Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin...Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin B is characterized by an unprecedented rearranged 5/6/8 tricyclic ring system,while hymoin C represents the first rearranged PPAP with a fantastic spirocyclic 5/6/7 ring system.Their structures were established by extensive spectroscopic analysis,X-ray crystallography,and computational methods.The plausible biosynthetic routes for the compounds were also proposed.In oleic acid(OA)-induced HepG2 cells,all compounds exhibited significant lipid-lowering activity at the concentrations of 2–8μmol/L.Further mechanistic study implied that compound 1 exhibited excellent lipid-lowering activity in OA-induced HepG2 cells through inhibiting the proteins of free fatty acids synthesis and improving lipidolysis.展开更多
Background:Atherosclerotic cardiovascular disease remains the leading cause of death worldwide.This study aims to explore the impact of national volume-based procurement(NVBP)on Chinese patent medicines and provide ev...Background:Atherosclerotic cardiovascular disease remains the leading cause of death worldwide.This study aims to explore the impact of national volume-based procurement(NVBP)on Chinese patent medicines and provide evidence for improving policies and promoting rational drug use.Methods:The study was based on data from the China National Health Insurance Agency that spanned January 2019 to December 2020.Descriptive analysis was conducted using volume and expenditure as variables.Interrupted time series analysis was applied to further analyze Chinese patent medicines.Results:The unit prices of atorvastatin and rosuvastatin decreased by 25%-96%,whereas the prices of Zhibitai and Xuezhikang fluctuated slightly.The affordability is measured as the monthly expenditure on treatment divided by the daily wage.After policy implementation,the affordability of atorvastatin and rosuvastatin improved from 0.242 to 0.014 and from 0.247 to 0.019,respectively.The defined daily doses(DDDs)for atorvastatin and rosuvastatin also increased,whereas total expenditures decreased in hospitals of all levels.Both at the national level and at all levels of hospital,the policy had no significant impact on expenditures for Zhibitai and Xuezhikang and their defined daily doses.Conclusions:The NVBP saved costs in the short term by incorporating high-quality,widely used lipid-lowering drugs.Notably,the policy impacted lipid-lowering chemical drugs,whereas Chinese patent medicines remained largely unaffected.Doctors'use of Chinese patent medicines did not decline,highlighting the clinical specificity of these medicines.展开更多
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
(±)-Mycosphatide A(1a/1b),a pair of highly oxidized enantiomeric polyketides featuring a unique5/5/6/5-fused tetracyclic ring system,were isolated from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01....(±)-Mycosphatide A(1a/1b),a pair of highly oxidized enantiomeric polyketides featuring a unique5/5/6/5-fused tetracyclic ring system,were isolated from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01.Their structures were established by extensive spectroscopic analyses,single crystal Xray diffraction,and experimental electronic circular dichroism(ECD)spectra comparison.The plausible biosynthetic pathway of 1 was proposed,which involved the generation of a key spiro[4.5]decane scaffold.Compounds(+)-1a and(-)-1b exhibited significant lipid-lowering activity in 3T3-L1 adipocytes model,with EC50values of 7.85±1.56 and 8.87±0.80μmol/L,respectively.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
Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus(DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined...Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus(DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined in the last decades, its prevalence increased and is expected to rise further as a result of the increasing incidence of type 2 DM(T2DM) and the longer life expectancy of patients with DM. The pathogenesis of diabetic retinopathy is multifactorial. Some observational studies suggested an association between dyslipidemia and the development and progression of retinopathy in patients with DM but others did not confirm this association. Regarding lipid-lowering agents, studies that evaluated the role of statins in the management of these patients are mostly small and yielded discrepant results. Large randomized studies with statins in patients with T2DM showed no benefit of these agents on diabetic retinopathy but were not designed to address this effect. In contrast, both preclinical data and two large randomized controlled studies, the FIELD and the ACCORD trial, showed that fenofibrate delays the progression of diabetic retinopathy. Even though the mechanisms underpinning this favorable effect are not entirely clear, these findings suggest that fenofibrate might represent a useful tool for the management of diabetic retinopathy.展开更多
AIM：To clarify this controversy and to provide evidence for application of lipid lowering agents in treatment of diabetic retinopathy（DR）.METHODS：We searched the databases of Pub Med,Embase and Cochrane Library Ce...AIM：To clarify this controversy and to provide evidence for application of lipid lowering agents in treatment of diabetic retinopathy（DR）.METHODS：We searched the databases of Pub Med,Embase and Cochrane Library Central Register of Controlled Trials（CENTRAL）and abstracts from main annual meetings up to January 1,2017.Google scholar and Clinical Trials.gov were also searched for unpublished relevant studies.We included randomized controlled trials（RCTs）that studied lipid-lowering agents in type 1 or type 2 diabetes in this Meta-analysis.The primary endpoint was the progression of DR,and the secondary endpoints included vision loss,development of diabetic macular edema（DME）and aggravation of hard exudates.The pooled odds ratios（OR）with corresponding 95%confidence intervals（95%CIs）were calculated.RESULTS：After systemic and manual literature search by two independent investigators,we included 8 RCTs from 7 published articles with 13 454 participants in this Meta-analysis.The results revealed that lipid-lowering drugs were associated with reduced risk in DR progression[OR=0.77（95%CI：0.62,0.96）,P=0.02].Lipid-lowering agents might have protective effect on DME compared to placebo,although the difference was not statistically significant[OR=0.60（95%CI：0.34,1.08）,P=0.09].However,no significant differences in the worsening of vision acuity[OR=0.96（95%CI：0.81,1.14）,P=0.64]and hard exudates[OR=0.50（95%CI：0.15,1.74）,P=0.28]were found between the lipidlowering drugs and the placebo groups.CONCLUSION：In DR patients,lipid-lowering agents show a protective effect on DR progression and might be associated with reduced risk in the development of DME.However,lipid-lowering agents have no effects on vision loss and hard exudates aggravation.Further clinical trials in larger scale are required to confirm the conclusion of this study and thus justify the use of intensive control lipids with anti-lipid agents at the early stages of DR.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
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
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
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
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
Objective:To investigate the impact of early initiation of intensive lipid-lowering therapy on the postoperative efficacy and inflammatory factors in patients with acute coronary syndrome(ACS)undergoing percutaneous c...Objective:To investigate the impact of early initiation of intensive lipid-lowering therapy on the postoperative efficacy and inflammatory factors in patients with acute coronary syndrome(ACS)undergoing percutaneous coronary intervention(PCI).Methods:A total of 100 ACS patients undergoing PCI admitted to our hospital were selected as the study subjects.They were randomly divided into a control group(treated with statin combined with ezetimibe,n=41),a study group 1(initiated with statin combined with PCSK9 inhibitor immediately after surgery,n=32),and a study group 2(routinely administered oral statin and initiated with combined PCSK9 inhibitor before discharge,n=27).The therapeutic efficacy,inflammatory factor levels,and incidence of adverse events were compared and analyzed among the three groups.Results:The therapeutic regimen in study group 1 demonstrated the optimal efficacy and impact on inflammatory factors,followed by study group 2,while the control group showed relatively weaker efficacy,with statistically significant differences(p<0.05).The overall incidence of adverse reactions was 30.00%in the control group,5.00%in study group 1,and 10.00%in study group 2,with statistically significant differences among the groups(p<0.05),with the lowest incidence observed in study group 1.Conclusion:Early intensive lipid-lowering therapy can effectively improve lipid metabolism,suppress inflammatory responses,and reduce cardiovascular events in ACS patients after PCI,suggesting its pleiotropic cardiovascular protective effects.展开更多
Cardiovascular diseases(CVDs)are a major threat to public health globally.A large proportion of people with dyslipidaemia have poorly controlled lipid levels,emphasizing the need for alternative lipid-lowering treatme...Cardiovascular diseases(CVDs)are a major threat to public health globally.A large proportion of people with dyslipidaemia have poorly controlled lipid levels,emphasizing the need for alternative lipid-lowering treatments that are both effective and safe.Xuezhikang,a red yeast rice(RYR)extract,containing 13 kinds of monacolins and other bioactive components,emerges as one such promising option.Its discovery was built on a long history of RYR use as a functional food supplement and traditional Chinese medicine.Several randomized,controlled clinical trials have substantiated its lipid-lowering effects and its potential to protect against CVDs.Safety concerns with statins did not arise during decades of experience with Xuezhikang treatment in clinical practice.The approval of Xuezhikang in multiple regions of Asia marked a conceptual shift in CVD management,moving from single agents to polypills and from synthetic medicines to natural extracts.This review comprehensively addresses important topics related to this medicinal natural extract,including the ancient utilization of RYR,the development of Xuezhikang,its mechanisms of action,pleiotropic effects,clinical studies,challenges,and future perspectives to enhance our understanding regarding the role of Xuezhikang,a representative,domestic lipid-lowering drug of RYR,in prevention and treatment of CVD.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
A pair of coumarin-based polycyclic meroterpenoid enantiomers(+)/(-)-gerbeloid A[(+)-1a and(-)-1b]were isolated from the medicinal plant Gerbera piloselloides,which have a unique caged oxatricyclo[4.2.2.0^(3,8)]decene...A pair of coumarin-based polycyclic meroterpenoid enantiomers(+)/(-)-gerbeloid A[(+)-1a and(-)-1b]were isolated from the medicinal plant Gerbera piloselloides,which have a unique caged oxatricyclo[4.2.2.0^(3,8)]decene scaffold.Their planar and three-dimensional structures were exhaustively characterized by comprehensive spectroscopic data and X-ray diffraction analysis.Guided by the hypothetical biosynthetic pathway,the biomimetic synthesis of racemic 1 was achieved using 4-hydroxy-5-methylcoumarin and citral as the starting material via oxa-6πelectrocyclization and intramolecular[2+2]photocycloaddition.Subsequently,the results of the biological activity assay demonstrated that both(+)-1a and(-)-1b exhibited potent lipid-lowering effects in 3T3-L1 adipocytes and the high-fat diet zebrafish model.Notably,the lipid-lowering activity of(+)-1a is better than that of(-)-1b at the same concentration,and molecular mechanism study has shown that(+)-1a and(-)-1b impairs adipocyte differentiation and stimulate lipolysis by regulating C/EBPα/PPARγsignaling and Perilipin signaling in vitro and in vivo.Our findings provide a promising drug model molecule for the treatment of obesity.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
This study aimed to provide a comprehensive overview of the pigment and non-pigment phenolic profile of polyphenol extracts of jujube peel and their bioactivities.Firstly,the pigment and non-pigment phenolic compositi...This study aimed to provide a comprehensive overview of the pigment and non-pigment phenolic profile of polyphenol extracts of jujube peel and their bioactivities.Firstly,the pigment and non-pigment phenolic composition as well as antioxidant activities of free and bound polyphenol extracts in jujube peel were compared among twelve varieties systematically.Then the antioxidant and lipid-lowering activities of free and bound polyphenol extracts of‘Junzao’jujube peel were investigated representatively.Overall,23 phenolic compounds were identified,in which flavonols were the main pigments and all varieties showed similar qualitative patterns but different quantitative characteristics.The antioxidant activities significantly correlated with the content of total phenolics and total flavonoids.Furtherly,both free and bound polyphenol extracts of‘Junzao’jujube peel exhibited DPPH,ABTS free radical scavenging capacity,and oxygen radical absorbance capacity in a dose-dependent manner.Besides,both of them improved the resistance of Caenorhabditis elegans under H_(2)O_(2) oxidative stress and heat stress at 37℃(20-100μg/mL).What’s more,compared to free polyphenol extract,bound polyphenol extract decreased the level of body lipid accumulation and triglyceride more effectively.These results suggest that jujube peel is an exploitable source of natural flavonoid pigments and phenolic ingredients with strong antioxidant and lipid-lowering properties.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
Peripheral artery disease(PAD)is a common condition characterized by atherosclerosis in the peripheral arteries,associated with concomitant coronary and cerebrovascular diseases.Proprotein convertase subtilisin/kexin ...Peripheral artery disease(PAD)is a common condition characterized by atherosclerosis in the peripheral arteries,associated with concomitant coronary and cerebrovascular diseases.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors are a class of drugs that have shown potential in hypercholesterolemic patients.This review focuses on the efficacy,safety,and clinical outcomes of PCSK9 inhibitors in PAD based on the literature indexed by PubMed.Trials such as FOURIER and ODYSSEY demonstrate the efficacy of evolocumab and alirocumab in reducing cardiovascular events,offering a potential treatment option for PAD patients.Safety evaluations from trials show few adverse events,most of which are injection-site reactions,indicating the overall safety profile of PCSK9 inhibitors.Clinical outcomes show a reduction in cardiovascular events,ischemic strokes,and major adverse limb events.However,despite these positive findings,PCSK9 inhibitors are still underutilized in clinical practice,possibly due to a lack of awareness among care providers and cost concerns.Further research is needed to establish the long-term effects and cost-effectiveness of PCSK9 inhibitors in PAD patients.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.32270413,82060631,82160808,and 82360035)the Science and Technology Department of Guizhou Province(Nos.QKHJC 2020–1Z076,QKHJC-ZK[2023]YB156,QKHJC-ZK[2021]YB569,and QKHPTRC[2020]5008)+4 种基金Excellent Young Talents Plan of Guizhou Medical University(2023,No.106)the 13thbatch of outstanding young scientific and technological talents in Guizhou Province(No.QKHPTRC[2021]5633)Guizhou Science and Technology Innovation Talent Team(No.QKHPTRC–CXTD[2022]007)High-level Innovative Talents in Guizhou Province(Thousand Levels of Talent for Chunmao Yuan in 2018)the project of State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University(Nos.FAMP202102K and QJJ[2023]113)。
文摘Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin B is characterized by an unprecedented rearranged 5/6/8 tricyclic ring system,while hymoin C represents the first rearranged PPAP with a fantastic spirocyclic 5/6/7 ring system.Their structures were established by extensive spectroscopic analysis,X-ray crystallography,and computational methods.The plausible biosynthetic routes for the compounds were also proposed.In oleic acid(OA)-induced HepG2 cells,all compounds exhibited significant lipid-lowering activity at the concentrations of 2–8μmol/L.Further mechanistic study implied that compound 1 exhibited excellent lipid-lowering activity in OA-induced HepG2 cells through inhibiting the proteins of free fatty acids synthesis and improving lipidolysis.
基金funded by the Beijing Natural Science Foundation(grant number 9232010)Capital's Funds for Health Improvement and Research(grant number 2022-2-4079).
文摘Background:Atherosclerotic cardiovascular disease remains the leading cause of death worldwide.This study aims to explore the impact of national volume-based procurement(NVBP)on Chinese patent medicines and provide evidence for improving policies and promoting rational drug use.Methods:The study was based on data from the China National Health Insurance Agency that spanned January 2019 to December 2020.Descriptive analysis was conducted using volume and expenditure as variables.Interrupted time series analysis was applied to further analyze Chinese patent medicines.Results:The unit prices of atorvastatin and rosuvastatin decreased by 25%-96%,whereas the prices of Zhibitai and Xuezhikang fluctuated slightly.The affordability is measured as the monthly expenditure on treatment divided by the daily wage.After policy implementation,the affordability of atorvastatin and rosuvastatin improved from 0.242 to 0.014 and from 0.247 to 0.019,respectively.The defined daily doses(DDDs)for atorvastatin and rosuvastatin also increased,whereas total expenditures decreased in hospitals of all levels.Both at the national level and at all levels of hospital,the policy had no significant impact on expenditures for Zhibitai and Xuezhikang and their defined daily doses.Conclusions:The NVBP saved costs in the short term by incorporating high-quality,widely used lipid-lowering drugs.Notably,the policy impacted lipid-lowering chemical drugs,whereas Chinese patent medicines remained largely unaffected.Doctors'use of Chinese patent medicines did not decline,highlighting the clinical specificity of these medicines.
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National Natural Science Foundation of China(Nos.U20A2001,81973195,21877133)the Guangdong Marine Economy Development Special Project(Nos.GDNRC[2022]35,GDNRC[2023]39)。
文摘(±)-Mycosphatide A(1a/1b),a pair of highly oxidized enantiomeric polyketides featuring a unique5/5/6/5-fused tetracyclic ring system,were isolated from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01.Their structures were established by extensive spectroscopic analyses,single crystal Xray diffraction,and experimental electronic circular dichroism(ECD)spectra comparison.The plausible biosynthetic pathway of 1 was proposed,which involved the generation of a key spiro[4.5]decane scaffold.Compounds(+)-1a and(-)-1b exhibited significant lipid-lowering activity in 3T3-L1 adipocytes model,with EC50values of 7.85±1.56 and 8.87±0.80μmol/L,respectively.
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Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus(DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined in the last decades, its prevalence increased and is expected to rise further as a result of the increasing incidence of type 2 DM(T2DM) and the longer life expectancy of patients with DM. The pathogenesis of diabetic retinopathy is multifactorial. Some observational studies suggested an association between dyslipidemia and the development and progression of retinopathy in patients with DM but others did not confirm this association. Regarding lipid-lowering agents, studies that evaluated the role of statins in the management of these patients are mostly small and yielded discrepant results. Large randomized studies with statins in patients with T2DM showed no benefit of these agents on diabetic retinopathy but were not designed to address this effect. In contrast, both preclinical data and two large randomized controlled studies, the FIELD and the ACCORD trial, showed that fenofibrate delays the progression of diabetic retinopathy. Even though the mechanisms underpinning this favorable effect are not entirely clear, these findings suggest that fenofibrate might represent a useful tool for the management of diabetic retinopathy.
基金Supported by the National Natural Science Foundation of China(No.81500726)Science&Technology project for Social development of Shaanxi Province in China(No.2017SF-249)
文摘AIM：To clarify this controversy and to provide evidence for application of lipid lowering agents in treatment of diabetic retinopathy（DR）.METHODS：We searched the databases of Pub Med,Embase and Cochrane Library Central Register of Controlled Trials（CENTRAL）and abstracts from main annual meetings up to January 1,2017.Google scholar and Clinical Trials.gov were also searched for unpublished relevant studies.We included randomized controlled trials（RCTs）that studied lipid-lowering agents in type 1 or type 2 diabetes in this Meta-analysis.The primary endpoint was the progression of DR,and the secondary endpoints included vision loss,development of diabetic macular edema（DME）and aggravation of hard exudates.The pooled odds ratios（OR）with corresponding 95%confidence intervals（95%CIs）were calculated.RESULTS：After systemic and manual literature search by two independent investigators,we included 8 RCTs from 7 published articles with 13 454 participants in this Meta-analysis.The results revealed that lipid-lowering drugs were associated with reduced risk in DR progression[OR=0.77（95%CI：0.62,0.96）,P=0.02].Lipid-lowering agents might have protective effect on DME compared to placebo,although the difference was not statistically significant[OR=0.60（95%CI：0.34,1.08）,P=0.09].However,no significant differences in the worsening of vision acuity[OR=0.96（95%CI：0.81,1.14）,P=0.64]and hard exudates[OR=0.50（95%CI：0.15,1.74）,P=0.28]were found between the lipidlowering drugs and the placebo groups.CONCLUSION：In DR patients,lipid-lowering agents show a protective effect on DR progression and might be associated with reduced risk in the development of DME.However,lipid-lowering agents have no effects on vision loss and hard exudates aggravation.Further clinical trials in larger scale are required to confirm the conclusion of this study and thus justify the use of intensive control lipids with anti-lipid agents at the early stages of DR.
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.
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).
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Objective:To investigate the impact of early initiation of intensive lipid-lowering therapy on the postoperative efficacy and inflammatory factors in patients with acute coronary syndrome(ACS)undergoing percutaneous coronary intervention(PCI).Methods:A total of 100 ACS patients undergoing PCI admitted to our hospital were selected as the study subjects.They were randomly divided into a control group(treated with statin combined with ezetimibe,n=41),a study group 1(initiated with statin combined with PCSK9 inhibitor immediately after surgery,n=32),and a study group 2(routinely administered oral statin and initiated with combined PCSK9 inhibitor before discharge,n=27).The therapeutic efficacy,inflammatory factor levels,and incidence of adverse events were compared and analyzed among the three groups.Results:The therapeutic regimen in study group 1 demonstrated the optimal efficacy and impact on inflammatory factors,followed by study group 2,while the control group showed relatively weaker efficacy,with statistically significant differences(p<0.05).The overall incidence of adverse reactions was 30.00%in the control group,5.00%in study group 1,and 10.00%in study group 2,with statistically significant differences among the groups(p<0.05),with the lowest incidence observed in study group 1.Conclusion:Early intensive lipid-lowering therapy can effectively improve lipid metabolism,suppress inflammatory responses,and reduce cardiovascular events in ACS patients after PCI,suggesting its pleiotropic cardiovascular protective effects.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-12M-C&T-B-043,China).
文摘Cardiovascular diseases(CVDs)are a major threat to public health globally.A large proportion of people with dyslipidaemia have poorly controlled lipid levels,emphasizing the need for alternative lipid-lowering treatments that are both effective and safe.Xuezhikang,a red yeast rice(RYR)extract,containing 13 kinds of monacolins and other bioactive components,emerges as one such promising option.Its discovery was built on a long history of RYR use as a functional food supplement and traditional Chinese medicine.Several randomized,controlled clinical trials have substantiated its lipid-lowering effects and its potential to protect against CVDs.Safety concerns with statins did not arise during decades of experience with Xuezhikang treatment in clinical practice.The approval of Xuezhikang in multiple regions of Asia marked a conceptual shift in CVD management,moving from single agents to polypills and from synthetic medicines to natural extracts.This review comprehensively addresses important topics related to this medicinal natural extract,including the ancient utilization of RYR,the development of Xuezhikang,its mechanisms of action,pleiotropic effects,clinical studies,challenges,and future perspectives to enhance our understanding regarding the role of Xuezhikang,a representative,domestic lipid-lowering drug of RYR,in prevention and treatment of CVD.
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 Natural Sciences Foundation of China(82374035)the CAMS Innovation Fund for Medical Sciences(CIFMS,2022-I2M-1-017,China).
文摘A pair of coumarin-based polycyclic meroterpenoid enantiomers(+)/(-)-gerbeloid A[(+)-1a and(-)-1b]were isolated from the medicinal plant Gerbera piloselloides,which have a unique caged oxatricyclo[4.2.2.0^(3,8)]decene scaffold.Their planar and three-dimensional structures were exhaustively characterized by comprehensive spectroscopic data and X-ray diffraction analysis.Guided by the hypothetical biosynthetic pathway,the biomimetic synthesis of racemic 1 was achieved using 4-hydroxy-5-methylcoumarin and citral as the starting material via oxa-6πelectrocyclization and intramolecular[2+2]photocycloaddition.Subsequently,the results of the biological activity assay demonstrated that both(+)-1a and(-)-1b exhibited potent lipid-lowering effects in 3T3-L1 adipocytes and the high-fat diet zebrafish model.Notably,the lipid-lowering activity of(+)-1a is better than that of(-)-1b at the same concentration,and molecular mechanism study has shown that(+)-1a and(-)-1b impairs adipocyte differentiation and stimulate lipolysis by regulating C/EBPα/PPARγsignaling and Perilipin signaling in vitro and in vivo.Our findings provide a promising drug model molecule for the treatment of obesity.
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This work was supported by the National Key R&D Program of China(2019YFD1002300)the North Jiangsu Science and Technology Project(XZ-SZ201929).
文摘This study aimed to provide a comprehensive overview of the pigment and non-pigment phenolic profile of polyphenol extracts of jujube peel and their bioactivities.Firstly,the pigment and non-pigment phenolic composition as well as antioxidant activities of free and bound polyphenol extracts in jujube peel were compared among twelve varieties systematically.Then the antioxidant and lipid-lowering activities of free and bound polyphenol extracts of‘Junzao’jujube peel were investigated representatively.Overall,23 phenolic compounds were identified,in which flavonols were the main pigments and all varieties showed similar qualitative patterns but different quantitative characteristics.The antioxidant activities significantly correlated with the content of total phenolics and total flavonoids.Furtherly,both free and bound polyphenol extracts of‘Junzao’jujube peel exhibited DPPH,ABTS free radical scavenging capacity,and oxygen radical absorbance capacity in a dose-dependent manner.Besides,both of them improved the resistance of Caenorhabditis elegans under H_(2)O_(2) oxidative stress and heat stress at 37℃(20-100μg/mL).What’s more,compared to free polyphenol extract,bound polyphenol extract decreased the level of body lipid accumulation and triglyceride more effectively.These results suggest that jujube peel is an exploitable source of natural flavonoid pigments and phenolic ingredients with strong antioxidant and lipid-lowering properties.
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Peripheral artery disease(PAD)is a common condition characterized by atherosclerosis in the peripheral arteries,associated with concomitant coronary and cerebrovascular diseases.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors are a class of drugs that have shown potential in hypercholesterolemic patients.This review focuses on the efficacy,safety,and clinical outcomes of PCSK9 inhibitors in PAD based on the literature indexed by PubMed.Trials such as FOURIER and ODYSSEY demonstrate the efficacy of evolocumab and alirocumab in reducing cardiovascular events,offering a potential treatment option for PAD patients.Safety evaluations from trials show few adverse events,most of which are injection-site reactions,indicating the overall safety profile of PCSK9 inhibitors.Clinical outcomes show a reduction in cardiovascular events,ischemic strokes,and major adverse limb events.However,despite these positive findings,PCSK9 inhibitors are still underutilized in clinical practice,possibly due to a lack of awareness among care providers and cost concerns.Further research is needed to establish the long-term effects and cost-effectiveness of PCSK9 inhibitors in PAD patients.
