprotein cholesterol had decreased significantly （P 〈0.001） compared to levels during the 4th week. By the 12th week the levels of campesterol and sitosterol in the combination group had decreased significantly （P〈0.05） compared with levels measured during the 4th week. Conclusions Coronary heart disease patients with high cholesterol synthesis at baseline might gain a greater benefit from simvastatin treatment. Combination therapy with simvastatin plus ezetimibe in patients with low cholesterol synthesis at baseline might increase the success rate of lipid-lowering throuah decreasing the absorption of cholesterol.

Leucosceptroid B from glandular trichomes of Leucosceptrum canum reduces fat accumulation in Caenorhabditis elegans through suppressing unsaturated fatty acid biosynthesis

Obesity that is highly associated with numerous metabolic diseases has become a global health issue nowdays.Plant sesterterpenoids are an important group of natural products with great potential;thus,their bioactivities deserve extensive exploration.RNA-seq analysis indicated that leucosceptroid B,a sesterterpenoid previously discovered from the glandular trichomes of Leucosceptrum canum,significantly regulated the expression of 10 genes involved in lipid metabolism in Caenorhabditis elegans.Furthermore,leucosceptroid B was found to reduce fat storage,and downregulate the expression of two stearoyl-CoA desaturase(SCD)genes fat-6 and fat-7,and a fatty acid elongase gene elo-2 in wild-type C.elegans.In addition,leucosceptroid B significantly decreased fat accumulation in both fat-6 and fat-7 mutant worms but did not affect the fat storage of fat-6;fat-7 double mutant.These findings indicated that leucosceptroid B reduced fat storage depending on the downregulated expression of fat-6,fat-7 and elo-2 and thereby inhibiting the biosynthesis of the corresponding unsaturated fatty acid.These findings provide new insights into the development and utilization of plant sesterterpenoids as potential antilipemic agents.