Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&E.H.Wilson in C.S.Sargent,and it in traditional Chinese medicine has been known for promoting blood circulation and removing ...Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&E.H.Wilson in C.S.Sargent,and it in traditional Chinese medicine has been known for promoting blood circulation and removing blood stasis as recorded in the ancient book“Illustrated Classics of Materia Medica”.It has been used effectively to treat blood stasis too in modern clinical practice.However,the anti-hyperlipidemia effect of SC is not fully understood.This paper aims at exploring the use of SC stems to improve the balance of blood lipids in the body,and its new role in treating hyperlipidemia.Methods:The effects of SC extract on hyperlipidemia were explored by combining lipidomics and gut microbiota.Secondly,we explored the potential mechanism of SC in treating hyperlipidemia by pathway analysis.Results:The results showed that the stem extract of SC could restore the physiological and biochemical indices of hyperlipidemia in mice,as well as repair the morphological and structural damage to tissues.Compared to the Model group,the SC extract significantly reduced the liver index,epididymal fat index,and Lee’s index.It also significantly decreased serum levels of total cholesterol,triglycerides,low-density lipoprotein cholesterol,peroxisome proliferator-activated receptor gamma(PPAR-γ),D-lactate,and free fatty acids,while significantly increasing the relative content of peroxisome proliferator-activated receptor alpha(PPAR-α).These changes were statistically significant.Non-targeted lipidomics,based on LC-MS,were utilized to investigate the lipid metabolism characteristics in serum,liver,and epididymal fat of the subjects.It was observed that,compared to the blank group,the Model group exhibited significant changes primarily in glycerol lipids and glycerophospholipids.The treatment group also displayed alterations in these lipids.A total of 38,81,and 27 differential lipids were identified in serum,liver,and epididymal fat samples,respectively.Among these,14 common differential lipids were found in both serum and liver samples,and their KEGG enrichment pathways were largely consistent.Among them,the sphingolipid signaling pathway and the glycerophospholipid metabolic pathway were identified as key metabolic pathways that were regulated.Our gut microbiota analysis revealed that SC diminishes the abundance of Actinobacteria by altering the cecal flora in mice.Conclusion:This alteration leads to the downregulation of genes involved in triglyceride metabolism,which in turn changes lipid processing and reduces triglyceride levels.Consequently,SC effectively combats hyperlipidemia.Notably,SC impacts key metabolic pathways,including the sphingolipid signaling and glycerophospholipid metabolism.These findings underscore SC’s therapeutic potential,positioning it as a promising alternative for reducing the health risks associated with hyperlipidemia.展开更多
Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrat...Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrate fucoxanthin efficacy in modulating lipid metabolism in serum and liver of high-fat-induced hyperlipidemia mice,as well as investigate the underlying association with gut microbiota changes.Results showed that fucoxanthin significantly reduced body weight gain and body white fat of the mice.In the serum,total triglycerides(TG),total cholesterol(TC)contents were significantly decreased and high-densitylipoprotein cholesterol levels was significantly upregulated.Moreover,fucoxanthin remarkedly prevented lipid accumulation in the liver.Especially,metabolomics results showed that lipids and lipid-like molecules were significantly downregulated compared with the control,indicating the advance of hepatic lipid metabolism.Bile acids profile in the liver was also greatly changed by fucoxanthin.Meanwhile,fucoxanthin remodeled gut microbiota composition and promoted the relative abundance of Desulfovibrio,Blautia and Clostridia genera.Finally,correlation analysis revealed that these gut microbiota changes were closely related with hepatic metabolites/metabolism and serum lipids.Altogether,this study showed great potential of fucoxanthin in improving serum lipids profile,hepatic lipids and bile acids metabolism of hyperlipidemia mice,which was associated with gut microbiota alteration.展开更多
The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used ...The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used to screen the polyphenols present in sea buckthorn,and then the SwissTargetPrediction and Uniprot databases were used to obtain the potential targets of sea buckthorn polyphenols,which were supplemented by the literature.In total,7 polyphenols and 154 potential targets were obtained.Through GeneCards,OMIM database,1358 hyperlipidemia-related targets were collected.We found that there were 101 targets at the intersection of components and diseases.Through GO and KEGG enrichment analysis,27 core targets were obtained,which were AKT1,TNF,TP53,IL-6,etc.in order of degree value.174 pathways were obtained from KEGG enrichment analysis,including AGE-RAGE signaling pathway in diabetic complications,fl uid shear stress and atherosclerosis,lipid and atherosclerosis,etc.The molecular docking of the main components to the targets was performed using OpenBabelGUI,AutoDockTools-1.5.6 software.Finally,the results were visualized using Cytoscape 3.9.1 software.The molecular docking results showed that sea buckthorn polyphenols have good binding ability with the key targets.Among them,such as quercetin and kaempferol,have good binding ability with TNF,TP53 and IL-6.For example,TNF binds to quercetin with a binding energy of-5.34 kcal/mol and to kaempferol with a binding energy of-6.22 kcal/mol;TP53 binds to kaempferol with a binding energy of-5.32 kcal/mol;IL-6 binds to quercetin with a binding energy of-5.62 kcal/mol,etc.Therefore,the network pharmacology study showed that the treatment of hyperlipidemia by sea buckthorn polyphenols can be realized by multi-component-multi-target-multi-pathway together,which provides some reference for the later study of sea buckthorn polyphenols in the treatment of hyperlipidemia.展开更多
Objective:To explore the mechanism of action of Zangjiangzhi capsule(ZJZC)in treating hyperlipidemia(HLP).Methods:The components of ZJZC were analyzed and identified using ultra-high performance liquid chromatography ...Objective:To explore the mechanism of action of Zangjiangzhi capsule(ZJZC)in treating hyperlipidemia(HLP).Methods:The components of ZJZC were analyzed and identified using ultra-high performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry(UHPLC-Q-Exactive-Orbitrap-MS/MS).Network pharmacology analysis was used to explore the mechanism of action of ZJZC in HLP treatment.The SwissTargetPrediction database was used to predict compound targets,and GeneCards,DisGeNet,OMIM,and DRUGBANK databases were used to identify HLP-related targets.Proteineprotein interaction diagrams were constructed using the STRING database.The targets were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.The“herbingredient-target”network was visualized using Cytoscape.Preliminary validation was performed using molecular docking and enzyme-linked immunosorbent assay.Results:Ninety compounds were identified in ZJZC,including 34 flavonoids,12 phenols,10 terpenoids,10 alkaloids,8 organic acids,8 anthraquinones,and 9 other compounds.In total,904 targets were identified for these compounds.Among them,158 targets intersected with the HLP target network.Network pharmacology analysis showed that MAPK1,PPAR-a,RXRA,HSP90AA1,PIK3R1,AKT1,PIK3CA,IL6,TNF,and ESR1 are the key targets of action.KEGG enrichment analysis identified 164 pathways.Among these,the AGE-RAGE signaling pathway in diabetic complications,lipid and atherosclerosis pathways,regulation of lipids in adipocytes,and insulin resistance are related to HLP.Molecular docking showed good affinity between the key targets and ingredients.Further,ZJZC treatment in mice resulted in lower expression of MAPK1 protein and increased expression of PPAR-a protein,which have been shown to be strongly associated with HLP.Conclusions:This study showed that ZJZC contains various active ingredients and can modulate multiple targets and pathways associated with HLP,providing evidence at the molecular level for its clinical application in the treatment of HLP.展开更多
Low-density lipoprotein cholesterol(LDL-C)is the most causal risk factor for atherosclerotic cardiovascular disease(ASCVD).Red yeast rice(RYR)is a nutraceutical widely used as a lipid-lowering dietary supplement.The m...Low-density lipoprotein cholesterol(LDL-C)is the most causal risk factor for atherosclerotic cardiovascular disease(ASCVD).Red yeast rice(RYR)is a nutraceutical widely used as a lipid-lowering dietary supplement.The main cholesterol-lower agents in RYR are monacolins,particularly monacolin K,a weak reversible inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase,whose daily consumption(up to 10 mg/day)reduces LDL-C plasma levels up to 34%within 6-8 weeks when compared to placebo.The reduction in LDL-C is often accompanied by lower levels of plasma apolipoprotein B,total cholesterol,matrix metalloproteinases 2 and 9,high-sensitivity C-reactive protein,non-high-density lipoprotein cholesterol,and blood pressure.RYR has also demonstrated favorable reductions of up to 45%compared to placebo in the risk of ASCVD events in secondary prevention studies.The mechanism of action is similar to statins.When consumed appropriately,RYR is associated with only minimal side effects.Mild myalgia may be seen in patients who cannot tolerate low-dose statins.In individuals with no additional ASCVD risk factors,RYR is a safe and effective supplement in treating mild to moderate hyperlipidemia.展开更多
Hyperlipidemia constitutes a critical factor in the pathogenesis of vascular disease and gut microbiota dysbiosis.This study aims to investigate the role of sea buckthorn fruit oil(SBFO)in ameliorating hyperlipidemia,...Hyperlipidemia constitutes a critical factor in the pathogenesis of vascular disease and gut microbiota dysbiosis.This study aims to investigate the role of sea buckthorn fruit oil(SBFO)in ameliorating hyperlipidemia,modulating gut microbiota,and elucidating the underlying mechanisms of its lipid-lowering effects.SBFO intervention in hyperlipidemic mice significantly reduced body weight and visceral adiposity index while mitigating symptoms associated with hyperlipidemia,including dyslipidemia,infla mmation,liver damage,and endothelial dysfunction.Real-time quantitative PCR and Western blot analyses revealed that SBFO enhanced the response of free fatty acid oxidation and breakdown(adenosine 5'-monophosphateactivated protein kinaseα,carnitine palmitoyltransferase1a,peroxisome proliferator-activated receptorα,and peroxisome proliferator-activated receptorγ)while suppressing the synthesis of triglycerides and fatty acids(sterol-regulatory element binding protein 1,fatty acid synthase,and acetyl CoA carboxylase)at the gene and protein expression levels.Moreover,SBFO intervention enriched the gut microbiota of hyperlipidemic mice by increasing the relative abundances of Lactobacillus,Faecalibaculum,and Allobaculum,while decreasing the Firmicutes/Bacteroidetes ratio.These findings suggest that SBFO exhibits promising therapeutic potential in attenuating hyperlipidemia in mice through the regulation of lipid metabolism and modulation of gut microbiota.展开更多
Objective Recaticimab(SHR-1209)significantly reduces low-density lipoprotein cholesterol levels.However,its effect on glucose metabolism remains unclear.This study aimed to evaluate its effect on glycemic parameters i...Objective Recaticimab(SHR-1209)significantly reduces low-density lipoprotein cholesterol levels.However,its effect on glucose metabolism remains unclear.This study aimed to evaluate its effect on glycemic parameters in a Chinese population.Methods Recaticimab versus placebo was administered in a 5:1 ratio to 110 hyperlipidemia patients who were followed up for 24 weeks.Glycated hemoglobin(HbA1c)levels were measured at baseline every 12 weeks.Fasting plasma glucose(FPG)levels were measured at baseline at week 1,3,5,8,12,16,20,and 24.Repeated-measures mixed-effects models were used to determine the longitudinal association between reacticimab and FPG and HbA1c levels.Results Among the 81 participants with normal glucose metabolism,HbA1c levels significantly decreased(F=4.568,P=0.036).In the 29 participants with abnormal glucose metabolism,a significant time effect was observed for FPG levels(F=2.492,P=0.016).For participants with normal and abnormal glucose metabolism,no significant group×time interaction effects on FPG or HbA1c levels were identified.Conclusion Recaticimab showed no adverse glycemic effects in participants with normal or abnormal glucose metabolism,indicating its safety in patients with or without diabetes.展开更多
BACKGROUND Alagille syndrome is a rare autosomal dominant genetic disorder involving multiple organ systems.Its most common manifestations are chronic cholestasis caused by intrahepatic bile duct deficiency and severe...BACKGROUND Alagille syndrome is a rare autosomal dominant genetic disorder involving multiple organ systems.Its most common manifestations are chronic cholestasis caused by intrahepatic bile duct deficiency and severe hypercholesterolemia as a result of impaired cholesterol metabolism.This report describes a patient with Alagille syndrome in whom a JAG1 mutation was detected by whole-exome sequencing.CASE SUMMARY The patient presented with severe hypercholesterolemia,biliary and hepatic impairment,pruritus,and triangular facial features.Mutations in the JAG1 gene,which encodes the Notch signaling pathway,were detected by whole-exome sequencing,leading to a diagnosis of Alagille syndrome.The patient was treated using a combination of traditional Chinese and Western medicines.Her cholesterol levels,liver function,and pruritus subsequently improved.CONCLUSION The possibility of Alagille syndrome should be considered in children who present with abnormal liver function and severe hypercholesterolemia.Genetic testing is needed to screen for disease-causing mutations and the disease can be treated with Traditional Chinese medicine.展开更多
The gut microbiota and it’s metabolism are vital targets of probiotics regulating high fat-diet(HFD)induced hyperlipidemia,which can relieve the pressure caused by the striking growth of sub-health people.Pediococcus...The gut microbiota and it’s metabolism are vital targets of probiotics regulating high fat-diet(HFD)induced hyperlipidemia,which can relieve the pressure caused by the striking growth of sub-health people.Pediococcus pentosaceus PP04(PP04)could colonize in intestine to regulate gut microbiota and it’s metabolites directly,the rebalanced intestinal flora mediated by PP04 could facilitate the secretion of short chain fatty acids to control body weight gain,PP04 intervention also changed bile acid(BA)profiles and enhanced the ileal concentrations of antagonists including tauro-α/β-muricholic acid sodium salt and ursodeoxycholic acid to inhibit intestinal farnesoid X receptor/fibroblast growth factor 15(FXR/FGF15)signaling coupled with the activation of hepatic FXR/small heterodimer partners signaling,which accelerated the hepatic BA de novo synthesis and excretion with feces to eliminate HFD caused hyperlipemia effectively.This study provided important evidence regarding PP04 as dietary supplement to relieve hyperlipidemia by influencing BA enterohepatic circulation.展开更多
Hyperlipidemia is a major risk factor for erectile dysfunction(ED).Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells(CcSMCs)are the key pathological factors of ED.N-acetylcysteine(NAC...Hyperlipidemia is a major risk factor for erectile dysfunction(ED).Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells(CcSMCs)are the key pathological factors of ED.N-acetylcysteine(NAC)can inhibit oxidative stress;however,whether NAc can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear.A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley(SD)rats fed a high-fat and high-cholesterol diet(hyperlipidemic rats,HR).In addition,9 male SD rats were fed a normal diet to serve as controls(NC).HR rats were divided into three groups:HR,HR+normal saline(NS),and HR+NAC(n=9 for each group;NS or NAc intraperitoneal injections were administered daily for 16 weeks).Subsequently,the lipid profiles,erectile function,oxidative stress,phenotypic modulation markers of ccsMCs,and tissue histology were analyzed.The experimental results revealed that erectile function was significantly impaired in the HR and HR+NS groups,but enhanced in the HR+NAC group.Abnormal lipid levels,over-activated oxidative stress,and multi-organ lesions observed in the HR and HR+NS groups were improved in the HR+NAC group.Moreover,the HR group showed significant phenotypic modulation of CCSMCs,which was also inhibited by NAC treatment.This report focuses on the therapeutic effect of NAc in restoring erectile function using a hyperlipidemic rat model by preventing CcSMC phenotypic modulationand attenuating oxidativestress.展开更多
Objective: Hyperlipidemia is a representative nutritional metabolic disease in clinic, which is easy to induce atherosclerotic cardiovascular and cerebrovascular diseases, with complex classification. Traditional Chin...Objective: Hyperlipidemia is a representative nutritional metabolic disease in clinic, which is easy to induce atherosclerotic cardiovascular and cerebrovascular diseases, with complex classification. Traditional Chinese Medicine (TCM) syndrome aims to reflect the characteristics of diseases and is the basic principle of TCM treatment of diseases. This study aimed to summarize the distribution pattern of TCM syndromes in patients with hyperlipidemia. Methods: The frequency, characteristics and distribution of all TCM syndromes of 1012 patients with hyperlipidemia were analyzed. Results: The main disease types determined by frequency of 1012 patients included hypertriglyceridemia combined with hypo high-density lipoprotein cholesterolemia (19.76%), hypo high-density lipoprotein cholesterolemia (18.58%), hypercholesterolemia (16.50%), mixed hyperlipidemia (16.40%), and hypertriglyceridemia (15.12%). The distribution of TCM syndromes, in order of frequency, was as follows: Qi-deficiency and blood stasis syndrome (23.52%), liver depression and spleen deficiency (9.88%), syndrome of qi stagnation and blood stasis (9.29%), phlegm stasis syndrome (7.41%), and syndrome of yang deficiency of spleen and kidney (6.92%). Conclusion: Qi-deficiency and blood stasis syndrome and liver depression and spleen deficiency are the most common TCM syndromes in patients with hyperlipidemia.展开更多
Hyperlipidemia is a kind of pancreatitis caused by high triglyceride levels in the blood. The morbidity and mortality of this disease continue to increase worldwide, and it has become one of the most common gastrointe...Hyperlipidemia is a kind of pancreatitis caused by high triglyceride levels in the blood. The morbidity and mortality of this disease continue to increase worldwide, and it has become one of the most common gastrointestinal diseases in developed countries worldwide. Although many studies have been conducted, the pathogenesis still cannot be defined. Many studies have shown that this may be related to the triglyceride decomposition products free fatty acids are the main toxic substances, which can directly damage pancreatic acinar cells and vascular endothelial cells, causing tissue ischemia and acidic environment. Therefore, this paper focuses on the correlation of triglycerides and their decomposition products in plasma and provides evidence on the pathogenesis of AP and the disease progression of AP. Finally, the future potential to prevent and treat acute pancreatitis by some new drugs to reduce plasma triglycerides is summarized.展开更多
Background Population aging has become a common concern in the world.coronary heart disease(CHD)is one of the major diseases that lead to the death of the elderly and affect the quality of life.Studies have confirmed ...Background Population aging has become a common concern in the world.coronary heart disease(CHD)is one of the major diseases that lead to the death of the elderly and affect the quality of life.Studies have confirmed that increase in blood lipids is an independent risk factor for the occurrence and development of coronary heart disease.Therefore,adjusting the level of blood lipids effectively has significant value to alleviate the severity,slow the progression and reduce the occurrence of complications of coronary heart disease.Statins can play a role in regulating the blood lipids.Although rosuvastatin is a kind of highly potent statin that is often used at present,the effects of different doses of rosuvastatin on elderly patients with coronary heart disease and hyperlipidemia were seldom reported.Methods In this study,60 elderly patients with coronary heart disease and hyperlipidemia admitted to our hospital from 2021 to July to September 2023 were retrospectively selected.30 patients with 10 mg/d rosuvastatin were assigned to the control group and 30 patients with 20 mg/d rosuvastatin were assigned to the observation group,and their efficacy and safety were compared and analyzed.Results The total effective rate of observation group was 96.67%,which was higher than that of control group 86.67%(P<0.05).Before treatment,there was no significant difference in blood lipid levels between the two groups(P>0.05).After treatment,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL-C)and high density lipoprotein(HDL-C)were lower in the observation group(P<0.05).And there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusions The effect of 20 mg/d of rosuvastatin in the treatment of elderly CHD patients with hyperlipidemia is better than that of 10 mg/d of rosuvastatin,which can effectively regulate the level of blood lipids in the body without causing excessive adverse reactions.[S Chin J Cardiol 2024;25(3):149-155]展开更多
This study aims to identify a natural plant chemical with hypolipidemic effects that can be used to treat high cholesterol without adverse reactions.Through network pharmacology screening,it was found that Rosae Rugos...This study aims to identify a natural plant chemical with hypolipidemic effects that can be used to treat high cholesterol without adverse reactions.Through network pharmacology screening,it was found that Rosae Rugosae Flos(RF)flavonoids had potential therapeutic effects on hyperlipidemia and its mechanism of action was discussed.TCMSP and GeneCards databases were used to obtain active ingredients and disease targets.Venn diagrams were drawn to illustrate the findings.The interaction network diagram was created using Cytoscape 3.8.0 software.The PPI protein network was constructed using String.GO and KEGG enrichment analysis was performed using Metascape.The results revealed 2 active flavonoid ingredients and 60 potential targets in RF.The key targets,including CCL2,PPARG,and PPARA,were found to play a role in multiple pathways such as the AGE-RAGE signaling pathway,lipid and atherosclerosis,and cancer pathway in diabetic complications.The solvent extraction method was optimized for efficient flavonoid extraction based on network pharmacology prediction results.This was achieved through a single factor and orthogonal test,resulting in an optimum process with a reflux time of 1.5 h,a solid-liquid ratio of 1:13 g/mL,and an ethanol concentration of 50%.展开更多
This study aimed to investigate the mechanism of action of Sophora Flos(SF)in the treatment of hyperlipidemia(HLP)using network pharmacology and molecular docking methods,and to optimize the extraction process of the ...This study aimed to investigate the mechanism of action of Sophora Flos(SF)in the treatment of hyperlipidemia(HLP)using network pharmacology and molecular docking methods,and to optimize the extraction process of the predicted active components.The STRING database was used for protein interaction analysis and PPI network construction via Cytoscape 3.9.1.Pymol was employed for docking and visualization.An extensive review of SF identifi ed 6 active ingredients,297 related objectives,84 disease objectives,and 57 total objectives.After protein interaction and topology analysis,18 core targets were identified.These included 146 gene function entries(P<0.05).Active compounds,mainly flavonoids,can modulate the expression of various proteins such as TNF,IL-6,IL-1β,PPARG,and TGFB1 to achieve therapeutic effects on HLP.The network pharmacology and molecular docking results suggested that the active fl avonoids component in SF may be related to the treatment of hyperlipidemia.Therefore,the orthogonal experiment method was used to optimize the extraction process of total fl avonoid from SF using ethanol refl ux extraction,based on a single factor experiment.The effects of refl ux time,solid-liquid ratio,ethanol concentration,and other factors on the extraction of total fl avonoid from SF were investigated.The optimum process conditions were refl ux time of 1.25 h,solid-liquid ratio of 1:15 g/mL and ethanol concentration of 60%.Using these conditions,the purity of total fl avonoid extracted from SF was 70.33±0.22%.展开更多
Objective To observe the effect and explore the mechanism of acupuncture on hyperlipemia in mice. Methods One hundred and twenty male Kunming mice of clean grade were randomly divided into a normal group （40 mice）, ...Objective To observe the effect and explore the mechanism of acupuncture on hyperlipemia in mice. Methods One hundred and twenty male Kunming mice of clean grade were randomly divided into a normal group （40 mice）, a model group （40 mice）, an acupuncture group （20 mice）, and a drug group （20 mice）. The hyperlipidemia model was prepared in the latter 3 groups by feeding with high fat diet. After the successful modeling, bilateral ＂Fenglong＂ （丰隆 ST 40）, ＂Quchi＂ （曲池 LI 11）, and ＂Sanyinjiao＂ （三阴交 SP 6） were selected in the acupuncture group and Han＇s Acupuncture Stimulator was connected to intervent for 10 rain, once daily, for 10 successive days. Mice in the drug group were orally given Simvastatin, once daily, for 10 successive days. No intervention was given to the normal group and the model group. Serum contents of total cholesterol （TC）, triglyeeride （TG）, low-density lipoprotein cholesterol （LDL-C）, high-density lipoprotein cholesterol （HDL-C）, malondialdehyde （MDA）, nitric oxide （NO）, endothelin （ET）, and the activity of superoxide dismutase （SOD） were detected. Results The serum contents of TG, TC and LDL-C in the model group detected on the 15th day were all higher than those of the normal group [（1.31±0.32） mmol/L vs （0.70±0.21） retool/L, （5.72±0.85） mmol/L vs （3.08±0.74） retool/L, （2.68±0.55） mmol/L vs （1.83±0.36） retool/L, respectively]. The serum content of HDL-C in the model group was lower than that in the normal group [（0.60±0.26） mmol/L vs （0.94±0.30） mmol/L], showing successful modeling. On the lOth day of successful modeling, the serum contents of MDA and ET in the acupuncture group were lower than those in the model group [（21.58±3.54） p, mol/mL vs （29.94±2.79） p, mol/mL, （44.51±5.23） pg/mL vs （67.07±11.98） pg/mL]. The serum SOD activities and NO content in the acupuncture group were higher than those in the model gropu [（264.57±14.46） U/mL vs （222.66±25.48） U/mL, （85.02±10.06） μmol/L vs （63.83±9.19） μmol/L]. Conclusion Acupuncture could lower serum contents of MDA and ET, improve SOD activities and NO content, showing acupuncture could fight against lipid peroxidation, clear free radicals, regulate as well as ameliorate the metabolic balance of free radicals, and protect the vascular endothelium in hyperlipidemia mice.展开更多
Objective To examine the relationship between occurrence of hyperlipidemia, plasma homocysteine and polymorphisms of methylenetetra hydrofolate reductase （MTHFR） gene and methionine synthase （MS） gene. Methods A t...Objective To examine the relationship between occurrence of hyperlipidemia, plasma homocysteine and polymorphisms of methylenetetra hydrofolate reductase （MTHFR） gene and methionine synthase （MS） gene. Methods A total of 192 hyperlipidemia patients were selected and divided into hypercholesterolemia group, hypertriglyceridemia group, and combined hyperlipidemia group. Another 208 normal individuals were selected as control. Total plasma homocysteine （tHcy） concentration was measured by high-performance liquid chromatography （HPLC）. Lipid profiles were measured for all subjects The polymorphisms of MTHFR gene C677T and MS gene A2756G were analyzed by PCR-RFLP. Results The tHcy concentration in the combined hyperlipidemia patients was significantly higher than that in the control （15.95μmol/L vs 13.43 μmol/L, P〈0.05）. The prevalence of hyperhomocysteinemia （HHcy） in the combined hyperlipidemia group was significantly higher than that in the control （42.2% vs 23.0%, P=0.015）, with the odds ratio （OR） of 3.339 （95%CI： 1.260-8.849）. The hyperlipidemia patients with HHcy had a higher concentration of total cholesterol （TC） than that in the normal tHcy patients （5.67±0.95 mmol/L vs 5.47±0.92 retool/L, P=0.034）. There was no significant difference in genotype or allele frequencies of MTHFR C677T between the hyperlipidemic and control groups. The hyperlipidemia patients with MTHFR CT/TT genotype had a higher concentration of triglyceride （TG） than those with CC genotype （2.24±1.75 mmol/L vs 1.87±0.95 mmol/L, P〈0.05）. Individuals with CT/TT genotype had a higher concentration of tHcy than those with 677CC genotype both in the hyperlipidemia group （12.61±1.24μmol/L vs 11.20±1.37 μmol/L, P〈0.05） and in the control group （14.04±1.48 μmol/L vs 12.61±1.24 μmol/L, P〈0.05）. The percentage of MS 2756 GG/AG genotype in the combined hyperlipidemia group was significantly higher than that in the control （26.7% vs 13.0%, P=0.012）, with the OR of 3.121 （95%C1： 1.288-7.65/）. The hyperlipidemia patients with MS 2756AG/GG genotype had a higher concentration of TC （5.87±0.89 mmol/L vs 5.46±0.93 retool/L, P〈0.05） and LDL-C （3.29±0.81 mmol/L vs 2.94±0.85 retool/L, P〈0.05） than those with AA genotype. However, individuals with 2756AG/GG genotype showed no significant difference in tHcy among those with AA genotype. Conclusion HHcy and MS A2756G mutation may be the risk factors for combined hyperlipidemia. Further study is needed to confirm the role of HHcy and MS A2756G mutation in the development of hyperlipidemia.展开更多
AIM: To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) from seal oils for patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. METHODS: One hundred and ...AIM: To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) from seal oils for patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. METHODS: One hundred and forty-four patients with NAFLD associated with hyperlipidemia were included in the 24-wk, randomized, controlled trial. The patients were randomized into two groups. Group A (n = 72) received recommended diet and 2 g n-3 PUFA from seal oils, three times a day. Group B (n = 72) received recommended diet and 2 g placebo, three times a day. Primary endpoints were fatty liver assessed by symptom scores, liver alanine aminotransferase (ALT) and serum lipid levels after 8, 12, 16, and 24 wk. Hepatic fat inf iltration was detected by ultrasonography at weeks 12 and 24 after treatment. RESULTS: A total of 134 patients (66 in group A, 68 in group B) were included in the study except for 10 patients who were excluded from the study. After 24 wk of treatment, no change was observed in body weight, fasting blood glucose (FBG), renal function and blood cells of these patients. Total symptom scores, ALT and triglyceride (TG) levels decreased more significantly in group A than in group B (P < 0.05). As expected, there was a tendency toward improvement in aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), and total cholesterol (TCHO) and high- density lipoprotein (HDL) cholesterol levels (P < 0.05) after administration in the two groups. However, no significant differences were found between the two groups. The values of low-density lipoprotein (LDL) were significantly improved in group A (P < 0.05), but no significant change was found in group B at different time points and after a 24-wk treatment. After treatment, complete fatty liver regression was observed in 19.70% (13/66) of the patients, and an overall reduction was found in 53.03% (35/66) of the patients in group A. In contrast, in group B, only f ive patients (7.35%, 5/68) achieved complete fatty liver regression (P = 0.04), whereas 24 patients (35.29%, 24/68) had a certain improvement in fatty liver (P = 0.04). No serious adverse events occurred in all the patients who completed the treatment. CONCLUSION: Our results indicate that n-3 PUFA from seal oils is safe and effi cacious for patients with NAFLD associated with hyperlipidemia and can improve their total symptom scores, ALT, serum lipid levels and normalization of ultrasonographic evidence. Further study is needed to confi rm these results.展开更多
OBJECTIVE:To assess the clinical effectiveness and adverse effects of Yinchenwuling powder(YCWLP)in the treatment of hyperlipidemia using Meta-analysis.METHODS:Seven electronic databases were searched for randomized c...OBJECTIVE:To assess the clinical effectiveness and adverse effects of Yinchenwuling powder(YCWLP)in the treatment of hyperlipidemia using Meta-analysis.METHODS:Seven electronic databases were searched for randomized controlled trials designed to evaluate the clinical effectiveness of YCWLP for hyperlipidemia published in any language prior to February 2015.Two reviewers independently identified articles,extracted data,assessed quality,and cross-checked the results.Revman 5.3 was used to analyze the data.RESULTS:Only five randomized controlled trials with poor methodology were included in the analy-sis.The five trials compared YCWLP with conventional lipid-lowering drugs.Meta-analysis indicated that YCWLP was more effective at the levels of total cholesterol and triglycerides,while increasing the level of high-density lipoprotein cholesterol without serious adverse effects.However,it was not more effective than lipid-lowering drugs in reducing low-density lipoprotein cholesterol and improving hemorheology.CONCLUSION:YCWLP appeared to improve lipid levels.However,given the high risk of bias among the trials,we could not conclude that YCWLP was beneficial to patients with hyperlipidemia.More rigorous trials are required to provide stronger evidence for the conclusion.展开更多
AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the ...AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver damage,which was confirmed by liver histology.In addition,HL combined with I/R also caused significantly increased hepatocyte apoptosis,as evidenced by increased TUNEL-positive cells(6.20 ± 0.29 vs 1.5 ± 0.22,4.47 ± 0.45 or 1.97 ± 0.47,P < 0.01),elevated expression of caspase-3 and lower expression of bcl-2.Furthermore,when compared to HL or I/R alone,HL plus I/R enhanced serum TNF-,IL-1,liver mitochondrial MDA and Ca 2+ levels,suppressed SOD and GSH-Px in liver mitochondria,and markedly up-regulated the activity(11.76 ± 2.36 vs 4.77 ± 2.31 or 3.11 ± 1.35,P < 0.01) and expression(3.24 ± 0.38 vs 1.98 ± 0.88 or 1.72 ± 0.58,P < 0.01) of CYP2E1 in liver.CONCLUSION:The coexistence of HL and acute cerebral I/R induces severe liver damage,suggesting that cerebral ischemic stroke would exaggerate the damage of liver caused by HL.This effect is possibly due to en-hanced CYP2E1 induction which further promotes oxidative damage,inflammation and hepatocyte apoptosis.展开更多
基金supported by the Science and Technology Program of Tianjin in China(No.23ZYJDSS00030)the Public Applied Technology Research Project of Zhejiang Province(No.LGD22H090010)。
文摘Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&E.H.Wilson in C.S.Sargent,and it in traditional Chinese medicine has been known for promoting blood circulation and removing blood stasis as recorded in the ancient book“Illustrated Classics of Materia Medica”.It has been used effectively to treat blood stasis too in modern clinical practice.However,the anti-hyperlipidemia effect of SC is not fully understood.This paper aims at exploring the use of SC stems to improve the balance of blood lipids in the body,and its new role in treating hyperlipidemia.Methods:The effects of SC extract on hyperlipidemia were explored by combining lipidomics and gut microbiota.Secondly,we explored the potential mechanism of SC in treating hyperlipidemia by pathway analysis.Results:The results showed that the stem extract of SC could restore the physiological and biochemical indices of hyperlipidemia in mice,as well as repair the morphological and structural damage to tissues.Compared to the Model group,the SC extract significantly reduced the liver index,epididymal fat index,and Lee’s index.It also significantly decreased serum levels of total cholesterol,triglycerides,low-density lipoprotein cholesterol,peroxisome proliferator-activated receptor gamma(PPAR-γ),D-lactate,and free fatty acids,while significantly increasing the relative content of peroxisome proliferator-activated receptor alpha(PPAR-α).These changes were statistically significant.Non-targeted lipidomics,based on LC-MS,were utilized to investigate the lipid metabolism characteristics in serum,liver,and epididymal fat of the subjects.It was observed that,compared to the blank group,the Model group exhibited significant changes primarily in glycerol lipids and glycerophospholipids.The treatment group also displayed alterations in these lipids.A total of 38,81,and 27 differential lipids were identified in serum,liver,and epididymal fat samples,respectively.Among these,14 common differential lipids were found in both serum and liver samples,and their KEGG enrichment pathways were largely consistent.Among them,the sphingolipid signaling pathway and the glycerophospholipid metabolic pathway were identified as key metabolic pathways that were regulated.Our gut microbiota analysis revealed that SC diminishes the abundance of Actinobacteria by altering the cecal flora in mice.Conclusion:This alteration leads to the downregulation of genes involved in triglyceride metabolism,which in turn changes lipid processing and reduces triglyceride levels.Consequently,SC effectively combats hyperlipidemia.Notably,SC impacts key metabolic pathways,including the sphingolipid signaling and glycerophospholipid metabolism.These findings underscore SC’s therapeutic potential,positioning it as a promising alternative for reducing the health risks associated with hyperlipidemia.
基金funded by the National Natural Science Foundation of China(31901624)the Key-Area Research and Development Program of Guangdong Province(2018B020206001)+2 种基金Guangdong Province Zhujiang Talent Program(2019ZT08H476)Shenzhen Science and Technology Program(KQTD20180412181334790)the Innovation Team Project of Universities in Guangdong Province(2020KCXTD023)。
文摘Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrate fucoxanthin efficacy in modulating lipid metabolism in serum and liver of high-fat-induced hyperlipidemia mice,as well as investigate the underlying association with gut microbiota changes.Results showed that fucoxanthin significantly reduced body weight gain and body white fat of the mice.In the serum,total triglycerides(TG),total cholesterol(TC)contents were significantly decreased and high-densitylipoprotein cholesterol levels was significantly upregulated.Moreover,fucoxanthin remarkedly prevented lipid accumulation in the liver.Especially,metabolomics results showed that lipids and lipid-like molecules were significantly downregulated compared with the control,indicating the advance of hepatic lipid metabolism.Bile acids profile in the liver was also greatly changed by fucoxanthin.Meanwhile,fucoxanthin remodeled gut microbiota composition and promoted the relative abundance of Desulfovibrio,Blautia and Clostridia genera.Finally,correlation analysis revealed that these gut microbiota changes were closely related with hepatic metabolites/metabolism and serum lipids.Altogether,this study showed great potential of fucoxanthin in improving serum lipids profile,hepatic lipids and bile acids metabolism of hyperlipidemia mice,which was associated with gut microbiota alteration.
基金supported by 2024 Liaoning Province Graduate Education Teaching Reform Research Project(LNYJG2024251).
文摘The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used to screen the polyphenols present in sea buckthorn,and then the SwissTargetPrediction and Uniprot databases were used to obtain the potential targets of sea buckthorn polyphenols,which were supplemented by the literature.In total,7 polyphenols and 154 potential targets were obtained.Through GeneCards,OMIM database,1358 hyperlipidemia-related targets were collected.We found that there were 101 targets at the intersection of components and diseases.Through GO and KEGG enrichment analysis,27 core targets were obtained,which were AKT1,TNF,TP53,IL-6,etc.in order of degree value.174 pathways were obtained from KEGG enrichment analysis,including AGE-RAGE signaling pathway in diabetic complications,fl uid shear stress and atherosclerosis,lipid and atherosclerosis,etc.The molecular docking of the main components to the targets was performed using OpenBabelGUI,AutoDockTools-1.5.6 software.Finally,the results were visualized using Cytoscape 3.9.1 software.The molecular docking results showed that sea buckthorn polyphenols have good binding ability with the key targets.Among them,such as quercetin and kaempferol,have good binding ability with TNF,TP53 and IL-6.For example,TNF binds to quercetin with a binding energy of-5.34 kcal/mol and to kaempferol with a binding energy of-6.22 kcal/mol;TP53 binds to kaempferol with a binding energy of-5.32 kcal/mol;IL-6 binds to quercetin with a binding energy of-5.62 kcal/mol,etc.Therefore,the network pharmacology study showed that the treatment of hyperlipidemia by sea buckthorn polyphenols can be realized by multi-component-multi-target-multi-pathway together,which provides some reference for the later study of sea buckthorn polyphenols in the treatment of hyperlipidemia.
基金supported by the National Natural Science Foundation of China(22067016)the Project of Qinghai Outstanding Youth Fund Project(2023-ZJ-964J).
文摘Objective:To explore the mechanism of action of Zangjiangzhi capsule(ZJZC)in treating hyperlipidemia(HLP).Methods:The components of ZJZC were analyzed and identified using ultra-high performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry(UHPLC-Q-Exactive-Orbitrap-MS/MS).Network pharmacology analysis was used to explore the mechanism of action of ZJZC in HLP treatment.The SwissTargetPrediction database was used to predict compound targets,and GeneCards,DisGeNet,OMIM,and DRUGBANK databases were used to identify HLP-related targets.Proteineprotein interaction diagrams were constructed using the STRING database.The targets were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.The“herbingredient-target”network was visualized using Cytoscape.Preliminary validation was performed using molecular docking and enzyme-linked immunosorbent assay.Results:Ninety compounds were identified in ZJZC,including 34 flavonoids,12 phenols,10 terpenoids,10 alkaloids,8 organic acids,8 anthraquinones,and 9 other compounds.In total,904 targets were identified for these compounds.Among them,158 targets intersected with the HLP target network.Network pharmacology analysis showed that MAPK1,PPAR-a,RXRA,HSP90AA1,PIK3R1,AKT1,PIK3CA,IL6,TNF,and ESR1 are the key targets of action.KEGG enrichment analysis identified 164 pathways.Among these,the AGE-RAGE signaling pathway in diabetic complications,lipid and atherosclerosis pathways,regulation of lipids in adipocytes,and insulin resistance are related to HLP.Molecular docking showed good affinity between the key targets and ingredients.Further,ZJZC treatment in mice resulted in lower expression of MAPK1 protein and increased expression of PPAR-a protein,which have been shown to be strongly associated with HLP.Conclusions:This study showed that ZJZC contains various active ingredients and can modulate multiple targets and pathways associated with HLP,providing evidence at the molecular level for its clinical application in the treatment of HLP.
文摘Low-density lipoprotein cholesterol(LDL-C)is the most causal risk factor for atherosclerotic cardiovascular disease(ASCVD).Red yeast rice(RYR)is a nutraceutical widely used as a lipid-lowering dietary supplement.The main cholesterol-lower agents in RYR are monacolins,particularly monacolin K,a weak reversible inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase,whose daily consumption(up to 10 mg/day)reduces LDL-C plasma levels up to 34%within 6-8 weeks when compared to placebo.The reduction in LDL-C is often accompanied by lower levels of plasma apolipoprotein B,total cholesterol,matrix metalloproteinases 2 and 9,high-sensitivity C-reactive protein,non-high-density lipoprotein cholesterol,and blood pressure.RYR has also demonstrated favorable reductions of up to 45%compared to placebo in the risk of ASCVD events in secondary prevention studies.The mechanism of action is similar to statins.When consumed appropriately,RYR is associated with only minimal side effects.Mild myalgia may be seen in patients who cannot tolerate low-dose statins.In individuals with no additional ASCVD risk factors,RYR is a safe and effective supplement in treating mild to moderate hyperlipidemia.
基金supported by the National Natural Science Foundation of China(31201416)Programme of Introducing Talents of Discipline to Universities(B17018)。
文摘Hyperlipidemia constitutes a critical factor in the pathogenesis of vascular disease and gut microbiota dysbiosis.This study aims to investigate the role of sea buckthorn fruit oil(SBFO)in ameliorating hyperlipidemia,modulating gut microbiota,and elucidating the underlying mechanisms of its lipid-lowering effects.SBFO intervention in hyperlipidemic mice significantly reduced body weight and visceral adiposity index while mitigating symptoms associated with hyperlipidemia,including dyslipidemia,infla mmation,liver damage,and endothelial dysfunction.Real-time quantitative PCR and Western blot analyses revealed that SBFO enhanced the response of free fatty acid oxidation and breakdown(adenosine 5'-monophosphateactivated protein kinaseα,carnitine palmitoyltransferase1a,peroxisome proliferator-activated receptorα,and peroxisome proliferator-activated receptorγ)while suppressing the synthesis of triglycerides and fatty acids(sterol-regulatory element binding protein 1,fatty acid synthase,and acetyl CoA carboxylase)at the gene and protein expression levels.Moreover,SBFO intervention enriched the gut microbiota of hyperlipidemic mice by increasing the relative abundances of Lactobacillus,Faecalibaculum,and Allobaculum,while decreasing the Firmicutes/Bacteroidetes ratio.These findings suggest that SBFO exhibits promising therapeutic potential in attenuating hyperlipidemia in mice through the regulation of lipid metabolism and modulation of gut microbiota.
基金funded by Jiangsu Hengrui Pharmaceutical Co.,Ltd.(formerly,Jiangsu Hengrui Medicine Co.,Ltd.).
文摘Objective Recaticimab(SHR-1209)significantly reduces low-density lipoprotein cholesterol levels.However,its effect on glucose metabolism remains unclear.This study aimed to evaluate its effect on glycemic parameters in a Chinese population.Methods Recaticimab versus placebo was administered in a 5:1 ratio to 110 hyperlipidemia patients who were followed up for 24 weeks.Glycated hemoglobin(HbA1c)levels were measured at baseline every 12 weeks.Fasting plasma glucose(FPG)levels were measured at baseline at week 1,3,5,8,12,16,20,and 24.Repeated-measures mixed-effects models were used to determine the longitudinal association between reacticimab and FPG and HbA1c levels.Results Among the 81 participants with normal glucose metabolism,HbA1c levels significantly decreased(F=4.568,P=0.036).In the 29 participants with abnormal glucose metabolism,a significant time effect was observed for FPG levels(F=2.492,P=0.016).For participants with normal and abnormal glucose metabolism,no significant group×time interaction effects on FPG or HbA1c levels were identified.Conclusion Recaticimab showed no adverse glycemic effects in participants with normal or abnormal glucose metabolism,indicating its safety in patients with or without diabetes.
基金Natural Science Foundation of Hebei Province,China,No.H2020209160Scientific Research Projects in Chinese Medicine of Hebei Province,China,No.2019168.
文摘BACKGROUND Alagille syndrome is a rare autosomal dominant genetic disorder involving multiple organ systems.Its most common manifestations are chronic cholestasis caused by intrahepatic bile duct deficiency and severe hypercholesterolemia as a result of impaired cholesterol metabolism.This report describes a patient with Alagille syndrome in whom a JAG1 mutation was detected by whole-exome sequencing.CASE SUMMARY The patient presented with severe hypercholesterolemia,biliary and hepatic impairment,pruritus,and triangular facial features.Mutations in the JAG1 gene,which encodes the Notch signaling pathway,were detected by whole-exome sequencing,leading to a diagnosis of Alagille syndrome.The patient was treated using a combination of traditional Chinese and Western medicines.Her cholesterol levels,liver function,and pruritus subsequently improved.CONCLUSION The possibility of Alagille syndrome should be considered in children who present with abnormal liver function and severe hypercholesterolemia.Genetic testing is needed to screen for disease-causing mutations and the disease can be treated with Traditional Chinese medicine.
基金supported by the Jilin Province Science and Technology Plan Project(20230402032GH)the Jilin Province Science and Technology Development Project(20220508115RC).
文摘The gut microbiota and it’s metabolism are vital targets of probiotics regulating high fat-diet(HFD)induced hyperlipidemia,which can relieve the pressure caused by the striking growth of sub-health people.Pediococcus pentosaceus PP04(PP04)could colonize in intestine to regulate gut microbiota and it’s metabolites directly,the rebalanced intestinal flora mediated by PP04 could facilitate the secretion of short chain fatty acids to control body weight gain,PP04 intervention also changed bile acid(BA)profiles and enhanced the ileal concentrations of antagonists including tauro-α/β-muricholic acid sodium salt and ursodeoxycholic acid to inhibit intestinal farnesoid X receptor/fibroblast growth factor 15(FXR/FGF15)signaling coupled with the activation of hepatic FXR/small heterodimer partners signaling,which accelerated the hepatic BA de novo synthesis and excretion with feces to eliminate HFD caused hyperlipemia effectively.This study provided important evidence regarding PP04 as dietary supplement to relieve hyperlipidemia by influencing BA enterohepatic circulation.
基金This work is supported by a grant from the National Natural Science Foundation of China(No.82060809)the Natural Science Foundation of Guangdong Province(No.2017A030313453 and No.2018A030313638)Guangzhou Basic and Applied Basic Research Foundation(No.202102020417).
文摘Hyperlipidemia is a major risk factor for erectile dysfunction(ED).Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells(CcSMCs)are the key pathological factors of ED.N-acetylcysteine(NAC)can inhibit oxidative stress;however,whether NAc can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear.A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley(SD)rats fed a high-fat and high-cholesterol diet(hyperlipidemic rats,HR).In addition,9 male SD rats were fed a normal diet to serve as controls(NC).HR rats were divided into three groups:HR,HR+normal saline(NS),and HR+NAC(n=9 for each group;NS or NAc intraperitoneal injections were administered daily for 16 weeks).Subsequently,the lipid profiles,erectile function,oxidative stress,phenotypic modulation markers of ccsMCs,and tissue histology were analyzed.The experimental results revealed that erectile function was significantly impaired in the HR and HR+NS groups,but enhanced in the HR+NAC group.Abnormal lipid levels,over-activated oxidative stress,and multi-organ lesions observed in the HR and HR+NS groups were improved in the HR+NAC group.Moreover,the HR group showed significant phenotypic modulation of CCSMCs,which was also inhibited by NAC treatment.This report focuses on the therapeutic effect of NAc in restoring erectile function using a hyperlipidemic rat model by preventing CcSMC phenotypic modulationand attenuating oxidativestress.
文摘Objective: Hyperlipidemia is a representative nutritional metabolic disease in clinic, which is easy to induce atherosclerotic cardiovascular and cerebrovascular diseases, with complex classification. Traditional Chinese Medicine (TCM) syndrome aims to reflect the characteristics of diseases and is the basic principle of TCM treatment of diseases. This study aimed to summarize the distribution pattern of TCM syndromes in patients with hyperlipidemia. Methods: The frequency, characteristics and distribution of all TCM syndromes of 1012 patients with hyperlipidemia were analyzed. Results: The main disease types determined by frequency of 1012 patients included hypertriglyceridemia combined with hypo high-density lipoprotein cholesterolemia (19.76%), hypo high-density lipoprotein cholesterolemia (18.58%), hypercholesterolemia (16.50%), mixed hyperlipidemia (16.40%), and hypertriglyceridemia (15.12%). The distribution of TCM syndromes, in order of frequency, was as follows: Qi-deficiency and blood stasis syndrome (23.52%), liver depression and spleen deficiency (9.88%), syndrome of qi stagnation and blood stasis (9.29%), phlegm stasis syndrome (7.41%), and syndrome of yang deficiency of spleen and kidney (6.92%). Conclusion: Qi-deficiency and blood stasis syndrome and liver depression and spleen deficiency are the most common TCM syndromes in patients with hyperlipidemia.
文摘Hyperlipidemia is a kind of pancreatitis caused by high triglyceride levels in the blood. The morbidity and mortality of this disease continue to increase worldwide, and it has become one of the most common gastrointestinal diseases in developed countries worldwide. Although many studies have been conducted, the pathogenesis still cannot be defined. Many studies have shown that this may be related to the triglyceride decomposition products free fatty acids are the main toxic substances, which can directly damage pancreatic acinar cells and vascular endothelial cells, causing tissue ischemia and acidic environment. Therefore, this paper focuses on the correlation of triglycerides and their decomposition products in plasma and provides evidence on the pathogenesis of AP and the disease progression of AP. Finally, the future potential to prevent and treat acute pancreatitis by some new drugs to reduce plasma triglycerides is summarized.
文摘Background Population aging has become a common concern in the world.coronary heart disease(CHD)is one of the major diseases that lead to the death of the elderly and affect the quality of life.Studies have confirmed that increase in blood lipids is an independent risk factor for the occurrence and development of coronary heart disease.Therefore,adjusting the level of blood lipids effectively has significant value to alleviate the severity,slow the progression and reduce the occurrence of complications of coronary heart disease.Statins can play a role in regulating the blood lipids.Although rosuvastatin is a kind of highly potent statin that is often used at present,the effects of different doses of rosuvastatin on elderly patients with coronary heart disease and hyperlipidemia were seldom reported.Methods In this study,60 elderly patients with coronary heart disease and hyperlipidemia admitted to our hospital from 2021 to July to September 2023 were retrospectively selected.30 patients with 10 mg/d rosuvastatin were assigned to the control group and 30 patients with 20 mg/d rosuvastatin were assigned to the observation group,and their efficacy and safety were compared and analyzed.Results The total effective rate of observation group was 96.67%,which was higher than that of control group 86.67%(P<0.05).Before treatment,there was no significant difference in blood lipid levels between the two groups(P>0.05).After treatment,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL-C)and high density lipoprotein(HDL-C)were lower in the observation group(P<0.05).And there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusions The effect of 20 mg/d of rosuvastatin in the treatment of elderly CHD patients with hyperlipidemia is better than that of 10 mg/d of rosuvastatin,which can effectively regulate the level of blood lipids in the body without causing excessive adverse reactions.[S Chin J Cardiol 2024;25(3):149-155]
文摘This study aims to identify a natural plant chemical with hypolipidemic effects that can be used to treat high cholesterol without adverse reactions.Through network pharmacology screening,it was found that Rosae Rugosae Flos(RF)flavonoids had potential therapeutic effects on hyperlipidemia and its mechanism of action was discussed.TCMSP and GeneCards databases were used to obtain active ingredients and disease targets.Venn diagrams were drawn to illustrate the findings.The interaction network diagram was created using Cytoscape 3.8.0 software.The PPI protein network was constructed using String.GO and KEGG enrichment analysis was performed using Metascape.The results revealed 2 active flavonoid ingredients and 60 potential targets in RF.The key targets,including CCL2,PPARG,and PPARA,were found to play a role in multiple pathways such as the AGE-RAGE signaling pathway,lipid and atherosclerosis,and cancer pathway in diabetic complications.The solvent extraction method was optimized for efficient flavonoid extraction based on network pharmacology prediction results.This was achieved through a single factor and orthogonal test,resulting in an optimum process with a reflux time of 1.5 h,a solid-liquid ratio of 1:13 g/mL,and an ethanol concentration of 50%.
文摘This study aimed to investigate the mechanism of action of Sophora Flos(SF)in the treatment of hyperlipidemia(HLP)using network pharmacology and molecular docking methods,and to optimize the extraction process of the predicted active components.The STRING database was used for protein interaction analysis and PPI network construction via Cytoscape 3.9.1.Pymol was employed for docking and visualization.An extensive review of SF identifi ed 6 active ingredients,297 related objectives,84 disease objectives,and 57 total objectives.After protein interaction and topology analysis,18 core targets were identified.These included 146 gene function entries(P<0.05).Active compounds,mainly flavonoids,can modulate the expression of various proteins such as TNF,IL-6,IL-1β,PPARG,and TGFB1 to achieve therapeutic effects on HLP.The network pharmacology and molecular docking results suggested that the active fl avonoids component in SF may be related to the treatment of hyperlipidemia.Therefore,the orthogonal experiment method was used to optimize the extraction process of total fl avonoid from SF using ethanol refl ux extraction,based on a single factor experiment.The effects of refl ux time,solid-liquid ratio,ethanol concentration,and other factors on the extraction of total fl avonoid from SF were investigated.The optimum process conditions were refl ux time of 1.25 h,solid-liquid ratio of 1:15 g/mL and ethanol concentration of 60%.Using these conditions,the purity of total fl avonoid extracted from SF was 70.33±0.22%.
基金Supported by Key Project Foundation of Hebei Administration of TCM:2009058
文摘Objective To observe the effect and explore the mechanism of acupuncture on hyperlipemia in mice. Methods One hundred and twenty male Kunming mice of clean grade were randomly divided into a normal group （40 mice）, a model group （40 mice）, an acupuncture group （20 mice）, and a drug group （20 mice）. The hyperlipidemia model was prepared in the latter 3 groups by feeding with high fat diet. After the successful modeling, bilateral ＂Fenglong＂ （丰隆 ST 40）, ＂Quchi＂ （曲池 LI 11）, and ＂Sanyinjiao＂ （三阴交 SP 6） were selected in the acupuncture group and Han＇s Acupuncture Stimulator was connected to intervent for 10 rain, once daily, for 10 successive days. Mice in the drug group were orally given Simvastatin, once daily, for 10 successive days. No intervention was given to the normal group and the model group. Serum contents of total cholesterol （TC）, triglyeeride （TG）, low-density lipoprotein cholesterol （LDL-C）, high-density lipoprotein cholesterol （HDL-C）, malondialdehyde （MDA）, nitric oxide （NO）, endothelin （ET）, and the activity of superoxide dismutase （SOD） were detected. Results The serum contents of TG, TC and LDL-C in the model group detected on the 15th day were all higher than those of the normal group [（1.31±0.32） mmol/L vs （0.70±0.21） retool/L, （5.72±0.85） mmol/L vs （3.08±0.74） retool/L, （2.68±0.55） mmol/L vs （1.83±0.36） retool/L, respectively]. The serum content of HDL-C in the model group was lower than that in the normal group [（0.60±0.26） mmol/L vs （0.94±0.30） mmol/L], showing successful modeling. On the lOth day of successful modeling, the serum contents of MDA and ET in the acupuncture group were lower than those in the model group [（21.58±3.54） p, mol/mL vs （29.94±2.79） p, mol/mL, （44.51±5.23） pg/mL vs （67.07±11.98） pg/mL]. The serum SOD activities and NO content in the acupuncture group were higher than those in the model gropu [（264.57±14.46） U/mL vs （222.66±25.48） U/mL, （85.02±10.06） μmol/L vs （63.83±9.19） μmol/L]. Conclusion Acupuncture could lower serum contents of MDA and ET, improve SOD activities and NO content, showing acupuncture could fight against lipid peroxidation, clear free radicals, regulate as well as ameliorate the metabolic balance of free radicals, and protect the vascular endothelium in hyperlipidemia mice.
基金supported by Beijing Natural Science Foundation, China (No. 7072044).
文摘Objective To examine the relationship between occurrence of hyperlipidemia, plasma homocysteine and polymorphisms of methylenetetra hydrofolate reductase （MTHFR） gene and methionine synthase （MS） gene. Methods A total of 192 hyperlipidemia patients were selected and divided into hypercholesterolemia group, hypertriglyceridemia group, and combined hyperlipidemia group. Another 208 normal individuals were selected as control. Total plasma homocysteine （tHcy） concentration was measured by high-performance liquid chromatography （HPLC）. Lipid profiles were measured for all subjects The polymorphisms of MTHFR gene C677T and MS gene A2756G were analyzed by PCR-RFLP. Results The tHcy concentration in the combined hyperlipidemia patients was significantly higher than that in the control （15.95μmol/L vs 13.43 μmol/L, P〈0.05）. The prevalence of hyperhomocysteinemia （HHcy） in the combined hyperlipidemia group was significantly higher than that in the control （42.2% vs 23.0%, P=0.015）, with the odds ratio （OR） of 3.339 （95%CI： 1.260-8.849）. The hyperlipidemia patients with HHcy had a higher concentration of total cholesterol （TC） than that in the normal tHcy patients （5.67±0.95 mmol/L vs 5.47±0.92 retool/L, P=0.034）. There was no significant difference in genotype or allele frequencies of MTHFR C677T between the hyperlipidemic and control groups. The hyperlipidemia patients with MTHFR CT/TT genotype had a higher concentration of triglyceride （TG） than those with CC genotype （2.24±1.75 mmol/L vs 1.87±0.95 mmol/L, P〈0.05）. Individuals with CT/TT genotype had a higher concentration of tHcy than those with 677CC genotype both in the hyperlipidemia group （12.61±1.24μmol/L vs 11.20±1.37 μmol/L, P〈0.05） and in the control group （14.04±1.48 μmol/L vs 12.61±1.24 μmol/L, P〈0.05）. The percentage of MS 2756 GG/AG genotype in the combined hyperlipidemia group was significantly higher than that in the control （26.7% vs 13.0%, P=0.012）, with the OR of 3.121 （95%C1： 1.288-7.65/）. The hyperlipidemia patients with MS 2756AG/GG genotype had a higher concentration of TC （5.87±0.89 mmol/L vs 5.46±0.93 retool/L, P〈0.05） and LDL-C （3.29±0.81 mmol/L vs 2.94±0.85 retool/L, P〈0.05） than those with AA genotype. However, individuals with 2756AG/GG genotype showed no significant difference in tHcy among those with AA genotype. Conclusion HHcy and MS A2756G mutation may be the risk factors for combined hyperlipidemia. Further study is needed to confirm the role of HHcy and MS A2756G mutation in the development of hyperlipidemia.
基金Supported by Shanghai Natural Science Fund of China, 05ZR14156
文摘AIM: To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) from seal oils for patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. METHODS: One hundred and forty-four patients with NAFLD associated with hyperlipidemia were included in the 24-wk, randomized, controlled trial. The patients were randomized into two groups. Group A (n = 72) received recommended diet and 2 g n-3 PUFA from seal oils, three times a day. Group B (n = 72) received recommended diet and 2 g placebo, three times a day. Primary endpoints were fatty liver assessed by symptom scores, liver alanine aminotransferase (ALT) and serum lipid levels after 8, 12, 16, and 24 wk. Hepatic fat inf iltration was detected by ultrasonography at weeks 12 and 24 after treatment. RESULTS: A total of 134 patients (66 in group A, 68 in group B) were included in the study except for 10 patients who were excluded from the study. After 24 wk of treatment, no change was observed in body weight, fasting blood glucose (FBG), renal function and blood cells of these patients. Total symptom scores, ALT and triglyceride (TG) levels decreased more significantly in group A than in group B (P < 0.05). As expected, there was a tendency toward improvement in aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), and total cholesterol (TCHO) and high- density lipoprotein (HDL) cholesterol levels (P < 0.05) after administration in the two groups. However, no significant differences were found between the two groups. The values of low-density lipoprotein (LDL) were significantly improved in group A (P < 0.05), but no significant change was found in group B at different time points and after a 24-wk treatment. After treatment, complete fatty liver regression was observed in 19.70% (13/66) of the patients, and an overall reduction was found in 53.03% (35/66) of the patients in group A. In contrast, in group B, only f ive patients (7.35%, 5/68) achieved complete fatty liver regression (P = 0.04), whereas 24 patients (35.29%, 24/68) had a certain improvement in fatty liver (P = 0.04). No serious adverse events occurred in all the patients who completed the treatment. CONCLUSION: Our results indicate that n-3 PUFA from seal oils is safe and effi cacious for patients with NAFLD associated with hyperlipidemia and can improve their total symptom scores, ALT, serum lipid levels and normalization of ultrasonographic evidence. Further study is needed to confi rm these results.
基金Supported by the Chinese National Natural Science Foundation Key Project(Identification of the Molecular Signature Contributing to the Susceptibility of Phlegmatic Hygrosis Constitution to Metabolic Syndrome,No.81030064)
文摘OBJECTIVE:To assess the clinical effectiveness and adverse effects of Yinchenwuling powder(YCWLP)in the treatment of hyperlipidemia using Meta-analysis.METHODS:Seven electronic databases were searched for randomized controlled trials designed to evaluate the clinical effectiveness of YCWLP for hyperlipidemia published in any language prior to February 2015.Two reviewers independently identified articles,extracted data,assessed quality,and cross-checked the results.Revman 5.3 was used to analyze the data.RESULTS:Only five randomized controlled trials with poor methodology were included in the analy-sis.The five trials compared YCWLP with conventional lipid-lowering drugs.Meta-analysis indicated that YCWLP was more effective at the levels of total cholesterol and triglycerides,while increasing the level of high-density lipoprotein cholesterol without serious adverse effects.However,it was not more effective than lipid-lowering drugs in reducing low-density lipoprotein cholesterol and improving hemorheology.CONCLUSION:YCWLP appeared to improve lipid levels.However,given the high risk of bias among the trials,we could not conclude that YCWLP was beneficial to patients with hyperlipidemia.More rigorous trials are required to provide stronger evidence for the conclusion.
文摘AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver damage,which was confirmed by liver histology.In addition,HL combined with I/R also caused significantly increased hepatocyte apoptosis,as evidenced by increased TUNEL-positive cells(6.20 ± 0.29 vs 1.5 ± 0.22,4.47 ± 0.45 or 1.97 ± 0.47,P < 0.01),elevated expression of caspase-3 and lower expression of bcl-2.Furthermore,when compared to HL or I/R alone,HL plus I/R enhanced serum TNF-,IL-1,liver mitochondrial MDA and Ca 2+ levels,suppressed SOD and GSH-Px in liver mitochondria,and markedly up-regulated the activity(11.76 ± 2.36 vs 4.77 ± 2.31 or 3.11 ± 1.35,P < 0.01) and expression(3.24 ± 0.38 vs 1.98 ± 0.88 or 1.72 ± 0.58,P < 0.01) of CYP2E1 in liver.CONCLUSION:The coexistence of HL and acute cerebral I/R induces severe liver damage,suggesting that cerebral ischemic stroke would exaggerate the damage of liver caused by HL.This effect is possibly due to en-hanced CYP2E1 induction which further promotes oxidative damage,inflammation and hepatocyte apoptosis.
