In Vivo Evaluation of Dendropanax morbifera Leaf Extract for Anti-Obesity and Cholesterol-Lowering Activity in Mice

Metabolic syndrome is a worldwide health problem, and obesity is closely related to type 2 diabetes, cardiovascular disease, hypertension, and cancer. According to WHO in 2018, the prevalence of obesity in 2016 tripled compared to 1975. D. morbifera reduces bad cholesterol and triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice. The group treated with DLW 500 mg∙kg−1∙d−1 had significantly lower body weights compared to the control group. In addition, High-density lipoprotein (HDL) cholesterol increased in the group treated with DLW 500 mg∙kg−1∙d−1. The effect of DLW on the serum lipid profile could be helpful to prevent obesity. DLW suppresses lipid formation in adipocytes and decreases body fat. In conclusion, DLW can be applied to develop anti-obesity functional foods and other products to reduce body fat.

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

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.340.337 ◽

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.

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In vivo evaluation of a recombinant N-acylhomoserine lactonase formulated in a hydrogel using a murine model infected with MDR Pseudomonas aeruginosa clinical isolate, CCASUP2

AMB Express ◽

10.1186/s13568-021-01269-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Masarra M. Sakr ◽

Walid F. Elkhatib ◽

Khaled M. Aboshanab ◽

Eman M. Mantawy ◽

Mahmoud A. Yassien ◽

...

Keyword(s):

Survival Rate ◽

Murine Model ◽

Histopathological Examination ◽

Healing Process ◽

Bacterial Count ◽

Treated Group ◽

Control Group ◽

In Vivo Evaluation ◽

Systemic Spread

AbstractFailure in the treatment of P. aeruginosa, due to its broad spectrum of resistance, has been associated with increased patient mortality. One alternative approach for infection control is quorum quenching which was found to decrease virulence of such pathogen. In this study, the efficiency of a recombinant Ahl-1 lactonase formulated as a hydrogel was investigated to control the infection of multidrug resistant (MDR) P. aeruginosa infected burn using a murine model. The recombinant N-acylhomoserine lactonase (Ahl-1) was formulated as a hydrogel. To test its ability to control the infection of MDR P. aeruginosa, a thermal injury model was used. Survival rate, and systemic spread of the infection were evaluated. Histopathological examination of the animal dorsal skin was also done for monitoring the healing and cellular changes at the site of infection. Survival rate in the treated group was 100% relative to 40% in the control group. A decrease of up to 3 logs of bacterial count in the blood samples of the treated animals relative to the control group and a decrease of up to 4 logs and 2.3 logs of bacteria in lung and liver samples, respectively were observed. Histopathological examination revealed more enhanced healing process in the treated group. Accordingly, by promoting healing of infected MDR P. aeruginosa burn and by reducing systemic spread of the infection as well as decreasing mortality rate, Ahl-1 hydrogel application is a promising strategy that can be used to combat and control P. aeruginosa burn infections.

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

Molecules ◽

10.3390/molecules26154634 ◽

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.

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

Molecules ◽

10.3390/molecules26020331 ◽

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.

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Impaired postprandial clearance of triacylglycerol-rich lipoproteins in adipose tissue in obese subjects

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.268.4.e588 ◽

1995 ◽

Vol 268 (4) ◽

pp. E588-E594 ◽

Cited By ~ 8

Author(s):

J. L. Potts ◽

S. W. Coppack ◽

R. M. Fisher ◽

S. M. Humphreys ◽

G. F. Gibbons ◽

...

Keyword(s):

Adipose Tissue ◽

Low Density Lipoprotein ◽

Postprandial Lipemia ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Control Group ◽

Postprandial Period ◽

Before And After ◽

Obese Subjects ◽

Subcutaneous Adipose

Adipose tissue is an important site of clearance of circulating triacylglycerol (TAG), especially in the postprandial period. Postprandial lipemia is usually increased in obesity. We studied the extraction of TAG from plasma and TAG-rich lipoproteins (TRLs) in subcutaneous adipose tissue in 11 control and 8 obese subjects before and after a mixed meal. Clearance of plasma TAG and very low-density lipoprotein (VLDL)-TAG was decreased in the obese subjects after an overnight fast. After the meal, chylomicron-TAG extraction increased in the control group whereas VLDL-TAG clearance decreased; these changes were not seen in the obese group, in whom the VLDL particles appeared to be better able to compete with the chylomicrons for clearance by lipoprotein lipase. In the control subjects, removal of TAG from the TRL in the postprandial period was accompanied by a shift toward addition of cholesterol to the high-density lipoprotein (HDL) fraction; this was not observed in the obese subjects. We conclude that disturbed TRL-TAG clearance in adipose tissue is related both to the elevated plasma TAG concentrations and the depressed HDL-cholesterol concentrations typical of obesity.

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HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders

Journal of Experimental Medicine ◽

10.1084/jem.20121357 ◽

2013 ◽

Vol 210 (2) ◽

pp. 339-353 ◽

Cited By ~ 35

Author(s):

Emmanuel L. Gautier ◽

Marit Westerterp ◽

Neha Bhagwat ◽

Serge Cremers ◽

Alan Shih ◽

...

Keyword(s):

Mouse Models ◽

Cholesterol Efflux ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Myeloproliferative Disorders ◽

Tissue Loss ◽

Human Leukemia ◽

Glut1 Expression ◽

Underlying Mechanisms

A high metabolic rate in myeloproliferative disorders is a common complication of neoplasms, but the underlying mechanisms are incompletely understood. Using three different mouse models of myeloproliferative disorders, including mice with defective cholesterol efflux pathways and two models based on expression of human leukemia disease alleles, we uncovered a mechanism by which proliferating and inflammatory myeloid cells take up and oxidize glucose during the feeding period, contributing to energy dissipation and subsequent loss of adipose mass. In vivo, lentiviral inhibition of Glut1 by shRNA prevented myeloproliferation and adipose tissue loss in mice with defective cholesterol efflux pathway in leukocytes. Thus, Glut1 was necessary to sustain proliferation and potentially divert glucose from fat storage. We also showed that overexpression of the human ApoA-I transgene to raise high-density lipoprotein (HDL) levels decreased Glut1 expression, dampened myeloproliferation, and prevented fat loss. These experiments suggest that inhibition of Glut-1 and HDL cholesterol–raising therapies could provide novel therapeutic approaches to treat the energy imbalance observed in myeloproliferative disorders.

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

Tạp chí Nghiên cứu Y học ◽

10.52852/tcncyh.v141i5.217 ◽

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.

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Evaluation of Lipid Lowering Effect of Milk Thistle (Silybum Marianum) in Comparison with Rosuvastatin in Rats by Using Ace-alera® Analyzer

International Journal of Biology and Biomedical Engineering ◽

10.46300/91011.2020.14.13 ◽

2020 ◽

Vol 14 ◽

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Lipid Lowering ◽

Control Group ◽

Milk Thistle ◽

High Dose ◽

Hypolipidemic Effect ◽

Low Density ◽

Therapeutic Protocols

Dyslipidemia is a metabolic disorder that is characterized with an elevation in the cholesterol serum levels that can be treated with various hypolipidemic drugs like rosuvastatin. The present study was undertaken to determine and evaluate the hypolipidemic effect of milk thistle seeds extract in comparison with rosuvastatin and the combination of both for the treatment of dyslipidemia in rats. Also its effect on blood glucose levels on experimentally induced dyslipidemic rats. In vivo studies were conducted on wister albino laboratory rats, in which 49 rats were induced to be dyslipidemic by a daily intragastric administration of cholesterol (2 g/kg). The induction of dyslipidemia was evaluated by comparing these rats with a negative control group that was composed of 10 healthy rats. Then, after one month dyslipidemia was induced in 49 rats that were divided into 6 groups, as the following; positive control group (n=9) received cholesterol (2 g/kg) for another one month, and the other five groups each of 8 rats continued to receive cholesterol (2 g/kg) for one month along with therapy as; rosuvastatin low dose (RL) group received 10 mg/kg, rosuvastatin high dose (RH) group received 20 mg/kg, milk thistle (MT) group received 7.15 mg/kg, (RL+MT) group received a combination of 10 mg/kg of rosuvastatin and 7.15 mg/kg of milk thistle, and (RH+MT) group received a combination of 20 mg/kg of rosuvastatin and 7.15 mg/kg of milk thistle. The statistical results of biochemical analysis showed that all the studied therapeutic protocols whether given alone; RL, RH, and MT or in a combination; RL+MT and RH+MT led to a significant (p≤0.05) hypolipidemic effect that reduced the total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) and increased the high density lipoprotein (HDL) cholesterol levels. In conclusion, all therapeutic protocols were effective in treating dyslipidemia, as they all reduced the TC, TG, LDL, and VLDL, and increased the HDL cholesterol significantly (p≤0.05). Furthermore, we found that milk thistle can be used in the management of dyslipidemia, as it has a hypolipidemic effect. Also, the addition of milk thistle to rosuvastatin therapy reduced the risk of developing diabetes mellitus (DM), as it has a glucose modulating activity either when it was given alone or in combination with rosuvastatin. Moreover, the combination of milk thistle and rosuvastatin was of a great benefit, as it gave an intensive goal of therapy than each one alone in altering all lipid profile parameters.

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Promoter-Specific Roles for Liver X Receptor/Corepressor Complexes in the Regulation of ABCA1 and SREBP1 Gene Expression

Molecular and Cellular Biology ◽

10.1128/mcb.23.16.5780-5789.2003 ◽

2003 ◽

Vol 23 (16) ◽

pp. 5780-5789 ◽

Cited By ~ 167

Author(s):

Brandee L. Wagner ◽

Annabel F. Valledor ◽

Gang Shao ◽

Chris L. Daige ◽

Eric D. Bischoff ◽

...

Keyword(s):

Fatty Acid ◽

Hormone Receptors ◽

Target Genes ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Whole Body ◽

Abca1 Gene ◽

Element Binding Protein ◽

X Receptors

ABSTRACT Liver X receptors (LXRs) regulate the expression of genes involved in cholesterol and fatty acid homeostasis, including the genes for ATP-binding cassette transporter A1 (ABCA1) and sterol response element binding protein 1 (SREBP1). Loss of LXR leads to derepression of the ABCA1 gene in macrophages and the intestine, while the SREBP1c gene remains transcriptionally silent. Here we report that high-density-lipoprotein (HDL) cholesterol levels are increased in LXR-deficient mice, suggesting that derepression of ABCA1 and possibly other LXR target genes in selected tissues is sufficient to result in enhanced HDL biogenesis at the whole-body level. We provide several independent lines of evidence indicating that the repressive actions of LXRs are dependent on interactions with the nuclear receptor corepressor (NCoR) and the silencing mediator of retinoic acid and thyroid hormone receptors (SMRT). While dissociation of NCoR and SMRT results in derepression of the ABCA1 gene in macrophages, it is not sufficient for derepression of the SREBP1c gene. These findings reveal differential requirements for corepressors in the regulation of genes involved in cholesterol and fatty acid homeostasis and raise the possibility that these interactions may be exploited to develop synthetic ligands that selectively modulate LXR actions in vivo.

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

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a76 ◽

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.

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