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Background & objectives: Statin use has been shown to be associated with a decreased risk of several types of cancer, however, the data on diffuse large B-cell lymphoma (DLBCL) are still inconclusive. This study aimed to systematically summarize all available data on this association and conduct a meta-analysis on the same. Methods: A systematic review was performed using EMBASE and MEDLINE databases from inception upto October 2019 with a search strategy that included terms such as ‘statin’ and ‘DLBCL’. Eligible studies included either case–control or cohort studies that reported the association between statin use and the risk of DLBCL. Relative risk, odds ratio (OR), hazard: risk ratio or standardized incidence ratio of this association and standard error were extracted and combined for calculating the pooled effect estimate using random-effects, generic inverse variance method. Results: A total of 1139 articles were screened. Of these six studies satisfied the inclusion criteria and were included for the meta-analysis. Statin use was associated with a significantly reduced risk of DLBCL with the pooled OR of 0.70 (95% confidence interval, 0.56-0.88; I2=70%). The funnel plot (fairly symmetric) was not suggestive of the presence of a publication bias. Interpretation & conclusions: The present systematic review and meta-analysis found that statin use is associated with a 30 per cent reduced odds of DLBCL. However, the pooled analysis utilized data from observational studies so causation cannot be concluded upon. Hence, it suggested that randomized-controlled studies are still needed to confirm this potential benefit.
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Objective:To observe the lipid-lowering effect of atorvastatin on patients with acute cerebral infarction with different ATP-binding cassette subfamily B member 1(ABCB1) genotypes, and thus to provide clinical research evidence for individual application of atorvastatin in patients with acute cerebral infarction.Methods:From March 2021 to December 2021, 131 patients with acute cerebral infarction admitted to the Department of Neurology of Xuchang Central Hospital were included. The ABCB1 G2677T gene polymorphism rs2032582 of patients was detected by fluorescence staining in situ hybridization.Based on the detection results, patients were divided into GG group, GT group and TT group.All patients were given atorvastatin (20 mg/d) for lipid-lowering treatment.The levels of low density lipoprotein cholesterol(HDL-C), high density lipoprotein cholesterol(HDL-C), total cholesterol(TC)and triglyceride(TG) in serum of patients in the three groups before and 2 months after treatment were recorded and analyzed.The adverse drug reactions in the three groups were recorded. When the serum LDL-C level was less than 1.8 mmol/L, it was considered that the lipid-lowering treatment was effective.The binary Logistic regression analysis was used to explore the influencing factors of atorvastatin lipid lowering therapy.The software of SPSS 25.0 was used for statistical analysis.Results:There were 50 (38.17%), 49 (37.40%) and 32 (24.43%) patients in GG group, GT group and TT group, respectively. The serum TC levels of patients in GG group, GT group and TT group after treatment were (3.47±0.70) mmol/L, (3.59±1.09) mmol/L and (3.48±1.02) mmol/L, respectively, which were lower than those before treatment ((4.27± 0.99) mmol/L, (4.02±0.98) mmol/L and (4.03±1.31) mmol/L), all of which were statistically significant ( t=7.652, 3.092, 5.593, all P<0.01). The serum LDL-C levels in GG group, GT group and TT group after treatment were (1.89±0.53) mmol/L, (2.07±0.92) mmol/L and (1.96±0.79) mmol/L, respectively, which were lower than those before treatment ((2.87±0.92) mmol/L, (2.56±0.89) mmol/L and (2.55±1.11) mmol/L) ( t=9.896, 4.055, 5.980, all P<0.001). The differences of serum LDL-C level before and after treatment in GG group, GT group and TT group were (-0.97±0.69) mmol/L, (-0.50±0.86) mmol/L and (-0.59±0.56) mmol/L, respectively. The difference of serum LDL-C level before and after treatment in the three groups was statistically significant ( F=5.614, P=0.005). The difference of TC, TG and HDL-C before and after treatment was not statistically significant( F=2.783, 0.490, 1.677, all P>0.05). The binary Logistic regression analysis showed that ABCB1 G2677T gene type and staying up late were independent influencing factors for atorvastatin lipid-lowering therapy. The probability of effective lipid-lowering in GT patients with ABCB1 G2677T gene was 27.9% of that in GG patients ( OR=0.279, 95% CI: 0.110-0.709, P=0.007), and the probability of TT type patients was 33.8% of GG type patients ( OR=0.338, 95% CI: 0.121-0.943, P=0.038). The probability of effective lipid-lowering in patients who had the habit of staying up late was 26.4% of the patients who did not stay up late ( OR=0.264, 95% CI: 0.118-0.591, P=0.001). There was no significant difference in the total incidence of adverse drug reactions among the three groups( χ2=0.868, P=0.648). Conclusion:The lipid-lowering effect in patients with GG type of ABCB1 G2677T is better than that of GT type and TT type when atorvastatin is used to treat patients with acute cerebral infarction.
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The main clinical manifestation of dyslipidemia is hyperlipidemia， which is an important risk factor leading to the occurrence of cardiovascular and cerebrovascular diseases such as atherosclerosis， coronary heart disease and stroke. In clinical practice， lipid-lowering drugs are mainly used for treatment， but there are issues such as individual differences and genetic effects. Therefore， it is necessary to perform gene detection on patients， so as to guide individualized application of lipid-lowering drugs. This review mainly previews the definition of gene detection and the individualized treatment of lipid-lowering drugs， and introduces the application of gene detection in the individualized treatment of lipid-lowering drugs （statins， fibrates， nicotinic acid and ezetimibe）. Among them， the gene polymorphisms of APOE， SLCO1B1 and CYP450 family play a key role in the efficacy and safety of statins； the gene polymorphisms of APOA/B/C family have a significant impact on the efficacy of fenofibrate； the gene polymorphisms of HCAR2 and DGAT2 have an important impact on the efficacy of niacin； the gene polymorphisms of NPC1L1 have a significant impact on the efficacy of ezetimibe. It is suggested to conduct genotype detection for patients with dyslipidemia to select appropriate treatment strategies， so as to provide individualized medication guidance.
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ObjectiveTo evaluate the lipid-lowering activity of Quansanqi tablets（QSQ）， an innovative new drug of Panax notoginseng. MethodMice and golden hamsters were used to establish a hyperlipidemia model by injecting egg yolk milk and feeding high-fat diets. The levels of total cholesterol （TC），triglyceride （TG），low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected， and liver function indicators ［alanine aminotransferase （ALT）， aspartate amino-transferase （AST）， and alkaline phosphatase （ALP）］ of golden hamsters were detected. Hematoxylin-eosin （HE） staining was used to observe the degree of liver injury. In the experiments， a normal group， a model group， an atorvastatin calcium group， and low-， medium-， and high-dose QSQ groups （0.32， 0.64， 1.28 g·kg-1 for mice， and 0.16， 0.32， 0.64 g·kg-1 for golden hamsters） were set up. ResultCompared with the normal group， the acute hyperlipidemia model mice showed increased TC， TG， and LDL-C levels （P<0.01）， and the hyperlipidemia model mice showed increased TC and LDL-C levels （P<0.01）. Additionally， the hyperlipidemia model golden hamsters showed increased serum TC， TG， LDL-C， ALT， AST， and ALP levels （P<0.05， P<0.01）. HE staining indicated the presence of fat accumulation in the liver， accompanied by inflammatory reactions. Compared with the model group， QSQ of various doses could reduce TC， TG， and LDL-C levels in acute hyperlipidemia model mice （P<0.05， P<0.01）， and the high-dose QSQ could reduce TC and LDL-C levels （P<0.01） and increase HDL-C level （P<0.05） in hyperlipidemia model mice， as well as reduce TC， TG， and LDL-C levels in hyperlipidemia model golden hamsters （P<0.05， P<0.01）， especially in the first two weeks. In addition， atorvastatin calcium could further increase ALT， AST， and ALP levels （P<0.05， P<0.01） and aggravate liver function damage， while low-dose QSQ could reduce ALT， AST， and ALP （P<0.05）， and medium- and high-dose QSQ did not cause further liver function damage. ConclusionQSQ have a significant lipid-lowering effect on different hyperlipidemia model animals and can improve liver function and liver injury.
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Atherosclerosis is usually the underlying cause of cardiovascular diseases. With the change in diet structure and living environment, it has become an increasingly serious global health problem, posing a huge challenge to public health. Berberine, also known as flavonidol, is an isoquinoline-type quaternary alkaloid with purgative and detoxifying effects. Berberine and its derivatives have antibacterial, antiviral, anti-inflammatory, antioxidant, hypoglycemic, hypolipidemic, and atherosclerosis prevention effects, etc. Recent research results showed that berberine and its derivatives can play an important role in atherosclerosis prevention through a hypolipidemic effect, anti-oxidative stress and anti-inflammatory activity, improvement of vascular endothelial dysfunction, and regulation of intestinal microbiota. In this review paper, the research progress on the mechanism of action of berberine and its derivatives in the prevention of atherosclerosis was reviewed from the perspectives of a lipid-regulating effect, inhibition of oxidative stress and the inflammatory response, improvement of vascular endothelial dysfunction, and regulation of intestinal microbiota. The aim of this paper is to provide a theoretical basis for reducing the occurrence of atherosclerosis, improving the clinical symptoms of patients, and further developing berberine-based drugs.
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Comprehensive clinical evaluation of drugs is an important technical tool to promote the return of drugs to clinical value. Under the background of normalization and institutionalization of centralized drug volume-based procurement ，it is very crucial to actively organize and carry out comprehensive clinical evaluation of drugs. As of March 2022，there are 5 lipid-lowing drugs that have been included in the centralized drug volume-based procurement of the state and Shandong Province. In order to actively promote the medical institutions to develop the comprehensive clinical evaluation of lipid-lowing drugs standardly ，led by the Shandong Provincial Hospital Affiliated to Shandong First Medical University ，supported by Shandong Hospital Association ，and 19 third grade class A hospitals in Shandong Province jointly participated ，Using Delphi method ，through three rounds of expert opinion investigation and extensive discussion ，Expert Consensus on the Comprehensive Clinical Evaluation of Lipid-lowering Drugs under the Centralized Drug Volume-based Procurement Policy in Shandong Province was developed. The expert consensus adopted the percentage system for quantitative evaluation. The comprehensive clinical evaluation on 15 lipid-lowing drugs involved in centralized drug volume-based procurement in Shandong Province was implemented from eight dimensions including pharmaceutical characteristics ，effectiveness，safety，economy，suitability，accessibility，innovation and other attributes ，and different recommendation levels were formed according to the scores. The development of this consensus will help medical institutions to reasonably allocate and use lipid-lowering drugs in the context of centralized drug volume-based procurement ，so as to better satisfy the national policy needs and continuously improve the quality of pharmaceutical services.
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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 chromatography-mass 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.
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O BJECTIVE To investigate the regulatory effect of total fla vonoids of Matricaria recutita on lipid abnormalities in human hepatoma HepG 2 cells and its lipid-lowering mechanism. METHODS The high-content total flavonoids extract from M. recutita was isolated and purified by macroporous resin. HepG 2 cells were divided into control group （without administration ）， model group （without administration ），fenofibrate group （positive control ，3.61 μg/mL）and M. recutita total flavonoids low-dose ， medium-dose and high-dose groups （100，150 and 200 μg/mL）. Except for control group ，lipid deposition model of HepG 2 cells in other groups were established by 1 mmol/L mixture of oleic acid and palmitic acid. After 24 hours of intervention ，the levels of free fatty acids （FFA）in cell supernatant and triglyceride （TG）and FFA in cells were detected ；Oil red O staining was used to observe the deposition of lipid droplets in cells and detect the content of lipid ；DAPI staining was used to observe the protein expression of diacylglycerol acyltransferase 2（DGAT2）in cells ，and fluorescence intensity of protein expression of DGAT 2 were also detected ； protein expressions of key enzymes of TG synthesis as acetyl CoA carboxylase （ACC），fatty acid synthase （FAS）and DGAT 2 were detected by Western blot. RESULTS After separation and purification ，the content of total flavonoids from M. recutita increased from 6.72％ to 56.20％. The results of cell experiment showed that compared with control group ，the levels of TG and FFA in cells and FFA in the cell supernatant increased significantly in the model group ，the content of lipid in cells increased significantly，the fluorescence intensity of protein expression of DGAT 2 increased significantly ，and the protein expressions of ACC，FAS and DGAT 2 increased significantly （P＜0.01）； large number of lipid dro plets were accumulated in the cells. Compared with model group ，the levels of above indexes in M. recutita total flavonoids low-dose ， medium-dose andhigh-dose groups were significantly reversed （P＜0.01）；the accumulation of lipid droplets in cells decreased significantly. CONCLUSIONS M. recutita total flavonoids can inhibit the TG synthesis of lipid depos ition model HepG 2 cell，reduce the lipid accumulation of cells and prevent the lipid damage of cells. Its mechanism may be related to the down-regulation of the expression of ACC/FAS/DGAT 2 pathway.
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@#Patients undergoing coronary artery bypass grafting (CABG) belong to the very high-risk group of atherosclerotic cardiovascular disease. Although CABG gets advantages in relieving symptoms and improving long-term outcomes, a significant risk of cardiovascular adverse events after surgery still exists and standardized secondary prevention is needed. Lipid management plays a critical role as a secondary preventive strategy in CABG. However, lipid management of CABG patients in real clinical setting is inadequate, including lack of standardized lipid-lowering strategy, low goal attainment rate, as well as poor long-term medication adherence. In recent years, a series of clinical trials have provided a lot of groundbreaking new evidence for lipid management in patients with cardiovascular diseases which offers new strategies together with objectives of lipid-lowering and comprehensive management for patients undergoing CABG. This article reviews the strategy and research progress of lipid management after CABG, aiming to provide objective reference for clinical treatment.
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Zexietang is a Chinese herbal compound prescription with a long history， which consists of Rhizoma alismatis and Atractylodes macrocephala. Zexietang comes from "Synopsis of Golden Chamber"， as "there is a drink under the heart， and its people are bitter and dizzy". Zexietang has the effect of removing water from drinking water and invigorating spleen for diuresis. Modern pharmacological studies have shown that its lipid-lowering and anti-inflammatory effects are very significant. It can be used to treat hyperlipidemia， anti-atherosclerosis and non-alcoholic fatty liver disease. With the continuous development of molecular biology， the research on the pharmacological effects of Zexietang， extracts and their monomers has deepened to the molecular level gradually， and the relevant mechanism of action has also been continuously elucidated. In terms of lipid-lowering effect of Zexietang， the levels of cytokines or receptors such as 3-hydroxy-3-methyl glutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， and liver X receptors （LXR） are affected. It is widely involved in adenosine 5'-monophosphate-activated protein kinase （AMPK） and peroxisome proliferators-activated receptors （PPAR） pathways， while Zexietang's anti-inflammatory effect mainly affects inflammatory factors such as interleukins （IL） and tumor necrosis factors （TNF）， and simultaneously nuclear factor κB （NF-κB）， toll-like receptors （TLR） and other cytokines or receptor-related pathways. In order to promote the further research and clinical application of Zexietang and contribute to the development of modernization of traditional Chinese medicine， the studies of the past 15 years on molecular mechanism of the lipid-lowering and anti-inflammatory effect of Zexietang， Alisma and Atractylodes extract as well as their monomer components were reviewed.
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OBJECTIVE：To study the antioxidan t activity and lipid-lowering effect of ethanol extract and its different solvent extracts from the stems and leaves of Scutellaria amoena . METHODS ：The stem and leaves of S. amoena was extracted with 95％ ethanol to obtain ethanol extract ，and then extracted with petroleum ，ethyl acetate and n-butanol to obtain corresponding different solvent extracts. Using vitamin C （Vc）as positive control ，the antioxidant activities of ethanol extract ，petroleum ether extract ， ethyl acetate extract and n-butanol extract from the stems and leaves of S. amoena were determined by hydroxyl radical ，superoxide anion radical and DPPH radical scavenging method ，and the IC 50 was calculated. Steatosis L 02 hepatocyte model was established with fat emulsion. Using fenofibrate （20 μg/mL）as positive control ，the effects of high and low concentration （100 and 50 μg/mL） ethanol extract ，ethyl acetate extract and n-butanol extract from the stems and leaves of S. amoena on the contents of TC and TG in cells were investigated. RESULTS ：The order of scavenging ability to hydroxyl radicals was n-butanol extract ＞ethyl acetate extract＞Vc＞ethanol extract ＞petroleum ether extract ；IC50 of them were 0.15，0.17，0.35，0.75，1.17 mg/mL，respectively. The order of scavenging ability to superoxide anion radical was Vc ＞n-butanol extract ＞ethyl acetate extract ＞ethanol extract ＞ petroleum ether extract ；IC50 of them were 0.034，0.55，0.75，3.32，3.73 mg/mL，respectively. The order of DPPH scavenging ability to DPPH radical was Vc ＞n-butanol extract ＞ethyl acetate extract ＞ethanol extract ＞petroleum ether extract ；IC50 of them were 0.003 2，0.028，0.033，0.048，0.057 mg/mL， respectively. The ethanol extract ，ethyl acetate extract and n-butanol extract from the stems and leaves of S. amoena could significantly decrease the contents of TC and TG in steatosis L 02 hepatocytes （P＜0.01）. The order of lipid-lowering ability was n-butanol extract （low dose ）≈fenofibrate＞ethyl acetate extract （high dose ）＞ethanol extract （high dose ）＞ n-butanol extract （high dose ）＞ethyl acetate extract （low dose ）＞ethanol extract （low dose ）. CONCLUSIONS ：The ethanol extract ， petroleum ether extract ，ethyl acetate extract and n-butanol extract from the stems and leaves of S. amoena show good antioxidant activity and lipid-lowering effect （except for petroleum ether extract ）. Ethyl acetate extract and n-butanol extract possess the strongest antioxidant activity and lipid-lowering effect.
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High fat diet induced hyperlipidemia hamster model was used to explore the anti-hyperlipidemia effect of water extract of Moringa oleifera leaves( WEMOL). On this basis,the possible action mechanism was predicted by network pharmacology. Golden hamsters were randomly divided into normal diet group( NFD),high-fat diet group( HFD),simvastatin group,high dose group of WEMOL( HIWEMOL) and low dose group of WEMOL( LOWEMOL). The model was administered simultaneously for 66 days,during which the body weight changes of hamsters were recorded. At the end of the experiment,serum lipid level and serum transaminase level of golden hamsters in each group were detected,and the pathological changes of liver were observed by hematoxylin-eosin( HE) staining. The results showed that WEMOL could significantly decrease the serum total cholesterol( TC),total triglyceride( TG),low density lipoprotein cholesterol( LDL-c) levels,and reduce the lipid deposition in liver tissue,thus improving the hyperlipidemia of golden hamsters. According to the prediction of network pharmacology,219 targets of potential active components of M.oleifera leaves and 185 targets of water-soluble potential active components of M. oleifera leaves for the treatment of hyperlipidemia were obtained separately. The MCODE analysis was performed on the PPI network of 219 targets and 185 targets obtained above and got five and four clusters respectively. The signaling pathway analysis of clusters showed that among the common pathways,nonalcoholic fatty liver,insulin resistance,MAPK signaling pathway,estrogen signaling pathway,cell apoptosis and HIF-1 signaling pathway were associated with hyperlipidemia. In addition,the potential active components of M. oleifera leaves could also inhibit the metabolic inflammation of hyperlipidemia by modulating complement and coagulation cascades signaling pathway,and GSK3 B,F2,AKT1,RELA,SERPINE1 might be the key targets. The water-soluble potential active components of M. oliefera leaves could modulate lipid metabolism by modulating AMPK signaling pathway and JAK-STAT signaling pathway,with PIK3 CB,PIK3 CA,CASP3,AKT1 and BCL2 as the key targets. These results suggested that WEMOL had anti hyperlipidemia effect,and its mechanism might be related to the protein expression regulation of lipid metabolism,nonalcoholic fatty liver disease and atherosclerosis related signaling pathways.
Subject(s)
Animals , Cricetinae , Diet, High-Fat , Glycogen Synthase Kinase 3 , Hyperlipidemias/drug therapy , Liver , Moringa oleifera , Plant LeavesABSTRACT
This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.
Subject(s)
Animals , Rats , Biological Transport , Cholesterol/metabolism , Diet, High-Fat/adverse effects , Hyperlipidemias/metabolism , Liver/metabolism , Rats, Sprague-Dawley , Triglycerides/metabolismABSTRACT
Background: Stroke is one of the major global health problems. Stroke is the most common clinical manifestation of cerebrovascular disease of which more than 99% are due to arterial involvement and less than 1% due to venous involvement in the form of Cerebral Venous Thrombosis (CVT). Among arterial causes 85% are due to infarction and 15% due to haemorrhage.1,2 There is difference in serum lipid levels in subtypes of strokes to guide lipid-lowering therapy which can reduce incidence of stroke and stroke related mortality by adapting primary and secondary preventive measures.3,4 Authors have endeavoured to correlate severity of lipid derangement and stroke.Methods: In this study 64 consecutive eligible ischaemic stroke cases and 64 eligible hemorrhagic stroke cases would be included. Cases of strokes will be divided into ischaemic and hemorrhagic as per clinical features and with help of brain imaging by CT scan and MRI at the time of admission and 8 hour fasting lipid profile was collected from all cases. All this information will be filled in preformed format.Results: Serum lipid profile of two categories of stroke showed raised serum total cholesterol in 39.1% patients of ischaemic stroke in contrast to 18.8% patients with haemorrhagic stroke (p=0.019).Stroke patients showed raised in LDL cholesterol in 29.7% patients of ischaemic stroke in contrast to 9.4% patients with haemorrhagic stroke, (p=0.007).Conclusions: Based on the finding of our study we conclude that ischemic stroke patient had higher lipid derangement as compare to haemorrhagic stroke in terms of raise total cholesterol, LDL cholesterol and decrease HDL cholesterol.
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OBJECTIVE：To study the ef fects of Gegen qinlian decoction （GGQLD）on blood lipid and blood glucose of hyperlipidemia（HLP）model rats ，and to explore its mechanism from the perspective of intestinal flora. METHODS ：Totally 48 rats were randomly divided into blank control group （n＝8）and modeling group （n＝40）. For consecutive 5 weeks，model group was given high-lipid diet to induce HLP model ；blank control group was given routine diet. After modeling ，30 modeling rats were randomly divided into model group ，simvastatin group （positive control ，10 mg/kg），GGQLD high-dose ，medium-dose and low-dose groups （14.85，4.95，1.65 g/kg，by crude drug ），with 6 rats in each group. Blank control group and model group were given constant volume of normal saline intragastrically ；administration groups were given relevant medicine intragastrically ，once a day，for consecutive 11 weeks. At the same time ，each group was continuously given corresponding diet. After the last medication ， body mass and body length of rats were determined ，and Lee ’s index was calculated. Serum levels of TG ，TC，HDL-C，LDL-C and fasting blood glucose （FBG）were determined in rats. DNA of rat caecum content was extracted for 16S rRNA V 3-V4 region sequencing. The Two-part model was used to analyze the correlation between intestinal flora with lipids and blood glucose. RESULTS：After 11 weeks of administration ，compared with blank control group ，the body mass ，body length ，Lee’s index ， serum levels of TC ，TG，HDL-C and FBG of model group were increased significantly （P＜0.05 or P＜0.01），while the level of HDL-C was decreased significantly （P＜0.05）. Compared with model group ，body mass and Lee ’s index and serum levels of TG ， FBG of rats in GGQLD high-dose group ，and serum levels of TC ，TG in GGQLD medium-dose group ，as well as serum level of TG of rats in GGQLD low-dose group was decreased significantly （P＜0.05 or P＜0.01）. Correlation analysis with intestinal flora showed that TC and TG shared 3 operational taxonomic units （OTU），including OTU 559，OTU701 and OTU 135（OTU135 was also shared with FBG ），which were all positively correlated with the level of TC ，TG and FBG （P＜0.01）. The three OTU were annotated as Tyzzerella of Spirillaceae ，Anaerotruncus of Verrucaceae and Peptoclostridium of Streptococcidae ，respectively. High-dose and low-dose GGQLD had a down-regulating effect on Tyzzerella and Anaerotruncus（P＜0.05 or P＜0.01），while had up-regulating effect on Peptoclostridium（P＜0.01）. CONCLUSIONS ：High-dose GGQLD （14.85 g/kg）can effectively reduce the body mass and blood lipid of HLP model rats ，and can prevent the abnormal increase of blood glucose of model rats. The mechanism may be associated with that the reduction of intestinal flora （Tyzzerella，Anaerotruncus）content.
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Objective:To investigate the pharmacodynamics effects of antiobesity, lipid-lowering and the regulations of serum bile acid profiles of Lidan Ruanjian prescription (LDRJ) in obesity rats induced by high-fat diet. Method:The 42 rats were fed high-fat diet for 9 weeks to establish model of obese rats，24 rats were randomly divided into model group, high and low-dose LDRJ group (30,15 g·kg-1). Another 8 normal rats were selected as the normal group.The model group and normal group were given normal saline, and drug group was given the corresponding dose of drug for 4 weeks. Body weight, liver weight, white adipose tissue (WAT) weight were determined after administration medicine for 4 weeks. The bile flow of the rats was measured by bile duct intubation and fasting serum lipid levels of total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) were detected by automatic biochemical analyzer. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay was used to test serum bile acid profile of each group rats. Result:Compared with the control group, the average body weight, liver weight, WAT weight of the model group were significantly increased (P<0.01), while the fasting serum TC, TG and LDL-C levels were elevated (P<0.05，P<0.01). The total bile secretion and bile flow at each test point within 2 h were decreased and the proportion of primary bile acids was decreased (P<0.05).The serum total bile acid content decreased significantly（P<0.01），levels of cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), taurochenodeoxycholic acid (TCDCA), taurohyodeoxycholic acid (THDCA) and glycodeoxycholic acid (GDCA) were significantly reduced (P<0.05，P<0.01). Compare with model group, body weight, liver weight in high and low-dose LDRJ groups reduced significantly(P<0.05，P<0.01). Fasting serum TC, TG and LDL-C levels were decreased in high-dose group(P<0.05，P<0.01), so did as TG levels in low-dose group(P<0.05). The bile flow rate increased significantly in high-dose group 1~1.5 h after administration (P<0.05). All dose treatment groups increased the proportion of primary bile acids (P<0.05) and changed the bile acid profile, especially elevated the bile acid levels of TCA, DCA, glycocholic acid (GCA), GDCA in high-dose LDRJ group (P<0.05，P<0.01), while TCA and TCDCA in low-dose group (P<0.05). Conclusion:LDRJ has significant lipid-lowering and antiobesity effects and the mechanism might involve the increase of bile secretion, the stimulation of primary bile acid synthesis and the regulation of bile acid profile.
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Methylophiopogonanone A (MO-A), a homoisoflavonoid extracted from Ophiopogon japonicus, has been shown to attenuate myocardial apoptosis and improve cerebral ischemia/reperfusion injury. However, the hypolipidemic effects remain unknown. This study was performed to investigate a potential hypolipidemic effect of MO-A in hyperlipidemia rats, as well as its underlying mechanism of action. A rat model of hyperlipidemia was induced by a high-fat diet (HFD). Animals were randomly divided into three groups (n=8/group): normal control group (NC), HFD group, and HFD+MO-A (10 mg·kg-1·d-1) treatment group. The effects of MO-A on serum lipids, body weight, activity of lipoprotein metabolism enzyme, and gene expression of lipid metabolism were evaluated in HFD-induced rats. In HFD-induced rats, pretreatment with MO-A decreased the body weight gain and reduced serum and hepatic lipid levels. In addition, pretreatment with MO-A improved the activities of lipoprotein lipase and hepatic lipase in serum and liver, down-regulated mRNA expression of acetyl CoA carboxylase and sterol regulatory element-binding protein 1c, and up-regulated mRNA expression of low-density lipoprotein receptor and peroxisome proliferator-activated receptor α in the liver. Our results indicated that MO-A showed strong ability to ameliorate the hyperlipidemia in HFD-induced rats. MO-A might be a potential candidate for prevention of overweight and dyslipidemia induced by HFD.
Subject(s)
Animals , Male , Rats , Ophiopogon/chemistry , Benzodioxoles/pharmacology , Lipid Metabolism , Diet, High-Fat , Hyperlipidemias/prevention & control , Isoflavones/pharmacology , Blotting, Western , Rats, Sprague-Dawley , Disease Models, Animal , Benzodioxoles/isolation & purification , Feces/chemistry , Real-Time Polymerase Chain Reaction , Hyperlipidemias/metabolism , Isoflavones/isolation & purification , Lipids/analysisABSTRACT
@#The metabolic reprogramming in cancer cells has recently attracted more and more attention from researchers. Lipid metabolism is involved in many cell processes such as cell growth, apoptosis, exercise, membrane homeostasis, chemotherapy response and drug resistance. This article summerizes the advances in research on fatty acids, cholesterol and phospholipid metabolism in non-small cell lung cancer, which may provide new ideas for the prevention, early diagnosis and treatment of non-small cell lung cancer.
ABSTRACT
The paper studies and compares the metabolic difference of active ingredients of lipid-lowering flavonoid extract of Daidai in rat livers and intestinal microsomes,in order to explore the phase Ⅰ metabolism characteristics of active ingredients in livers and intestines. UPLC-MS/MS was used to establish a quantitative analysis method for active ingredients,neohesperidin and narngin,in a phase Ⅰ metabolism incubation system of liver and intestinal microsomes. Differential centrifugation was used to make liver and intestinal microsomes of rats. A phase Ⅰ metabolism incubation system was established,and the concentrations of the residual at different incubation time points were analyzed. Graphs were plotted to calculate the metabolic elimination half-life of the main active parts,with the natural logarithm residual percentage values ln( X) at different time points as the y axis,and time t as the x axis. The metabolism characteristics of the active ingredients were compared. The established UPLC-MS/MS quantitative analysis method has a good specialization,standard curve and linear range,accuracy and precision,with a satisfactory lower quantitative limit. The method allows quantitative detection of the active ingredients in a phase Ⅰ metabolism incubation system of liver and intestinal microsomes of rats. In the rats liver microsomes incubation system,the metabolic elimination half-life of neohesperidin and narngin were( 2. 20 ± 0. 28) h and( 1. 97±0. 28) h respectively. The elimination half-life of neohesperidin was larger than that of narngin,but with no statistically significant difference. In the rats intestinal microsomes incubation system,the metabolic elimination half-lives of neohesperidin and narngin were( 3. 68±0. 54) h and( 2. 26±0. 13) h respectively. The elimination half-life of neohesperidin was larger than that of narngin,with statistically significant differences( P<0. 05). The elimination half-lives of the active ingredients in liver microsomes were smaller than those in intestinal microsomes. The experiment results showed that the active ingredients of lipid-lowering flavonoid extract of Daidai had different elimination half-lives in phase Ⅰ rats liver and intestinal microsomes incubation system. This implied that they had different metabolic characteristics in rats liver and intestine,and liver may be the main metabolism site of the active ingredients. The phaseⅠ metabolism of narngin was stronger than that of neohesperidin. The differences between their metabolic characteristics may be related to the binding sites of B-ring hydroxyl in flavonoid glycosides and the number of methoxyl group. The results provided an important experimental basis for further development and clinical application of lipid-lowering flavonoid extract preparation of Daidai.
Subject(s)
Animals , Rats , Chromatography, Liquid , Citrus sinensis , Flavonoids , Intestines , Lipids , Liver , Microsomes, Liver , Rats, Sprague-Dawley , Tandem Mass SpectrometryABSTRACT
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 3T3-L1 cell model revealed that 1 and 2 could significantly inhibit the lipid droplet formation (EC = 0.41 and 0.92 μmol·L, respectively) and lower triglyceride levels by 50%-60% at the concentration of 1 μmol·L, being more potent than the positive drug luteolin (EC = 2.63 μmol·L). A mechanistic study indicated that 1 and 2 could intercalate into supercoiled DNA, which consequently inhibited the mitotic clonal expansion of 3T3-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 development of anti-obesity drugs.