Antrodia Camphorata in Submerged Culture Protects Low Density Lipoproteins Against Oxidative Modification

2006 ◽  
Vol 34 (02) ◽  
pp. 217-231 ◽  
Author(s):  
Hsin-Ling Yang ◽  
You-Cheng Hseu ◽  
Jing-Yi Chen ◽  
Yi-Jen Yech ◽  
Fung-Jou Lu ◽  
...  
Keyword(s):  
Oxidized Ldl ◽  
Oxidant Stress ◽  
Antioxidant Properties ◽  
Low Density Lipoproteins ◽  
Oxidative Modification ◽  
Low Density ◽  
Dependent Manner ◽  
Antrodia Camphorata ◽  
Concentration Dependent Manner ◽  
Apo B

Antrodia camphorata is well known in Taiwan as a traditional Chinese medicine. In this study, we have investigated the antioxidant properties of a fermented culture broth of Antrodia camphorata (FCBA) and the aqueous extracts of mycelia from Antrodia camphorata (AEMA) on the oxidative modification of human low-density lipoproteins (LDL), as induced by either copper sulfate ( CuSO 4) or 2,2′-azo-bis(2-amidinopropane) hydrochloride (AAPH). Under such oxidant stress, FCBA and AEMA appear to possess antioxidant properties with respect to oxidation of LDL in a time-and concentration-dependent manner, as assessed by inhibition of thiobarbituric acid-reactive substances (TBARS) formation, conjugated diene production, and cholesterol degradation of oxidized LDL. In addition, both FCBA and AEMA exhibited a remarkable ability to rescue the relative electrophoretic mobility and fragmentation of the Apo B moiety of the oxidized LDL. Furthermore, FCBA and AEMA effectively protected the endothelial cells from the damaging effects of the CuSO 4-oxidized LDL. Our findings suggest that the antioxidant properties of Antrodia camphorata may also provide effective protection from atherosclerosis.

scholarly journals Non-oxidative modification of native low-density lipoprotein by oxidized low-density lipoprotein

1996 ◽  
Vol 316 (2) ◽  
pp. 377-380 ◽  
Author(s):  
Min YANG ◽  
David S. LEAKE ◽  
Catherine A. RICE-EVANS
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Oxidative Modification ◽  
Low Density ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Process Studies

The oxidative modification of low-density lipoprotein (LDL) has been implicated in the pathogenesis of atherosclerosis, although little is known as yet about the precise mechanism of oxidation in vivo. The studies presented here demonstrate that, in the absence of cells or transition metals, oxidized LDL can modify native LDL through co-incubation in vitro such as to increase its net negative charge, in a concentration-dependent manner. The interaction is not inhibited by peroxyl radical scavengers or metal chelators, precluding the possibility that the modification of native LDL by oxidized LDL is through an oxidative process. Studies with radioiodinated oxidized LDL showed no transfer of radioactivity to the native LDL, demonstrating that fragmentation of protein and the transfer of some of the fragments does not account for the modified charge on the native LDL particle. The adjacency of native to oxidized LDL in the arterial wall may be a potential mechanism by which the altered recognition properties of the apolipoprotein B-100 may arise rapidly without oxidation or extensive modification of the native LDL lipid itself.

scholarly journals Detection of new epitopes formed upon oxidation of low-density lipoprotein, lipoprotein (a) and very-low-density lipoprotein. Use of an antiserum against 4-hydroxynonenal-modified low-density lipoprotein

1990 ◽  
Vol 265 (2) ◽  
pp. 605-608 ◽  
Author(s):  
G Jürgens ◽  
A Ashy ◽  
H Esterbauer
Keyword(s):  
Unsaturated Fatty Acids ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Oxidative Modification ◽  
Lipid Hydroperoxides ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Dependent Manner ◽  
Lipoprotein A

4-Hydroxynonenal (HNE) is a major aldehydic propagation product formed during peroxidation of unsaturated fatty acids. The aldehyde was used to modify freshly prepared human low-density lipoprotein (LDL). A polyclonal antiserum was raised in the rabbit and absorbed with freshly prepared LDL. The antiserum did not react with human LDL, but reacted with CuCl2-oxidized LDL and in a dose-dependent manner with LDL, modified with 1, 2 and 3 mM-HNE, in the double-diffusion analysis. LDL treated with 4 mM of hexanal or hepta-2,4-dienal or 4-hydroxyhexenal or malonaldehyde (4 or 20 mM) did not react with the antiserum. However, LDL modified with 4 mM-4-hydroxyoctenal showed a very weak reaction. Lipoprotein (a) and very-low-density lipoprotein were revealed for the first time to undergo oxidative modification initiated by CuCl2. This was evidenced by the generation of lipid hydroperoxides and thiobarbituric acid-reactive substances, as well as by a marked increase in the electrophoretic mobility. After oxidation these two lipoproteins also reacted positively with the antiserum against HNE-modified LDL.

Abstract 15019: Differential Effects of Omega-3 Fatty Acid Combinations on the Inhibition of Oxidation Of Human Low-density Lipoproteins in vitro

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Samuel Sherratt ◽  
James J Ferguson ◽  
Deepak L Bhatt ◽  
Preston Mason
Keyword(s):  
Docosapentaenoic Acid ◽  
Low Density Lipoproteins ◽  
Oxidative Modification ◽  
Time Dependent ◽  
Ldl Oxidation ◽  
Low Density ◽  
Dependent Manner ◽  
Omega 3 ◽  
Antioxidant Effects

Background: Omega-3 fatty acids (O3FAs) reduce levels of triglyceride but may also have additional atheroprotective benefits. Randomized trials have suggested potential clinical outcome differences among O3FAs formulations. Oxidative modification of low-density lipoproteins (LDL) contributes to endothelial dysfunction, inflammation, and other aspects of atherogenesis. Individual O3FAs have been shown to inhibit LDL oxidation to varying degrees, but the antioxidant effects of combining O3FAs is unknown. Objective: To compare the dose- and time-dependent antioxidant effects of eicosapentaenoic acid (EPA, 20:5) alone and in combination with either docosapentaenoic acid (DPA, 22:5) or docosahexaenoic acid (DHA, 22:6) in human LDL in vitro . Methods: Human LDL was isolated from healthy subjects and adjusted to a final ApoB concentration of 100 μg/mL in physiologic buffer (PBS) before being incubated with O3FAs at 37°C. The EPA levels in the combinations were fixed at either 2.0, 3.0, or 4.5 μM, while the DPA or DHA levels were set at 0, 0.5, 1.0, and 2.0 μM. Oxidation was initiated by copper sulfate (10 μM) and measured over time by formation of malondialdehyde (MDA), a lipid oxidation product. Results: When combined with EPA, both DPA and DHA increased inhibition of oxidation in a dose- and time-dependent manner, with DPA showing a greater effect and more prolonged inhibition. At high levels of EPA (4.5 μM), DPA showed significantly greater antioxidant activity than equimolar DHA; these differences were more apparent with time. After 8 hours, adding 1.0 μM DPA reduced MDA formation by 61% versus vehicle (3.10 ± 0.42 vs. 7.98 ± 0.56, p <0.001), while adding 1.0 μM DHA only reduced MDA formation by 20% (6.40 ± 1.23, p <0.05). When 2 μM DPA or DHA were added, after 10 hours only DPA still had a significant degree of inhibition versus vehicle (37%; 6.65 ± 0.95 vs. 8.21 ± 0.53, p <0.05). Similar trends were observed in combinations containing 2.0 and 3.0 μM EPA. Conclusion: Adding DPA or DHA to EPA provide dose-dependent incremental antioxidant effects, with DPA providing a larger degree and a longer duration of inhibition. These observations highlight potential differences among O3FAs (and their combinations) in novel mechanisms of atheroprotection.

scholarly journals Secondary radicals derived from chloramines of apolipoprotein B-100 contribute to HOCl-induced lipid peroxidation of low-density lipoproteins

1999 ◽  
Vol 339 (3) ◽  
pp. 489-495 ◽  
Author(s):  
Linda J. HAZELL ◽  
Michael J. DAVIES ◽  
Roland STOCKER
Keyword(s):  
Lipid Peroxidation ◽  
Protein Oxidation ◽  
Apolipoprotein B ◽  
Oxidized Ldl ◽  
Radical Reaction ◽  
Low Density Lipoproteins ◽  
Initial Reaction ◽  
Low Density ◽  
Dependent Manner ◽  
Antioxidative Therapy

Oxidation of low-density lipoproteins (LDL) is thought to contribute to atherogenesis. Although there is increasing evidence for a role of myeloperoxidase-derived oxidants such as hypochlorite (HOCl), the mechanism by which HOCl modifies LDL remains controversial. Some studies report the protein component to be the major site of attack, whereas others describe extensive lipid peroxidation. The present study addresses this controversy. The results obtained are consistent with the hypothesis that radical-induced oxidation of LDL's lipids by HOCl is a secondary reaction, with most HOCl consumed via rapid, non-radical reaction with apolipoprotein B-100. Subsequent incubation of HOCl-treated LDL gives rise to lipid peroxidation and antioxidant consumption in a time-dependent manner. Similarly, with myeloperoxidase/H2O2/Cl- (the source of HOCl in vivo), protein oxidation is rapid and followed by an extended period of lipid peroxidation during which further protein oxidation does not occur. The secondary lipid peroxidation process involves EPR-detectable radicals, is attenuated by a radical trap or treatment of HOCl-oxidized LDL with methionine, and occurs less rapidly when the lipoprotein was depleted of α-tocopherol. The initial reaction of low concentrations of HOCl (400-fold or 800-fold molar excess) with LDL therefore seems to occur primarily by two-electron reactions with side-chain sites on apolipoprotein B-100. Some of the initial reaction products, identified as lysine-residue-derived chloramines, subsequently undergo homolytic (one-electron) reactions to give radicals that initiate antioxidant consumption and lipid oxidation via tocopherol-mediated peroxidation. The identification of these chloramines, and the radicals derived from them, as initiating agents in LDL lipid peroxidation offers potential new targets for antioxidative therapy in atherogenesis.

Tumor necrosis factor-alpha inhibits lipid and lipoprotein transport by Caco-2 cells

1995 ◽  
Vol 269 (6) ◽  
pp. G953-G960 ◽  
Author(s):  
M. Mehran ◽  
E. Seidman ◽  
R. Marchand ◽  
C. Gurbindo ◽  
E. Levy
Keyword(s):  
Lipid Metabolism ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Low Density Lipoproteins ◽  
Tnf Alpha ◽  
Low Density ◽  
Necrosis Factor Alpha ◽  
Apo B ◽  
Factor Alpha ◽  
Necrosis Factor

Cytokines, important mediators of inflammation, have been shown to cause disturbances in circulating and hepatic lipid metabolism. Although the intestine plays a major role in dietary fat transport and largely contributes to plasma lipoproteins, the effects of cytokines on intestinal lipid handling remain unknown. In the present study, the modulation of lipid, apoprotein, and lipoprotein synthesis and secretion by tumor necrosis factor-alpha (TNF-alpha) was investigated in Caco-2 cells. Highly differentiated and polarized cells (20 days in culture) were incubated for 20 h with recombinant human TNF-alpha (100-500 ng/ml). No cytotoxic effect of TNF-alpha cells was observed, as indicated by the determinations of Caco-2 cell viability and monolayer transepithelial resistance. Moreover, no differences in cell maturation (sucrase activity) or cell proliferation ([3H]thymidine incorporation and cell cycle analysis) were detected between treated and control cultures. Significant inhibition of lipid secretion by TNF-alpha was observed, with the greatest reduction at 500 ng/ml. TNF-alpha significantly decreased Caco-2 cell secretion of phospholipids (22%), triglycerides (30%), and cholesteryl ester (37%). It also significantly diminished the export of newly synthesized low-density lipoproteins (LDL; 20%) and high-density lipoproteins (HDL; 13%), with a lesser effect on very low-density lipoproteins (VLDL; 3%). The lipid composition of these lipoproteins was minimally affected. De novo synthesis of apo A-I, apo B-100, and apo B-48 was also markedly reduced by TNF-alpha. Sphingomyelinase activity was not increased and cell content of sphingomyelin was not altered, suggesting that inhibitory effects on lipid and apoprotein of TNF-alpha were not mediated by the ceramide pathway. Our results indicate that TNF-alpha may play a role in modulating intestinal lipid metabolism, thus affecting circulating lipoproteins.

Oxidized low-density lipoproteins and microvascular responses to ischemia-reperfusion

1996 ◽  
Vol 271 (6) ◽  
pp. H2508-H2514 ◽  
Author(s):  
L. Liao ◽  
N. R. Harris ◽  
D. N. Granger
Keyword(s):  
Mast Cell ◽  
Oxidized Ldl ◽  
Ischemia Reperfusion ◽  
Low Density Lipoproteins ◽  
Mast Cell Degranulation ◽  
Low Density ◽  
Oxidized Low Density Lipoproteins ◽  
Rat Mesentery ◽  
Albumin Leakage ◽  
Wistar Kyoto

The objective of this study was to determine whether ischemia and reperfusion (I/R) and/or chronic arterial hypertension potentiates the leukocyte-endothelial cell adhesion (LECA) and microvascular dysfunction elicited by oxidized low-density lipoproteins (ox-LDL). Mast cell degranulation, leukocyte adherence and emigration, and albumin leakage were monitored in postcapillary venules of rat mesentery. Intra-arterial infusion of copper-oxidized LDL (Cu-LDL), at a concentration that does not directly affect the microvasculature, significantly enhanced the I/R-induced recruitment of adherent and emigrated leukocytes but does not affect the increased albumin leakage and mast cell degranulation responses normally observed after I/R. Infusion of a higher concentration of Cu-LDL in nonischemic mesentery of either normotensive Wistar-Kyoto or spontaneously hypertensive rats elicited significant yet similar increases in LECA, mast cell degranulation, and albumin leakage. These findings indicate that 1) ox-LDL act synergistically with I/R to promote leukocyte recruitment in postcapillary venules but without an accompanying exacerbation of albumin leakage, and 2) ox-LDL do not elicit a more intense inflammatory response in the microvasculature of hypertensive versus normotensive animals.

scholarly journals In vitro inhibitory potentials of ethanolic extract of Moringa oleifera flower against enzymes activities linked to diabetes

2021 ◽  
Vol 10 (4) ◽  
pp. 408-414
Author(s):  
Oluwaseun Ruth Olasehinde ◽  
Olakunle Bamikole Afolabi ◽  
Benjamin Olusola Omiyale ◽  
Oyindamola Adeniyi Olaoye
Keyword(s):  
Free Radical ◽  
Moringa Oleifera ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Ethanolic Extract ◽  
Antidiabetic Activity ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Antioxidant Power

Introduction: Diabetes mellitus (DM) has been recognized as the seventh leading cause of global mortality; however, researchers seek alternative means to manage the menace. The current study sought to investigate antioxidant potentials, α-amylase, and α-glucosidase inhibitory activities of ethanolic extract of Moringa oleifera flower in vitro. Methods: Antioxidant properties of the extract were appraised by assessing its inhibition against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH•), and hydrogen peroxide (H2O2) free radicals, as well as ferric reducing antioxidant power (FRAP), the antidiabetic activity was evaluated by α-amylase and α-glucosidase inhibition.Results: In this study, ethanolic extract of M. oleifera flower demonstrated a significant (P < 0.05) inhibition against DPPH free radical (43.57–83.56%) in a concentration-dependent manner, while FRAP (101.76 ± 1.63 mg/100 g), OH• scavenging ability (71.62 ± 0.95 mg/100 g), and H2O2 free radical scavenging capacity (15.33 ± 1.20 mg/100 g) were also observed. In the same manner, ethanolic extract of M. oleifera flower revealed a significant (P < 0.05) inhibition against α-amylase (IC50= 37.63 mg/mL) and α-glucosidase activities (IC50= 38.30 mg/mL) in the presence of their respective substrates in a concentration-dependent manner in comparison with acarbose. Conclusion: Ethanoic extract of M. oleifera flower could be useful as an alternative phytotherapy in the management of DM, having shown a strong antioxidative capacity and substantial inhibition against the activities of key enzymes involved in carbohydrate hydrolysis in vitro.

Antigenic differences between apo-B in native and circulating modified low-density lipoproteins

2004 ◽  
Vol 138 (7) ◽  
pp. 42-44 ◽  
Author(s):  
I. V. Suprun ◽  
A. A. Mel’nichenko ◽  
E. V. Yanushevskaya ◽  
T. N. Vlasik ◽  
I. A. Sobenin ◽  
...  
Keyword(s):  
Low Density Lipoproteins ◽  
Low Density ◽  
Apo B ◽  
Modified Low Density Lipoproteins

scholarly journals New pathogenetic hypothesis for Wolman disease: possible role of oxidized low-density lipoproteins in adrenal necrosis and calcification

1994 ◽  
Vol 301 (1) ◽  
pp. 267-273 ◽  
Author(s):  
G Fitoussi ◽  
A Nègre-Salvayre ◽  
M T Pieraggi ◽  
R Salvayre
Keyword(s):  
Cytotoxic Effect ◽  
Oxidized Ldl ◽  
Low Density Lipoproteins ◽  
Ldl Oxidation ◽  
Low Density ◽  
Cholesteryl Esters ◽  
Lysosomal Degradation ◽  
Wolman Disease ◽  
Adrenal Cells ◽  
Oxidized Low Density Lipoproteins

Wolman disease in an inherited metabolic disease, characterized by a severe deficiency of the acid lipase and a massive lysosomal storage of triacylglycerols and cholesteryl esters, associated with hepatosplenomegaly, adrenal calcification and nearly always fatal in the first year of life. Cultured human lymphoblastoid cells and human adrenal cells are able to promote the formation of mildly oxidized low-density lipoproteins (LDL), which in turn exhibit a non-negligible cytotoxic effect on these cells. In contrast, fibroblasts induce only very low levels of LDL oxidation. Comparative experiments have shown that the cytotoxic effect of oxidized LDL was higher to Wolman-disease cells than to controls. The oxidative ability of Wolman cells was similar to that of normal ones. The over-cytotoxicity of mildly oxidized LDL to Wolman cells resulted from the higher uptake of mildly oxidized LDL through the LDL-receptor pathway, which is only poorly down-regulated in Wolman cells subsequently to the block of the lysosomal degradation of LDL-cholesteryl esters. In cultured adrenal cells, oxidized LDL induced a sustained rise in intracellular [Ca2+] which is directly involved in the cellular damage and cell death induced by oxidized LDL [Nègre-Salvayre and Salvayre (1992) Biochim. Biophys. Acta 1123, 207-215]. This Ca2+ peak is followed by a dramatic deposition of calcium in damaged or/and dead cultured adrenal cells, quite similar to that observed in Wolman-disease adrenal cortex. The cell-induced LDL oxidation and the subsequent cytotoxic effect can be prevented, at least in part, by antioxidants such as alpha-tocopherol and nordihydroguaiaretic acid. These findings support the hypothesis that the Wolman-disease adrenal damage (necrosis and calcification) could result from the association of the following events: mild oxidation of LDL by adrenal cells, over-uptake of mildly oxidized LDL by Wolman cells (resulting from the block of the lysosomal degradation of cholesteryl esters in Wolman cells), and cytotoxicity related to the amount of mildly oxidized LDL internalized by cells. The reported data also suggest that LDL oxidation induced by adrenal cells and their subsequent cytotoxicity can be prevented (in part) by antioxidants, and the potential therapeutic use of antioxidants in Wolman disease is discussed.

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