GH002: A Novel and Potent Agents for Elevating HDL-Cholesterol

2011 ◽  
Vol 340 ◽  
pp. 337-343
Author(s):  
Guo Lei
Keyword(s):  
Hepg2 Cells ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Control Group ◽  
Vitro Assay ◽  
Cholesterol Levels ◽  
Promoter Effects ◽  
Positive Effect

The aim of this study was to evaluate whether the positive effect of GH002 on high-density lipoprotein (HDL) cholesterol in vitro and in vivo. In vitro assay, effects of GH002 on apolipoprotein (apo) A-I was studied using stable-transfected HepG2 cells with recombinant vector including apoA-I promoter; Effects of GH002 on apoA-I, apoA-II and apoC-III production were determined using HepG2 cells. In vivo assay, Effects of GH002 on lipid profile were investigated in hyperlipidemic rats. The results showed that GH002 can effectively activate apoA-I promoter, enhance apoA-I and apoA-II secretion in vitro, whereas reduce apoC-III production significantly. Furthermore, after in vivo study that the hyperlipidemic rats were treated with GH002, HDL-cholesterol levels were increased significantly (P<0.01) at 2 weeks (100 mg/kg, 28.8%) and 3 weeks (30mg/kg, 19.8% and 100mg/kg, 36.4%, respectively) compared with control group. Triglyceride levels were reduced significantly at 2 and 3 weeks (19.5%, P<0.05 and 28.1%, P<0.01 respectively). Total cholesterol levels also were reduced at 3 weeks (19.1%, P<0.05) after 100mg/kg GH002 administration, but GH002 didn’t increase the ratio of liver/body weight compared with the control group at the end of the experiments. It is therefore reasonable to assume that GH002 is an effectively HDL-cholesterol enhancer by regulating apoA-I gene expression, consequently enhancing apoA-I, apoA-II secretion and reducing apoC-III production.

scholarly journals Effects of retinoid therapy on insulin sensitivity, lipid profile and circulating adipocytokines

2006 ◽  
Vol 154 (1) ◽  
pp. 83-86 ◽  
Author(s):  
S Corbetta ◽  
R Angioni ◽  
A Cattaneo ◽  
P Beck-Peccoz ◽  
A Spada
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Lipid Profile ◽  
Oral Treatment ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Glucose And Lipid Metabolism ◽  
Cholesterol Levels

Objective: In vitro and in vivo models indicate that all-trans retinoic acids influence glucose and lipid metabolism. We aimed to evaluate the effects of chronic treatment with acitretin, an all-trans retinoic acid, on glucose metabolism, lipid profile and adiponectin and resistin levels. Design: Ten normoglycemic, normolipemic patients affected with psoriasis vulgaris were studied before and after 1 and 3 months of oral treatment with 35 μg of acitretin. Methods: Glucose metabolism, lipid profile, and adiponectin and resistin levels were evaluated in basal conditions and after acitretin treatment. Ten healthy subjects matched for age, body mass index (BMI) and insulin sensitivity were studied as controls. Results: One-month acitretin treatment reduced psoriasis activity, insulin sensitivity, evaluated as QUICKI values (0.364 ± 0.034 versus 0.329 ± 0.051; P < 0.05) and HOMA-IR index (1.53 ± 0.73 versus 2.59 ± 1.41; P < 0.05), and high-density lipoprotein (HDL)-cholesterol levels (45.2 ± 11.7 versus 39.4 ± 10.4 mg/dl; P = 0.01). The impairment in glucose and lipid homeostasis was transient and not associated to BMI variations. Adiponectin levels did not change during the treatment, while resistin levels, which were higher in untreated patients than in controls (9.4 ± 4.4 versus 6.2 ± 2.1 ng/ml; P = 0.05), fell within the normal range after 1 and 3 months of therapy. The normalization of resistin levels occurred without significant changes in circulating tumor necrosis factor α (TNFα) levels, which persisted elevated throughout the treatment. Conclusions: Treatment with a low dose of acitretin induced a mild, transient reduction of insulin sensitivity and HDL-cholesterol levels that was not related to modifications of adiponectin, resistin and TNFα levels. Although the role of resistin in humans remains elusive, the levels of this adipocytokine seem to be affected, at least in part, by retinoids.

scholarly journals Pharmacoinformatics and UPLC-QTOF/ESI-MS-Based Phytochemical Screening of Combretum indicum against Oxidative Stress and Alloxan-Induced Diabetes in Long–Evans Rats

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4634
Author(s):  
Md. Shaekh Forid ◽  
Md. Atiar Rahman ◽  
Mohd Fadhlizil Fasihi Mohd Aluwi ◽  
Md. Nazim Uddin ◽  
Tapashi Ghosh Roy ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Immune Modulation ◽  
Computational Study ◽  
Density Lipoprotein ◽  
Control Group ◽  
Esi Ms ◽  
Long Evans ◽  
Antidiabetic Effects

This research investigated a UPLC-QTOF/ESI-MS-based phytochemical profiling of Combretum indicum leaf extract (CILEx), and explored its in vitro antioxidant and in vivo antidiabetic effects in a Long–Evans rat model. After a one-week intervention, the animals’ blood glucose, lipid profile, and pancreatic architectures were evaluated. UPLC-QTOF/ESI-MS fragmentation of CILEx and its eight docking-guided compounds were further dissected to evaluate their roles using bioinformatics-based network pharmacological tools. Results showed a very promising antioxidative effect of CILEx. Both doses of CILEx were found to significantly (p < 0.05) reduce blood glucose, low-density lipoprotein (LDL), and total cholesterol (TC), and increase high-density lipoprotein (HDL). Pancreatic tissue architectures were much improved compared to the diabetic control group. A computational approach revealed that schizonepetoside E, melianol, leucodelphinidin, and arbutin were highly suitable for further therapeutic assessment. Arbutin, in a Gene Ontology and PPI network study, evolved as the most prospective constituent for 203 target proteins of 48 KEGG pathways regulating immune modulation and insulin secretion to control diabetes. The fragmentation mechanisms of the compounds are consistent with the obtained effects for CILEx. Results show that the natural compounds from CILEx could exert potential antidiabetic effects through in vivo and computational study.

scholarly journals Anti-Obesity and Anti-Adipogenic Effects of Chitosan Oligosaccharide (GO2KA1) in SD Rats and in 3T3-L1 Preadipocytes Models

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 331
Author(s):  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Jungbae Oh ◽  
Joo Woong Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Control Group ◽  
Chitosan Oligosaccharide ◽  
Sd Rats ◽  
Adipogenic Gene

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

scholarly journals Effects of Hamo NK hard capsule on serum lipid profiles in dyslipidemia experimental animals

2021 ◽  
Vol 141 (5) ◽  
pp. 10-18
Author(s):  
Pham Thuy Phuong ◽  
Pham Quoc Binh ◽  
Dinh Thi Hong Minh ◽  
Tran Thi Thu Hien ◽  
Nguyen Trong Thong ◽  
...  
Keyword(s):  
Serum Lipid ◽  
Therapeutic Strategy ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Poloxamer 407 ◽  
Control Group ◽  
Cholesterol Levels ◽  
Daily Dose ◽  
Previously Treated ◽  
Cholesterol Control

Dyslipidemia is a major risk factor for cardiovascular disease. Polyherbal formulation is a traditional therapeutic strategy used to treat dyslipidemia over many years of tradition. The aim of this study was designed to evaluate the effects of Hamo NK hard capsule on endogenous dyslipidemia and exogenous dyslipidemia experimental animal model. In endogenous hyperlipidemia model, mice were previously treated by Hamo NK hard capsule, and intraperitoneally injected by poloxamer - 407 to induce hyperlipidemia. Rats were oral administration of oil - cholesterol mixture and Hamo NK for 4 consecutive weeks (exogenous dyslipidemia). Parameters of serum lipid were determined. Hamo NK ameliorated the elevation of serum total cholesterol, Non - HDL - cholesterol at the daily dose of 1.5g/kg b.w (p < 0.05). Also, there was no signicant difference in increase on high - density lipoprotein cholesterol levels and decrease triglyceride levels between the groups. Hamo NK at two doses of 0.25g/kg b.w and 0.75g/kg b.w significantly reduced serum LDL - C levels compared to the cholesterol control group. Hamo NK hard capsule affected on serum lipid modulations in dyslipidemia models.

scholarly journals Sagunja-Tang Improves Lipid Related Disease in a Postmenopausal Rat Model and HepG2 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Hiroe Go ◽  
Jin Ah Ryuk ◽  
Hye Won Lee ◽  
In Sil Park ◽  
Ki-Jung Kil ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Cholesterol Synthesis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Protein Levels ◽  
Related Disease

The present study was conducted to investigate the effect of Sagunja-tang on the lipid related disease in a rat model of menopausal hyperlipidemia and lipid accumulation in methyl-β-cyclodextrin-induced HepG2 cells. Inin vivostudy using menopausal hyperlipidemia rats, Sagunja-tang reduced retroperitoneal and perirenal fat, serum lipids, atherogenic index, cardiac risk factor, media thickness, and nonalcoholic steatohepatitis score, when compared to menopausal hyperlipidemia control rats. In HepG2 cells, Sagunja-tang significantly decreased the lipid accumulation, total cholesterol levels, and low-density/very-low-density lipoprotein levels. Moreover, Sagunja-tang reversed the methyl-β-cyclodextrin-induced decrease in the protein levels of critical molecule involved in cholesterol synthesis, sterol regulatory element binding protein-2, and low-density lipoprotein receptor and inhibited protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase as well as activity. Phosphorylation level of AMP-activated protein kinase was stimulated by Sagunja-tang. These results suggest that Sagunja-tang has effect on inhibiting hepatic lipid accumulation through regulation of cholesterol synthesis and AMPK activityin vitro. These observations support the idea that Sagunja-tang is bioavailable bothin vivoandin vitroand could be developed as a preventive and therapeutic agent of hyperlipidemia in postmenopausal females.

Abstract 76: MicroRNA-144 Regulates Hepatic ABCA1 and Plasma HDL Following Activation of the Nuclear Receptor FXR

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Thomas Vallim ◽  
Elizabeth Tarling ◽  
Tammy Kim ◽  
Mete Civelek ◽  
Angel Baldan ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Nuclear Receptor ◽  
Molecular Mechanisms ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Farnesoid X Receptor ◽  
Abca1 Protein

Rationale The bile acid receptor Farnesoid-X-Receptor (FXR) regulates many aspects of lipid metabolism by various complex and not fully understood molecular mechanisms. We set out to investigate the molecular mechanisms for FXR-dependent regulation of lipid and lipoprotein metabolism. Objective To identify FXR-regulated microRNAs that were subsequently involved in regulating lipid metabolism. Methods and Results ATP binding cassette transporter A1 (ABCA1) is a major determinant of plasma High Density Lipoprotein (HDL)-cholesterol levels. Here we show that activation of the nuclear receptor FXR in vivo increases hepatic levels of miR-144, which in turn lower hepatic ABCA1 and plasma HDL levels. We identified two complementary sequences to miR-144 in the 3’ untranslated region (UTR) of ABCA1 mRNA that are necessary for miR-144-dependent regulation. Overexpression of miR-144 in vitro decreased both cellular ABCA1 protein and cholesterol efflux to lipid-poor apolipoprotein A-I (ApoA-I) protein, whilst overexpression in vivo reduced hepatic ABCA1 protein and plasma HDL- cholesterol. Conversely, silencing miR-144 in mice increased hepatic ABCA1 protein and HDL- cholesterol. In addition, we utilized tissue-specific FXR deficient mice to show that induction of miR-144 and FXR-dependent hypolipidemia requires hepatic, but not intestinal FXR. Finally, we identified functional FXR response elements (FXREs) upstream of the miR-144 locus, consistent with direct FXR regulation. Conclusion In conclusion, we have identified a pathway involving FXR, miR-144 and ABCA1 that together regulate plasma HDL cholesterol. This pathway may be therapeutically targeted in the future in order to increase HDL levels.

scholarly journals 3-Pentylcatechol, a Non-Allergenic Urushiol Derivative, Displays Anti-Helicobacter pylori Activity In Vivo

2020 ◽  
Vol 13 (11) ◽  
pp. 384
Author(s):  
Hang Yeon Jeong ◽  
Tae Ho Lee ◽  
Ju Gyeong Kim ◽  
Sueun Lee ◽  
Changjong Moon ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Triple Therapy ◽  
Inflammatory Cells ◽  
Control Group ◽  
Vitro Assay ◽  
Low Concentrations ◽  
H Pylori ◽  
Stomach Mucous Membrane

We previously reported that 3-pentylcatechol (PC), a synthetic non-allergenic urushiol derivative, inhibited the growth of Helicobacter pylori in an in vitro assay using nutrient agar and broth. In this study, we aimed to investigate the in vivo antimicrobial activity of PC against H. pylori growing in the stomach mucous membrane. Four-week-old male C57BL/6 mice (n = 4) were orally inoculated with H. pylori Sydney Strain-1 (SS-1) for 8 weeks. Thereafter, the mice received PC (1, 5, and 15 mg/kg) and triple therapy (omeprazole, 0.7 mg/kg; metronidazole, 16.7 mg/kg; clarithromycin, 16.7 mg/kg, reference groups) once daily for 10 days. Infiltration of inflammatory cells in gastric tissue was greater in the H. pylori-infected group compared with the control group and lower in both the triple therapy- and PC-treated groups. In addition, upregulation of cytokine mRNA was reversed after infection, upon administration of triple therapy and PC. Interestingly, PC was more effective than triple therapy at all doses, even at 1/15th the dose of triple therapy. In addition, PC demonstrated synergism with triple therapy, even at low concentrations. The results suggest that PC may be more effective against H. pylori than established antibiotics.

Beneficial effect of 3,4,5,6-tetrahydroxyxanthone on dyslipidemia in apolipoprotein E-deficient mice

2008 ◽  
Vol 86 (12) ◽  
pp. 815-826 ◽  
Author(s):  
Hong-Bo Xiao ◽  
Zhi-Liang Sun ◽  
Xiang-Yang Lu ◽  
Da-Zhi Li ◽  
Jian-Ping Xu ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
Apolipoprotein E ◽  
Density Lipoprotein ◽  
Control Group ◽  
Elevated Expression ◽  
Plasma High Density ◽  
Adipose Tissue Lipoprotein Lipase ◽  
Xanthone Compound

Previous investigations have shown that decreased expression of angiopoietin-like protein 3 (Angptl3) is protective against dyslipidemia in atherosclerosis. The present study was conducted to test the effect of 3,4,5,6-tetrahydroxyxanthone, a xanthone compound, on dyslipidemia in apolipoprotein E-deficient (ApoE−/−) mice. Forty mice were randomly divided into 4 groups (n = 10): control group (C57BL/6J mice), ApoE−/− mice group, and two groups of ApoE−/− mice treated with 3,4,5,6-tetrahydroxyxanthone (10 or 30 mg/kg per day). Eight weeks after treatment, lipid levels in the blood and liver, expression of hepatic Angptl3, and adipose tissue lipoprotein lipase (LPL) were determined. Treatment with 3,4,5,6-tetrahydroxyxanthone (10 or 30 mg/kg) significantly decreased plasma and hepatic total cholesterol and triglyceride concentrations, increased plasma high-density lipoprotein cholesterol, and significantly downregulated expression of Angptl3 mRNA and protein concomitantly with upregulated expression of LPL mRNA. In addition, T0901317 (a liver X receptor ligand) caused elevated expression of hepatic Angptl3 mRNA and protein, and the effect of T0901317 was also abrogated by 3,4,5,6-tetrahydroxyxanthone in vivo and in vitro. The present results suggest that the beneficial effect of 3,4,5,6-tetrahydroxyxanthone on dyslipidemia may be related to reduced expression of Angptl3.

Melatonin does not affect the black pigment migration in the crab Neohelice granulata

Biologia ◽  
2009 ◽  
Vol 64 (1) ◽  
Author(s):  
Fábio Maciel ◽  
Márcio Geihs ◽  
Marcelo Vargas ◽  
Bianca Ramos ◽  
Bruno Cruz ◽  
...  
Keyword(s):  
Physiological Function ◽  
Physiological Solution ◽  
Control Group ◽  
Constant Darkness ◽  
Pigment Dispersion ◽  
Vitro Assay ◽  
Neohelice Granulata ◽  
Pigment Migration

AbstractN-acetyl-5-methoxytryptamine or melatonin is a multifunctional molecule. The main physiological function, at least in vertebrates, is to transduce to the animal the photoperiodic information and regulate rhythmic parameters. But studies have also observed the action of this molecule on pigment migration in ectothermic vertebrates. Thus the aim of this paper was to investigate in vivo and in vitro the influence of melatonin on the pigment migration in melanophores of the crab Neohelice granulate. Injections of melatonin (2 × 10−9 moles · crab−1) at 07:00 h or 19:00 h did not affect (p > 0.05) the circadian pigment migration of the melanophores in constant darkness. Additionally no significant pigment migration (p > 0.05) was verified in normal and eyestalkless crabs injected with melatonin (10−10–10−7 moles · crab−1) during the day or night. In the in vitro assay, the response of melanophores to the pigment-dispersing hormone in eyestalkless crabs injected with melatonin (2 × 10−9 moles · crab−1) 1 and 12 hours before the observations did not differ (p > 0.05) from the control group (injected with physiological solution). These results suggest that melatonin does not act as a signaling factor for pigment dispersion or aggregation in the melanophores of N. Granulate.

scholarly journals Study of the Effects of Total Flavonoids of Astragalus on Atherosclerosis Formation and Potential Mechanisms

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Deqing Wang ◽  
Yuan Zhuang ◽  
Yaping Tian ◽  
Graham Neil Thomas ◽  
Mingzhong Ying ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Ischemia Reperfusion ◽  
Animal Experiments ◽  
Hdl Cholesterol ◽  
Total Flavonoids ◽  
Protective Effects ◽  
In Vivo Experiments ◽  
Cholesterol Levels

Astragalus mongholicusBunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protective effects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments and diet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of total cholesterol and LDL cholesterol (P<0.05to 0.01), increased HDL cholesterol levels (P<0.01), and reduced the aortic fatty streak area by 43.6 to 63.6% (P<0.01). We also found that TFA scavenged superoxide and hydroxyl radicals and this effect increased with higher TFA concentration. In in vivo experiments, TFA effectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component ofAstragalus mongholicusBunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve the atherosclerosis profile.

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