Palmitic Acid Curcumin Ester Facilitates Protection of Neuroblastoma against Oligomeric Aβ40 Insult

Background/Aims: The generation of reactive oxygen species (ROS) caused by amyloid-β (Aβ) is considered to be one of mechanisms underlying the development of Alzheimer’s disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin) which can be cultivated on the cell membrane and investigated the neuroprotective effect of P-curcumin and its interaction with Aβ. Methods: P-curcumin was prepared through chemical synthesis. Its structure was determined via nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). An MTT assay was used to assess Aβ cytotoxicity and the protective effect of P-curcumin on SH-SY5Y cells. The effect of P-curcumin on Aβ-induced ROS production in vitro and in vivo were assessed based on changes in dichlorofluorescein (DCF) fluorescence. A spectrophotometric method was employed to detect lipid peroxidation. To mimic the interaction of P-curcumin on cell membranes with Aβ, liposomes were prepared by thin film method. Finally, the interactions between free P-curcumin and P-curcumin cultivated on liposomes and Aβ were determined via spectrophotometry. Results: A novel derivative, palmitic acid curcumin ester was prepared and characterized. This curcumin, cultivated on the membranes of neurocytes, may prevent Aβ-mediated ROS production and may inhibit the direct interaction between Aβ and the cellular membrane. Furthermore, P-curcumin could scavenge Aβ-mediated ROS as curcumin in vitro and in vivo, and had the potential to prevent lipid peroxidation. Morphological analyses showed that P-curcumin was better than curcumin at protecting cell shape. To examine P-curcumin’s ability to attenuate direct interaction between Aβ and cell membranes, the binding affinity of Aβ to curcumin and P-curcumin was determined. The association constants for free P-curcumin and curcumin were 7.66 × 104 M-1 and 7.61 × 105 M-1, respectively. In the liposome-trapped state, the association constants were 3.71 × 105 M-1 for P-curcumin and 1.44× 106 M-1 for curcumin. With this data, the thermodynamic constants of P-curcumin association with soluble Aβ (ΔH, ΔS, and ΔG) were also determined. Conclusion: Cultivated curcumin weakened the direct interaction between Aβ and cell membranes and showed greater neuroprotective effects against Aβ insult than free curcumin.

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Melatonin synthesis enzymes interact with ascorbate peroxidase to protect against oxidative stress in cassava

Journal of Experimental Botany ◽

10.1093/jxb/eraa267 ◽

2020 ◽

Vol 71 (18) ◽

pp. 5645-5655 ◽

Cited By ~ 1

Author(s):

Yujing Bai ◽

Jingru Guo ◽

Russel J Reiter ◽

Yunxie Wei ◽

Haitao Shi

Keyword(s):

Oxidative Stress ◽

Antioxidant Capacity ◽

Stress Tolerance ◽

Ascorbate Peroxidase ◽

Stress Responses ◽

Direct Interaction ◽

Ros Scavenging ◽

Melatonin Synthesis

Abstract Melatonin is an important indole amine hormone in animals and plants. The enzymes that catalyse melatonin synthesis positively regulate plant stress responses through modulation of the accumulation of reactive oxygen species (ROS). However, the relationship between melatonin biosynthetic enzymes and ROS-scavenging enzymes has not been characterized. In this study, we demonstrate that two enzymes of the melatonin synthesis pathway in Manihot esculenta (MeTDC2 and MeASMT2) directly interact with ascorbate peroxidase (MeAPX2) in both in vitro and in vivo experiments. Notably, in the presence of MeTDC2 and MeASMT2, MeAPX2 showed significantly higher activity and antioxidant capacity than the purified MeAPX2 protein alone. These findings indicate that MeTDC2–MeAPX2 and MeASMT2–MeAPX2 interactions both activate APX activity and increase antioxidant capacity. In addition, the combination of MeTDC2, MeASMT2, and MeAPX2 conferred improved resistance to hydrogen peroxide in Escherichia coli. Moreover, this combination also positively regulates oxidative stress tolerance in cassava. Taken together, these findings not only reveal a direct interaction between MeTDC2, MeASMT2, and MeAPX2, but also highlight the importance of this interaction in regulating redox homoeostasis and stress tolerance in cassava.

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Protective Effect of Pirenoxine and U74389F on Induced Lipid Peroxidation in Mammalian Lenses. An in vitro, ex vivo and in vivo study

Experimental Eye Research ◽

10.1006/exer.1998.0612 ◽

1999 ◽

Vol 68 (3) ◽

pp. 347-359 ◽

Cited By ~ 9

Author(s):

MARIO CIUFFI ◽

SILVIA NERI ◽

SERGIO FRANCHI-MICHELI ◽

PAOLA FAILLI ◽

LUCILLA ZILLETTI ◽

...

Keyword(s):

Lipid Peroxidation ◽

Protective Effect ◽

Ex Vivo ◽

In Vivo Study

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Abstract 28: Carboxyalkyl-pyrrole Phosphatidylethanolamine Adducts Are Present In Vivo And Induce Platelet Activation Via Toll-like Receptor

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a28 ◽

2013 ◽

Vol 33 (suppl_1) ◽

Author(s):

Sudipta Biswas ◽

Soumya Panigrahi ◽

Alejandro Zimman ◽

Eugene Podrez

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Platelet Activation ◽

Platelet Reactivity ◽

Biological Activities ◽

Direct Interaction ◽

Covalent Modification ◽

Downstream Signaling

A prothrombotic state and increased platelet reactivity are common in pathophysiological conditions associated with oxidative stress. Lipid peroxidation, a major consequence of oxidative stress generates highly reactive products capable of modifying autologous proteins as well as lipids. Hydroxy-ω-oxoalkenoic acids and their carboxyalkylpyrrole (CAP) protein adducts are recently described products of lipid peroxidation with strong biological activity mediated by Toll like receptors (TLR). Phosphatidylethanolamine (PE) is the second most abundant phospholipid in the living organisms. While recent studies suggest that PE is a major target for covalent modification by reactive products of lipid peroxidation, the presence of such products in vivo, their biological activities and receptors involved are not established. We now report that CAP-PE adducts are present in vivo in circulation and are significantly elevated in plasma of hyperlipidemic apoE-/- mice. In vitro experiments demonstrated that CAP-PE adducts induce platelet integrin αIIbβ3 activation, P-selectin expression and promote platelet aggregation. Multiple complimentary approaches demonstrated that platelet activation by CAP-PE is mediated by TLR2 and TLR1. Furthermore, direct interaction of CAP-PE and TLR2 was demonstrated. CAP-PE induced assembly of TLR2/TLR1 receptor complex in platelets leading to downstream signaling via MyD88/TIRAP-dependent pathway. CAPs-PE induced signaling included phosphorylation and activation of IRAK4 and subsequent activation of TRAF6, Src family kinase, Syk and PLCγ2. Thus, our study identified carboxyalkylpyrrole adducts of phosphatidylethanolamine as novel end products accumulating in circulation in hyperlipidemia that can induce platelet activation via innate immunity signaling pathway.

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Adiponectin inhibits palmitic acid-induced NLRP3 inflammasome activation in hepatocytes through AMPK-JNK/ErK1/2-NFκB/ROS signaling pathways

10.21203/rs.3.rs-16972/v1 ◽

2020 ◽

Author(s):

Zhixia Dong ◽

Qian Zhuang ◽

Xin Ye ◽

Min Ning ◽

Shan Wu ◽

...

Keyword(s):

Protein Expression ◽

Palmitic Acid ◽

Signaling Pathways ◽

Nlrp3 Inflammasome ◽

Inflammasome Activation ◽

Ros Production ◽

Wild Type ◽

Nlrp3 Inflammasome Activation

Abstract Background Adiponectin, an adipose-derived adipokine, possesses a hepatoprotective role in various liver disorders. Inflammasome activation has been recognized to play a major role during the progression of non-alcoholic fatty liver diseases (NAFLD). However, the effect of adiponectin on NLRP3 inflammasome activation in liver and the exact mechanism remains largely unclear. Here, we assessed the effect of adiponectin on NLRP3 inflammasome activation and its potential molecular mechanisms through both in vivo and in vitro experiments. Methods Male adiponectin-knockout (adiponectin-KO) mice and C57BL/6 (wild-type) mice were fed a high-fat-diet (HFD) for 12 weeks as an in vivo model of non-alcoholic steatohepatitis (NASH). Serum biochemical markers, liver histology and inflammasome-related gene and protein expression were determined. In addition, the hepatocytes isolated from SD rats were exposed to palmitic acid(PA) in the absence or presence of adiponectin and/or AMPK inhibitor. The activation of NLRP3 inflammasome was assessed by mRNA and protein expression. Furthermore, ROS production and related signaling pathways were also evaluated. Results In the in vivo experiments, we found that adiponectin deficiency mice fed with HFD presented excessive hepatic steatosis with increased NLRP3 inflammasome activation compared to wild-type mice. Moreover, the expression levels of NLRP3 inflammasome activation pathway molecules (NFκB and ROS) were upregulated, while the phosphorylation levels of AMPK, JNK and Erk1/2 were downregulated in adiponectin-knockout mice compared with wild-type mice. In the in vitro study, PA significantly promoted NLRP3 inflammasome activation in hepatocytes. Additionally, PA increased lipid droplet deposition, NF-kB signaling and ROS production, while adiponectin could abolish PA-mediated NLRP3 inflammasome activation and decrease ROS production, which was reversed by AMPK inhibitor (compound C). The results indicated that the inhibitory effect of adiponectin on PA-mediated NLRP3 inflammasome activation was regulated by AMPK-JNK/ErK1/2-NFκB/ROS signaling pathway. Conclusion Adiponectin inhibited PA-mediated NLRP3 inflammasome activation in hepatocytes. Adiponectin analogs or AMPK agonists could serve as a potential novel agent for preventing or delaying the progression of NASH and NAFLD.

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Biological activities of pyrazoline-indole based Re(I) carbonyls: DNA interaction, antibacterial, anticancer, ROS production, lipid peroxidation, in vivo and in vitro cytotoxicity studies

Chemico-Biological Interactions ◽

10.1016/j.cbi.2020.109231 ◽

2020 ◽

Vol 330 ◽

pp. 109231

Author(s):

Reena R. Varma ◽

Juhee G. Pandya ◽

Foram U. Vaidya ◽

Chandramani Pathak ◽

Bhupesh S. Bhatt ◽

...

Keyword(s):

Lipid Peroxidation ◽

Biological Activities ◽

Dna Interaction ◽

In Vitro Cytotoxicity ◽

Ros Production ◽

Cytotoxicity Studies

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Defibrotide Inhibits Platelet Activation by Cathepsin G Released From Stimulated Polymorphonuclear Leukocytes

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648519 ◽

1992 ◽

Vol 67 (06) ◽

pp. 660-664 ◽

Cited By ~ 17

Author(s):

Virgilio Evangelista ◽

Paola Piccardoni ◽

Giovanni de Gaetano ◽

Chiara Cerletti

Keyword(s):

Platelet Activation ◽

Polymorphonuclear Leukocytes ◽

Direct Interaction ◽

Cathepsin G ◽

In Vivo Test ◽

Cell Functions ◽

Test Models ◽

Antithrombotic Effects

SummaryDefibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.

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Protective Effect of Boswellic Resin Against Memory Loss and Alzheimer’s Induced by Aluminum Tetrachloride and D-Galactose (Experimental study in Mice)

Phytothérapie ◽

10.3166/phyto-2020-0222 ◽

2020 ◽

Author(s):

K. Zerrouki ◽

N. Djebli ◽

L. Gadouche ◽

I. Erdogan Orhan ◽

F. SezerSenol Deniz ◽

...

Keyword(s):

Chemical Composition ◽

Protective Effect ◽

Cell Damage ◽

Memory Loss ◽

Control Group ◽

Total Extract ◽

Swiss Mice ◽

Octyl Acetate

Nowadays, because of the industrialization, a lot of contaminant were available ; the consequences of this availability are apparition of diseases including neurodegeneration. Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. This study is based on the effect of the Boswellic resin, which is from a medicinal plant and known for its antioxidant effects on nerve cell damage. The objective of this work was to evaluate the in vitro and in vivo effects of the Boswellic resin on anticholinesterase activity and Alzheimer’s disease (AD) induced by D-galactose and aluminum tetrachloride in Swiss mice. Chemical composition of the resin essential oil was identified by the CG-MS analysis. The antioxidant activity was also assessed by the DMPD and metal chelation methods. In order to understand the mechanism of memory improvement, the acetylcholinesterase, AChE, and butyrylcholinesterase, BChE, inhibitory assays were performed. In vivo part of the study was achieved on Swiss mice divided into four groups: control, AD model, treated AD, and treated control group. The identification of chemical composition by CG-MS reach the 89.67% of the total extract compounds presented some very important molecules (p-Cymene, n-Octyl acetate, α-Pinene…). The present study proves that Boswellic resin improves memory and learning in treated Alzheimer’s group, modulates the oxidative stress and be involved in the protective effect against amyloid deposition and neurodegeneration, and stimulates the immune system in mice’s brain.

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Chemosensitizing Activity of Histone Deacetylases Inhibitory Cyclic Hydroxamic Acids for Combination Chemotherapy of Lymphatic Leukemia

Current Cancer Drug Targets ◽

10.2174/1568009617666170623104030 ◽

2018 ◽

Vol 18 (4) ◽

pp. 365-371 ◽

Cited By ~ 2

Author(s):

Denis V. Mishchenko ◽

Margarita E. Neganova ◽

Elena N. Klimanova ◽

Tatyana E. Sashenkova ◽

Sergey G. Klochkov ◽

...

Keyword(s):

Lipid Peroxidation ◽

Acute Toxicity ◽

Histone Deacetylases ◽

Hydroxamic Acids ◽

Water Soluble ◽

Male Rat ◽

Hybrid Male ◽

Cyclic Hydroxamic Acids

Background: Anti-tumor effect of hydroxamic acid derivatives is largely connected with its properties as efficient inhibitors of histone deacetylases, and other metalloenzymes involved in carcinogenesis. Objective: The work was aimed to (i) determine the anti-tumor and chemosensitizing activity of the novel racemic spirocyclic hydroxamic acids using experimental drug sensitive leukemia P388 of mice, and (ii) determine the structure-activity relationships as metal chelating and HDAC inhibitory agents. Method: Outbreed male rat of 200-220 g weights were used in biochemical experiments. In vivo experiments were performed using the BDF1 hybrid male mice of 22-24 g weight. Lipid peroxidation, Fe (II) -chelating activity, HDAC fluorescent activity, anti-tumor and anti-metastatic activity, acute toxicity techniques were used in this study. Results: Chemosensitizing properties of water soluble cyclic hydroxamic acids (CHA) are evaluated using in vitro activities and in vivo methods and found significant results. These compounds possess iron (II) chelating properties, and slightly inhibit lipid peroxidation. CHA prepared from triacetonamine (1a-e) are more effective Fe (II) ions cheaters, as compared to CHA prepared from 1- methylpiperidone (2a-e). The histone deacetylase (HDAC) inhibitory activity, lipophilicity and acute toxicity were influenced by the length amino acids (size) (Glycine < Alanine < Valine < Leucine < Phenylalanine). All compounds bearing spiro-N-methylpiperidine ring (2a-e) are non-toxic up to 1250 mg/kg dose, while compounds bearing spiro-tetramethylpiperidine ring (1a-e) exhibit moderate toxicity which increases with increasing lipophility, but not excite at 400 mg/kg. Conclusion: It was shown that the use of combination of non-toxic doses of cisplatin (cPt) or cyclophosphamide with CHA in most cases result in the appearance of a considerable anti-tumor effect of cytostatics. The highest chemosensitizing activity with respect to leukemia Р388 is demonstrated by the CHA derivatives of Valine 1c or 2c.

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