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.

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.

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 A two-step homogeneous assay for apolipoprotein E-containing high-density lipoprotein-cholesterol

2018 ◽  
Vol 56 (1) ◽  
pp. 123-132 ◽  
Author(s):  
Yuji Takahashi ◽  
Yasuki Ito ◽  
Toshihiro Sakurai ◽  
Norio Wada ◽  
Atsushi Nagasaka ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Apolipoprotein E ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
In Vivo Studies ◽  
Homogeneous Assay

Background Apolipoprotein E-containing high-density lipoprotein shows antiatherogenic properties in vitro. There is a need for a homogeneous assay to determine the concentration of apolipoprotein E-containing high-density lipoprotein for in vivo studies. Methods In the proposed homogeneous assay, lipoproteins other than apolipoprotein E-containing high-density lipoprotein were eliminated in the first step. Apolipoprotein E-containing high-density lipoprotein-cholesterol was measured in the second step. The control study used a 13% polyethylene glycol precipitation assay (control assay). Results The homogeneous assay showed good performance in validation studies. In subjects with normal liver function ( n = 78), a significant correlation was found between the control assay and the homogeneous assay ( r = 0.824). Serum apolipoprotein E-containing high-density lipoprotein cholesterol concentrations, determined by the control assay and the homogeneous assay, respectively, were 0.05 (0.04–0.10) (median [25th–75th percentile]) mmol/L and 0.10 (0.06–0.13) mmol/L for healthy individuals ( n = 12), and 0.03 (0.01–0.13) mmol/L and 0.02 (0.01–0.02) mmol/L for patients with cholestasis ( n = 6). The results indicate that the homogeneous assay recovers cholesterol contained in physiological apolipoprotein E-containing high-density lipoprotein, but not in pathological apolipoprotein E-containing high-density lipoprotein from cholestatic patients. Conclusions The proposed two-step homogeneous assay enables selective measurement of physiological apolipoprotein E-containing high-density lipoprotein cholesterol in common autoanalysers. This assay might uncover a role for apolipoprotein E-containing high-density lipoprotein in physiological conditions.

scholarly journals Tweaking the cholesterol efflux capacity of reconstituted HDL

2012 ◽  
Vol 90 (5) ◽  
pp. 636-645 ◽  
Author(s):  
Cheng-I J. Ma ◽  
Jennifer A. Beckstead ◽  
Airlia Thompson ◽  
Anouar Hafiane ◽  
Rui Hao Leo Wang ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Intervention Strategy ◽  
Density Lipoprotein ◽  
Cellular Cholesterol ◽  
Bhk Cells ◽  
Plasma High Density ◽  
Competing Interaction ◽  
Cellular Cholesterol Efflux

Mechanisms to increase plasma high-density lipoprotein (HDL) or to promote egress of cholesterol from cholesterol-loaded cells (e.g., foam cells from atherosclerotic lesions) remain an important target to regress heart disease. Reconstituted HDL (rHDL) serves as a valuable vehicle to promote cellular cholesterol efflux in vitro and in vivo. rHDL were prepared with wild type apolipoprotein (apo) A-I and the rare variant, apoA-I Milano (M), and each apolipoprotein was reconstituted with phosphatidylcholine (PC) or sphingomyelin (SM). The four distinct rHDL generated were incubated with CHO cells, J774 macrophages, and BHK cells in cellular cholesterol efflux assays. In each cell type, apoA-I(M) SM-rHDL promoted the greatest cholesterol efflux. In BHK cells, the cholesterol efflux capacities of all four distinct rHDL were greatly enhanced by increased expression of ABCG1. Efflux to PC-containing rHDL was stimulated by transfection of a nonfunctional ABCA1 mutant (W590S), suggesting that binding to ABCA1 represents a competing interaction. This interpretation was confirmed by binding experiments. The data show that cholesterol efflux activity is dependent upon the apoA-I protein employed, as well as the phospholipid constituent of the rHDL. Future studies designed to optimize the efflux capacity of therapeutic rHDL may improve the value of this emerging intervention strategy.

Abstract 429: Structural Stability of Streptococcal Serum Opacity Factor

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Corina Rosales ◽  
Baiba K Gillard ◽  
Dedipya Yelamanchili ◽  
Antonio M Gotto ◽  
Henry J Pownall
Keyword(s):  
Disulfide Bonds ◽  
Plasma Cholesterol ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Cholesterol Levels ◽  
Serum Opacity Factor ◽  
Apo E ◽  
Plasma High Density

Despite its putative cardioprotective qualities, raising plasma high density lipoprotein-cholesterol (HDL-C) levels via pharmacologic means has failed to add protection against atherosclerosis, particularly when used as co-therapy with a statin. Two scenarios argue against the raising-plasma-HDL-is-better hypothesis and suggest that enhancing the final RCT step, hepatic cholesterol disposal, is a better cardioprotective strategy. First, probucol prevents CVD events and increases survival in humans and reduces CVD in SR-BI/apo E DKO mice. Despite its anti atherogenic properties, probucol lowers plasma HDL-C levels. Second, SR-BI over expressing vs. WT mice have lower plasma HDL-C but less atherosclerosis whereas the converse is true in SR-BI KO mice, suggesting that increasing HDL-C disposal is a rational cardioprotective strategy. One possible agent for therapeutic development is streptococcal serum opacity factor (SOF), a 100 kDa protein that clouds human serum via a novel HDL-targeting mechanism. SOF diverts HDL-CE to the LDL receptor and to bile acid secretion in vitro and in vivo, increases plasma HDL-C clearance in mice in an apo E-, LDLR-dependent mechanism thereby increasing hepatic CE uptake and reducing plasma cholesterol levels. SOF is active at 10 -14 M. Given its novel mechanism and potent reduction of plasma cholesterol levels in mice, we studied the structure and stability of SOF using its activity as a marker of its integrity versus several physicochemical challenges—extremes of pH, the denaturant, guanidinium chloride, heat, and ionic strength. SOF was highly resistant to all of these challenges. SOF has only one cysteine so it cannot be stabilized by internal disulfide bonds. Thus, SOF is an unusually stable protein that undergoes reversible unfolding-folding when challenged with a variety of physicochemical perturbants. These studies have helped us identify optimal conditions for crystallizing SOF for X-ray structure analysis.

Magnesium orotate elicits acute cardioprotection at reperfusion in isolated and in vivo rat hearts

2013 ◽  
Vol 91 (2) ◽  
pp. 108-115 ◽  
Author(s):  
Silvia N. Mirica ◽  
Oana M. Duicu ◽  
Simona L. Trancota ◽  
Ovidiu Fira-Mladinescu ◽  
Denis Angoulvant ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
Orotic Acid ◽  
Myocardial Function ◽  
Ex Vivo ◽  
Control Group ◽  
Mptp Opening ◽  
Rat Hearts ◽  
Magnesium Orotate

Orotic acid and its salts chronically administered have been shown to significantly improve cardiac function in pathological settings associated with ischemia–reperfusion (I/R) injury. The aim of our study was to investigate the effect of magnesium orotate (Mg-Or) administration at the onset of post-ischemic reperfusion on myocardial function and infarct size (IS). Ex-vivo experiments performed on isolated perfused rat hearts were used to compare Mg-Or administration with a control group (buffer treated), ischemic post-conditioning, orotic acid treatment, and MgCl2 treatment. Mg-Or administration was also investigated in an in-vivo model of regional I/R performed in rats undergoing reversible coronary ligation. The effect of Mg-Or on mitochondrial permeability transition pore (mPTP) opening after I/R was investigated in vitro to gain mechanistic insights. Both ex-vivo and in-vivo experiments showed a beneficial effect from Mg-Or administration at the onset of reperfusion on myocardial function and IS. In-vitro assays showed that Mg-Or significantly delayed mPTP opening after I/R. Our data suggest that Mg-Or administered at the very onset of reperfusion may preserve myocardial function and reduce IS. This beneficial effect may be related to a significant reduction of mPTP opening, a usual trigger of cardiac cell death following I/R.

scholarly journals A novel ANG-BSA/BCNU/ICG MNPs integrated for targeting therapy of glioblastoma

2021 ◽  
Author(s):  
Fan Lin ◽  
Xiao-Li Xiong ◽  
En-Ming Cui ◽  
Yi Lei
Keyword(s):  
Drug Delivery ◽  
Density Lipoprotein ◽  
Superparamagnetic Iron Oxide ◽  
Inhibitory Effect ◽  
Diagnosis And Treatment ◽  
Control Group ◽  
Targeting Therapy ◽  
Bimodal Imaging

Abstract Nanomedicine can improve the traditional disease treatment by actively targeting and enhancing the controlled release of drugs in the focus tissue in vivo, moreover the integration of diagnosis and treatment can be achieved by using tracer molecules to indicate the accumulation of nanodrugs in the focus. However ， almost all chemotherapeutic drugs and gene drugs failed to effectively treat glioblastoma (GBM) on account of the existence of blood-brain barrier (BBB) which play a role in GBM. So far, the survival rate of patients with GBM has been hardly improved. In the present study, we constructed an integrated nanoprobe based on albumin nanoparticles (NPs) for targeted diagnosis and treatment of GBM. The nanoprobe consists of albumin-coated superparamagnetic iron oxide (SPIO), Carmustine (BCNU) and indocyanine green (ICG) to achieve bimodal imaging and drug delivery. And the surface-coupled Angopep-2 (ANG, TFFYGGSRGKRNNFKTEEY) polypeptide can specifically bind to low density lipoprotein receptor-related protein (LRP), which is overexpressed in BBB and GBM cells. In the in vitro experiments, we verified that the targeting ability of nanoprobes to GBM cells was significantly better than that of the control group. In addition, in the in vivo experiments, nanoprobes significantly increased the accumulation of brain tumors compared with the control group. Cell killing of GBM cells (U87MG) with ANG-BSA/BCNU/ICG magnetic NPs shows a higher inhibitory effect compared with controls. This novel targeting imaging and drug delivery system provides an efficient strategy for targeted therapy and intraoperative localization of GBM.

Effect of Curcumin on LDL Oxidation in Vitro, and Lipid Peroxidation and Antioxidant Enzymes in Cholesterol Fed Rabbits

2011 ◽  
Vol 81 (6) ◽  
pp. 378-391 ◽  
Author(s):  
M. Mahfouz ◽  
Zhou ◽  
A. Kummerow
Keyword(s):  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Thiobarbituric Acid ◽  
Ldl Oxidation ◽  
Control Group ◽  
Liver Lipids ◽  
Pure Cholesterol

In this study we examined the antioxidant effect of curcumin on lipid oxidation in vitro and in vivo. In vitro, curcumin at 5 microgM concentration completely prevented low-density lipoprotein (LDL) oxidation by CuS04, indicating that curcumin is an effective antioxidant in vitro. In vivo, feeding a pure cholesterol (PC)-rich diet to rabbits significantly increased the plasma and liver lipids as well as thiobarbituric acid reactive substances (TBARS) levels. Addition of curcumin to the PC diet did not show any effect on either plasma lipid and TBARS or liver lipids. Liver TBARS tended to decrease but that decrease was not significant. Erythrocyte glutathione peroxidase (GSH-Px) activity was significantly decreased while catalase activity was significantly increased in rabbits fed a PC diet. The addition of curcumin to a PC diet did not show any significant effect on erythrocyte enzyme activities compared to the rabbits fed a PC diet. The liver GSH-Px and catalase activities were significantly decreased in rabbits fed a PC diet, but the addition of curcumin to the PC diet enhanced the liver GSH-Px activity, which became nonsignificantly different from the control group. These results were discussed considering that curcumin may not be well absorbed and it did not reach a level high enough in vivo to overcome the severe hypercholesterolemia and oxidative stress produced by the PC-rich diet.

In-vitro- und In-vivo-Wirkung von Schilddrüsenhormon auf das Wachstum von Neuroblastomzellen

1990 ◽  
Vol 29 (03) ◽  
pp. 120-124
Author(s):  
R. P. Baum ◽  
E. Rohrbach ◽  
G. Hör ◽  
B. Kornhuber ◽  
E. Busse
Keyword(s):  
Cell Differentiation ◽  
Neuroblastoma Cells ◽  
Control Group ◽  
Initial Value ◽  
Initial Rise ◽  
Biphasic Effect ◽  
Contrast Microscopy ◽  
Morphological Sign

The effect of triiodothyronine (T3) on the differentiation of cultured neuroblastoma (NB) cells was studied after 9 days of treatment with a dose of 10-4 M/106 cells per day. Using phase contrast microscopy, 30-50% of NB cells showed formation of neurites as a morphological sign of cellular differentiation. The initial rise of the mitosis rate was followed by a plateau. Changes in cyclic nucleotide content, in the triphosphates and in the activity of the enzyme ornithine decarboxylase (ODC) were assessed in 2 human and 2 murine cell lines to serve as biochemical parameters of the cell differentiation induced by T3. Whereas the cAMP level increased significantly (3 to 7 fold compared with its initial value), the cGMP value dropped to 30 to 50% of that of the control group. ATP and GTP increased about 200%, the ODC showed a decrease of about 50%. The present studies show a biphasic effect of T3 on neuroblastoma cells: the initial rise of mitotic activity is followed by increased cell differentiation starting from day 4 of the treatment.

Sign in / Sign up

Export Citation Format

Share Document