Dramatic differences in the conformational equilibria of chalcogen-bridged compounds: the case of diallyl ether versus diallyl sulfide

Rotational spectroscopy and quantum mechanical calculations reveal a significant change in conformational landscapes when oxygen is substituted with sulfur: observation of features from nine conformers of diallylether versus one of the sulfide.

Diallyl Sulfide Attenuation of Carcinogenesis in Mammary Epithelial Cells through the Inhibition of ROS Formation, and DNA Strand Breaks

Garlic has long been used medicinally for many diseases, including cancer. One of the active garlic components is diallyl sulfide (DAS), which prevents carcinogenesis and reduces the incidence rate of several cancers. In this study, non-cancerous MCF-10A cells were used as a model to investigate the effect of DAS on Benzo (a)pyrene (BaP)-induced cellular carcinogenesis. The cells were evaluated based on changes in proliferation, cell cycle arrest, the formation of peroxides, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, the generation of DNA strand breaks, and DNA Polymerase β (Pol β) expression. The results obtained indicate that when co-treated with BaP, DAS inhibited BaP-induced cell proliferation (p < 0.05) to levels similar to the negative control. BaP treatment results in a two-fold increase in the accumulation of cells in the G2/M-phase of the cell cycle, which is restored to baseline levels, similar to untreated cells and vehicle-treated cells, when pretreated with 6 μM and 60 μM DAS, respectively. Co-treatment with DAS (60 μM and 600 μM) inhibited BaP-induced reactive oxygen species (ROS) formation by 132% and 133%, respectively, as determined by the accumulation of H2O2 in the extracellular medium and an increase in 8-OHdG levels of treated cells. All DAS concentrations inhibited BaP-induced DNA strand breaks through co-treatment and pre-treatment methods at all time points evaluated. Co-Treatment with 60 μM DAS increased DNA Pol β expression in response to BaP-induced lipid peroxidation and oxidative DNA damage. These results indicate that DAS effectively inhibited BaP-induced cell proliferation, cell cycle transitions, ROS, and DNA damage in an MCF-10A cell line. These results provide more experimental evidence for garlic’s antitumor abilities and corroborate many epidemiological studies regarding the association between the increased intake of garlic and the reduced risk of several types of cancer.

Garlic extract diallyl sulfide protects against dilated cardiomyopathy through inhibition of oxidative stress and apoptosis in mice

Background: Diallyl sulfide (DAS) is an active ingredient in garlic that is induced when the garlic is chopped and ground. DAS has been found to act as a competitive inhibitor of CYP2E1, which is a member of the cytochrome P450 enzyme family and catalyses the metabolism of various substrates.CYP2E1 is upregulated in multiple heart diseases and causes damage mainly through the production of ROS. In mice, increased CYP2E1 expression induces cardiac myocyte apoptosis, and CYP2E1 knockdown can attenuate the pathological development of DCM. Nevertheless, Targeted inhibition of CYP2E1 for the treatment of dilated cardiomyopathy (DCM) remain limited. The aim of this study was to investigate the therapeutic effect of DAS on cardiomyopathy and its possible molecular mechanisms, and provide new clues and approaches for the clinical treatment of cardiomyopathy and heart failure.Methods: Echocardiography were performed to identify mouse heart function and structure. histological analysis and RT-PCR were conducted to investigate that improved Myocardial morphology and fibrosis and measurement of reactive oxygen species (ROS) and tunel Assay were used to detected DAS inhibit ROS production and myocyte apoptosis in cTnTR141W DCM mice. Western Blot were performed to investigate the mechanism of apoptosis pathway.Results: Diallyl sulfide (DAS), a competitive inhibitor of CYP2E1, improves the typical DCM phenotype, including chamber dilation, wall thinning, fibrosis, poor myofibril organization and decreased ventricular blood ejection, by inhibiting ROS production and myocyte apoptosis in cTnTR141W DCM mice.Conclusions: Our results suggest that inhibition of CYP2E1 might be a valuable therapeutic strategy to control the development of heart diseases associated with CYP2E1 overexpression. Moreover, the development of DAS analogues with superior inhibitory properties and lower substrate potential for CYP2E1 might be beneficial for patients with heart disease.