Synthesis and In Vivo Hypolipidemic Effect of Some N-(Benzoylphenyl)-Carboxamide Derivatives in Triton WR-1339-Induced Hyperlipidemic Rats

A series of N-(benzoylphenyl)-carboxamide derivatives (2a, 2b, 3a, 3b, 4a, 4b, 5a, 5b, 6a and 6b) was prepared with good yields by reacting the corresponding carbonyl chlorides with aminobenzophenones at room temperature. This was followed by evaluating the hypotriglyceridemic and hypocholesterolemic effects of 3b, 5a and 5b. Triton WR-1339 (300 mg/kg) was intraperitoneally administered to overnight-fasted rats to induce hyperlipidemia. Rats were divided into six groups: control, hyperlipidemic, hyperlipidemic plus compounds 3b, 5a and 5b and hyperlipidemic plus bezafibrate. Results showed that after 18 h of treatment at a dose of 15 mg/kg body weight of each of the test compounds, the elevated plasma levels of triglycerides (TG) and total cholesterol (TC) were significantly lowered by compounds 5b and 3b (p < 0.001) and by 5a (p < 0.0001), compared to the hyperlipidemic control group. Compounds 3b and 5a significantly increased levels of high-density lipoprotein cholesterol (HDL-C) by 58 and 71%, respectively. In addition, compounds 3b and 5a caused significant reduction (p < 0.0001) of low-density lipoprotein cholesterol (LDL-C) levels compared to the control group. These results suggest a promising potential for compounds 3b, 5a and 5b as lipid-lowering agents, which may contribute to reducing the risk of atherosclerosis and cardiovascular disease

Metabolites profiling and hypolipidemic/hypocholesterolemic effects of persimmon (Diosyros kaki Thumb.) by different processing procedures: in vitro and in vivo studies / 한국영양학회지

PURPOSE: Our previous study demonstrated that persimmon (Diospyros kaki Thumb.) at different stages of ripening provided different protective effects against high-fat/cholesterol diet (HFD)-induced dyslipidemia in rats. In this study, we compared the metabolites profile and gene expressions related to triglyceride (TG)/cholesterol metabolism in vitro and in vivo after treating with persimmon water extracts (PWE) or tannin-enriched persimmon concentrate (TEP). METHODS: Primary and secondary metabolites in test materials were determined by GC-TOF/MS, UHPLC-LTQ-ESI-IT-MS/MS, and UPLC-Q-TOF-MS. The expression of genes related to TG and cholesterol metabolism were determined by RT-PCR both in HepG2 cells stimulated by oleic acid/palmitic acid and in liver tissues obtained from Wistar rats fed with HFD and PWE at 0, 150, 300, and 600 mg/d (experiment I) or TEP at 0, 7, 14, and 28 mg/d (experiment II) by oral gavage for 9 weeks. RESULTS: PLS-DA analysis and heatmap analysis demonstrated significantly differential profiling of metabolites of PWE and TEP according to processing of persimmon powder. In vitro, TEP showed similar hypolipidemic effects as PWE, but significantly enhanced hypocholesterolemic effects compared to PWE in sterol regulatory element-binding protein 2 (SREBP2), HMG-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesterol 7α-hydroxylase (CYP7A1), and low density lipoprotein receptor (LDLR) gene expression. Consistently, TEP and PWE showed similar hypolipidemic capacity in vivo, but significantly enhanced hypocholesterolemic capacity in terms of SREBP2, HMGCR, and bile salt export pump (BSEP) gene expression. CONCLUSION: These results suggest that column extraction after hot water extraction may be a good strategy to enhance tannins and long-chain fatty acid amides, which might cause stimulation of hypocholesterolemic actions through downregulation of cholesterol biosynthesis gene expression and upregulation of LDL receptor gene expression.

Effect of Compound Sanggou Granules on the Fibrinogen, Antithrombin Ⅲ and Fibrinolytic Activity in Hyperlipidemia Rats / 中国药师

Objective:To investigate the effect of compound Sanggou granules on the activity of Fib, AT-Ⅲ, t-PA, PAI-1 and t-PA/ PAI-1 in hyperlipidemic rats. Methods: The hyperlipidemic rat model was established by feeding high fat diet to SD male rats. Sixty healthy SD rats were randomly divided into five groups: the normal diet control group, high fat control group, high dose drug group, low dose drug group and fluvastatin sodium group. Four weeks after the administration, the blood samples were withdrawn for the determination of the levels of blood lipid, Fib, A-Ⅲ, t-PA, PAI-1 and t-PA/ PAI-1. Results:Compared with those of the normal diet control group, the levels of TC, LDL-C, Fib and PAI-1 were increased and the levels of HDL-C, t-PA , AT-Ⅲand t-PA/ PAI-1 were decreased significantly (P<0. 01) in the high fat control group. Compared with those of the high fat control group, the levels of TC, LDL-C, PAI-1 and Fib were decreased(P<0. 01 or P<0. 05),and the levels of HDL-C, t-PA AT-Ⅲ and t-PA/PAI-1 were in-creased significantly in the high dose drug group (P<0. 05 or P<0. 01). The similar effects were shown in the fluvastatin sodium group with the stability of AT-Ⅲ. The levels of TC, LDL-C and PAI-1 were decreased and the levels of t-PA/PAI-1 were increased no-tably in the low dose drug group. Conclusion: Compound Sanggou granules exhibit hypolipidemic effect in hyperlipidemic rats, and can improve hypercoagulability and enhance anticoagulation and fibrinolytic activity in hyperlipidemic rats. Furthermore, compound Sanggou granules at high dose show the same effect as fluvastatin sodium, even in anticoagulation, the granules are superior to fluvasta-tin sodium.

Hypotriglyceridemic effect of Morus alba L., Moraceae, leaves in hyperlipidemic rats / Efeito hipotrigliceridêmico de folhas de Morus alba L., Moraceae, em ratos hiperlipidêmicos

Mulberry Morus alba L., Moraceae, leaves are used in Brazil medicines against fever, to protect the liver, to lower the blood pressure and cholesterol. The aqueous extract of leaves of M. alba given by oral route to hyperlipidemic rats with diet enriched by cholesterol (1 percent by weight) with dose of 150 mg/kg/day for forteen days reduced significantly by 55,01 percent the plasma triglycerides level. Therefore, the treatment not only decreased the plasma level of triglycerides but also affected a hepatic enzyme tested supportting the fact that the extracts of Morus alba that have been used by folk medicine have a great potential to be further developed into a phytomedicine.

As folhas de amoreira branca Morus alba L., Moraceae, são utilizadas no Brasil na medicina popular para tratar febre, como protetor do fígado, para baixar a pressão e o colesterol. O extrato aquoso de folhas de M. alba foi administrado via oral através de gavagem em ratos hiperlipidêmicos com uma dieta enriquecida com colesterol (1 por cento) com uma dose de 150 mg/kg/dia por quatorze dias que reduziu significativamente em 55,01 por cento o nível de triglicerídios plasmáticos. Desta forma, o tratamento diminuiu o nível de triglicerídios e uma enzima hepática testada, demonstrando que extratos de Morus alba que tem sido popularmente utilizados possuem um grande potencial para se tornar um fitomedicamento.

Effect of beta-carotene Supplementation on Lipid Peroxides and Antioxidative Enzyme Activities in Hyperlipidemic Rats

This study was performed to investigate the effect of dietary beta-carotene supplementation on lipid metabolism and antioxidant enzyme activities in hyperlipidemic rats. Fifty Sprague-Dawley male rats aging 7 weeks were fed the control diet (CD, 5% corn oil) and the high fat diet (HFD, 15% beef tallow + 1% cholesterol) for 4 weeks and then 0.02% beta-carotene was supplemented to CD and HFD group for 8 more weeks. Serum lipid compositions, lipid peroxides and antioxidative enzymes in liver were analyzed at 4, 8 and 12week of the experiment. Serum levels of total lipid, total cholesterol, triglyceride, LDL-cholesterol, VLDL-cholesterol were higher in HFD groups than in CD groups (p < 0.001). Serum levels of HDL-cholesterol were higher in CD groups than in HFD groups (p < 0.01). The effect of beta-carotene supplementation was not significant in all groups but tended to be lower in total lipid, total cholesterol and triglyceride. Thiobarbituric acid reactive substances (TBARS) levels in plasma and liver were showed significantly higher in HFD groups (p < 0.001, p < 0.05). The effects of beta-carotene supplementation on the level of plasma and liver TBARS were not found except HFD groups at 12 week. Liver conjugated diene levels in HFD groups were higher than in CD groups (p < 0.01), but the effect of beta-carotene supplementation did not show any differences. Liver lipofuscin levels were not significantly different among all groups. The activities of superoxide dismutase (SOD) and catalase were significantly lower in HFD groups at 8 week (p < 0.001) but were not significantly different at 4 and 12week. The activity of SOD in beta-carotene supplemented HFD group was significantly higher at 8 week (p < 0.01). Glutathione peroxidase (GSHPx) activity was significantly lower in HFD groups (p < 0.01) and was significantly increased in groups supplemented beta-carotene (p < 0.05). It is suggested that beta-carotene supplementation partly decreases the serum lipid and lipid peroxide levels and increases the activities of antioxidant enzymes in hyperlipidemic rats.