Effect of icariin on ubiquitination of amyloid precur-sor protein in Alzheimer's disease mice / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of icariin(ICA)on the ubiquitination modification of β-amy-loid precursor protein(APP)in Alzheimer's disease mice.METHODS In vitro,① HEK 293 cells stably overex-pressing human APP695(OE-hAPP)were treated with different concentrations of ICA(10-100 μmol·L-1)for 24 h and the cell viability was detected by MTT assay.②CHX(50 mg·L-1)was used to block protein synthesis and MG132(20 μmol·L-1)inhibits proteasome activity,then the level of APP in different time(0,0.5,1,2,3 and 4 h)and the ubiquitination were tested by Western blotting.③ E3 ubiquitin ligases HMG-CoA reductase degradation pro-tein 1(HRD1)protein expression in OE-hAPP was tested by Western blotting,as well as the level and ubiquitination of APP were tested under HRD1 silent condition by Co-IP and Western blotting.In vivo,① male APP/PS1 mice and wild type(WT)mice were randomly divided into 5 groups:WT,WT+ICA,APP/PS1,APP/PS1+ICA,and APP/PS1+donepezil(DPZ)groups.ICA(60 mg·kg-1·d-1)and DPZ(1 mg·kg-1·d-1)were treated for 3 months by gavage from 6 months of age,and WT mice were given equal volume of distilled water.②Morris water maze and Y-maze experiments were used to detect the alteration of spatial learning memory function.③ After then,the brain tissues were collected,total proteins were extracted,APP antibodies were subjected to Co-IP,and total ubiqui-tination(Ub),K48-linked polyubiquitination(UbK48)and K63-linked polyubiquitination of APP level,APP and HRD1 proteins were detected by Western blotting.RESULTS In vitro results showed that ICA significantly enhanced APP degradation(vs control,P＜0.01),up-reg-ulated HRD1 expression(vs control,P＜0.05;vs OE-hAPP,P＜0.05),elevated the level Ub and UbK48 of APP,as well as increased APP degradation.Moreover,silenced HRD1 gene abolished abovementioned effects of ICA(vs control-siRNA,P＜0.05;vs HRD1-siRNA,P＜0.05).In vivo results showed that ICA improved the spa-tial learning and memory function APP/PS1 mice by Mor-ris water maze and Y-maze tests,increased HRD1 expres-sion(vs APP/PS1 + vehicle,P＜0.05),enhanced APP ubiquitination and reduced APP protein level(vs APP/PS1 + vehicle,P＜0.01).CONCLUSION ICA promotes the ubiquitination and proteasome-dependent degrada-tion of APP by up-regulating HRD1,thereby improving the spatial learning and memory function of Alzheimer disease mice.

Effects of statin response on cardiovascular outcomes in patients with ST-segment elevation myocardial infarction

SUMMARY OBJECTIVE: This study aimed to evaluate the effects of statin response on cardiovascular outcomes in patients with ST-segment elevation myocardial infarction. METHODS: A total of 1029 ST-segment elevation myocardial infarction patients were enrolled in the study. The patients who failed to achieve >40% reduction in baseline low-density lipoprotein cholesterol levels within 30 days to 12 months after statin initiation were defined as suboptimal statin responders. The adjusted hazard ratios for cardiovascular outcomes for low-density lipoprotein cholesterol response to statins were estimated via the Cox proportional regression model. The relationship between the statin response and cardiovascular outcomes was also evaluated in a subgroup of on-treatment low-density lipoprotein cholesterol levels below 55 mg/dL. RESULTS: Among the study population, 573 (55.6%) patients demonstrated suboptimal low-density lipoprotein cholesterol response to statin therapy. These patients showed a significantly higher incidence of the composite of major adverse cardiovascular events, including cardiovascular death, reinfarction, recurrent myocardial infarction, and target vessel revascularization during the follow-up compared with optimal responders (adjusted hazard ratios 3.99; 95%CI 2.66-6.01; p<0.001). In a subgroup of patients with on-treatment low-density lipoprotein cholesterol levels below 55 mg/dL, suboptimal statin responders also showed unfavorable cardiovascular outcomes (adjusted hazard ratios 8.73; 95%CI 2.81-27.1; p<0.001). CONCLUSIONS: The present study showed that over half of the patients with ST-segment elevation myocardial infarction did not exhibit optimal low-density lipoprotein cholesterol response to statin. These patients have an increased risk of future major adverse cardiovascular events.

Clinical significance of NRSN2-AS1 expression in ovarian cancer and its biological effect in vitro / 中华内分泌外科杂志

Objective:To investigate the clinical significance and biological effect of long non-coding RNA (lncRNA) NRSN2-AS1 in ovarian cancer.Methods:The expression of NRSN2-AS1 was detected by real-time quantitative PCR (RT-qPCR) in 84 cases of ovarian cancer tissues and corresponding normal adjacent tissues, and the relationship between NRSN2-AS1 expression and clinical data of patients was analyzed. Human ovarian epithelial cells HOSEpiC and human ovarian cancer cells A2780 and OVCAR3 were cultured in vitro, and overexpression or interference of NRSN2-AS1 and control plasmids were respectively transfected into A2780 and OVCAR3 cells as the blank group, overexpression group and control group, interference group. CCK-8 assay was used to detect cell proliferation, while transwell invasion and migration assay were used to detect the change of cell metastasis ability, RT-qPCR and Western blot were used to detect the expressions of SRY related HMG box transcription factor 12 (SOX12), a potential downstream gene of NRSN2-AS1.Results:The expressions of NRSN2-AS1 in ovarian cancer tissues and cells were significantly higher than normal adjacent tissues, and the high expression of NRSN2-AS1 was significantly correlated with poor prognosis, lymph node metastasis and high clinical stage ( P<0.05). In the blank and overexpression group, the expressions of NRSN2-AS1 were 1.00±0.08 and 5.78±0.41, the expressions of SOX12 mRNA were 1.00±0.10 and 3.08±0.23, the expression of SOX12 protein were 1.00±0.08 and 7.26±0.39, the invasion cells per field were 22.7±4.9 and 79.0±6.2, and the migration cells per field were 26.5±4.1 and 43.5±4.5. In the control and interference group, the expression of NRSN2-AS1 were 1.00±0.11 and 0.37±0.04, the expressions of SOX12 mRNA were 1.00±0.07 and 0.59±0.05, the expression of SOX12 protein were 1.00±0.07 and 0.36±0.03, the invasion cells per field were 68.3±6.1 and 30.6±5.5, and the migration cells per field were 85.2±7.0 and 22.7±4.2. Compared with the blank group, the expression of SOX12 mRNA and protein in the overexpression group was significantly increased ( P<0.05), and the cell proliferation and metastasis ability were significantly enhanced ( P<0.05). Compared with the control group, the expression of SOX12 mRNA and protein in the interference group was significantly decreased, and the ability of cell proliferation and metastasis was suppressed significantly ( P<0.05) . Conclusion:The expression of NRSN2-AS1 is up-regulated in ovarian cancer, which is closely related to poor prognosis and progression of ovarian cancer. NRSN2-AS1 can promote the expression of SOX12 and the malignant behavior of ovarian cancer cells in vitro.

Design and Evaluation of Lovastatin Solid Dispersions Incorporated Trilayer Matrix Tablets

The current work is aimed to design, prepare and evaluate the trilayer matrix tablets incorporated with lovastatin solid dispersion (SD) for extend drug release. The lovastatin SD prepared by using solvent evaporation technique with varying amounts of polymers (GMS II, Soluplus, Kolliphor ELP, PEG 2000 and Urea) for enhancing the drug solubility. All the formulations examined for physicochemical parameters are within the permissible limits. The optimized SD formulation was incorporated into trilayer matrix tablets which were prepared using different polymers (HPMC 15M & K100M, Chitosan, xanthan gum) by direct compression method for sustaining the drug release. The drug dissolution of optimized lovastatin SD formulation SD15 (drug, soluplus and SLN) was 99.88±5.32% within 60 min which is higher than pure drug 47.33±2.25% and other formulations. The FT-IR, XRD and SEM data assure the compatibility of drug and excipients and amorphous nature of lovastatin. The solid dispersions were further incorporated in to trilayer matrix tablets with active layer and barrier layers. Eight formulations of lovastatin trilayer matrix tablets (AF9-HF9) designed and checked for pre compression parameters. Formulation GF9 demonstrated highest drug release of 99.41±5.28% for 24 hours sustainably over an extended period of time and excellent flow properties. The release order kinetics data indicate the zero order release with highest R2 of 0.9957 for GF9, superior than market extended release formulation (R2=0.9934). All the formulations showed best fit to Higuchi model and Korsmeyer-Peppa’s model indicating diffusion and non-Fickian diffusion process of drug release. GF90 was found to be stable for 180 days at accelerated conditions. Hence the solubility, dissolution rate of lovastatin was enhanced by SD technique further incorporated in to trilayer matrix tablets for sustainable extended drug release upto 24 h.

Evaluation of hyperglycaemic risk of atorvastatin: a dose dependent study on hyperlipidaemic rats

Background: Statins (?-hydroxy ?-methylglutaryl-CoA (HMG-CoA) reductase inhibitors) are the most prescribed medications worldwide to treat hyperlipidaemia with a proven ability to reduce major cardiovascular events. Recent data have revealed that statin therapy is associated with an increased risk for developing diabetes. The risk was most significant in patients taking atorvastatin, rosuvastatin and simvastatin.Methods: Rats were divided into 3 groups, each comprising of 6 rats. Hyperlipidaemia was induced in all the animals after feeding with high fat diet for 15 days. Rats of groups 1, 2 and 3 were given atorvastatin 1.8 mg/kg (low-dose), 3.6 mg/kg (moderate-dose) and 7.2 mg/kg (intensive-dose) respectively orally for 60 days. 12 hours fasted blood samples were collected and analyzed for serum lipid profile, fasting blood glucose and HbA1c levels.Results: The percentage increase in plasma blood glucose after 60 days of treatment in groups 1, 2, and 3 is 29.93%, 60.03% and 72.42% respectively and the variation in all the groups is statistically significant, p<0.0001. Regarding HbA1c values, the variation in low-dose group is statistically insignificant whereas the percentage increase in moderate-dose and intensive-dose groups is 19.45% (p<0.001) and 43.37% (p<0.0001) respectively.Conclusions: In conclusion, there is significant increase in blood glucose and HbA1c levels leading to new-onset diabetes in both moderate-dose and intensive-dose groups. The risk is more in intensive-dose group when compared to moderate-dose group.

Statins & risk of Clostridium difficile infection: A meta-analysis

Background & objectives: Clostridium difficile infection is one of the most common healthcare-associated infections worldwide. Recent epidemiologic studies have suggested that statin users may have a lower risk of C. difficile infection, although the results are inconsistent. This meta-analysis was conducted with the aim of summarizing all available data to assess the risk of C. difficile infection among statin users versus non-users. Methods: A literature review was performed using the MEDLINE and EMBASE databases from inception to October 2017. Cohort, case-control and cross-sectional studies that compared the risk of C. difficile infection among statin users versus non-users were included. Pooled odds ratio (OR) and 95 per cent confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Results: Six case-control studies and two cross-sectional studies met the eligibility criteria and were included in this meta-analysis. The risk of C. difficile infection among statin users was significantly lower than non-users with the pooled OR of 0.74 (95% CI, 0.61-0.89). The statistical heterogeneity of this study was high (I[2]=90%). Interpretation & conclusions: This meta-analysis demonstrated a decreased risk of C. difficile infection among statin users versus non-users. Further studies are required to clarify the role of statins for prevention of C. difficile infection in clinical practice.

Effect of statins treatment on glycemic status and development of new onset diabetes mellitus in a tertiary care teaching hospital: a cross sectional study

Background: Several observational studies, well controlled randomized trials and meta-analyses reported that patients treated with statins has high risk of new onset diabetes mellitus (NODM), but the exact incidence and mechanism is still unclear and controversy. The present study was planned to find out the incidence of prediabetes and NODM and possible mechanism of action.Methods: This was a prospective, cross‑sectional study carried out at the Department of General Medicine for a period of one and half year between August 2017 and February 2019. Normoglycemic patients whose fasting blood glucose levels below 100 mg/dL and at least one year of treatment with statins were recruited in the study. Glycaemic status, development of prediabetes and NODM and insulin resistance were the primary outcomes whereas lipid profile, adverse drug effects of statins were secondary outcomes. Collected data was analysed by suitable statistical methods.Results: A total of 146 patients were recruited and 120 completed the entire study. Mean fasting blood glucose levels before initiation of statin therapy was 89.45±10.21. After one year of statin therapy, patients were separated as prediabetics and new onset diabetics and there mean fasting blood glucose levels were 116.24±12.86 (n=10) and 152.44±20.12 (n=12) respectively. A total of 12 (10.0%) patients were developed NODM and 10 (8.2%) patients developed prediabetes at the end of statin therapy. Atorvastatin 40mg was most frequency prescribed statin followed by Atorvastatin 20mg. A total of 70 (58.3%) study participants developed mild to moderate drug related adverse effects (ADRs), statin‑induced myalgia (55.7%) was the most common ADR.Conclusions: Patients treatment with statins had developed prediabetes and NODM. Atorvastatin 40mg and greater dose significantly induced NODM. Fasting blood glucose levels should be measured periodically with prescription contains higher doses of statins

The Modulating Effect Of Barley Β-Glucan Extract On High Fat Diet Induced Obesity-A Biochemical Study In Albino Wistar Rats

Objective: Diet-inducedhyperlipidemia and obesity are the major risk factors for type II diabetes mellitus, hypertension, musculoskeletal and cardiovascular disorders (CVD). The objective of the present study is to furnish scientific proof for the lipid-lowering effect of β-glucan, a lead compound present in barley with a defined mechanism of action. Methods: Obesity was induced in male albino Wistar rats by feeding ahigh-fat diet (HFD) for 14 w and were randomly divided into four groups of equal number (n=6). Group 1 and 2 served as control fed with normal diet (5% fat). Group 3 and 4 were fed HFD (23%fat) for 14 w. In addition, group 2 and 4 rats were administered orally with 200 mg/kg body weight of barley β glucan (BRBG) from the third week. After 14 w, the rats were sacrificed, and serum/plasma levels of total cholesterol (TC), phospholipids, triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and adiponectin were determined. Results: Biochemical changes were observed in weight gain, body mass index (BMI),adiposity index (ADI), total fat pad mass (TFP), blood lipids, LDL, lipid peroxides (LPO) and antioxidant enzyme activity of HFD fed rats when compared with BRBG co-administered rats. In addition, serum adiponectin levels and 3-hydroxy-3methyl-glutaryl-coenzyme Areductase(HMG CoA reductase)activity were elevated in rats administered BRBG along with HFD. Histological examination in HFD induced rats revealed a profound change in cell size with increased hypertrophy in visceral adipose tissue. Conclusions: The results indicate that barley consumption could reverse most of these biochemical and histological changes in HFD fed rats owing to its hypolipidemic and antioxidant effect.

Nrf2-inducing and HMG-CoA reductase inhibitory activities of a polyphenol-rich fraction of Guazuma ulmifolia leaves

To fractionate and identify polyphenols from Guazuma ulmifolia Lam. leaves, and to explore their antioxidant, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitory, and Nrf2 modulatory activities. Methods: The 1,1-diphenyl-2-picrylhydrazyl assay was used to evaluate the antioxidant activity of a polyphenolic fraction of the extract of Guazuma ulmifolia Lam. leaves. THP-1 gene reporter cell lines constructed with a transcriptional response element specific for Nrf2 and a minimal promoter for the firefly luciferase–green fluorescent protein transgene were used to determine the effect of the polyphenolic fraction on the Nrf2 signaling pathway. Furthermore, an assay of HMG-CoA reductase inhibitory activity was performed by using a commercial enzyme kit. Polyphenolic compounds were identified by liquid chromatography-tandem mass spectrometry. Results: The polyphenolic fraction showed fairly strong antioxidant activity [IC50 = (14.90 ± 4.70) μg/mL] and inhibited HMG-CoA reductase activity by 69.10％, which was slightly lower than that by pravastatin (84.37％) and quercetin (84.25％). Additionally, the polyphenolic fraction activated the Nrf2 antioxidant signaling pathway at 500 μg/mL. Eleven subfractions resulting from the column chromatography separation of the polyphenolic fraction also showed relatively strong antioxidant activities (IC50: 17.46–217.14 μg/mL). The subfraction (F6) stimulated the Nrf2 signaling pathway and had HMG-CoA reductase inhibitory activity (65.43％). Moreover, the subfraction contained two main flavonoids: quercetin and quercimeritrin. Conclusions: The polyphenolic fraction of Guazuma ulmifolia could induce antioxidant genes via the Nrf2/antioxidant regulatory elements pathway, and is a promising candidate for an inhibitor of HMG-CoA reductase.

Zaluzania montagnifolia: essential oil composition and biological properties / Zaluzania montagnifolia: composición del aceite esencial y actividades biológicas

The chemical composition of the seasonal essential oils (2015-2016) from the leaves and flowers of Zaluzania montagnifolia is presented. The chemical content of those oils showed quantitative and qualitative differences. Germacrene D (19.9-29.8%), camphor (12.4- 19.4%) and ß-caryophyllene (13.7-18.5%) were the most abundant volatiles in the leaves. The essential oils from the flowers contained high amounts of camphor (32.7-37.2%) limonene (19.8-24.9%) and germacrene D (3.2-7.3%). All the seasonal essential oils showed a potent in vitro inhibition against HMG-CoA reductase. The essential oils from flowers (IC50, 40.5-55.1 µg mL-1) showed better inhibition properties than those of leaves (IC50, 84.4-123.5 µg mL-1). Camphor (IC50, 72.5 µg mL-1) and borneol (IC50, 84.4 µg mL-1) exerted a non-competitive inhibition on the enzyme. Additionally, the hydrodistillates exhibited antibacterial activity against the phytopathogenic Pseudomonas syringae pv. tabaci TBR2004 (MIC, 62.7-76.5 µg mL-1) P. syringae pv. tomato DC3000 (MIC, 45.4-50.4 µg mL-1) and P. syringae pv. phaseolicola NPS3121 (MIC, 26.7-31.9 µg mL-1). Germacrene D (MIC, 35.4-66.2 µg mL-1) and ß-caryophyllene (MIC, 36.5-54.2 µg mL-1) were the strongest anti-Pseudomonas syringae agents.

Se presenta la composición química de los aceites esenciales estacionales (2015-2016) provenientes de hojas y flores de Zaluzania montagnifolia. El contenido químico de los aceites esenciales mostró diferencias cualitativas y cuantitativas. El germacreno D (19.9-29.8%), alcanfor (12.4-19.4%) y ß-cariofileno (13.7-18.5%) fueron los volátiles más abundantes en las hojas. Los aceites esenciales de las flores contuvieron altas concentraciones de alcanfor (32.7-37.2%), limoneno (19.8-24.9%) y germacreno D (3.2-7.3%). Todos los aceites esenciales estacionales mostraron una potente inhibición in vitro contra la HMG-CoA reductasa. Los aceites esenciales de las flores (IC50, 40.5-55.1 µg mL-1) mostraron mejores propiedades inhibitorias que aquellos de las hojas (IC50, 84.4-123.5 µg mL-1). El alcanfor (IC50, 72.5 µg mL-1) y el borneol (IC50, 84.4 µg mL-1) ejercieron una inhibición no competitiva sobre la enzima. Adicionalmente, los hidrodestilados exhibieron una actividad antibacterial contra los fitopatógenos Pseudomonas syringae pv. tabaci TBR2004 (MIC, 62.7-76.5 µg mL-1) P. syringae pv. tomato DC3000 (MIC, 45.4-50.4 µg mL-1) y P. syringae pv. phaseolicola NPS3121 (MIC, 26.7-31.9 µg mL-1). El germacreno D (MIC, 35.4-66.2 µg mL-1) y ß-cariofileno (MIC, 36.5-54.2 µg mL-1) fueron los agentes más fuertes contra los patovares de Pseudomonas syringae.

Prescribing trends of HMG Co-A reductase inhibitors in outdoor patients at tertiary care teaching hospital of central India: a retrospective observational study

Background: To analyze the prescribing patterns of statins a hypolipidemic agents by using HMIS database in outdoor patients at tertiary care teaching hospital of central India.Methods: In this retrospective study Using HMIS database, 1000 prescriptions were analyzed for statin use for various WHO prescription indicators using ATC code of statins, the ratio of prescribed daily dose (PDD) and defined daily dose (DDD) was calculated.Results: Atorvastatin was the only statin which was prescribed as monotherapy (61.1%), whereas as combination with aspirin (38.9%). While analyzing the prescriptions, it was found that patients having abnormal lipid profiles (51.8%) and normal lipid profiles (48.2%) were prescribed atorvastatin. Hypertension with diabetes (37%) was the most common disease followed by hypertension (21.2%) and diabetes mellitus (21%) for which atorvastatin was prescribed. The average number of drugs per prescription were 3.8±1.65.Conclusions: This study depicts the use of atorvastatin in various disease conditions, both as primary and secondary preventive measures. There was no polypharmacy. Such studies should be done to educate the physicians on good prescribing practices and to rationalize use of hypolipidemic drugs.

Functional Implications of HMG-CoA Reductase Inhibition on Glucose Metabolism

HMG-CoA reductase inhibitors, i.e. statins, are effective in reducing cardiovascular disease events but also in cardiac-related and overall mortality. Statins are in general well-tolerated, but currently the concerns are raised if statins may increase the risk of new-onset diabetes mellitus (NOD). In this review, the possible effects of statins on organs/tissues being involved in glucose metabolism, i.e. liver, pancreas, adipose tissue, and muscles, had been discussed. The net outcome seems to be inconsistent and often contradictory, which may be largely affected by in vitro experimental settings or/and in vivo animal conditions. The majority of studies point out statin-induced changes of regulations of isoprenoid metabolites and cell-associated cholesterol contents as predisposing factors related to the statin-induced NOD. On the other hand, it should be considered that dysfunctions of isoprenoid pathway and mitochondrial ATP production and the cholesterol homeostasis are already developed under (pre)diabetic and hypercholesterolemic conditions. In order to connect the basic findings with the clinical manifestation more clearly, further research efforts are needed.

Effect of Huangqi San on AMPK/ACC/CPT1 pathway in hyperlipidemia rats / 中国中药杂志

To investigate the mechanism of the treatment of hyperlipidemia rats induced by Huangqi San. The 40 male SD rats were randomly divided into normal group, model group, Huangqi San low and high dose group (1, 2 g·kg⁻¹), and positive lipitor group (2 mg·kg⁻¹). The normal group feeds on base feed, and other groups feed on high-fat feed. After 8 weeks, the hyperlipidemia model was successful. After intervention by drugs for 13 weeks, fasting blood glucose, total cholesterol, triglycerides and LDL cholesterol content of all rats were measured. The pathological changes of liver and skeletal muscle of rats were observed in rats. Real-time PCR and Western blot were used to detect the mRNA and protein expression levels of AMPK signaling pathway in the liver and skeletal muscles (AMPK, ACC, CPT1A, SREBP2, HMGCR). The degree of FPG, TC, TG and LDL-C were the highest in the model group, and the liver and skeletal muscle pathology were the most obvious. After intervention by Huangqi San and lipitor, a significant reduction in the blood sugar blood fat, liver, and skeletal muscle injury has improved significantly, except SREBF2 and HMGCR mRNA and protein expression of this enzyme is reduced, other AMPK pathway related mRNA and protein expression increased significantly. Huangqi San effect is superior to lipitor. Huangqi San may improve hyperlipidemia by regulating the AMPK signaling pathway, increasing the oxidation of fatty acids and inhibiting cholesterol synthesis.

Hypocholesterolemic Effect of Moringa oleifera Polyphenols in Rats Fed High Fat-Cholesterol Diet?

Introduction: One of the greatest risk factors for cardiovascular diseases is hypercholesterolemia. Moringa oleifera is a good source of phytochemicals and is well explored for its antioxidant properties. Methods: The main aim of the present study was to assess the potential cholesterol lowering effect of Moringa oleifera leaf polyphenols (MOP) in an animal model. Five groups of male Wister rats were fed for 45 days as follows: a standard diet (GI); high fat-cholesterol diet (GII); high fat-cholesterol with MOP (100 and 200mg/kg body wt GIII & GIV respectively); and high fat-cholesterol with statins (Atorvastatin) (G-V). Results: Administration of MOP rich extract (GII and GIV) significantly (p=0.05) lowered the serum cholesterol, triglycerides and low-density lipoprotein cholesterol. A significant (p=0.05) decrease in the activity of the HMG CoA reductase enzyme was observed in GIII, GIV and GV but not in GI & GII. Conclusion: The results demonstrate that the polyphenol extract of Moringa oleifera leaves has a significant cholesterol lowering effect through inhibiting HMG CoA reductase activity and faecal bile acid binding.

Effect of Rosuvastatin on Bovine Pericardial Aortic Tissue Valve Calcification in a Rat Subdermal Implantation Model

BACKGROUND AND OBJECTIVES: There are pathophysiologic similarities between calcification and atherosclerosis because both are the product of an active inflammatory process. The aim of this study was to examine the effects of statin treatment on calcification in bovine pericardial tissue valves. MATERIALS AND METHODS: Forty Sprague-Dawley rats were randomly divided into 4 groups according to hypercholesterolemia induction and statin intake (Group 1, n=10: normal diet without statin treatment, Group 2, n=10: normal diet with statin treatment, Group 3, n=10: high fat diet without statin treatment, Group 4, n=10: high fat diet with statin treatment). Serum lipid levels were measured just before the experiment and after 4 and 12 weeks. Bovine pericardial tissue valve cusps were surgically implanted in rat dorsal subcutis at 4 weeks. After the surgery, statin was administered daily to Groups 2 and 4. Serum interleukin-6 (IL-6) level was measured at 5 weeks. Cusps were explanted at 12 weeks and calcium levels were determined by atomic absorption spectroscopy. RESULTS: Mean IL-6 was significantly higher in Group 3 at 5 weeks (7.14, 2.03, 31.70, and 6.90 pg/dL for each group, respectively). Mean calcium level in Group 3 was significantly higher among groups but Group 4 was significantly lower compared to Group 3 and was similar to Group 1, 2 (1.86, 1.92, 2.55, and 1.80 mg/g for each group, respectively, p<0.01). CONCLUSION: Hypercholesterolemia may be a significant risk factor for bovine pericardial valve calcification. Statin treatment significantly attenuated calcification of bovine pericardial valve tissue in a rat subdermal implantation model and might prolong the durability of bioprostheses.

Anti-atherosclerotic activity of root bark of Premna integrifolia Linn. in high fat diet induced atherosclerosis model rats / 药物分析学报

Premna integrifolia Linn. is a medicinal plant used inDhasamuladrug preparation of Ayurvedic systems of medicine in the treatment of various ailments like bronchitis, dyspepsia, liver disorders, piles, constipation, hyperlipidemia and fever. The anti-atherosclerotic activity of hydroalcoholic extract (HAE) of root bark of P. integrifolia was evaluated in high fat diet induced atherosclerosis rats. Sixty Wistar rats were divided into six groups:the first group served as control, the second group was fed with high fat diet and the other three groups were fed with high fat diet along with various concentrations of HAE and the last group was treated with atorvastatin for 30 days. Lipid and lipoprotein profile, atherogenic index, and cardiac markers and histopathological evaluation of aorta were determined in high fat diet induced atherosclerosis rats. HAE of P. integrifolia produced a significant and dose-dependent anti-atherosclerotic activity in terms of reduction in lipids and lipoprotein profile, atherogenic index, HMG-CoA reductase activity, marker enzymes such as lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP), alteration in collagen and calcium contents, mild mineralization and focal rupture of intima and media of aorta was noticed in treated groups as compared to the control. The results suggested that anti-atherosclerotic activity of HAE of P. integrifolia Linn. was due to its modulatory activity on metabolic pathway of lipid. The results contribute to the validation of the traditional use of Agnimantha in high fat diet induced atherosclerosis rats.

Inhibition of HMG-CoA reductase activity and cholesterol permeation through Caco-2 cells by caffeoylquinic acids from Vernonia condensata leaves

ABSTRACT The aim of this study was to provide scientific knowledge to support the use of Vernonia condensata Baker, Asteraceae, beverages for their alleged hypocholesterolemic properties by testing their action as HMG-CoA reductase inhibitors and their capacity to lower dietary cholesterol permeation. Chlorogenic acid, and other caffeoylquinic acids derivatives were identified as the main components of these beverages by LC–MS/MS. No changes in the composition were notice after the in vitro gastrointestinal digestion and no toxicity against Caco-2 and HepG2 cell lines was detected. Cholesterol permeation through Caco-2 monolayers was reduced in 37% in the presence of these herbal teas, and the caffeoylquinic acids permeated the monolayers in 30–40% of their initial amount in 6 h. HMG-CoA reductase activity was reduced with these beverages, showing an IC50 of 217 µg ml−1. It was concluded that caffeoylquinic acids, the major components, justified 98% of the enzyme inhibition measured.

Effect of hydroalcoholic fruit extract of Persea americana Mill. on high fat diet induced obesity: A dose response study in rats.

The fruits of Persea Americana Mill., commonly known as Avocado, are traditionally consumed for various health benefits including weight reduction. Here, we studied the effect of hydroalcoholic fruit extract of Persea americana (HAEPA) on high fat diet (HFD) induced obesity in rats. Obesity was induced in male Sprague Dawley rats by feeding HFD for 14 wk. The hypolipidemic effect was evaluated by co-administering 25, 50, 100 and 200 mg/kg body wt. of HAEPA. There was a significant increase in weight gain, body mass index (BMI), blood lipids, low density lipoproteins (LDL), lipid peroxides (LPO) and serum transaminases in HFD fed rats. HFD+HAEPA fed rats showed a significant decrease in blood lipids, LPO, liver lipids and increase in antioxidant status when compared to HFD control rats. The activity of lipid metabolic key enzymes such as fatty acid synthase and HMG CoA reductase in liver were also found to be decreased significantly in HAEPA co-administered rats. Lipoprotein lipase activity was found increased in HFD+HAEPA rats. Among the 4 doses studied, 100 mg of HAEPA/kg body wt. exhibited optimum hypolipidemic activity. Histopathological observations in liver and visceral adipose tissue added more evidence for the lipid lowering effect of HAEPA. It can be concluded that avocado fruit extract can act as hypolipidemic agent probably by modulating the activities of HMG CoA reductase and fatty acid synthase in liver.

Effect of Coenzyme Q10 Supplementation in Statin-Treated Obese Rats

Statins, HMG-CoA reductase inhibitors, are known to cause serious muscle injuries (e.g. myopathy, myositis and rhabdomyolysis), and these adverse effects can be rescued by co-administration of coenzyme Q10 (CoQ10) with statins. The goal of the current research is to assess the efficacy of combined treatment of CoQ10 with Atorvastatin for hyperlipidemia induced by high-fat diet in SD rats. 4-week-old Sprague-Dawley male rats were fed normal diet or high-fat diet for 6 weeks. Then, rats were treated with either Statin or Statin with various dosages of CoQ10 (30, 90 or 270 mg/kg/day, p.o.) for another 6 weeks. Compared to Statin only-treatment, CoQ10 supplementation significantly reduced creatine kinase and aspartate aminotransferase levels in serum which are markers for myopathy. Moreover, CoQ10 supplementation with Statin further reduced total fat, triglycerides, total cholesterol, and low-density lipoprotein-cholesterol. In contrast, the levels of high-density lipoprotein-cholesterol and CoQ10 were increased in the CoQ10 co-treated group. These results indicate that CoQ10 treatment not only reduces the side effects of Statin, but also has an anti-obesity effect. Therefore an intake of supplementary CoQ10 is helpful for solving problem of obese metabolism, so the multiple prescription of CoQ10 makes us think a possibility that can be solved in being contiguous to the obesity problem, a sort of disease of the obese metabolism.

Expression and clinical significance of stem cell marker Sox2 in human gastric cancer / 天津医药

Objective To detect the expression of stem cell marker Sox2 in gastric cancer (GC). Methods The mRNA and protein expressions of Sox2 in paired primary tumor tissues and their matching, adjacent non-cancerous tissues in a series of 60 cases of human GC were examined by reverse transcription-PCR (RT-PCR) and immunohistochemistry (IHC). χ2 test was used to analyze the correlation of Sox2 expression with clinicopathological parameters of GC tissues including age, gender, tumor size, histological type, TNM stage, differentiation degree, depth of invasion and lymph node metastasis. Results RT-PCR results showed that the positive rate of Sox2 expression was significantly increased in gastric tumor tissues (53.3%, 32/60) compared with that of matching, adjacent non-cancerous tissues (20.0%, 12/60, P<0.01). Semi-quantitative analysis showed that the relative intensity of Sox2 mRNA expression was significantly higher in gastric cancer tissues (0.724±0.209) than that in tissues adjacent to carcinoma (0.256±0.065,P<0.01). The positive expression of Sox2 was significantly higher in gastric tumor tissues (50.0%, 30/60) than that of matching, adjacent non-cancerous tissues (16.7%, 10/60,P<0.01). The positive expression of Sox2 was significantly higher in gastric tumor patients with TNM stage (Ⅲ+Ⅳ) than that of TNM stage (Ⅰ+Ⅱ). The positive expression of Sox2 was significantly higher in gastric tumor patients with low differentiation and undifferentiated tumor cells than that of patients with middle and high differented cells. The positive expression of Sox2 was also significantly higher in gastric tumor patients with the depth of invasion T3-T4 than that of patients with T1-T2. The positive expression of Sox2 was significantly higher in gastric tumor patients with lymph node metastasis than that of patients without lymph node metastasis (P<0.05 or P<0.01). Conclusion The elevated expression of Sox2 is associated with the initiation, invasion, progression, and metastasis of GC. Sox2 may serve as a novel diagnostic and therapeutic marker for human GC.