Hypoglycemic effect of <Emphasis Type="Italic">Gynostemma pentaphyllum</Emphasis> saponins by enhancing the Nrf2 signaling pathway in STZ-inducing diabetic rats

Gynostemma pentaphyllum (GP) is a natural plant resources for diabetes therapy, however, there is little research on the mechanisms of GP. The present study was undertaken to characterize if G. pentaphyllum saponins (GPs) is the principal active compound of GP responsible for anti-diabetes, and to examine the relativity between blood glucose modulate and antioxidation. The GPs-treated streptozotocin diabetic rats had a more effective hypoglycemic status than those of diabetic control rats, which also ameliorate dyslipidemia. GPs has increased SOD and GSH-px activities, and the spleen and thymus indexes in diabetic rats. The insulin levels in the GPs-treated groups were significantly higher than diabetic control group. Our finding provides a new insight into the application of GPs for the treatment of oxidative stress related diseases.     

Antihyperlipidaemic effect of triterpenic acid-enriched fraction from Cyclocarya paliurus leaves in hyperlipidaemic rats

Context: Cyclocarya paliurus (Batal) Iljinskaja (Juglandaceae) is an edible and medicinal plant; the leaves are used in Chinese folkloric medicine to treat dyslipidaemia and diabetes.

Objective: This study evaluates the antihyperlipidaemic potential of the triterpenic acid-enriched fraction (TAE) from C. paliurus and the underlying mechanism.

Materials and methods: The hyperlipidaemic rats were induced by high fat diet for 6 weeks. After oral administration of TAE (200 and 400?mg/kg), the neutral fraction (150 and 300?mg/kg) and statin (4?mg/kg) to the hyperlipidaemic rats for 4 weeks, lipid profile and apolipoprotein (apoB48) level in plasma, and the expression levels of apoB48, microsomal triglyceride transfer protein (MTP), phosphorylation of mitogen-activated protein kinase (MAPK) and tumour necrosis factor α (TNF-α) in intestine were examined. The main constituents in the TAE were identified by HPLC-MS.

Results: TAE administration (400?mg/kg) decreased the levels of atherogenic lipids in serum and liver (p?p?Conclusion and discussion: These findings suggested that TAE possessed antihyperlipidaemic activity partially involved in the inhibitory effect on apoB48 overproduction, which may provide evidence about its potential role in ameliorating dyslipidaemia.     

Galangin,a dietary flavonoid,ameliorates hyperglycaemia and lipid abnormalities in rats with streptozotocin-induced hyperglycaemia

Context: Galangin, a natural flavonoid, is found in honey and Alpinia officinarum Hance (Zingiberaceae). Galangin has antiviral, antimicrobial, antidiabetic and anticancer properties, without side effects. The effects of galangin on hyperglycaemia and lipid abnormalities are not known.

Objective: To elucidate the effectiveness of galangin on hyperglycaemia-associated complications and lipid changes in rats with streptozotocin (STZ)-induced hyperglycaemia.

Materials and methods: Diabetes was induced in adult Wistar rats by administering 40?mg/kg of STZ. In our previous study, galangin had no toxicity at concentrations up to 320?mg/kg. Therefore three doses of galangin (4, 8 or 16?mg/kg BW) or glibenclamide (600 µg/kg BW) were administered daily to diabetic rats orally for 45 days.

Results: Diabetic rats showed a significant (p?p?p?Discussion and conclusions: Administration of galangin reduced hyperlipidaemia related to the risk of diabetic complications and could be beneficial for diabetic hyperlipidaemic patients. Further work detailing its mechanism-of-action for improving hyperglycaemic-associated lipid abnormalities is needed.     

Triterpenoid saponins from Gynostemma pentaphyllum

Four new dammarane-type triterpene saponins, 1–4, were isolated from the aerial parts of Gynostemma pentaphyllum (Thunb.) Makino. Their structural elucidations were accomplished mainly on the basis of spectroscopic methods, such as IR, HR-TOF-MS, and NMR. Compounds 1–4 showed moderate cytotoxic activities against cancer cell lines HL-60, Colon205, and Du145 in vitro.     

Hepatoprotective effects of Cassia semen ethanol extract on non-alcoholic fatty liver disease in experimental rat

Context: Cassia semen (Cs), a seed of Cassia obtusifolia L. (Leguminosae), is a popular functional beverage. Previous studies reported that Cs displayed antioxidant, antifungal and strong liver protective effects.

Objective: This study evaluates the hepatoprotective effects of Cs on non-alcoholic fatty liver disease (NAFLD).

Materials and methods: Seventy-two male Wistar rats raised with high-fat diet (HFD) were randomly allotted into model, metformin (0.2?g/kg) and Cs (0.5, 1, and 2?g/kg)-treated groups. Another 12 rats were raised with normal feed as control group; all the rats were orally administrated with drugs and vehicle for 6?weeks. Alanine transferase (ALT), aspartate transaminase (AST), triglycerides (TG), total cholesterol (TC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and low density lipoprotein receptor (LDL-R) mRNA levels were measured at the end of the experiment.

Results: Twelve weeks of HFD administration significantly increased the levels of AST, ALT, TG, TC, TNF-α, IL-6, IL-8 and MDA, decreased SOD (199.42 vs. 137.70?U/mg protein) and GSH (9.76 vs. 4.55?mg/g protein) contents, compared to control group. Cs administration group significantly decreased the elevated biomarkers with the ED₅₀?=?1.2?g/kg for NAFLD rats. Cs treatment also prevents the decreased expression of LDL-R mRNA, and improved the histopathological changes compared to model group.

Conclusions: The hepatoprotective effect of Cs on NAFLD may possibly be due to its antioxidant effect. Cs may become a potent hepatoprotective agent in clinical therapy in the future.     

Two new triterpene saponins from Gynostemma pentaphyllum

Two new dammarane-type triterpene saponins, gypenbiosides A (1) and B (2), were isolated from the aerial parts of Gynostemma pentaphyllum (Thunb.) Makino. Their structural elucidations were accomplished mainly on the basis of the interrelation of spectroscopic methods, such as IR, HR-TOF-MS, and NMR. The cytotoxic activity was evaluated against one human cancer cell line HL-60 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.     

Decreased exposure of atorvastatin in diabetic rats partly due to induction of hepatic Cyp3a and Oatp2

1. Atorvastatin is frequently prescribed for lowering blood cholesterol and for prevention of events associated with cardiovascular disease. The aim of this study was to investigate the pharmacokinetics of atorvastatin in diabetic rats.

2. Diabetes was induced in rats by combination of high-fat diet and low-dose streptozotocin (35?mg/kg). Plasma concentrations of atorvastatin following oral (10?mg/kg) and intravenous (2?mg/kg) administrations to rats were measured by LC-MS. Metabolism and uptake of atorvastatin in primary hepatocytes of experimental rats were assessed. Protein expressions and activities of hepatic Cyp3a and Oatp2 were further investigated.

3. Clearances of atorvastatin in diabetic rats following oral and intravenous administrations were remarkably increased, leading to marked decreases in area-under-the-plasma concentration–time curve (AUC). The estimated oral and systematic clearances of atorvastatin in diabetic rats were 4.5-fold and 2.0-fold of control rats, respectively. Metabolism and uptake of atorvastatin in primary hepatocytes isolated from diabetic rats were significantly increased, which were consistent with the up-regulated protein expressions and activities of hepatic Cyp3a and Oatp2.

4. All these results demonstrated that the plasma exposure of atorvastatin was significantly decreased in diabetic rats, which was partly due to the up-regulated activities and expressions of both hepatic Cyp3a and Oatp2.     

Effect of rosuvastatin versus atorvastatin treatment on paraoxonase-1 activity in men with established cardiovascular disease and a low HDL-cholesterol

ABSTRACT

Objective: Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL) associated enzyme involved in the protective mechanisms of HDL. Our aim was to compare the effect of treatment with rosuvastatin and atorvastatin on serum PON-1 activity.

Methods: We performed a prespecified prospective study in 68 patients, part of a larger, multicentre randomized study – RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport). Patients aged 40–80 years, all men, with established cardiovascular disease and high-density lipoprotein cholesterol (HDL?C) < 1.0?mmol/L (< 40?mg/dL) entered a 6-week dietary run-in period before receiving treatment with rosuvastatin 10?mg or atorvastatin 20?mg daily for 6 weeks. Doses were increased after 6 weeks to rosuvastatin 20?mg or atorvastatin 40?mg and after 12 weeks to rosuvastatin 40?mg or atorvastatin 80?mg daily. Serum PON-1 activity and lipid profile were determined at baseline, 6 and 18 weeks.

Results: After 18 weeks, the rosuvastatin arm showed a significant increase of PON-1 activity (6.39?U/L, p = 0.02) whereas this was not observed in the atorvastatin arm (1.84?U/L, p = 0.77). The difference between groups did not reach significance (?p = 0.11). Both rosuvastatin and atorvastatin resulted in significant (?p = 0.0001) and similar increases in HDL?C after 6 weeks [0.06?mmol/L (2.32?mg/dL) vs. 0.05?mmol/L (1.93?mg/dL)] and after 18 weeks [0.10?mmol/L (3.87?mg/dL) vs. 0.10?mmol/L (3.87?mg/dL)].

Conclusions: Rosuvastatin treatment resulted in a significant increment of serum PON-1 activity with increasing dose while this was not observed with atorvastatin.     

Momordica charantia extracts ameliorate insulin resistance by regulating the expression of SOCS-3 and JNK in type 2 diabetes mellitus rats

Context: Momordica charantia L. (Cucurbitaceae) has long been widely used as a traditional remedy for diabetes mellitus in some countries. However, detailed antidiabetic mechanisms are largely unknown.

Objectives: This study clarified the ameliorating effects of M. charantia ethanol extracts (MCE) on the insulin resistance in type 2 diabetes mellitus (T2DM) rats.

Materials and methods: T2DM rat model was established by high-fat diet and streptozotocin (STZ) injection. Diabetic rats were randomized into five groups: the model control group (n?=?8) (common diet), the high-fat diet metformin (50?mg/kg/d), and the three-dose MCE (100, 200, and 400?mg/kg/d) groups (n?=?8 each). After 8 weeks, the fasting serum glucose, insulin, TNF-α, and IL-6 were measured, and the relevant factors of glucose and insulin were monitored by glycogen dyeing, RT-PCR, and western blot, respectively.

Results: The 8-week treatment of 400?mg/kg MCE significantly lowered body weight (330.1 versus 365.9?g), serum glucose (7.41 versus 16.63?mmol/L), insulin (12.06 versus 15.89 mIU/L), TNF-α (52.72 versus 81.83?ng/L), and IL-6 (104.81 versus 135.74?ng/L) in comparison with those of the diabetic control group (p?p?Conclusions: MCE can ameliorate insulin resistance in T2DM rats. This effect may be related to the regulation of mRNA and protein levels of SOCS-3 and JNK.     

Houttuynia cordata alleviates high-fat diet-induced non-alcoholic fatty liver in experimental rats

Abstract

Context: Houttuynia cordata Thunb. (Saururaceae) is used traditionally in Asian countries to treat various disease symptoms.

Objective: To study the effect of H. cordata ethyl acetate (HC-EA) extract on high-fat diet (HFD)-induced hepatic steatosis.

Materials and methods: HFD fed rats were orally dosed with HC-EA (100, 200, or 300?mg/kg) once daily for 8?weeks and the lipid profiles and protein expressions in hepatocytes were evaluated.

Results: HFD rats showed an increase (p?<?0.05) in the plasma lipid levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), free fatty acids (FFAs), and reduced the high-density lipoprotein (HDL) levels. Treatment with HC-EA extract (300?mg/kg) restored the changes in plasma lipid levels of TC, TG, LDL, FFA, and HDL in HFD-fed rats by 34.8, 31.1, 51.4, 32.4, and 56.3%, respectively, compared with control rats (p?<?0.01). HC-EA treatment also decreased the hepatic lipid accumulation (p?<?0.001 at 300?mg/kg) and improved hepatic histological lesions. HC-EA extract enhanced AMPK phosphorylation and its primary downstream targeting enzyme, acetyl-CoA carboxylase (ACC), up-regulated the gene expression of carnitine palmitoyl transferase-1 (CPT-1), and down-regulated sterol regulatory element binding protein 1, fatty acid synthase, and glutamate pyruvate transaminase protein levels in the livers of HFD-fed rats. Further, the increased expression of hepatic cytochrome P450 (CYP) composition such as CYP2E1 and CYP4A was also suppressed.

Discussion and conclusion: Data suggest that HC-EA extract might act by regulating the AMPK-dependent pathway and related mediators and might be used in treating obesity-related liver diseases.     

LDL‐C/HDL‐C ratio in subjects with cardiovascular disease and a low HDL‐C: results of the RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport) study

ABSTRACT

Background: The ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (LDL‐C/HDL‐C) is a reliable predictor of cardiovascular risk. Low HDL‐C levels in patients with coronary artery disease are associated with a high risk for cardiovascular events.

Objectives: This study compared the effects of rosuvastatin and atorvastatin on the LDL‐C/HDL‐C ratio in patients with cardiovascular disease and low HDL‐C.

Methods: Patients aged 40–80 years with established cardiovascular disease and HDL‐C < 1.0?mmol/L (< 40?mg/dL) entered a 6‐week dietary run-in period, before randomisation to open-label treatment with rosuvastatin 10?mg (n = 230) or atorvastatin 20?mg (n = 231) for 6 weeks. Doses were increased after 6 weeks to rosuvastatin 20?mg or atorvastatin 40?mg, and after 12 weeks to rosuvastatin 40?mg or atorvastatin 80?mg. Serum lipid parameters were measured at baseline and 6, 12 and 18 weeks.

Results: After 6 weeks of treatment, mean percentage change from baseline in LDL‐C/HDL‐C ratio was –47.0% in the rosuvastatin group and –41.9% in the atorvastatin group (?p < 0.05 for between-group comparison). After 12 and 18 weeks of treatment, change from baseline was –53.0% and –57.3%, respectively, for rosuvastatin, compared with –47.9% and –49.6%, respectively, for atorvastatin (?p < 0.01 and p < 0.001, respectively, for between-group comparison). Rosuvastatin also reduced LDL‐C, total cholesterol and non-HDL‐C significantly more than atorvastatin at all three time points, and significantly improved total cholesterol/HDL‐C and apolipoprotein B/A‐I ratios.

Conclusions: Rosuvastatin 10, 20 and 40?mg is significantly more effective than atorvastatin 20, 40 and 80?mg, respectively, in improving the LDL‐C/HDL‐C ratio in patients with cardiovascular disease and low HDL‐C. Further studies are required to clarify the benefits of rosuvastatin for reduction of cardiovascular risk.     

Effects of statin treatment in men and women with stable coronary heart disease: a subgroup analysis of the GREACE Study

ABSTRACT

Background: Reducing low-density lipoprotein cholesterol (LDL-C) levels to National Cholesterol Expert Panel (NCEP) goal is recommended. However, sex-specific effects may influence benefit.

Methods and results: In this post hoc analysis of the GREek Atorvastatin and Coronary heart disease (CHD) Evaluation [GREACE] study we investigated the extent in vascular event reduction by statin treatment according to sex. From a total of 1600 patients with stable CHD, 624/176 and 632/168 were men/women on atorvastatin or on usual care, respectively. During 3-year follow-up, comparison of atorvastatin treatment with usual care demonstrated a relative risk reduction (RRR) of the primary end point (all vascular events) of 54?%?in women (hazard ratio [HR] 0.46, 95?%?confidence interval [CI] 0.24–0.87, p?=?0.003) and of 50?%?in men (HR 0.50, 95?%?CI 0.32–0.70, p?<?0.001). The fall in LDL-C levels played the key role in end point reduction in both sexes. However, in men there was an additional benefit related to the atorvastatin-induced increase in high density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR), while in women end points were related to a substantial triglycerides (TG) reduction.

Conclusions: Treatment with atorvastatin to the NCEP LDL-C goal compared with “usual care” significantly reduced CHD morbidity and mortality in both men and women. Both men and women benefited from statin treatment possibly with different mechanisms making a contribution over and above LDL-C reduction.     

利用1H-NMR技术研究大黄素染毒后大鼠内源性代谢物的改变

目的 采用¹H NMR的代谢组学技术揭示大黄素的肾毒性机制,寻找肾脏损害的早期生物标志物.方法 雄性SD大鼠20只,随机分为溶剂对照,大黄素170、500、1 500 mg/(kg·d)3个剂量组,连续给药16 d,给药结束后收集24 h尿液,血浆及肾组织,测定¹H NMR谱,并进行血浆生化指标测定和肝脏组织病理学检查.结果 1 500 mg/(kg·d)大黄素服用16 d可引起大鼠血肌酐下降,大黄素可导致肾细胞胞浆中出现明显的空泡化改变.代谢成分的改变主要表现为血液中乳酸、糖、氨基酸和脂肪酸成分下降;尿液中乳酸、糖和氨基酸成分增加;肾脏组织中醋酸盐和肌酐/肌酸明显升高,乳酸和胆碱/磷酸卵磷脂水平下降,饱和与不饱和脂肪酸及磷脂的成分比例明显改变.结论 代谢组学分析在识别药物诱导代谢成分改变方面较传统技术更灵敏;脂肪和能量代谢紊乱参与了大黄素的肾毒性,尿液中氨基酸、葡萄糖氧化三甲胺(TMAO)及肌酐可作为大黄素诱导肾组织损害的潜在生物标志物.     

Patent Evaluation: Phenoxyalkanoic Acids as Cholesterol Lowering Agents

Summary

Novelty: Novel phenoxyalkanoic acids are disclosed and are said to be hyperlipidaemic agents. They are potentially useful in the treatment of hypercholesterolaemia, hyperlipidaemia and arteriosclerosis.

Biology: The effect of the compounds on serum total cholesterol (STC) levels in male Sprague-Dawley rats was demonstrated. The total cholesterol level in the serum was measured enzymatically according to a previously established method (Clinical Chemistry (1974) 20:470). The percentage decrease in STC was recorded for five compounds and was in the range 49-73%.

Chemistry: Three compounds are specifically claimed. A total of twenty-eight compounds are disclosed and are exemplified by synthesis. Yields, mps, IR, MS and ¹H nmr are detailed. One of the specifically claimed compounds is 2-[4-(2-(p-chlorobenzene sulphonylamino)propyl)phenoxy]-2-methylpropionic acid.

Structure:      

Designs of RADIANCE 1 and 2:carotid ultrasound studies comparing the effects of torcetrapib/atorvastatin with atorvastatin alone on atherosclerosis*

ABSTRACT

Objective: The RADIANCE studies were designed to assess the effects of torcetrapib/atorvastatin (T/A) compared with atorvastatin alone on slowing atherosclerotic progression in patients with heterozygous familial hypercholesterolemia (RADIANCE 1) or mixed hyperlipidemia (RADIANCE 2), as measured by change in carotid intima-media thickness (CIMT).

Research design and methods: RADIANCE 1 and 2 were random­ized, double-blind, controlled trials with a duration of 2 years. In both studies, eligible subjects began treatment with atorvastatin during a run-in period and were titrated to target LDL?C levels defined by NCEP ATP III guidelines. Subjects then proceeded to a double-blind randomized treatment period where they received one of two regimens: (i) fixed combination T/A (torcetrapib dose, 60?mg), or (ii) atorvastatin alone. In both regimens, the dose of atorvastatin was established during the run-in period (20–80?mg, RADIANCE 1; 10–80?mg RADIANCE 2). B-mode ultrasonography was performed in duplicate at baseline and at end of study, and every 6 months in between.

Main outcome measures: The primary efficacy measure in both studies was the annualized rate of change in maximum CIMT of 12 pre-defined carotid segments. Further outcome measures included lipid and safety assessments.

Current status: The number of subjects randomized was 904 in RADIANCE 1 and 752 in RADIANCE 2. Results are anticipated in 2007.

Trial registration: ClinicalTrials.gov identifier: NCT00136981.

Trial registration: ClinicalTrials.gov identifier: NCT00134238.     

Cytotoxic triterpenes from the acid hydrolyzate of Gynostemma pentaphyllum saponins

One new dammarane-type triterpene, gypsapogenin A (1), was isolated from the acid hydrolyzate of total saponins from Gynostemma pentaphyllum (Thunb.) Makino, together with two known compounds, (20S,24S)-3β,20,21β,23β,25-pentahydroxy-21,24-cyclodammarane (2) and (23S)-3β-hydroxydammar-20,24-dien-21-oic acid 21,23-lactone (3). Its structural elucidations were accomplished mainly on the basis of the interpretation of spectroscopic data, such as IR, HR-TOF-MS, and NMR. The cytotoxic activities were evaluated against HepG2 and A549 human cancer cell lines.     

Efficacy of atorvastatin after LDL-cholesterol-based dose selection in high risk dyslipidaemic patients: results of the target dose study

ABSTRACT

Background: Hypercholesterolaemia is one of the major risk factors for the development of coronary heart disease (CHD). European guidelines emphasize the importance of reducing low-density lipoprotein cholesterol (LDL?C) levels below 115?mg/dL (3.0?mmol/L) in patients with high CHD risk.

Objective: The present study evaluates whether selection of the atorvastatin starting dose based on baseline LDL?C levels and previous statin treatment status would result in an achievement of LDL?C targets without the need for up-titration.

Methods: A multicentre, prospective, open-label study conducted in Belgium. Patients were at high risk defined as either a history of CHD, another atherosclerotic disease, diabetes mellitus Type 2 or an estimated 10?year CHD risk > 20%. The primary endpoint was the proportion of patients achieving the LDL?C goal after 12 weeks of treatment.

Results: Overall, 96.4% of the 195 statin-naïve patients reached the LDL?C target after 12 weeks of treatment. The majority of the patients (95.4%) already reached LDL?C control at Week 6. Mean (SD) LDL?C levels decreased from 159 (25)?mg/dL[(4.1 (0.6)?mmol/L] to 86 (14)?mg/dL [2.2 (0.4)?mmol/L] after 12 weeks of treatment. Only 4.6% of the patients needed an up-titration at Week 6.

Conclusions: Taken together, the results demonstrate that LDL?C based dose selection of atorvastatin is highly efficacious for rapid achievement of target LDL?C levels with a low need for up-titration. Application of this flexible first dosing strategy in general practice will, based on available evidence, increase adherence to atorvastatin treatment in patients with high CHD risk.     

Atorvastatin affects C-reactive protein levels in patients with coronary artery disease

SUMMARY

Background: Elevated levels of C-reactive protein (CRP) are considered to be one of the indicators of poor prognosis in coronary artery disease (CAD). The aim of this study was to evaluate anti-inflammatory effects of atorvastatin in patients with CAD by measuring serum CRP levels.

Methods: After measuring the baseline levels of CRP and lipid fractions, the patients were divided into two groups. In Group A (n?=?46), atorvastatin (20?mg/day) was administered in addition to classic antianginal treatment (beta-blocker, nitrate and aspirin). In Group B (n?=?32), the usual antianginal treatment was continued. Following 4 weeks of treatment the same measurements were repeated.

Results: In Group A, CRP decreased from 20.3?mg/dl (95% CI, 9-31.8) to 10.8?mg/dl (95% CI, 2.7-18.9) (p?<?0.001). In Group B, CRP decreased from 17?mg/dl (95% CI, 13.1-21) to 12.8?mg/dl (95% CI, 9.7-15.9) (p?<?0.01). The decrease in group A was more than in group B (p?=?0.003).

Conclusions: In patients with CAD, atorvastatin exerted an anti-inflammatory effect represented by decreasing CRP levels. This effect was independent of the change in low density lipoprotein cholesterol (LDL-C) or high density lipoprotein cholesterol (HDL-C) levels.     

Antihyperlipidemic activity of adenosine triphosphate in rabbits fed a high-fat diet and hyperlipidemic patients

Context Recently, adenosine triphosphate (ATP) was occasionally found to decrease the triglyceride (TG) levels in several hyperlipidemic patients in our clinical practice.

Objective The study investigates the anti-hyperlipidemic effects of ATP in a high-fat fed rabbit model and hyperlipidemic patients.

Materials and methods Twenty-four rabbits were randomly divided into three groups of eight animals each as follows: normal diet, high-fat diet and high-fat diet?+?ATP group. ATP supplementation (40?mg/day) was started at the 20th day and lasted for 10 days. Serum concentrations of total cholesterol (TC), TG, LDL-C, HDL-C were measured on the 20th day and 30th day. Heart, liver and aorta were subjected histopathological examination. Twenty outpatients diagnosed primary hyperlipidemia took ATP at a dose of 60?mg twice a day for 1 week.

Results Feeding rabbits with a high-fat diet resulted in a significant elevation of lipid parameters including TC, TG, LDL-C, VLDL-C compared to the normal diet group (p?<?0.01). ATP treatment significantly decreased serum TG level (p?<?0.01), whilst other parameters remained statistically unaltered. Meanwhile, ATP significantly reduced the thickness of fat layer in cardiac epicardium (p?<?0.05) and pathological gradation of ballooning degeneration in hepatocytes (p?<?0.05). After taking ATP for 1 week, hyperlipidemia patients exhibited a significant decrease of TG (p?<?0.01), but other lipid parameters had no significant change.

Discussion and conclusion The study indicates that ATP selectively decreases serum TG levels in high-fat diet rabbits and hyperlipidemic patients. Therefore, ATP supplementation may provide an effective approach to control TG level.