amsonic-acid and diallyl-disulfide

Leukemia is a type of disease in which hematopoietic stem cells proliferate clonally at the genetic level. We discovered previously by high-resolution mass spectrometry that diallyl disulfide (DADS), which is one of the effective ingredients of garlic, reduces the performance of RhoGDI2 from APL HL-60 cells. Although RhoGDI2 is oversubscribed in several cancer categories, the effect of RhoGDI2 in HL-60 cells has remained unexplained. We aimed to investigate the influence of RhoGDI2 on DADS-induced differentiation of HL-60 cells to elucidate the association among the effect of inhibition or over-expression of RhoGDI2 with HL-60 cell polarization, migration and invasion, which is important for establishing a novel generation of inducers to elicit leukemia cell polarization. Co-transfection with RhoGDI2-targeted miRNAs apparently decreases the malignant biological behavior of cells and upregulates cytopenias in DADS-treated HL-60 cell lines, which increases CD11b and decreases CD33 and mRNA levels of Rac1, PAK1 and LIMK1. Meanwhile, we generated HL-60 cell lines with high-expressing RhoGDI2. The proliferation, migration and invasion capacity of such cells were significantly increased by the treated with DADS, while the reduction capacity of the cells was decreased. There was a reduction in CD11b and an increase in CD33 production, as well as an increase in the mRNA levels of Rac1, PAK1 and LIMK1. It also confirmed that inhibition of RhoGDI2 attenuates the EMT cascade via the Rac1/Pak1/LIMK1 pathway, thereby inhibiting the malignant biological behavior of HL-60 cells. Thus, we considered that inhibition of RhoGDI2 expression might be a new therapeutic direction for the treatment of human promyelocytic leukemia. The anti-cancer property of DADS against HL-60 leukemia cells might be regulated by RhoGDI2 through the Rac1-Pak1-LIMK1 pathway, which provides new evidence for DADS as a clinical anti-cancer medicine.

Topics: Allyl Compounds; Cell Differentiation; Disulfides; HL-60 Cells; Humans; Leukemia; Lim Kinases; Neoplasm Invasiveness; p21-Activated Kinases; rac1 GTP-Binding Protein; rho Guanine Nucleotide Dissociation Inhibitor beta; RNA, Messenger

The endoplasmic reticulum (ER) plays a pivotal role in maintaining cellular metabolic homeostasis. ER stress refers to the accumulation of misfolded proteins, which can trigger an unfolded protein response for survival or death in the cells. Diallyl disulfide (DADS), a major active compound in garlic, has many health benefits for patients with metabolic diseases, especially cardiovascular or fatty liver diseases. However, its role in attenuating hypercholesterolemia by suppressing ER stress remains unknown. Therefore, in this study, we determined whether DADS supplementation could reduce ER stress in apolipoprotein E-deficient (ApoE. ApoE. The metabolic parameters showed that increases in fat weight, leptin resistance, and hypercholesterolemia were reversed in DADS-supplemented mice (p < 0.05). In addition, DADS ameliorated not only the protein of ER stress markers, phospho-eukaryotic initiation factor 2 subunit alpha and C/EBP homologous protein in the liver (p < 0.05) but also glucose-related protein 78 localization in the aorta.. This indicates that DADS inhibits diet-induced hypercholesterolemia, at least in parts by regulating ER stress markers. DADS may be a good candidate for treating individuals with diet-induced hypercholesterolemia.

Topics: Animals; Apolipoproteins; Apolipoproteins E; Diet, Western; Endoplasmic Reticulum Stress; Hypercholesterolemia; Leptin; Mice

Numerous secondary metabolites in medicinal food homology plants such as Allium inhibit the activity of acetylcholinesterase (AChE), but the current understanding of the inhibition mechanism is limited. In this study, we employed ultrafiltration, spectroscopic, molecular docking, and matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-MS/MS) techniques to investigate the inhibition mechanism of AChE by garlic organic sulfanes, including diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS). The results of UV-spectrophotometry and ultrafiltration experiments showed the inhibition of AChE activity by DAS and DADS was reversible (competitive inhibition), but inhibition by DATS was irreversible. Molecular fluorescence and molecular docking indicated DAS and DADS changed the positions of key amino acids inside the catalytic cavity through hydrophobic interactions with AChE. By using MALDI-TOF-MS/MS, we found DATS irreversibly inhibited AChE activity by opening disulfide-bond switching of disulfide bond 1 (Cys-69 and Cys-96) and disulfide bond 2 (Cys-257 and Cys-272) in AChE, as well as by covalently modifying Cys-272 in disulfide bond 2 to generate AChE-SSA derivatives (strengthened switch). This study provides a basis for further exploration of natural AChE inhibitors using organic active substances in garlic and presents a hypothesis of U-shaped spring force arm effect based on the disulfide bond-switching reaction of DATS that can be used to evaluate the stability of disulfide bonds in proteins.

Topics: Acetylcholinesterase; Allyl Compounds; Antioxidants; Disulfides; Garlic; Molecular Docking Simulation; Plants, Medicinal; Sulfides; Tandem Mass Spectrometry

Lycopene Z-isomerization and degradation in a series of hydrophobic natural deep eutectic solvents (HNDES) was firstly studied. The highest lycopene retention (about 84.6%) was found in HNDES composed of thymol and menthol (TM), and fatty acid-based HNDES promoted lycopene Z-isomerization (about 70% for total Z-isomers) and degradation. The addition of allyl isothiocyanate (AITC), diallyl disulfide (DADS) and capric acid into TM promoted Z-isomerization of lycopene (80% for total Z-isomers), especially 5Z-isomer (>30%), while lycopene remaining rate in TM/-capric acid was below 20%. During lycopene extraction from tomato power and watermelon juice by TM, the ratios of Z-isomer significantly (p < 0.05) increased especially with AITC and DADS (up to about 80%), and extraction yields increased even > 100% with capric acid. Lycopene in TM/-capric acid extracts showed low degradation with Z-isomers increasing during storage. TM with capric acid could simultaneously promote lycopene Z-isomerization and extraction.

Topics: Deep Eutectic Solvents; Isomerism; Lycopene; Solvents

The effects of allyl isothiocyanate (AITC) and diallyl disulfide (DADS), widely found in edible vegetables, on thermal isomerization of unsaturated fatty acid esters (oleic acid methyl ester [OA-ME], linoleic acid methyl ester [LA-ME], and eicosapentaenoic acid ethyl ester [EPA-EE]) were investigated. Although heating with AITC and DADS significantly promoted cis to trans isomerization of all fatty acid esters, the isomerization trends varied greatly depending on the type of fatty acid. Specifically, AITC promoted thermal isomerization of OA-ME and LA-ME more efficiently than DADS; however, an opposite result was obtained for EPA-EE. For example, when OA-ME was heated at 180°C for 1 h with 1.0 equivalent of AITC and DADS, its trans isomer ratios reached 29.0 ± 7.1 and 7.6 ± 0.6%, respectively, and when EPA-EE was heated under the same conditions, its trans isomer ratios reached 4.2 ± 0.4 and 8.6 ± 0.2%, respectively. These results indicate that isothiocyanates and polysulfides would promote the formation of trans fatty acids in food processing under heating conditions.

Topics: Esters; Fatty Acids; Hot Temperature; Isomerism; Isothiocyanates; Sulfur Compounds

Hypoxic-ischemic encephalopathy (HIE) is a perinatal brain disease caused by hypoxia in neonates. It is one of the leading causes of neonatal death in the perinatal period, as well as disability beyond the neonatal period. Due to the lack of a unified and comprehensive treatment strategy for HIE, research into its pathogenesis is essential. Diallyl disulfide (DADS) is an allicin extract, with detoxifying, antibacterial, and cardiovascular disease protective effects. This study aimed to determine whether DADS can alleviate HIE induced brain damage in rats and oxygen-glucose deprivation (OGD)-induced pyroptosis in PC12 cells, as well as whether it can inhibit pyroptosis via the NLRP3/Caspase-1/IL-1β signaling pathway. In vivo, DADS significantly reduced the cerebral infarction volume, alleviated inflammatory reaction, reduced astrocyte activation, promoted tissue structure recovery, improved pyroptosis caused by HIE and improved the prognosis following HI injury. In vitro findings indicated that DADS increased cell activity, decreased LDH activity and reduced the expression of pyroptosis-related proteins, including IL-1β, IL-18, and certain inflammatory factors in PC12 cells caused by OGD. Mechanistically, DADS inhibited pyroptosis and protected against HIE via the NLRP3/Caspase-1/IL-1β pathway. The specific inhibitor of caspase-1, VX-765, inhibited caspase-1 activation, and IL-1β expression was determined. Additionally, the overexpression of NLRP3 reversed the protective effect of allicin against OGD-induced pyroptosis. In conclusion, these findings demonstrated that DADS inhibits the NLRP3/Caspase-1/IL-1β signaling pathway and decreases HI brain damage.

Topics: Animals; Animals, Newborn; Brain; Caspase 1; Female; Hypoxia-Ischemia, Brain; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Oxygen; Pregnancy; Pyroptosis; Rats; Signal Transduction

Verticillium wilt is a destructive vascular disease in eggplants. The complex defensive mechanisms of eggplant against this disease are very limited.. Our work examined the bioactive properties of garlic allelochemical diallyl disulfide (DADS) as potential biostimulants for defense against V. dahliae in eggplant seedlings. We, therefore, foliar sprayed DADS on eggplants to study the defense response during the early biotrophic phase of V. dahliae (a hemibiotroph).. DADS application significantly increased root peroxidase (POD), phenylalanine-ammonia lyase (PAL) enzyme activity, and reduced H. Our findings concluded that the biological function of garlic allelochemical DADS has a prominent role in the higher defense resistance of eggplants during the early infection of V. dahliae.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; Allyl Compounds; Disulfides; Hydrogen Peroxide; Solanum melongena; Verticillium

We studied the effects of sulfur-containing chemopreventive agents, including allyl sulfides and isothiocyanates, on human redox networks. Isothiocyanates inhibited isolated redox-active enzymes in a time- and dose-dependent manner. As shown for the most active compound, benzyl isothiocyanate (BITC), on thioredoxin reductase, the inhibition has an initial competitive part (Ki=6.1+/-1.0 microM) followed by a time-dependent irreversible inhibition (k2=72.8+/-25.5 M(-1) s(-1)). Also, glutathione reductase and glutathione S-transferase were irreversibly modified by BITC. Sulforaphane led to irreversible inhibition of the studied redox enzymes, but with 5-10 times lower k2 values. In contrast, allyl sulfides had only moderate effects on the tested enzymes. However, diallyl disulfide was found to react directly with reduced glutathione (k2=100 M(-2) s(-1)). This reaction might contribute to enhanced oxidative stress and the induction of the selenoprotein glutathione peroxidase as determined on activity and transcript levels. All chemopreventive agents tested induced transcript levels of genes associated with cell cycle arrest and apoptosis. This upregulation was accompanied by a dose-dependent decrease in cell number. Our data indicate that modulation of cellular redox networks is likely to contribute to the effects of sulfur-containing chemopreventive agents.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; Allyl Compounds; Anticarcinogenic Agents; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Disulfides; Dose-Response Relationship, Drug; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Humans; Isothiocyanates; Oxidation-Reduction; Sulfur Compounds; Thioredoxin-Disulfide Reductase; Thioredoxins; Up-Regulation