雷公藤多苷片对高脂小鼠血脂的影响

目的 研究雷公藤多苷片对高脂小鼠血脂的影响。方法 采用高血脂小鼠模型,通过小鼠尾静脉注射不同剂量（0.5,1.0,1.5 mg·kg^-1·d^-1）雷公藤多苷,测定不同时间段小鼠体质量和血清总胆固醇（total cholesterol,TC）、甘油三酯（totaltriglyceride,TG）、高密度脂蛋白胆固醇（high density lipoprotein cholesterol,HDL-C）、低密度脂蛋白胆固醇（low densitylipoprotein cholesterol,LDL-C）的含量及卵磷脂胆固醇酰基转移酶（lecithin cholesterol acyltransferase,LCAT）、肝脂酶（hepatic lipase,HL）和脂蛋白脂酶（lipoprotein lipase,LPL）的活性,研究雷公藤多苷对小鼠体质量、血脂代谢、动脉粥样硬化指数、肝脏LCAT水平等的影响。结果 给予高脂饲料后小鼠体质量和血脂显著升高（P<0.01）,动脉粥样硬化指数显著升高（P<0.01）,抗动脉粥样硬化指数显著下降（P<0.01）。注射雷公藤多苷能显著降低高血脂模型小鼠血清TC、TG和LDL-C,同时显著降低高脂饮食所导致的动脉粥样硬化指数升高。此外,雷公藤多苷片能显著提高血清LCAT水平和HL、LPL的活性。结论 雷公藤多苷片具有一定的降血脂功能,并能有效降低动脉粥样硬化的发生几率。     

Antidiabetic mechanism of Coptis chinensis polysaccharide through its antioxidant property involving the JNK pathway

Abstract

Context: Antidiabetic activity of Coptis chinensis Franch (Ranunculaceae) polysaccharide (CCPW) has been reported. However, its molecular mechanism remains unclear.

Objective: An attempt was made to further verify the antidiabetic activity of CCPW on type 2 diabetes mellitus (T2DM) and elucidate the mechanism of antidiabetic activity.

Materials and methods: Male Wistar rats were fed with high-fat diet (HFD) and injected with streptozotocin (STZ) to generate a T2DM model. Effects of CCPW on fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), glutathione (GSH), glutathione peroxidases (GSH-Px), superoxide dismutases (SOD), catalase (CAT), malondialdehyde (MDA), c-jun n-terminal kinase (JNK), phosphorylated insulin receptor substrate 1 (phospho-IRS1), phosphorylated phosphatidylinositol 3 kinase (phospho-PI3Kp85) and glucose transporter 4 (Glut4) were investigated.

Results: FBG level of diabetic rats could be significantly inhibited by 51.2, 42.7, and 23.3% through administration of CCPW at doses of 200, 100, and 50?mg/kg b.w., respectively (p?<?0.01). CCPW also could significantly reduce TG by 19.2, 12.1, and 7.4%, and TC by 24.2, 20.9, and 18.7%, respectively (p?<?0.05 or p?<?0.01). CCPW showed an obvious antioxidant effect through increasing GSH-Px, SOD, and CAT activities, and decreasing GSH and MDA contents (p?<?0.05 or p?<?0.01). Furthermore, CCPW could inhibit JNK and phospho-IRS1 expression and promote the expression of phospho-PI3Kp85 and Glut4 compared with those in the DM group (p?<?0.05 or p?<?0.01).

Discussion and conclusion: CCPW can produce antidiabetic activity in rats with T2DM through its antioxidative effect, which is closely related to the JNK/IRS1/PI3K pathway.     

Comparison of self-reported survey (SHIELD) versus NHANES data in estimating prevalence of dyslipidemia

ABSTRACT

Objectives: The study purpose was to compare the prevalence of dyslipidemia between a self-reported survey, Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD), and survey and laboratory data from National Health and Nutrition Examination Survey (NHANES 1999–2002).

Methods: A SHIELD questionnaire was mailed to 200?000 households representative of US adult population (64% response, n = 211?097 individuals) and included if ever diagnosed with diabetes, high blood pressure or cholesterol problems, high total cholesterol (TC), high bad cholesterol (LDL-C), low good cholesterol (HDL-C), or high triglycerides (TG). In NHANES using a combination of interviewer-administered survey and clinical and laboratory data, dyslipidemia was defined as any one of: TC ≥?240?mg/dL or diagnosis of high cholesterol; TG >?200?mg/dL;LDL-C ≥?160?mg/dL; or HDL-C <?40?mg/dL. NHANES diabetes mellitus definition was doctor diagnosis or fasting glucose >?125?mg/dL and hypertension was elevated blood pressure or taking anti-hypertensive medication. Prevalence of dyslipidemia was determined for SHIELD in 2004 and compared to NHANES 1999–2002. Prevalence of diabetes and hypertension was estimated for broader contextual comparison within cardiometabolic diseases.

Results: In contrast to the prevalence of diabetes (8% in SHIELD and 9% in NHANES, p < 0.01) and hypertension (23% in SHIELD and 29% in NHANES, p < 0.01), dyslipidemia was reported only half as frequently in SHIELD (26%) as in NHANES (53%), p < 0.01. Com­ponents of dyslipidemia were uniformly less in SHIELD than NHANES: high TC = 17 vs. 35%, high LDL-C = 10 vs. 14%, high TG = 7 vs. 17% and low HDL-C = 5 vs. 24%; all comparisons p < 0.01.

Limitations: Differences in survey methodology, non-response and timing may have impacted the comparison of SHIELD to NHANES.

Conclusions: Dyslipidemia prevalence was lower in self-reported SHIELD than the objectively assessed NHANES, with especially low self-report of high TG and low HDL-C. Self-reported prevalence of dyslipidemia may under-report the prevalence based on laboratory data.     

Statin plus ezetimibe treatment in clinical practice: the SI-SPECT (Slovenia (SI) Statin Plus Ezetimibe in Cholesterol Treatment) monitoring of clinical practice study

ABSTRACT

Background: Poor results from lipid-lowering therapy are mainly due to inadequate dosing and increased adverse effects with high-dose statin monotherapy or drug combinations.

Objectives: The SI-SPECT (Slovenia (SI) Statin Plus Ezetimibe in Cholesterol Treatment) study evaluated the effectiveness of either ezetimibe (EZE) 10?mg as monotherapy or co-administered with on-going statin treatment (S?+?EZE) in clinical practice.

Design and methods: A total of 1053 dyslipidaemic patients (52% men, age 60.3 years, 42.9% with CHD, 32.0% with diabetes mellitus and 69.6% with hypertension) were enrolled. The majority (n?=?986; 93.6%) were treated with EZE as ‘add-on’ to their already prescribed statin, the rest only received EZE (n?=?67).

Main outcome measures: Baseline lipid levels were compared with those obtained 16 weeks after initiating treatment.

Results: Total (TC) and low density lipoprotein cholesterol (LDL-C), as well as triglycerides (TG) decreased significantly with S?+?EZE (by 25.3%, 31.4% and 28.9%, respectively; p?<?0.0001 for all comparisons), while monotherapy with EZE resulted in a decrease of 20.8% for TC (?p?<?0.0001), 28.0% for LDL-C (?p?<?0.0001) and 28.8% for TG (?p?=?0.016). At the end of the study 43.9% of patients achieved target TC (<?5.0?mmol/L for primary prevention and <?4.5?mmol/L for secondary prevention), 50.5% target LDL-C (<?3.0?mmol/L for primary prevention and <?2.5?mmol/L for secondary prevention) and 61.6% target TG (<?2.0?mmol/L). The overall incidence of adverse effects during the treatment period, and probably related to EZE use, was low (n?=?6, 0.6% of patients).

Conclusions: (1) S?+?EZE combination therapy was effective and safe irrespective of the statin used, (2) the S?+?EZE combination resulted in significantly more patients reaching their recommended target lipid levels and (3) the lipid-lowering efficacy of EZE in monotherapy as well as of the S?+?EZE combination was related to initial lipid values. The much greater decrease of TG than expected could be, at least in part, due to better control/compliance regarding diet and drug treatment during the study and adherence to the need for an overnight fast before sampling.     

1H NMR-based metabolic study reveals the improvements of bitter melon (Momordica charantia) on energy metabolism in diet-induced obese mouse

Context: Obesity can be ameliorated by some natural products such as polyphenol, flavones and saponin. As a typical medicinal plant, Momordica charantia L. (Cucurbitaceae) (bitter melon, BM) contains these natural chemicals and reduces diet-induced obesity in mice.

Objective: This study evaluates the metabolic effects of dietary BM supplement, investigates a global metabolic profile and determines associated perturbations in metabolic pathways.

Materials and methods: Male C57BL/6 mice were fed with low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with 5% BM based on 37.6?g/kg body weight in average for 12 weeks, respectively. Then energy metabolism was quantified using PhenoMaster/LabMaster. The spectroscopy of urine was acquired by nuclear magnetic resonance and latent biomarkers were identified. Pattern recognition analysis was used to discriminate associated metabolic profiles.

Results: Dietary BM supplement reduced body weight gain (?0.15-fold, p?<?0.01) and blood glucose levels (?0.19-fold, p?<?0.01) in HFD-fed mice. Meanwhile, the levels of energy metabolism were enhanced (0.08–0.11-fold, p?<?0.01). According to pattern recognition analysis, dietary BM supplement changed metabolic profiles in HFD-fed mice and the modified profiles were similar to those in LFD-fed mice. Finally, the mapping of metabolic pathways showed that dietary BM supplement primarily affected glucose metabolism-associated pathways.

Discussion and conclusion: The results indicated that BM improves weight loss in diet-induced obesity and elevate energy expenditure in HFD-fed mice. The pattern recognition with metabolic study may be used as a noninvasive detection method to assess the effects of dietary BM supplement on mouse energy metabolism.     

Biological activities of salvianolic acid B from Salvia miltiorrhiza on type 2 diabetes induced by high-fat diet and streptozotocin

Abstract

Context: Salvia miltiorrhiza Bge. (Labiatae) has been widely used for treating diabetes for centuries. Salvianolic acid B (SalB) is the main bioactive component in Salvia miltiorrhiza; however, its antidiabetic activity and possible mechanism are not yet clear.

Objective: To investigate the effects of SalB on glycometabolism, lipid metabolism, insulin resistance, oxidative stress, and glycogen synthesis in type 2 diabetic rat model.

Materials and methods: High-fat diet (HFD) and streptozotocin-induced diabetic rats were randomly divided into model group, SalB subgroups (50, 100, and 200?mg/kg), and rosiglitazone group.

Results: Compared with the model group, SalB (100 and 200?mg/kg) significantly decreased blood glucose (by 23.8 and 21.7%; p?<?0.05 and p?<?0.01) and insulin (by 31.3 and 26.6%; p?<?0.05), and increased insulin sensitivity index (by 10.9 and 9.3%; p?<?0.05). They also significantly decreased total cholesterol (by 24.9 and 27.9%; p?<?0.01), low-density lipoprotein cholesterol (by 56.2 and 64.6%; p?<?0.01), non-esterified fatty acids (by 32.1 and 37.9%; p?<?0.01), hepatic glycogen (by 41.3 and 60.5%; p?<?0.01), and muscle glycogen (by 33.2 and 38.6%; p?<?0.05), and increased high-density lipoprotein cholesterol (by 50.0 and 61.4%; p?<?0.05 and p?<?0.01), which were originally altered by HFD and streptozotocin. In addition, SalB (200?mg/kg) markedly decreased triglyceride and malondialdehyde (by 31.5 and 29.0%; p?<?0.05 and p?<?0.01), and increased superoxide dismutase (by 56.6%; p?<?0.01), which were originally altered by HFD and streptozotocin.

Discussion and conclusion: The results indicate that SalB can inhibit symptoms of diabetes mellitus in rats and these effects may partially be correlated with its insulin sensitivity, glycogen synthesis and antioxidant activities.     

Abnormal lipids in high-risk patients achieving cholesterol targets: a cross-sectional study of routinely collected UK general practice data

ABSTRACT

Background and objectives: Lipid management in UK general practice targets the achievement of total cholesterol (TC) targets in high-risk individuals. Statins alone have a modest effect on non-LDL-C components of the lipid profile, leaving these patients at significant residual cardiovascular (CV) risk. Improving risk further would require the addition of non-statin therapies. This analysis explores what proportion of the UK population with cardiovascular disease (CVD) and TC levels at or below target may still be at risk because of residual dyslipidaemia.

Methods: CV risk profiles were extracted from a research database of 602?222 patients from 98 UK general practices. Patients were categorised according to their prior CV history and use of statins. Mean values and proportions achieving treatment targets were assessed for TC, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) and triglycerides (TG).

Results: In all, 48?499 patients with pre-existing CVD or diabetes were identified. 73% of statin-treated patients and 63% of untreated patients had a TC ≤?5?mmol/L. 28.6% of patients treated to a TC target had LDL-C?> 3?mmol/L. Amongst those with both TC and LDL-C treated to target, 22.5% had low HDL-C and 37.2% had high triglyceride (TG). Within this group, more women than men had abnormal HDL-C (25.4?vs. 20.7% p?< 0.0001). Patients with diabetes were more likely than non-diabetics to have abnormalities of both HDL-C (28.9?vs. 16.4% p?< 0.0001) and triglyceride (44.9?vs. 29.5% p?< 0.0001) despite normal TC and LDL-C.

Conclusions: Around 60% of high-risk patients have residual dyslipidaemias despite achieving the Quality and Outcomes Framework (QOF) TC target. New patterns of treatment are required in order to extend lipid management beyond simple total cholesterol lowering.     

Efficacy and safety of coenzyme A versus fenofibrate in patients with hyperlipidemia: a multicenter,double-blind,double-mimic,randomized clinical trial

Abstract

Background: We investigated the lipid-lowering efficacy and safety of coenzyme A (CoA) versus fenofibrate in Chinese patients with moderate dyslipidemia.

Methods: A total of 417 subjects (aged 18–75?years) diagnosed with moderate dyslipidemia (triglyceride 2.3–6.5?mmol/L) from 13 large cardiovascular centers in China were recruited and randomly divided into a fenofibrate group (n?=?207), which received 200?mg of fenofibrate orally once daily, and a CoA group (n?=?210), which received 400?mg of CoA orally once a day. Blood lipoproteins, liver and renal function, creatine kinase, and blood glucose were measured at baseline, and after 4 and 8?weeks of treatment.

Results: The baseline triglyceride (TG) level in the fenofibrate group and the CoA group was 3.39?±?0.99?mmol/L and 3.60?±?1.11?mmol/L, respectively. After treatment for 4 and 8?weeks with fenofibrate, TG was reduced by 31.62% and 33.13%. In the CoA group, TG was reduced by 17.29% and 23.80%. Compared with baseline, total cholesterol (TC) was significantly decreased in both groups after either 4 or 8?weeks of treatment (p?<?.05). CoA increased high-density lipoprotein cholesterol (HDL-C) after 4?weeks of treatment, whereas it had no significant effect on HDL-C after 8?weeks of treatment. Low-density lipoprotein cholesterol (LDL-C) was not modified in either group. The incidence of side effects was significantly lower in the CoA group compared with the fenofibrate group (p?<?.05).

Conclusions: Compared with fenofibrate, CoA has less effect on reducing plasma TG levels in subjects with moderate dyslipidemia. However, it has fewer adverse effects.     

Hypolipidemic effects of a new piperine derivative GB-N from Piper longum in high-fat diet-fed rats

Context: Long pepper, Piper longum Linn. (Piperaceae), is widely used in traditional Mongolian medicine for treating hyperlipidemia and coronary heart disease.

Objective: To investigate the hypolipidemic effects of a new piperine derivative GB-N isolated from long pepper in high-fat diet-fed rats.

Methods: The levels of serum total cholesterol, triacylglycerols (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined by enzymatic colorimetric method. The levels of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), CYP7A1, lecithin cholesterol acyltransferase (LCAT) and LDL receptor (LDLR) mRNA and protein expression were detected by real-time polymerase chain reaction and western blot analysis.

Results and discussion: Compared with model rats, oral administration of GB-N at doses of 2.5–10?mg/kg to hyperlipidemic rats could significantly decrease the levels of serum TG from 1.54 mmol/L in hyperlipidemic rats to 0.94–1.02 mmol/L, with an increase in serum HDL-C levels from 0.40 mmol/L in hyperlipidemic rats to 1.21–2.26 mmol/L. Treatment with GB-N (10?mg/kg) could also significantly upregulate levels of hepatic HMG-CoA reductase, CYP7A1, LCAT and LDLR mRNA and protein expression.

Conclusion: GB-N had hypolipidemic activity via regulating lipid metabolism pathways in liver of hyperlipidemic rats and could be explored as a potential agent for the prevention of hyperlipidemia diseases.     

Effect of mulberry leaf (Folium Mori) on insulin resistance via IRS-1/PI3K/Glut-4 signalling pathway in type 2 diabetes mellitus rats

Context: Folium Mori, the leaf of Morus alba L. (Moraceae), has been used in traditional Chinese medicine (TCM) for treating diabetes. However, it is unclear which components in the mulberry leaf are effective for the treatment of type 2 diabetes mellitus (T2DM).

Objective: To investigate the flavonoids and polyphenols in mulberry leaves and their antihyperglycemic and antihyperlipidemic effects in T2DM rats.

Materials and methods: Male Sprague-Dawley rats were divided into five groups: normal control (NC), diabetic control (DBC), diabetic group with 0.3?mg/kg b.w./day rosiglitazone (RSG), diabetic group with 7?g/kg b.w./day TCM formula and diabetic group with 2?g/kg b.w./day Folium Mori extract (FME). After 4 weeks, the rats were sacrificed; biochemical parameters, gene and protein expression were measured.

Results: The FBG level was significantly lower in the FME group than in the DBC group (p?<?0.05). In oral glucose tolerance test, the AUC was significantly lower in the FME group (p?<?0.05). The HOMA-IR level was significantly decreased in the FME group (p?<?0.05). FME decreased the total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) levels (p?<?0.05). FME increased the mRNA and protein expression of IRS-1, PI3K p85α and Glut-4 increased significantly (p?<?0.05). Histological analysis revealed amelioration of lipid accumulation following FME treatment. Additionally, immunohistochemical analysis displayed stronger staining of Glut-4 in the FME group compared to the DBC group.

Discussion and conclusion: FME could decrease the body weight, blood glucose, TG, TC and LDL levels, and improve insulin resistance. FME possessed significant antihyperglycemic and antihyperlipidemic activities via the IRS-1/PI3K/Glut-4 signalling pathway.     

Impact of adjunctive thiazolidinedione therapy on blood lipid levels and glycemic control in patients with type 2 diabetes

SUMMARY

Objective: This study was undertaken to assess the effect of pioglitazone hydrochloride and rosiglitazone maleate on blood lipid levels and glycemic control when these drugs are used as adjunctive therapy in type 2 diabetes.

Research design and methods: Patients with type 2 diabetes receiving metformin and/or sulfonylurea (n?=?829) were evaluated in this national, multicenter, retrospective study. Medical records from 318 endocrinology practices in the USA were randomly selected and screened for study inclusion. Data related to patient demographics and laboratory data were extracted from medical records and analyzed for primary and secondary outcomes.

Main outcome measures: The primary study outcome was the mean change in plasma triglyceride (TG) levels. Secondary outcome measures included mean changes in total cholesterol (TChol), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) concentrations and hemoglobin A1C levels.

Results:With pioglitazone, TG levels declined by a mean of 51.5?mg/dl (P?<?0.001), HDL-C levels rose by 3.3?mg/dl (P?<?0.001), and no change was seen in LDL-C or TChol. Treatment with rosiglitazone was associated with no significant change in TG levels and a 1.5?mg/dl mean increase in HDL-C (P?<?0.001). Furthermore, rosiglitazone therapy was associated with an 8?mg/dl mean increase in TChol (P?<?0.001), and a 5.8?mg/dl mean increase in LDL-C (P?<?0.001). Hemoglobin A1C levels were significantly reduced by approximately 1% within thiazolidinedione (TZD) cohorts (P?<?0.001), but were not significantly different between study groups (P?=?0.257).

Conclusions: Results from this study suggest that pioglitazone has a more favorable effect on lipid profiles of patients with type 2 diabetes compared with rosiglitazone. In particular, differences were observed in TG and LDL-C levels. Both TZDs were equivalent at reducing hemoglobin A1C levels. These differences in lipid effects may have an impact on cardiovascular outcomes. The full clinical importance of these lipid alterations must be further assessed in prospective trials.     

Profiling analysis of amino acids from hyperlipidaemic rats treated with Gynostemma pentaphyllum and atorvastatin

Context Gynostemma pentaphyllum (Thunb.) Makino has been used in traditional medicine for the treatment of hyperlipidaemic with a long history.

Objective: The objective of this study was to evaluate the influence of Gynostemma pentaphyllum (GP) and atorvastatin on amino acids from the plasma and liver tissue of hyperlipidaemic rats.

Materials and methods The rats were fed a high-fat diet continuously for 11 weeks for the construction of hyperlipidaemic model. The hyperlipidaemic rats were treated with Gynostemma pentaphyllum (120?mg/kg) and atorvastatin (1.8?mg/kg) for 4 weeks, and the rats were intragastric administration one time every day. Chromatographic separation was performed on a Shim-pack XR-ODSIII C18 analytical column (75?mm?×?2.0?mm i.d., 1.6?μm, Shmadazu Corp., Tokyo, Japan). The biomarkers of amino acids were identified by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA).

Results After feeding with a high-fat diet, the TC and LDL-C values of the hyperlipidaemic mode rats increased dramatically (p?<?0.01). The established method allowed a target analysis of 12 kinds of amino acids. PCA studies showed that the plasma amino acids had not returned to normal after GP treatment, but those had recovered slightly after atorvastatin treatment. GP has almost no impact on the metabolism of amino acids, while atorvastatin can modify the metabolism of amino acids via self-regulatory mechanisms.

Discussion and conclusion UPLC/DAD combined with SCX-SPE can be successfully used for profiling analysis of amino acids. By the comparison of biomarkers following treatment with GP and atorvastatin, the influence of the two drugs on biomarkers is revealed.     

Hepatoprotective effect of withanolide-rich fraction in acetaminophen-intoxicated rat: decisive role of TNF-α, IL-1β, COX-II and iNOS

Context: Overdose of acetaminophen (APAP) is common in humans and is often associated with hepatic damage. Withania somnifera (L.) Dunal (Solanaceae) shows multiple pharmacological activities including antioxidant and anti-inflammatory potential.

Objective: To evaluate the possible mechanism of hepatoprotective activity of withanolide-rich fraction (WRF) isolated from a methanolic extract of Withania somnifera roots.

Materials and methods: Hepatotoxicity was induced by oral administration of APAP (750?mg/kg, p.o.) for 14 d. The control group received the vehicle. APAP-treated animals were given either silymarin (25?mg/kg) or graded doses of WRF (50, 100 and 200mg/kg) 2?h prior to APAP administration. Animals were killed on 15th day and blood and liver tissue samples were collected for the further analysis.

Results: In WRF-treated group, there was significant and dose-dependent (p?<?0.01 and p?<?0.001) decrease in serum bilirubin, ALP, AST and ALT levels with significant and dose-dependent (p?<?0.01 and p?<?0.001) increase in hepatic SOD, GSH and total antioxidant capacity. The level of MDA and NO decreased significantly (p?<?0.01) by WRF treatment. Up-regulated mRNA expression of TNF-α, IL-1β, COX-II and iNOS was significantly down-regulated (p?<?0.001) by WRF. Histological alternations induced by APAP in liver were restored to near normality by WRF pretreatment.

Conclusion: WRF may exert its hepatoprotective action by alleviating inflammatory and oxido-nitrosative stress via inhibition of TNF-α, IL-1β, COX-II and iNOS.     

Prevention of arsenic-mediated reproductive toxicity in adult female rats by high protein diet

Abstract

Context: The detrimental effects of arsenic on female reproductive functions may involve overt oxidative stress. Casein and pea [Pisum sativum Linn. (Fabaceae)] proteins have antioxidant properties.

Objective: To investigate the role of casein- and pea-supplemented high-protein diet (HPD) in utero-ovarian protection from arsenic toxicity.

Materials and methods: Adult female Wistar rats were orally gavaged with vehicle (Gr-I) or arsenic at 3?ppm/rat/d (Gr-II and Gr-III) for 30 consecutive days, when they were maintained on either regular diet containing 18% protein (Gr-I and Gr-II), or HPD containing 27% protein in the form of casein (20%) and pea (7%) (Gr-III). Reproductive functions were evaluated using a battery of biochemical and histological techniques.

Results: As compared to Gr-I, the Gr-II rats suffered from loss of estrous cyclicity, reduction in weight (mg/100?g body weight) of ovary (Gr-I: 54.3?±?4.2 versus Gr-II: 35.8?±?1.6; p?<?0.001) and uterus (Gr-I: 161.7?±?24.6 versus Gr-II: 94.44?±?13.2; p?<?0.05), utero-ovarian degeneration, attenuated ovarian activities (unit/mg tissue/h) of Δ⁵, 3β-hydroxysteroid dehydrogenase (Gr-I: 3.41?±?0.12 versus Gr-II: 2.31?±?0.09; p?<?0.01) and 17β-hydroxysteroid dehydrogenase (Gr-I: 3.82?±?0.57 versus Gr-II: 1.24?±?0.19; p?<?0.001), and decreased serum estradiol level (pg/ml) (Gr-I: 61.5?±?2.06 versus 34.1?±?2.34; p?<?0.001). Ovarian DNA damage was preponderant with blatant generation of malondialdehyde (nM/mg tissue; Gr-I: 15.10?±?2.45 versus Gr-II: 29.51?±?3.44; p?<?0.01) and attenuated superoxide dismutase activity (unit/mg tissue) (Gr-I: 2.18?±?0.19 versus Gr-II: 1.33?±?0.18; p?<?0.05). The Gr-III rats were significantly protected from these ill effects of arsenic.

Discussion and conclusion: HPD, by way of antioxidant properties, may find prospective role in the protection of reproductive damage caused by arsenic.     

In vitro and in vivo antitumour activities of puerarin 6″-O-xyloside on human lung carcinoma A549 cell line via the induction of the mitochondria-mediated apoptosis pathway

Context Pueraria lobata (Leguminoseae) shows cytotoxic effects against cancer cells; however, its active components remain unclear.

Objective This study investigated the antitumour activity of puerarin 6″-O-xyloside (POS) on the human lung carcinoma A549 cell line.

Materials and methods The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the cytotoxicity of POS (at 10, 20 and 40?μM) in vitro, and xenograft nude mice were established to evaluate the antitumour effect of POS (at 40?mg/kg/d) in vivo by 15 days intraperitoneal injection (ip). To explore its mechanism of action, flow cytometry was performed to determine the pro-apoptotic effect of POS (at 10, 20 and 40?μM). Subsequently, the expression of caspase-3, caspase-7, caspase-9, Bcl-2 and Bax in A549 cells were determined.

Results POS showed significant cytotoxicity toward A549 cells (p?<?0.05) by inducing apoptosis. Treatment with POS significantly upregulated the levels of caspase-3 (p?<?0.01), caspase-7 (p?<?0.01), caspase-9 (p?<?0.01) and Bax (p?<?0.01) in A549 cells, and Bcl-2 was downregulated (p?<?0.01). Additionally, the in vivo animal study showed that POS significantly inhibited tumour growth in A549 cells (p?<?0.01).

Conclusion Our study demonstrated the POS has significant antitumour activities. The mechanisms are related to increased levels of caspase-3, caspase-7, caspase-9 and Bax, and reduced levels Bcl-2.     

Long-term treatment effect of atorvastatin on aortic stiffness in hypercholesterolaemic patients

Summary

Aim: To assess the effect of atorvastatin on aortic stiffness in hypercholesterolaemic patients free of arterial hypertension and diabetes mellitus.

Methods and Results: The study included 36 patients (25 men and 11 women, mean age 56?±?12 years); 18 patients had stable coronary heart disease (CHD) and 18 were free of CHD at baseline. All patients received atorvastatin (20mg/day) for a 2-year period. Aortic stiffness was assessed by transthoracic echocardiography at baseline and 2 years later. At baseline, total cholesterol, low density lipoprotein cholesterol (LDL-C) and LDL-C/high density lipoprotein cholesterol (HDL-C) ratio were positively related to aortic stiffness (p?<?0.001 for all). The mean change in lipid parameters during treatment was: total cholesterol ?38%, LDL-C ?46%, triglycerides ?29%, and HDL-C +6%, all significant (p?=?0.029 to <0.0001). After the 2-year treatment with atorvastatin, aortic stiffness was significantly reduced by 14% (p?=?0.019). An improvement of left ventricular (LV) ejection fraction by 13% (p?<?0.001) and a reduction of LV mass index by 9% (p?=?0.008) were also recorded. The change in aortic stiffness was similar in patients with or without CHD.

Conclusion: Long-term treatment with atorvastatin improves aortic stiffness; this index is related to total and coronary mortality. Moreover, assessment of aortic stiffness may be useful in identifying which hypercholesterolaemic patients should be treated aggressively, regardless of CHD. The aortic stiffness effect may eventually become an index of the efficacy of lipid lowering treatment.     

The effect of orlistat and ezetimibe,alone or in combination,on serum LDL and small dense LDL cholesterol levels in overweight and obese patients with hypercholesterolaemia

ABSTRACT

Background: Increased concentrations of low density lipoprotein cholesterol (LDL-C), as well as of small dense LDL-C (sdLDL-C), are considered as cardiovascular risk factors.

Objective: An assessment of the effects of ezetimibe and orlistat administration, alone or in combination, on LDL-C and sdLDL-C levels (primary endpoint), as well as on anthropometric variables and metabolic parameters (secondary endpoints) in overweight and obese patients [body mass index (BMI) > 28 kg/m²] with hypercholesterolaemia [total cholesterol > 200 mg/dL (5.2 mmol/L)].

Methods: Eighty six subjects were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg, 3 times daily (O group), ezetimibe 10 mg/day (E group) or both (OE group) for 6 months.

Results: Significant reductions in LDL-C (?19%, ?21%, ?32% in groups O, E and OE, respectively, all p < 0.01 vs. baseline) and sdLDL-C levels (?45%, ?48%, ?76% in groups O, E, OE, respectively, all p < 0.01 vs. baseline) were observed. Group OE experienced a significantly greater reduction in LDL-C and sdLDL-C levels compared with groups O and E (p < 0.05). Furthermore, significant reductions of BMI, homeostasis model assessment (HOMA) index, serum uric acid, transaminase activities and plasma lipoprotein-associated phospholipase A₂ (Lp-PLA₂) activity were observed in the O and OE groups. Gamma-glutamyl transpeptidase activity and Lp-PLA₂ activity improved significantly more with the combination treatment compared with either orlistat or ezetimibe monotherapy.

Conclusions: Orlistat and ezetimibe combination had a more favourable effect on LDL-C and sdLDL-C levels in overweight and obese hypercholesterolaemic patients than either drug alone. Furthermore, orlistat, alone or in combination with ezetimibe, additionally improved several anthropometric and metabolic variables.     

Hypolipidemic and antioxidant effects of ethanol extract of Cassia fistula fruit in hyperlipidemic mice

Context: The plant Cassia fistula L. (Caesalpiniaceae) fruit was widely used by traditional practitioners to treat cardiovascular diseases (CVDs) in India. Hyperlipidemia is a lipid metabolism disorder and the major risk factor for the development of CVDs. Although most of the current hypolipidemic drugs are expensive and have potential side effects, the research focusing on natural alternative medicines is relevant.

Objective: To investigate the hypolipidemic and antioxidant effects of ethanol extract of C. fistula fruit (CFE) in high-fat diet (HFD) induced hyperlipidemia in mice.

Materials and methods: Oral administration of CFE at 100, 300 and 500?mg/kg body weight on HFD induced hyperlipidemia mice for 30 days. The standard drug atorvastatin (20?mg/kg) was used to compare the efficacy of CFE. Hypolipidemic effect was evidenced by the measurement of serum lipid profile and further confirmed by Oil Red O staining of adipose tissue. The hepatic and cardiac melondialdehyde (MDA) level and antioxidant enzyme activities including superoxide dismutase, catalase and glutathione peroxidase were determined.

Results: Treatment with CFE at different doses has significantly restored the levels of serum lipid, MDA and enzymes activities in the liver and heart of hyperlipidemia mice. Oil Red O staining of visceral adipose tissue has shown marked reduction of lipid accumulation in adipocytes; whereas, administration of CFE at 500?mg/kg showed remarkable (p?<?0.001) hypolipidemic and antioxidant effects in HFD fed mice.

Conclusion: C. fistula fruit demonstrated hypolipidemic and antioxidant properties in vivo and the results corroborate the use of this plant in traditional medicine for cardiac ailments.     

The ginsenoside metabolite compound K exerts its anti-inflammatory activity by downregulating memory B cell in adjuvant-induced arthritis

Context: Compound K (CK, 20-O-d-glucopyranosyl-20(S)-protopanaxadiol), a novel ginsenoside metabolite, is structurally a member of the dammarane-type triterpene saponins. Several studies have identified the anti-inflammatory activity of CK. Our previous study demonstrated that CK exerted its anti-inflammatory effect via inhibition of abnormal activation and differentiation of T cells. However, its mechanism of action on B cells remains unclear.

Objective: The objective of this study is to investigate the effect and underlying mechanisms of CK’s effects on memory B cells in the setting of adjuvant-arthritis (AA).

Materials and methods: Complete Freund’s adjuvant was used to induce AA in rats. Rats were administered, either CK (10, 40, and 160?mg/kg), once daily for 15?d, or methotrexate (MTX; 0.5?mg/kg) once every 3?d, for a total of six times. To evaluate the anti-inflammatory effect of CK, a global assessment and a swollen joint count of AA rats were performed every 3?d. Spleen index and histopathology were examined. Subsets of B cells including CD45R⁺IgM⁺ (total B cells) and CD45R⁺CD27⁺ (memory B cells) and expression of CD40 and CD40L were assayed by flow cytometry.

Results: Compared with the AA rats, global assessment scores and swollen joint counts were significantly lower in the treated groups received CK (40 and 160?mg/kg; p?<?0.05 and p?<?0.01, respectively). CK (40 and 160?mg/kg) decreased the spleen index (p?<?0.01), and alleviated hyperplasia of lymph nodes (p?<?0.05 and p?<?0.01, respectively) and marginal zone (p?<?0.05) in the spleen. In addition, CK (40 and 160?mg/kg) suppressed memory B cell subsets (p?<?0.05), and suppressed CD40L expression on T cells and CD40 expression on B cells (p?<?0.05 and p?<?0.01, respectively).

Discussion and conclusion: This study demonstrated that CK downregulated memory B cells in AA rats, and this down-regulation may be T-cell dependent.