Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity.In practical application,the research of food combinat...Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity.In practical application,the research of food combinations is more significant than a specific food component.This study investigated the lipid-lowering effect of highland barley polyphenols via lipase assay in vitro and HepG2 cells induced by oleic acid(OA).Five indexes,triglyceride(TG),total cholesterol(T-CHO),low density lipoprotein-cholesterol(LDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were used to evaluate the lipidlowering effect of highland barley extract.We also preliminary studied the lipid-lowering mechanism by Realtime fluorescent quantitative polymerase chain reaction(q PCR).The results indicated that highland barley extract contains many components with lipid-lowering effects,such as hyperoside and scoparone.In vitro,the lipase assay showed an 18.4%lipase inhibition rate when the additive contents of highland barley extract were 100μg/m L.The intracellular lipid-lowering effect of highland barley extract was examined using 0.25 mmol/L OA-induced HepG2 cells.The results showed that intracellular TG,LDL-C,and T-CHO content decreased by 34.4%,51.2%,and 18.4%,respectively.ALT and AST decreased by 51.6%and 20.7%compared with the untreated hyperlipidemic HepG2 cells.q PCR results showed that highland barley polyphenols could up-regulation the expression of lipid metabolism-related genes such as PPARγand Fabp4.展开更多
lipid-lowering interventions on the disease.Methods:Two-sample Mendelian randomization analyses were conducted to evaluate the associations of high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,t...lipid-lowering interventions on the disease.Methods:Two-sample Mendelian randomization analyses were conducted to evaluate the associations of high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,triglycerides,apolipoprotein B and apolipoprotein A-I levels with risks for sepsis,and those of low-density lipoprotein cholesterol(HMGCR,PCSK9,NPC1L1),triglycerides(LPL,ANGPTL3,APOC3)and high-density lipoprotein cholesterol(CETP),apolipoprotein A-I(CETP),apolipoprotein B(HMGCR,PCSK9,NPC1L1,LPL,APOC3)with sepsis.Results:HMGCR-mediated low-density lipoprotein cholesterol and apolipoprotein B were associated with an increased risk of sepsis,with an odds ratio value of 1.4(95%confidence interval(CI):1.06-1.84,P=0.017)and 1.41(95%CI:1.01-1.98,P=0.046).CETP-mediated high-density lipoprotein cholesterol and apolipoprotein A-I were associated with a reduced risk of sepsis,with an odds ratio of 0.87(95%CI:0.82-0.92,P<0.01)respectively and 0.84(95%CI:0.78-0.9,P<0.01).Sensitivity analysis showed that the results were robust.Conclusion:HMG-CoA reductase inhibitors and CETP inhibitors may contribute to the prevention and treatment of sepsis.展开更多
Objective:To investigate the effect of Oroxylum indicum fruit extract on high-fat diet-induced hyperlipidemic mice.Methods:The phytochemical composition of Oroxylum indicum fruit extract was determined by liquid chrom...Objective:To investigate the effect of Oroxylum indicum fruit extract on high-fat diet-induced hyperlipidemic mice.Methods:The phytochemical composition of Oroxylum indicum fruit extract was determined by liquid chromatographymass spectrometry/mass spectrometry(LC-MS/MS)and gas chromatography-mass spectrometry.Forty-two male mice were used.The mice were divided into six groups:normal control,high-fat diet control,simvastatin treatment(20 mg/kg BW/day),and Oroxylum indicum fruit extract(100,200,300 mg/kg BW/day)treatment groups.Food intake,body weight,serum parameters,lipid profile,and histopathological lesions of the kidney,liver,and epididymal fat were observed.Results:LC-MS/MS results revealed four major components of Oroxylum indicum fruit extract:luteolin,apigenin,baicalein,and oroxylin A.Twenty-seven volatile oils were identified from Oroxylum indicum fruit extract.Daily oral administration of Oroxylum indicum fruit extract at 100 to 300 mg/kg BW/day significantly reduced the body weight,total cholesterol,triglyceride,and low-density lipoprotein cholesterol level(P<0.05),whereas high-density lipoprotein cholesterol was higher than the high-fat diet control group.Treatment with 300 mg/kg BW/day Oroxylum indicum fruit extract reduced the pathological lesion and prevented fat accumulation in the kidney and liver.Conclusions:Oroxylum indicum fruit extract has hypolipidemic effect in hyperlipidemic mice,and the active ingredients of Oroxylum indicum fruit extract,both flavonoids and volatile oils,should be further explored as an antihyperlipidemic agent.展开更多
Objective:The objective of this study was to verify the lipid-lowering effect of Juhe Fang extract(JHFE)and to determine its characteristic chemical profile in vitro and in vivo.Methods:A hyperlipidemia model was esta...Objective:The objective of this study was to verify the lipid-lowering effect of Juhe Fang extract(JHFE)and to determine its characteristic chemical profile in vitro and in vivo.Methods:A hyperlipidemia model was established by feeding mice a high-fat diet(HFD).After treatment for 30 days,serum total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)levels were measured with an automatic biochemistry analyzer.The components from JHFE obtained from in vivo and in vitro experiments were investigated using an UPLC-Q Exactive-Orbitrap MS/MS.Results:The TC,TG,and LDL-C in the serum significantly decreased and the HDL-C significantly increased after JHFE treatment.A total of 95 compounds from JHEF including 15 phenolic acids(PA),4 phenylethanoid glycosides(PG),24 flavonoids(F),14 triterpenoids(T),10 diterpenoid glycosides(D),18 alkaloids(A)and 10 others(O)were identified.Trigonelline was discovered for the first time in a herbal medicine of Juhe Fang.Furthermore,68 compounds were identified in vivo including 28 prototype compounds and 40 metabolites.The metabolic characteristics of these components were revealed including identification of new metabolites of 4-hydroxyphenyl ethyl-8-O-[a-L-arabinopyranosyl-(1/6)]-b-D-glucopyranoside(PEG)and lirinidine.A total of 43 components from JHFE were absorbed and/or metabolized.The contribution rate of each type of chemical component from JHFE to its lipidlowering effect from high to low were A,F,PG,PA,D and T.Conclusion:The results of this study showed that JHFE demonstrated a significant lipid-lowering effect in a high-fat diet(HFD)-induced hyperlipidemia mouse model.Specific types of PA,PG,F,D,T and A formed the pharmaceutical architecture of the lipid-lowering effect of JHFE.This study should prove useful for clarifying the components responsible for the lipid-lowering effect of JHFE and provide a basis for precision quality control research.展开更多
Statins have been shown to be effective in reducing cardiovascular events.Their magnitude of benefits has been proportionate to the reduction in low-density lipoprotein cholesterol(LDL-c).Intensive lipid-lowering ther...Statins have been shown to be effective in reducing cardiovascular events.Their magnitude of benefits has been proportionate to the reduction in low-density lipoprotein cholesterol(LDL-c).Intensive lipid-lowering therapies using ezetimibe and more recently proprotein convertase subtilisin kexin 9 inhibitors have further improved clinical outcomes.Unselective application of these treatments is undesirable and unaffordable and,therefore,has been guided by LDL-c level.Nonetheless,the residual risk in the post-statin era is markedly heterogeneous,including thrombosis and inflammation risks.Moreover,the lipoprotein related risk is increasingly recognised to be related to other non-LDL-c markers such as Lp(a).Emerging data show that intensive lipid-lowering therapy produce larger absolute risk reduction in patients with polyvascular disease,post coronary artery bypass graft and diabetes.Notably,these clinical entities share similar phenotype of large burden of atherosclerotic plaques.Novel plaque imaging may aid decision making by identifying patients with propensity to develop lipid rich plagues at multi-vascular sites.Those patients may be suitable candidates for intensive lipid lowering treatment.展开更多
Highland barley is a well-known cereal in Qinghai-Tibet Plateau area with high nutritional value,which has been reported to be a health-promoting grain for the obesity and the diabetes.Fermentation by certain microbio...Highland barley is a well-known cereal in Qinghai-Tibet Plateau area with high nutritional value,which has been reported to be a health-promoting grain for the obesity and the diabetes.Fermentation by certain microbiota can improve the flavor property and nutritional characteristics.In the present study,Lactiplantibacillus plantarum and Saccharomyces cerevisiae were singly or jointly applied to ferment highland barley,and the profile of volatile substances and lipid-lowering effects of the respective extracts were analyzed.Results indicated that either L.plantarum or S.cerevisiae or co-fermentation could consume the polysaccharides of highland barley to provide energy,and dramatically increase the contents of total protein and polyphenol.Gas chromatography-mass spectrometry(GC-MS)analysis revealed that the presence of S.cerevisiae was critical for production of the pleasant flavors,especially for the ethyl ester substances including hexadecanoic acid ethyl,hexanoic acid ethyl ester and so on.Meanwhile,we found that fermented highland barley extracts by L.plantarum exhibited stronger lipid-lowering effects in Caenorhabditis elegans than that by S.cerevisiae,while the co-fermentation not only emitted pleasant odors but also exerted high hypolipidemic function.In all,co-fermentation by L.plantarum and S.cerevisiae was proposed to be a promising processing to improve the flavor and functional properties of highland barley.展开更多
Based on a non-competitive and selective PTP1 B inhibitor reported by us previously, thirtynine benzamido derivatives were designed and synthesized as novel PTP1 B inhibitors. Among them,twelve compounds exhibited IC_...Based on a non-competitive and selective PTP1 B inhibitor reported by us previously, thirtynine benzamido derivatives were designed and synthesized as novel PTP1 B inhibitors. Among them,twelve compounds exhibited IC_(50) values at micromolar level against human recombinant PTP1 B, and most of them exhibited significant selectivity to PTP1 B over TC-PTP and CD45. Further evaluation of the most potent compound 27 on high-fat diet(HFD)-induced insulin-resistant(IR) obese mice indicated that27 could modulate glucose metabolism and ameliorate dyslipidemia simultaneously.& 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).展开更多
Bioassay-guided fractionation of an ethanolic extract of Ochrosia borbonica led to the isolation of two known pyridocarbazole alkaloids,ellipticine(1)and 9-methoxyellipticine(2),and six known monoterpenoid indole alka...Bioassay-guided fractionation of an ethanolic extract of Ochrosia borbonica led to the isolation of two known pyridocarbazole alkaloids,ellipticine(1)and 9-methoxyellipticine(2),and six known monoterpenoid indole alkaloids(3-8).Lipid-lowering assay in 3 T3-L1 cell model revealed that 1 and 2 could significantly inhibit the lipid droplet formation(EC50(28)0.41 and 0.92μmol·L^–1,respectively)and lower triglyceride levels by 50%-60%at the concentration of 1μmol·L^–1,being more potent than the positive drug luteolin(EC50(28)2.63μmol·L–^1).A mechanistic study indicated that 1 and 2 could intercalate into supercoiled DNA,which consequently inhibited the mitotic clonal expansion of 3 T3-L1 cells at the early differentiation phase,leading to the retardance of following adipogenesis and lipogenesis.These findings suggest that 1 and 2 may serve as promising leads for further d evelopment of anti-obesity drugs.展开更多
As a dark tea,Pu-erh tea(PET)is produced from sun-dried leaves of Camellia sinensis var.assamica mainly in Yunnan Province of China.Many microorganisms are involved in the fermentation of PET.Among them,Aspergillus ni...As a dark tea,Pu-erh tea(PET)is produced from sun-dried leaves of Camellia sinensis var.assamica mainly in Yunnan Province of China.Many microorganisms are involved in the fermentation of PET.Among them,Aspergillus niger is most important.It is believed that the longer the preservation period,the better is the quality and taste of PET,which is commercially available as loose,compressed or instant tea leaves.Chemical components of PET include flavones,flavanols,flavonols,phenolic acids,alkaloids and methylxanthines.In this overview,the lipid-lowering and anti-obesity effects of PET were discussed based on animal models and human trials,and our study provided some insights into possible mechanisms of bioactive compounds,such as theabrownin,catechins,lovastatin and gallic acid.Other bioactivities of PET and some information on Fuzhuan brick tea were also included.Sources of information cited were from Google Scholar,Pub Med,Pub Med Central,Science Direct,J-Stage,Pub Chem,Directory of Open Access Journals(DOAJ),and China National Knowledge Infrastructure(CNKI).展开更多
Moyamoya disease(MMD),characterized by progressive internal carotid artery stenosis and collateral vessel formation,prompts cerebral perfusion complications and is stratified into idiopathic and Moyamoya syndrome subt...Moyamoya disease(MMD),characterized by progressive internal carotid artery stenosis and collateral vessel formation,prompts cerebral perfusion complications and is stratified into idiopathic and Moyamoya syndrome subtypes.A multifa-ceted approach toward MMD management addresses cerebral infarctions through revascularization surgery and adjunctive medical therapy,while also navigating risks such as intracranial hemorrhage and cerebral infarction resulting from arte-rial stenosis and fragile collateral vessels.Addressing antithrombotic management reveals a potential role for treatments like antiplatelet agents and anticoagulants,despite the ambiguous contribution of thrombosis to MMD-related infarctions and the critical balance between preventing ischemic events and averting hemo-rrhagic complications.Transcranial doppler has proven useful in thromboembolic detection,despite persisting challenges concerning the efficacy and safety of an-tithrombotic treatments.Furthermore,antihypertensive interventions aim to ma-nage blood pressure meticulously,especially during intracerebral hemorrhage,with recommendations and protocols varying based on the patient’s hypertension status.Additionally,lipid-lowering therapeutic strategies,particularly employing statins,are appraised for their possible beneficial role in MMD management,even as comprehensive data from disease-specific clinical trials remains elusive.Com-prehensive guidelines and protocols to navigate the multifaceted therapeutic ave-nues for MMD,while maintaining a delicate balance between efficacy and safety,warrant further meticulous research and development.This protocol manuscript seeks to elucidate the various aspects and challenges imbued in managing and navigating through the complex landscape of MMD treatment.展开更多
Background: To study the influence of blood lipid levels on hemorrhagic transformation(HT) and prognosis after acute cerebral infarction(ACI).Methods: Patients with ACI within 72 h of symptoms onset between January 1 ...Background: To study the influence of blood lipid levels on hemorrhagic transformation(HT) and prognosis after acute cerebral infarction(ACI).Methods: Patients with ACI within 72 h of symptoms onset between January 1 st, 2015, and December 31 st, 2016, were retrospectively analyzed. Patients were divided into group A(without HT) and group B(HT). The outcomes were assessed after 3 months of disease onset using the modified Rankin Scale(m RS). An m RS score of 0–2 points indicated excellent prognosis, and an m RS score of 3–6 points indicated poor prognosis.Results: A total of 732 patients conformed to the inclusion criteria, including 628 in group A and 104 in group B. The incidence of HT was 14.2%, and the median onset time was 2 d(interquartile range, 1–7 d). The percentages of patients with large infarct size and cortex involvement in group B were 80.8% and 79.8%, respectively, which were both significantly higher than those in group A(28.7 and 33.4%, respectively). The incidence rate of atrial fibrillation(AF) in group B was significantly higher than that in group A(39.4% vs. 13.9%, P<0.001). The adjusted multivariate analysis results showed that large infarct size, cortex involvement and AF were independent risk factors of HT, while total cholesterol(TC) was a protective factor of HT(OR=0.359, 95% CI 0.136–0.944, P=0.038). With every 1 mmol/L reduction in normal TC levels, the risk of HT increased by 64.1%. The mortality and morbidity at 3 months in group B(21.2% and 76.7%, respectively) were both significantly higher than those in group A(8.0% and 42.8%, respectively). The adjusted multivariate analysis results showed that large infarct size(OR=12.178, 95% CI 5.390–27.516, P<0.001) was an independent risk factor of long-term unfavorable outcomes, whereas low-density lipoprotein cholesterol(LDL-C) was a protective factor(OR=0.538, 95% CI 0.300–0.964, P=0.037). With every 1 mmol/L reduction in normal LDL-C levels, the risk of an unfavorable outcome increased by 46.2%. Major therapies, including intravenous recombinant human tissue plasminogen activator(r TPA), intensive lipid-lowering statins and anti-platelets, were not significantly related to either HT or long-term, post-ACI poor prognosis.Conclusions: For patients with large infarct sizes, especially those with cortex involvement, AF, or lower levels of TC, the risk of HT might increase after ACI. The risk of a long-term unfavorable outcome in these patients might increase with a reduction in LDL-C.展开更多
Objective:To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats.Methods:Administration of dexamethasone was given at 10 mg/kg,sc.to the adult rats for 8...Objective:To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats.Methods:Administration of dexamethasone was given at 10 mg/kg,sc.to the adult rats for 8 d induces hyperlipidemia characterized by marked increase in serum cholesterol and triglyceride levels along with increase in atherogenic index.Results:Lemongrass oil(100 and 200 mg/kg,po.) treatment has showed significant inhibition against dexamethasone hyperlipidemia by maintaining the serum levels of cholesterol, triglycerides and atherogenic index near to the normal levels and the antihyperlipidemic effect of the lemongross oil was comparable with atorvastatin 10 mg/kg,po.The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase(LCAT) activity.Conclusions:These results suggested that Lemon gross oil possess significant antihyperlipidemic activity.展开更多
The American Diabetes Association (ADA) 2013 guidelines state that a reasonable hemoglobin A1c goal for many nonpregnant adults with diabetes is less than 7.0% a hemoglobin A1c level of less than 6.5% may be considere...The American Diabetes Association (ADA) 2013 guidelines state that a reasonable hemoglobin A1c goal for many nonpregnant adults with diabetes is less than 7.0% a hemoglobin A1c level of less than 6.5% may be considered in adults with short duration of diabetes, long life expectancy, and no significant cardiovascular disease if this can be achieved without significant hypoglycemia or other adverse effects of treatment. A hemoglobin A1c level less than 8.0% may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced macrovascular and microvascular complications, extensive comorbidities, and long-standing diabetes in whom the hemoglobin A1c goal is difficult to attain despite multiple glucoselowering drugs including insulin. The ADA 2013 guidelines recommend that the systolic blood pressure in most diabetics with hypertension should be reduced to less than 140 mmHg. These guidelines also recommend use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in the treatment of hypertension in diabetics unless they are pregnant. Diabetics at high risk for cardiovascular events should have theirserum low-density lipoprotein (LDL) cholesterol lowered to less than 70 mg/dL with statins. Lower-risk diabetics should have their serum LDL cholesterol reduced to less than 100 mg/dL. Combination therapy of a statin with either a fibrate or niacin has not been shown to provide additional cardiovascular benefit above statin therapy alone and is not recommended. Hypertriglyceridemia should be treated with dietary and lifestyle changes. Severe hypertriglyceridemia should be treated with drug therapy to reduce the risk of acute pancreatitis.展开更多
Background:To observe the inhibitory effects of Yigan Jiangzhi formula(liver-supplementing lipid-lowering formula,YGJZF)on hepatic metastasis of colorectal cancer.Methods:The hepatic metastasis BALB-c mice model of co...Background:To observe the inhibitory effects of Yigan Jiangzhi formula(liver-supplementing lipid-lowering formula,YGJZF)on hepatic metastasis of colorectal cancer.Methods:The hepatic metastasis BALB-c mice model of colorectal cancer was established by injecting HCT-116 cell suspension following splenectomy.Next,we randomly divided BALB-c mice into 5 groups,which were blank group,model group(tumor only),traditional Chinese medicine group(YGJZF),western medicine group(capecitabine),combined group(YGJZF and capecitabine),respectively.After 14 days treatment,the effects of different treatments were evaluated the serological indicators were evaluated,including the levels of alanine transaminase,aspartate transaminase,triglyceride,total cholesterol and vascular endothelial growth factor(VEGF)by ELISA.Results:Except the blank group,the other groups showed diffuse hepatic metastasis.Compared with the model group,the total number and weight of the metastatic tumors as well as serological indicators in medicine-given groups were sharply reduced(P<0.05 for all)the combined group had better effects.The serum levels of these indicators showed no statistical difference among each medicine-given group(P>0.05),but the combined group has a remarkable decrease of all the indicators than in western medicine group.Conclusion:YGJZF not only can inhibit the hepatic metastasis of colorectal cancer in BALB-c mice,but also affect the levels of hepatic enzymes and lipids.Meanwhile,it can reduce the expression of VEGF.All these results indicate that YGJZF,which lowers down lipids and protects hepatic functions,has the potential to block VEGF pathway,contributing to the inhibition of hepatic metastasis.展开更多
Proprotein convertase subtilisin/kexin type 9(PCSK9)modulators may attenuate PCSK9-induced low-density lipoprotein receptor(LDLR)degradation in lysosome and promote the clearance of circulating low-density lipoprotein...Proprotein convertase subtilisin/kexin type 9(PCSK9)modulators may attenuate PCSK9-induced low-density lipoprotein receptor(LDLR)degradation in lysosome and promote the clearance of circulating low-density lipoprotein cholesterol(LDL-C).A novel series of tetrahydroprotoberberine derivatives(THPBs)were designed,synthesized,and evaluated as PCSK9 modulators for the treatment of hyperlipidemia.Among them,eight compounds exhibited excellent activities in downregulatinghepatic PCSK9 expression better than berberine in HepG2 cells.In addition,five compounds 15,18,22,(R)-22,and(S)-22 showed better performance in the low-density lipoprotein,labeled with 1,1’-dioctadecyl-3,3,3’,3’-tetramethyl-indocarbocyanine perchlorate(Dil-LDL)uptake assay,compared with berberine at the same concentration.Compound 22,selected for in vivo evaluation,demonstrated significant reductions of total cholesterol(TC)and LDL-C in hyperlipidemic hamsters with a good pharmacokinetic profile.Further exploring of the lipid-lowering mechanism showed that compound 22 promoted hepatic LDLR expression in a dose-dependent manner in HepG2 cells.Additional results of human ether-ago-go related gene(hERG)inhibition assay indicated the potential druggability for compound 22,which is a promising lead compound for the development of PCSK9 modulator for the treatment of hyperlipidemia.展开更多
Background Statins are lipid-lowering drugs that are used widely around the world to treat and prevent cardiovascular diseases. Rare, but potentially fatal, cases of rhabdomyolysis(RM) have linked to the use of statin...Background Statins are lipid-lowering drugs that are used widely around the world to treat and prevent cardiovascular diseases. Rare, but potentially fatal, cases of rhabdomyolysis(RM) have linked to the use of statins,especially in the presence of other risk factors. Methods We retrospectively analyzed the causes, clinical characteristics, treatments and prognosis of RM patients who were hospitalized between January 2005 and March2016 at the Guangdong General Hospital, China. A total of 16 patients were included in the study(12 males and four females, mean age 60.69 years). Amongst the patients, there were three cases of coronary heart disease, eight cases of dilated cardiomyopathy, six cases of atrial fibrillation, one case of pulmonary embolism, one case of aortic dissection, six cases of hypertension and one case of paroxysmal ventricular tachycardia. All patients had some degree of liver and kidney dysfunction, with low hemoglobin and myoglobinuria. Seven patients had a fever and four had relevant neurological signs. All patients had digestive disorders and muscle weakness or pain during their stay in hospital. All patients received renal replacement therapy and 13 were placed on a ventilator to support breathing. Nine patients were eventually improved but seven patients died despite treatment. Results All sixteen cases of RM were associated with lipid-lowering drugs, with 14 patients taking statins and two patients taking fibrates. Conclusions Statins were the main cause of RM in patients with poor prognosis and high mortality rate.展开更多
Codonopsis pilosula(CP),a well-known food medicine homology plant,is commonly used in many countries.In our preliminary study,a series of pyrrolidine alkaloids with high MS responses were detected as characteristic ab...Codonopsis pilosula(CP),a well-known food medicine homology plant,is commonly used in many countries.In our preliminary study,a series of pyrrolidine alkaloids with high MS responses were detected as characteristic absorbed constituents in rat plasma after oral administration of CP extract.However,their structures were unclear due to the presence of various isomers and the lack of reference standards.In the present study,an MS-guided targeted isolation of pyrrolidine alkaloids of CP extract was performed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC/Q-TOF MS).For data analysis under fast data directed acquisition mode(Fast-DDA),an effective approach named characteristic fragmentation-assisted mass spectral networking was successfully applied to discover new pyrrolidine alkaloids with high MS response in CP extract.As a result,seven new pyrrolizidine alkaloids[codonopyrrolidiums C–I(3–9)],together with two known ones(1 and 2),were isolated and identified by NMR spectral analysis.Among them,codonopyrrolidium B(1),codonopyrrolidium D(4)and codonopyrrolidium E(5)were evaluated for lipid-lowering activity,and they could improve high fructose-induced lipid accumulation in HepG2 cells.In addition,the characteristic MS/MS fragmentation patterns of these pyrrolizidine alkaloids were investigated,and 17 pyrrolidine alkaloids were identified.This approach could accelerate novel natural products discovery and characterize a class of natural products with MS/MS fragmentation patterns from similar chemical scaffolds.The research also provides a chemical basis for revealing in vivo effective substances in CP.展开更多
The outcomes of patients with myocardial infarction(MI)have substantially improved given the rapid progress that has occurred in revascularization techniques and secondary prevention,and the majority of MI patients su...The outcomes of patients with myocardial infarction(MI)have substantially improved given the rapid progress that has occurred in revascularization techniques and secondary prevention,and the majority of MI patients subsequently enter a chronic stable phase.Therefore,the long-term management of patients with MI has become a core issue in daily clinical practice for cardiologists.The long-term incidence of adverse events can be further reduced using newly developed medications and therapies ranging from lipid-lowering agents(eg,proprotein convertase subtilisin/kexin type 9 inhibitors)to anti-thrombotic treatments(eg,shortened dual anti-platelet therapy).However,a considerable number of patients still experience adverse events,as some residual risk can remain despite intensive secondary prevention,such as continuously elevated cholesterol levels,chronic cardiovascular inflammation,and rapid atherosclerosis progression due to increased plaque instability.Therefore,the present review sought to summarize and discuss recent advances in several key aspects regarding the long-term management of MI patients,with the expectation of clarifying the available treatment strategies for various clinical scenarios,examining the gaps between trial evidence and clinical practice,and providing possible directions for future research.展开更多
Assessment of the overall risk of atherosclerotic cardiovascular disease(ASCVD)is the first step in managing dyslipidemia and is an important reference for the target and intensity of treatment.Recently,different guid...Assessment of the overall risk of atherosclerotic cardiovascular disease(ASCVD)is the first step in managing dyslipidemia and is an important reference for the target and intensity of treatment.Recently,different guidelines and consensuses on the management of this condition have successively recommended further risk stratification among patients with ASCVD,and a new“extreme risk”category has been proposed to identify patients who may obtain greater benefit from more intensive lipid-lowering therapy.The definition and terminology of extreme risk varies among different guidelines and consensuses;however,they all recommended an aggressive lipid-lowering therapeutic approach and/or a more stringent low-density lipoprotein cholesterol target for patients at extreme risk.Regardless of the definitions,this general approach may have a remarkable effect on the treatment of this condition in clinical practice.To help clinicians and patients to better understand the new strategy for the secondary prevention of ASCVD,this review provides a summary highlighting the necessity of further risk stratification among ASCVD patients,how patients at extreme risk can be identified,and the potential impact of applying the new“extreme risk”category in clinical practice.展开更多
基金financially supported by the National Key Research and Development Program of China(2021YFD2100904)the National Natural Science Foundation of China(31871729,32172147)+2 种基金the Modern Agriculture key Project of Jiangsu Province of China(BE2022317)the Modern Agricultural Industrial Technology System Construction Project of Jiangsu Province of China(JATS[2021]522)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity.In practical application,the research of food combinations is more significant than a specific food component.This study investigated the lipid-lowering effect of highland barley polyphenols via lipase assay in vitro and HepG2 cells induced by oleic acid(OA).Five indexes,triglyceride(TG),total cholesterol(T-CHO),low density lipoprotein-cholesterol(LDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were used to evaluate the lipidlowering effect of highland barley extract.We also preliminary studied the lipid-lowering mechanism by Realtime fluorescent quantitative polymerase chain reaction(q PCR).The results indicated that highland barley extract contains many components with lipid-lowering effects,such as hyperoside and scoparone.In vitro,the lipase assay showed an 18.4%lipase inhibition rate when the additive contents of highland barley extract were 100μg/m L.The intracellular lipid-lowering effect of highland barley extract was examined using 0.25 mmol/L OA-induced HepG2 cells.The results showed that intracellular TG,LDL-C,and T-CHO content decreased by 34.4%,51.2%,and 18.4%,respectively.ALT and AST decreased by 51.6%and 20.7%compared with the untreated hyperlipidemic HepG2 cells.q PCR results showed that highland barley polyphenols could up-regulation the expression of lipid metabolism-related genes such as PPARγand Fabp4.
基金The 2022 Educational Teaching Reform and Research Project of Guangxi University of Traditional Chinese Medicine(2022C032).
文摘lipid-lowering interventions on the disease.Methods:Two-sample Mendelian randomization analyses were conducted to evaluate the associations of high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,triglycerides,apolipoprotein B and apolipoprotein A-I levels with risks for sepsis,and those of low-density lipoprotein cholesterol(HMGCR,PCSK9,NPC1L1),triglycerides(LPL,ANGPTL3,APOC3)and high-density lipoprotein cholesterol(CETP),apolipoprotein A-I(CETP),apolipoprotein B(HMGCR,PCSK9,NPC1L1,LPL,APOC3)with sepsis.Results:HMGCR-mediated low-density lipoprotein cholesterol and apolipoprotein B were associated with an increased risk of sepsis,with an odds ratio value of 1.4(95%confidence interval(CI):1.06-1.84,P=0.017)and 1.41(95%CI:1.01-1.98,P=0.046).CETP-mediated high-density lipoprotein cholesterol and apolipoprotein A-I were associated with a reduced risk of sepsis,with an odds ratio of 0.87(95%CI:0.82-0.92,P<0.01)respectively and 0.84(95%CI:0.78-0.9,P<0.01).Sensitivity analysis showed that the results were robust.Conclusion:HMG-CoA reductase inhibitors and CETP inhibitors may contribute to the prevention and treatment of sepsis.
文摘Objective:To investigate the effect of Oroxylum indicum fruit extract on high-fat diet-induced hyperlipidemic mice.Methods:The phytochemical composition of Oroxylum indicum fruit extract was determined by liquid chromatographymass spectrometry/mass spectrometry(LC-MS/MS)and gas chromatography-mass spectrometry.Forty-two male mice were used.The mice were divided into six groups:normal control,high-fat diet control,simvastatin treatment(20 mg/kg BW/day),and Oroxylum indicum fruit extract(100,200,300 mg/kg BW/day)treatment groups.Food intake,body weight,serum parameters,lipid profile,and histopathological lesions of the kidney,liver,and epididymal fat were observed.Results:LC-MS/MS results revealed four major components of Oroxylum indicum fruit extract:luteolin,apigenin,baicalein,and oroxylin A.Twenty-seven volatile oils were identified from Oroxylum indicum fruit extract.Daily oral administration of Oroxylum indicum fruit extract at 100 to 300 mg/kg BW/day significantly reduced the body weight,total cholesterol,triglyceride,and low-density lipoprotein cholesterol level(P<0.05),whereas high-density lipoprotein cholesterol was higher than the high-fat diet control group.Treatment with 300 mg/kg BW/day Oroxylum indicum fruit extract reduced the pathological lesion and prevented fat accumulation in the kidney and liver.Conclusions:Oroxylum indicum fruit extract has hypolipidemic effect in hyperlipidemic mice,and the active ingredients of Oroxylum indicum fruit extract,both flavonoids and volatile oils,should be further explored as an antihyperlipidemic agent.
基金the innovative research team of the Twelfth Five-Year National Science and Technology Support Program(Grant no.2012BAI29B06)the Beijing University of Chinese Medicine of China(Grant no.2011-CXTD-12).
文摘Objective:The objective of this study was to verify the lipid-lowering effect of Juhe Fang extract(JHFE)and to determine its characteristic chemical profile in vitro and in vivo.Methods:A hyperlipidemia model was established by feeding mice a high-fat diet(HFD).After treatment for 30 days,serum total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)levels were measured with an automatic biochemistry analyzer.The components from JHFE obtained from in vivo and in vitro experiments were investigated using an UPLC-Q Exactive-Orbitrap MS/MS.Results:The TC,TG,and LDL-C in the serum significantly decreased and the HDL-C significantly increased after JHFE treatment.A total of 95 compounds from JHEF including 15 phenolic acids(PA),4 phenylethanoid glycosides(PG),24 flavonoids(F),14 triterpenoids(T),10 diterpenoid glycosides(D),18 alkaloids(A)and 10 others(O)were identified.Trigonelline was discovered for the first time in a herbal medicine of Juhe Fang.Furthermore,68 compounds were identified in vivo including 28 prototype compounds and 40 metabolites.The metabolic characteristics of these components were revealed including identification of new metabolites of 4-hydroxyphenyl ethyl-8-O-[a-L-arabinopyranosyl-(1/6)]-b-D-glucopyranoside(PEG)and lirinidine.A total of 43 components from JHFE were absorbed and/or metabolized.The contribution rate of each type of chemical component from JHFE to its lipidlowering effect from high to low were A,F,PG,PA,D and T.Conclusion:The results of this study showed that JHFE demonstrated a significant lipid-lowering effect in a high-fat diet(HFD)-induced hyperlipidemia mouse model.Specific types of PA,PG,F,D,T and A formed the pharmaceutical architecture of the lipid-lowering effect of JHFE.This study should prove useful for clarifying the components responsible for the lipid-lowering effect of JHFE and provide a basis for precision quality control research.
文摘Statins have been shown to be effective in reducing cardiovascular events.Their magnitude of benefits has been proportionate to the reduction in low-density lipoprotein cholesterol(LDL-c).Intensive lipid-lowering therapies using ezetimibe and more recently proprotein convertase subtilisin kexin 9 inhibitors have further improved clinical outcomes.Unselective application of these treatments is undesirable and unaffordable and,therefore,has been guided by LDL-c level.Nonetheless,the residual risk in the post-statin era is markedly heterogeneous,including thrombosis and inflammation risks.Moreover,the lipoprotein related risk is increasingly recognised to be related to other non-LDL-c markers such as Lp(a).Emerging data show that intensive lipid-lowering therapy produce larger absolute risk reduction in patients with polyvascular disease,post coronary artery bypass graft and diabetes.Notably,these clinical entities share similar phenotype of large burden of atherosclerotic plaques.Novel plaque imaging may aid decision making by identifying patients with propensity to develop lipid rich plagues at multi-vascular sites.Those patients may be suitable candidates for intensive lipid lowering treatment.
基金supported by the China Postdoctoral Science Foundation(2020M671373)Jiangsu Postdoctoral Research Funding Program(2020Z070)+2 种基金Jiangsu Agriculture Science and Technology Innovation Fund(CX(20)2036)Key Research and Development Project of Jiangsu Province(BE2020314)Innovation Training Program for College Students(202310299649X).
文摘Highland barley is a well-known cereal in Qinghai-Tibet Plateau area with high nutritional value,which has been reported to be a health-promoting grain for the obesity and the diabetes.Fermentation by certain microbiota can improve the flavor property and nutritional characteristics.In the present study,Lactiplantibacillus plantarum and Saccharomyces cerevisiae were singly or jointly applied to ferment highland barley,and the profile of volatile substances and lipid-lowering effects of the respective extracts were analyzed.Results indicated that either L.plantarum or S.cerevisiae or co-fermentation could consume the polysaccharides of highland barley to provide energy,and dramatically increase the contents of total protein and polyphenol.Gas chromatography-mass spectrometry(GC-MS)analysis revealed that the presence of S.cerevisiae was critical for production of the pleasant flavors,especially for the ethyl ester substances including hexadecanoic acid ethyl,hexanoic acid ethyl ester and so on.Meanwhile,we found that fermented highland barley extracts by L.plantarum exhibited stronger lipid-lowering effects in Caenorhabditis elegans than that by S.cerevisiae,while the co-fermentation not only emitted pleasant odors but also exerted high hypolipidemic function.In all,co-fermentation by L.plantarum and S.cerevisiae was proposed to be a promising processing to improve the flavor and functional properties of highland barley.
基金support from the National Natural Science Foundation of China (20972192)Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS, 2016-I2M-3–009)
文摘Based on a non-competitive and selective PTP1 B inhibitor reported by us previously, thirtynine benzamido derivatives were designed and synthesized as novel PTP1 B inhibitors. Among them,twelve compounds exhibited IC_(50) values at micromolar level against human recombinant PTP1 B, and most of them exhibited significant selectivity to PTP1 B over TC-PTP and CD45. Further evaluation of the most potent compound 27 on high-fat diet(HFD)-induced insulin-resistant(IR) obese mice indicated that27 could modulate glucose metabolism and ameliorate dyslipidemia simultaneously.& 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).
基金supported by the National Natural Science Foundation of China(Nos.81573302,81722042,and 81703336)the Guangdong Natural Science Funds for Distinguished Young Scholar(No.2014A0303 06047)+2 种基金the Science and Technology Planning Project of Guangdong Province,China(No.2015A020211007)the Fundamental Research Funds for the Central Universities(No.17ykzd12)the Guangdong Provincial Key Laboratory of Construction Foundation(No.2017B030314030)
文摘Bioassay-guided fractionation of an ethanolic extract of Ochrosia borbonica led to the isolation of two known pyridocarbazole alkaloids,ellipticine(1)and 9-methoxyellipticine(2),and six known monoterpenoid indole alkaloids(3-8).Lipid-lowering assay in 3 T3-L1 cell model revealed that 1 and 2 could significantly inhibit the lipid droplet formation(EC50(28)0.41 and 0.92μmol·L^–1,respectively)and lower triglyceride levels by 50%-60%at the concentration of 1μmol·L^–1,being more potent than the positive drug luteolin(EC50(28)2.63μmol·L–^1).A mechanistic study indicated that 1 and 2 could intercalate into supercoiled DNA,which consequently inhibited the mitotic clonal expansion of 3 T3-L1 cells at the early differentiation phase,leading to the retardance of following adipogenesis and lipogenesis.These findings suggest that 1 and 2 may serve as promising leads for further d evelopment of anti-obesity drugs.
文摘As a dark tea,Pu-erh tea(PET)is produced from sun-dried leaves of Camellia sinensis var.assamica mainly in Yunnan Province of China.Many microorganisms are involved in the fermentation of PET.Among them,Aspergillus niger is most important.It is believed that the longer the preservation period,the better is the quality and taste of PET,which is commercially available as loose,compressed or instant tea leaves.Chemical components of PET include flavones,flavanols,flavonols,phenolic acids,alkaloids and methylxanthines.In this overview,the lipid-lowering and anti-obesity effects of PET were discussed based on animal models and human trials,and our study provided some insights into possible mechanisms of bioactive compounds,such as theabrownin,catechins,lovastatin and gallic acid.Other bioactivities of PET and some information on Fuzhuan brick tea were also included.Sources of information cited were from Google Scholar,Pub Med,Pub Med Central,Science Direct,J-Stage,Pub Chem,Directory of Open Access Journals(DOAJ),and China National Knowledge Infrastructure(CNKI).
文摘Moyamoya disease(MMD),characterized by progressive internal carotid artery stenosis and collateral vessel formation,prompts cerebral perfusion complications and is stratified into idiopathic and Moyamoya syndrome subtypes.A multifa-ceted approach toward MMD management addresses cerebral infarctions through revascularization surgery and adjunctive medical therapy,while also navigating risks such as intracranial hemorrhage and cerebral infarction resulting from arte-rial stenosis and fragile collateral vessels.Addressing antithrombotic management reveals a potential role for treatments like antiplatelet agents and anticoagulants,despite the ambiguous contribution of thrombosis to MMD-related infarctions and the critical balance between preventing ischemic events and averting hemo-rrhagic complications.Transcranial doppler has proven useful in thromboembolic detection,despite persisting challenges concerning the efficacy and safety of an-tithrombotic treatments.Furthermore,antihypertensive interventions aim to ma-nage blood pressure meticulously,especially during intracerebral hemorrhage,with recommendations and protocols varying based on the patient’s hypertension status.Additionally,lipid-lowering therapeutic strategies,particularly employing statins,are appraised for their possible beneficial role in MMD management,even as comprehensive data from disease-specific clinical trials remains elusive.Com-prehensive guidelines and protocols to navigate the multifaceted therapeutic ave-nues for MMD,while maintaining a delicate balance between efficacy and safety,warrant further meticulous research and development.This protocol manuscript seeks to elucidate the various aspects and challenges imbued in managing and navigating through the complex landscape of MMD treatment.
文摘Background: To study the influence of blood lipid levels on hemorrhagic transformation(HT) and prognosis after acute cerebral infarction(ACI).Methods: Patients with ACI within 72 h of symptoms onset between January 1 st, 2015, and December 31 st, 2016, were retrospectively analyzed. Patients were divided into group A(without HT) and group B(HT). The outcomes were assessed after 3 months of disease onset using the modified Rankin Scale(m RS). An m RS score of 0–2 points indicated excellent prognosis, and an m RS score of 3–6 points indicated poor prognosis.Results: A total of 732 patients conformed to the inclusion criteria, including 628 in group A and 104 in group B. The incidence of HT was 14.2%, and the median onset time was 2 d(interquartile range, 1–7 d). The percentages of patients with large infarct size and cortex involvement in group B were 80.8% and 79.8%, respectively, which were both significantly higher than those in group A(28.7 and 33.4%, respectively). The incidence rate of atrial fibrillation(AF) in group B was significantly higher than that in group A(39.4% vs. 13.9%, P<0.001). The adjusted multivariate analysis results showed that large infarct size, cortex involvement and AF were independent risk factors of HT, while total cholesterol(TC) was a protective factor of HT(OR=0.359, 95% CI 0.136–0.944, P=0.038). With every 1 mmol/L reduction in normal TC levels, the risk of HT increased by 64.1%. The mortality and morbidity at 3 months in group B(21.2% and 76.7%, respectively) were both significantly higher than those in group A(8.0% and 42.8%, respectively). The adjusted multivariate analysis results showed that large infarct size(OR=12.178, 95% CI 5.390–27.516, P<0.001) was an independent risk factor of long-term unfavorable outcomes, whereas low-density lipoprotein cholesterol(LDL-C) was a protective factor(OR=0.538, 95% CI 0.300–0.964, P=0.037). With every 1 mmol/L reduction in normal LDL-C levels, the risk of an unfavorable outcome increased by 46.2%. Major therapies, including intravenous recombinant human tissue plasminogen activator(r TPA), intensive lipid-lowering statins and anti-platelets, were not significantly related to either HT or long-term, post-ACI poor prognosis.Conclusions: For patients with large infarct sizes, especially those with cortex involvement, AF, or lower levels of TC, the risk of HT might increase after ACI. The risk of a long-term unfavorable outcome in these patients might increase with a reduction in LDL-C.
文摘Objective:To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats.Methods:Administration of dexamethasone was given at 10 mg/kg,sc.to the adult rats for 8 d induces hyperlipidemia characterized by marked increase in serum cholesterol and triglyceride levels along with increase in atherogenic index.Results:Lemongrass oil(100 and 200 mg/kg,po.) treatment has showed significant inhibition against dexamethasone hyperlipidemia by maintaining the serum levels of cholesterol, triglycerides and atherogenic index near to the normal levels and the antihyperlipidemic effect of the lemongross oil was comparable with atorvastatin 10 mg/kg,po.The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase(LCAT) activity.Conclusions:These results suggested that Lemon gross oil possess significant antihyperlipidemic activity.
文摘The American Diabetes Association (ADA) 2013 guidelines state that a reasonable hemoglobin A1c goal for many nonpregnant adults with diabetes is less than 7.0% a hemoglobin A1c level of less than 6.5% may be considered in adults with short duration of diabetes, long life expectancy, and no significant cardiovascular disease if this can be achieved without significant hypoglycemia or other adverse effects of treatment. A hemoglobin A1c level less than 8.0% may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced macrovascular and microvascular complications, extensive comorbidities, and long-standing diabetes in whom the hemoglobin A1c goal is difficult to attain despite multiple glucoselowering drugs including insulin. The ADA 2013 guidelines recommend that the systolic blood pressure in most diabetics with hypertension should be reduced to less than 140 mmHg. These guidelines also recommend use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in the treatment of hypertension in diabetics unless they are pregnant. Diabetics at high risk for cardiovascular events should have theirserum low-density lipoprotein (LDL) cholesterol lowered to less than 70 mg/dL with statins. Lower-risk diabetics should have their serum LDL cholesterol reduced to less than 100 mg/dL. Combination therapy of a statin with either a fibrate or niacin has not been shown to provide additional cardiovascular benefit above statin therapy alone and is not recommended. Hypertriglyceridemia should be treated with dietary and lifestyle changes. Severe hypertriglyceridemia should be treated with drug therapy to reduce the risk of acute pancreatitis.
文摘Background:To observe the inhibitory effects of Yigan Jiangzhi formula(liver-supplementing lipid-lowering formula,YGJZF)on hepatic metastasis of colorectal cancer.Methods:The hepatic metastasis BALB-c mice model of colorectal cancer was established by injecting HCT-116 cell suspension following splenectomy.Next,we randomly divided BALB-c mice into 5 groups,which were blank group,model group(tumor only),traditional Chinese medicine group(YGJZF),western medicine group(capecitabine),combined group(YGJZF and capecitabine),respectively.After 14 days treatment,the effects of different treatments were evaluated the serological indicators were evaluated,including the levels of alanine transaminase,aspartate transaminase,triglyceride,total cholesterol and vascular endothelial growth factor(VEGF)by ELISA.Results:Except the blank group,the other groups showed diffuse hepatic metastasis.Compared with the model group,the total number and weight of the metastatic tumors as well as serological indicators in medicine-given groups were sharply reduced(P<0.05 for all)the combined group had better effects.The serum levels of these indicators showed no statistical difference among each medicine-given group(P>0.05),but the combined group has a remarkable decrease of all the indicators than in western medicine group.Conclusion:YGJZF not only can inhibit the hepatic metastasis of colorectal cancer in BALB-c mice,but also affect the levels of hepatic enzymes and lipids.Meanwhile,it can reduce the expression of VEGF.All these results indicate that YGJZF,which lowers down lipids and protects hepatic functions,has the potential to block VEGF pathway,contributing to the inhibition of hepatic metastasis.
基金the funds from National Program on Key Basic Research Project of China(2015CB910304)the National Natural Science Foundation(81620108027,21632008,and 21402226,China)+1 种基金National Science&Technology Major Project Key New Drug Creation and Manufacturing Program(2018ZX09711002-012-007,China)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12040213)for financial support.
文摘Proprotein convertase subtilisin/kexin type 9(PCSK9)modulators may attenuate PCSK9-induced low-density lipoprotein receptor(LDLR)degradation in lysosome and promote the clearance of circulating low-density lipoprotein cholesterol(LDL-C).A novel series of tetrahydroprotoberberine derivatives(THPBs)were designed,synthesized,and evaluated as PCSK9 modulators for the treatment of hyperlipidemia.Among them,eight compounds exhibited excellent activities in downregulatinghepatic PCSK9 expression better than berberine in HepG2 cells.In addition,five compounds 15,18,22,(R)-22,and(S)-22 showed better performance in the low-density lipoprotein,labeled with 1,1’-dioctadecyl-3,3,3’,3’-tetramethyl-indocarbocyanine perchlorate(Dil-LDL)uptake assay,compared with berberine at the same concentration.Compound 22,selected for in vivo evaluation,demonstrated significant reductions of total cholesterol(TC)and LDL-C in hyperlipidemic hamsters with a good pharmacokinetic profile.Further exploring of the lipid-lowering mechanism showed that compound 22 promoted hepatic LDLR expression in a dose-dependent manner in HepG2 cells.Additional results of human ether-ago-go related gene(hERG)inhibition assay indicated the potential druggability for compound 22,which is a promising lead compound for the development of PCSK9 modulator for the treatment of hyperlipidemia.
基金supported by the grants from Guangdong Natural Science Foundation(No.2015A030313660)the Technology Project Foundation of Guangzhou(No.2014y2-00140/No.1563000381)the Technology Project Foundation of Guangdong Province(No.2014B020212008/No.2007B031500010)
文摘Background Statins are lipid-lowering drugs that are used widely around the world to treat and prevent cardiovascular diseases. Rare, but potentially fatal, cases of rhabdomyolysis(RM) have linked to the use of statins,especially in the presence of other risk factors. Methods We retrospectively analyzed the causes, clinical characteristics, treatments and prognosis of RM patients who were hospitalized between January 2005 and March2016 at the Guangdong General Hospital, China. A total of 16 patients were included in the study(12 males and four females, mean age 60.69 years). Amongst the patients, there were three cases of coronary heart disease, eight cases of dilated cardiomyopathy, six cases of atrial fibrillation, one case of pulmonary embolism, one case of aortic dissection, six cases of hypertension and one case of paroxysmal ventricular tachycardia. All patients had some degree of liver and kidney dysfunction, with low hemoglobin and myoglobinuria. Seven patients had a fever and four had relevant neurological signs. All patients had digestive disorders and muscle weakness or pain during their stay in hospital. All patients received renal replacement therapy and 13 were placed on a ventilator to support breathing. Nine patients were eventually improved but seven patients died despite treatment. Results All sixteen cases of RM were associated with lipid-lowering drugs, with 14 patients taking statins and two patients taking fibrates. Conclusions Statins were the main cause of RM in patients with poor prognosis and high mortality rate.
基金The work was supported by the Science and Technology Projects in Guangzhou(No.202201010484)。
文摘Codonopsis pilosula(CP),a well-known food medicine homology plant,is commonly used in many countries.In our preliminary study,a series of pyrrolidine alkaloids with high MS responses were detected as characteristic absorbed constituents in rat plasma after oral administration of CP extract.However,their structures were unclear due to the presence of various isomers and the lack of reference standards.In the present study,an MS-guided targeted isolation of pyrrolidine alkaloids of CP extract was performed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC/Q-TOF MS).For data analysis under fast data directed acquisition mode(Fast-DDA),an effective approach named characteristic fragmentation-assisted mass spectral networking was successfully applied to discover new pyrrolidine alkaloids with high MS response in CP extract.As a result,seven new pyrrolizidine alkaloids[codonopyrrolidiums C–I(3–9)],together with two known ones(1 and 2),were isolated and identified by NMR spectral analysis.Among them,codonopyrrolidium B(1),codonopyrrolidium D(4)and codonopyrrolidium E(5)were evaluated for lipid-lowering activity,and they could improve high fructose-induced lipid accumulation in HepG2 cells.In addition,the characteristic MS/MS fragmentation patterns of these pyrrolizidine alkaloids were investigated,and 17 pyrrolidine alkaloids were identified.This approach could accelerate novel natural products discovery and characterize a class of natural products with MS/MS fragmentation patterns from similar chemical scaffolds.The research also provides a chemical basis for revealing in vivo effective substances in CP.
基金supported by the National Natural Science Foundation of China(81970308)the Fund of the“Sanming”Project of Medicine in Shenzhen(SZSM201911017)+1 种基金the Shenzhen Key Medical Discipline Construction Fund(SZXK001)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2016-I2M-1-009).
文摘The outcomes of patients with myocardial infarction(MI)have substantially improved given the rapid progress that has occurred in revascularization techniques and secondary prevention,and the majority of MI patients subsequently enter a chronic stable phase.Therefore,the long-term management of patients with MI has become a core issue in daily clinical practice for cardiologists.The long-term incidence of adverse events can be further reduced using newly developed medications and therapies ranging from lipid-lowering agents(eg,proprotein convertase subtilisin/kexin type 9 inhibitors)to anti-thrombotic treatments(eg,shortened dual anti-platelet therapy).However,a considerable number of patients still experience adverse events,as some residual risk can remain despite intensive secondary prevention,such as continuously elevated cholesterol levels,chronic cardiovascular inflammation,and rapid atherosclerosis progression due to increased plaque instability.Therefore,the present review sought to summarize and discuss recent advances in several key aspects regarding the long-term management of MI patients,with the expectation of clarifying the available treatment strategies for various clinical scenarios,examining the gaps between trial evidence and clinical practice,and providing possible directions for future research.
文摘Assessment of the overall risk of atherosclerotic cardiovascular disease(ASCVD)is the first step in managing dyslipidemia and is an important reference for the target and intensity of treatment.Recently,different guidelines and consensuses on the management of this condition have successively recommended further risk stratification among patients with ASCVD,and a new“extreme risk”category has been proposed to identify patients who may obtain greater benefit from more intensive lipid-lowering therapy.The definition and terminology of extreme risk varies among different guidelines and consensuses;however,they all recommended an aggressive lipid-lowering therapeutic approach and/or a more stringent low-density lipoprotein cholesterol target for patients at extreme risk.Regardless of the definitions,this general approach may have a remarkable effect on the treatment of this condition in clinical practice.To help clinicians and patients to better understand the new strategy for the secondary prevention of ASCVD,this review provides a summary highlighting the necessity of further risk stratification among ASCVD patients,how patients at extreme risk can be identified,and the potential impact of applying the new“extreme risk”category in clinical practice.
