Hydrophilic phytosterol derivatives: A short review on structural modifications, cholesterol-lowering activity and safety

Phytosterols have received extensive attention owing to their excellent cholesterol-lowering activity and the role in cardiovascular diseases prevention. However, poor solubility in both oil and water limited the application of free phytosterols in the food industry. Chemical or enzymatic modifications were effective to improve the physicochemical properties as well as the bioavailability and cholesterollowering activity of phytosterols. Higher oil solubility and lower melting point of phytosterols have been achieved by esterification and transesterification with fatty acids and triacylglycerols so as to enhance the bioavailability, reduce formation of precipitates, and improve the sensory quality of products.While the researches on the improvement on its water solubility is a hot topic. Hydrophilic phytosterol derivatives have promising applications in the food industry because most of foods belong to aqueous matrix. Hydrophilic modification is useful and meaningful for phytosterols in both industrial and commercial applications. This review mainly highlights the hydrophilic phytosterol derivatives in the following aspects:(i) hydrophilic modifications of phytosterols by coupling with various polar components;(ii) cholesterol-lowering activity and possible molecular mechanisms of hydrophilic phytosterol derivatives on reducing serum cholesterol level;and(iii) safety evaluation of hydrophilic phytosterol derivatives in cell-culture studies, animal models and clinical trials.

Effects of lactic acid bacteria isolated from fermented mustard on lowering cholesterol

Objective:To evaluate the ability of lactic acid bacteria(LAB)strains isolated from fermented mustard to lower the cholesterol in vitro.Methods:The ability of 50 LAB strains isolated from fermented mustard on lowering cholesterol in vitro was determined by modified o-phtshalaldehyde method.The LAB isolates were analyzed for their resistance to acid and bile salt.Strains with lowering cholesterol activity,were determined adherence to Caco-2 cells.Results:Strain B0007,B0006 and B0022 assimilated more cholesterol than BCRC10474 and BCRC17010.The isolated strains showed tolerance to pH 3.0 for 3h despite variations in the degree of viability and bile-tolerant strains,with more than 10~s CFU/mL after incubation for 24 h at 1%oxigall in MRS.In addition,strain B0007 and B0022 identified as Lactobacillus plantarum with 16S rDNA sequences were able to adhere to the Caco-2 cell lines.Conclusions:These strains B0007 and B0022 may be potential functional sources for cholesterollowering activities as well as adhering to Caco-2 cell lines.

Antithrombotic therapy and bleeding risk in the era of aggressive lipid-lowering:current evidence,clinical implications,and future perspectives

The clinical efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors(PCSK9i)in reducing major cardiovascular adverse events related to atherosclerotic cardiovascular disease(ASCVD)has been well established in recent large randomized outcome trials.Although the cardiovascular and all-cause mortality benefit of PCSK9i remains inconclusive,current cholesterol management guidelines have been modified toward more aggressive goals for lowering low-density lipoprotein cholesterol(LDL-C).Consequently,the emerging concept of"the lower the better"has become the paradigm of ASCVD prevention.However,there is evidence from observational studies of a U-shaped association between baseline LDL-C levels and all-cause mortality in population-based cohorts.Among East Asian populations,low LDL-C was associated with an increased risk for hemorrhagic stroke in patients not on antithrombotic therapy.Accumulating evidence showed that low LDL-C was associated with an enhanced bleeding risk in patients on dual antiplatelet therapy following percutaneous coronary intervention.Additionally,low LDL-C was associated with a higher risk for incident atrial fibrillation and thereby,a possible increase in the risk for intracranial hemorrhage after initiation of anticoagulation therapy.The mechanism of low-LDL-C-related bleeding risk has not been fully elucidated.This review summarizes recent evidence of low-LDL-C-related bleeding risk in patients on antithrombotic therapy and discusses potential measures for reducing this risk,underscoring the importance of carefully weighing the pros and cons of aggressive LDL-C lowering in patients on antithrombotic therapy.

A novel class of apical sodium–dependent bile salt transporter inhibitors:1-(2,4-bifluorophenyl)-7-dialkylamino-1,8-naphthyridine-3-carboxamides

The apical sodium-dependent bile acid transporter(ASBT) is the main transporter to promote re-absorption of bile acids from the intestinal tract into the enterohepatic circulation.Inhibition of ASBT could increase the excretion of bile acids,thus increasing bile acid synthesis and consequently cholesterol consumption.Therefore,ASBT is an attractive target for developing new cholesterol-lowering drugs.In this report,a series of 1-(2,4-bifluorophenyl)-7-dialkylamino-1,8-naphthyridine-3-carboxamides were designed as inhibitors of ASBT.Most of them demonstrated potency against ASBT transport of bile acids.In particular,compound 4a_1 was found to have the best activity,resulting in 80.1%inhibition of ASBT at10μmol/L.

Drug targets beyond HMG-CoA reductase:Why venture beyond the statins?

In this review,we aim to convey a brief,select history of the development of cholesterol-lowering therapies.We focus particularly on the highly successful statins as well as setbacks that should serve as cautionary tales.We go on to preview recent developments that may complement,if not one day replace,the statins.Our focus is on pharmacological interventions,particularly those targeting the cholesterol biosynthetic pathway.Also,we examine therapies under current investigation that target the assembly of atherogenic lipoproteins(via apolipoprotein B or microsomal triglyceride transfer protein),the stability of the low-density lipoprotein-receptor(via PCSK9,proprotein convertase subtilisin kexin 9),or are designed to increase high-density lipoprotein-cholesterol(via inhibition of cholesteryl ester transfer protein).