Diallyl Sulfide Research Articles

Dietary phytochemicals/nutrients as promising protector of breast cancer development: a comprehensive analysis.

Genetic change, particularly epigenetic alteration, is one of the imperative factors for sporadic breast cancer development in the worldwide population of women. The DNA methylation process is essential and natural for human cellular renewal and tissue homeostasis, but its dysregulation contributes to many pathological changes, including breast tumorigenesis. Chemopreventive agents mainly protect the abnormal DNA methylation either by hindering the division of pre-malignant cells or looming the DNA damage, which leads to malignancy. The present review article is about understanding the potential role of dietary phytochemicals in breast cancer prevention. Accordingly, a literature search of the published article until August 2021 has been performed. Further, we have investigated the binding affinity of different phytochemicals isolated from diverse dietary sources against the various oncogenic proteins related to breast cancer initiation to understand the common target(s) in breast cancer prevention mechanisms. Various small phytochemicals, especially dietary phytochemicals including sulforaphane, mahanine, resveratrol, linolenic acid, diallyl sulfide, benzyl/phenethyl isothiocyanate, etc. are being investigated as the chemopreventive agent to manage breast cancer development, and some of them have shown promising outcomes in the cited research. In this present review, we discuss the recent advancement in acceptance of such types of potential dietary phytochemicals as a chemopreventive agent against breast cancer development and their inner lining mechanism. The critical clinical trials and cohort studies have also been considered to understand the progress in contemporary perspectives.

An experimental and theoretical study of ROS scavenging by organosulfur compounds from garlic: In silico analysis of metabolic pathways and interactions on CYP2E1

Using experimental and computational methodologies, we analyzed the possible interactions of two organosulfur compounds (OSC), Allyl methyl sulfide (AMS) and Diallyl sulfide (DAS), with different reactive oxygen species (ROS), which cause oxidative stress. Additionally, we study both OSC as inhibitors of CYP2E1, an enzyme involved in the generation of ROS. Effective quantitative interaction of both OSC with H2O2, O2 • - and O2(1Δg) was found by experimental methods. The experimental k values at 288 K of H2O2 scavenging reaction for AMS (5.43 × 10−20 cm3 molecule−1 s−1) and DAS (1.65 × 10−21 cm3 molecule−1 s−1) indicate the reaction is more quick when AMS is the reactant. This trend was maintained when the HO• scavenging reactions were analyzed with computational methodologies using IRC calculations with M06-2x/6-311++G(3df, 2p) level of theory and gaseous, aqueous and no-polar phases. An in silico analysis of OSC and their metabolites derived from epoxidation and sulfoxidation reactions showed that these compounds present a high probability of being inhibitors of the CYP2E1 enzyme. The molecular docking showed an effective binding in the complexes enzyme-OSC and enzyme-metabolites, with a major interaction between the sulfur and oxygen atoms and the heme iron ion.

Garlic (Allium sativum L.): Its Chemistry, Nutritional Composition, Toxicity, and Anticancer Properties.

The current review discuss the chemistry, nutritional composition, toxicity, and biological functions of garlic and its bioactive compounds against various types of cancers via different anticancer mechanisms. Several scientific documents were found in reliable literature and searched in databases viz Science Direct, PubMed, Web of Science, Scopus, and Research Gate were carried out using keywords such as "garlic", "garlic bioactive compounds", "anticancer mechanisms of garlic", "nutritional composition of garlic", and others. Garlic contains several phytoconstituents with activities against cancer, and compounds such as diallyl trisulfide (DATS), allicin, and diallyl disulfide (DADS), diallyl sulfide (DAS), and allyl mercaptan (AM). The influence of numerous garlic- derived products, phytochemicals, and nanoformulations on the liver, oral, prostate, breast, gastric, colorectal, skin, and pancreatic cancers has been studied. Based on our search, the bioactive molecules in garlic were found to inhibit the various phases of cancer. Moreover, the compounds in this plant also abrogate the peroxidation of lipids, activity of nitric oxide synthase, epidermal growth factor (EGF) receptor, nuclear factor-kappa B (NF-κB), protein kinase C, and regulate cell cycle and survival signaling cascades. Hence, garlic and its bioactive molecules exhibit the aforementioned mechanistic actions, and thus, they could be used to inhibit the induction, development, and progression of cancer. The review describes the nutritional composition of garlic, its bioactive molecules, and nanoformulations against various types of cancers, as well as the potential for developing these agents as antitumor drugs.

Effect of garlic extract and diallyl sulfide immersion baths in the life stages of Zeuxapta seriolae, a parasite of California yellowtail (Seriola dorsalis)

Effect of garlic extract and diallyl sulfide immersion baths in the life stages of Zeuxapta seriolae, a parasite of California yellowtail (Seriola dorsalis)

Molecular Mechanisms of Action of Selected Substances Involved in the Reduction of Benzo[a]pyrene-Induced Oxidative Stress.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) primarily formed by burning of fossil fuels, wood and other organic materials. BaP as group I carcinogen shows mutagenic and carcinogenic effects. One of the important mechanisms of action of (BaP) is its free radical activity, the effect of which is the induction of oxidative stress in cells. BaP induces oxidative stress through the production of reactive oxygen species (ROS), disturbances of the activity of antioxidant enzymes, and the reduction of the level of non-enzymatic antioxidants as well as of cytokine production. Chemical compounds, such as vitamin E, curcumin, quercetin, catechin, cyanidin, kuromanin, berberine, resveratrol, baicalein, myricetin, catechin hydrate, hesperetin, rhaponticin, as well as taurine, atorvastatin, diallyl sulfide, and those contained in green and white tea, lower the oxidative stress induced by BaP. They regulate the expression of genes involved in oxidative stress and inflammation, and therefore can reduce the level of ROS. These substances remove ROS and reduce the level of lipid and protein peroxidation, reduce formation of adducts with DNA, increase the level of enzymatic and non-enzymatic antioxidants and reduce the level of pro-inflammatory cytokines. BaP can undergo chemical modification in the living cells, which results in more reactive metabolites formation. Some of protective substances have the ability to reduce BaP metabolism, and in particular reduce the induction of cytochrome (CYP P450), which reduces the formation of oxidative metabolites, and therefore decreases ROS production. The aim of this review is to discuss the oxidative properties of BaP, and describe protective activities of selected chemicals against BaP activity based on of the latest publications.

Investigation on Oral Toxicity of Diallyl Sulfide A Principle Organosulfur Compound Derived from Allium Sativum Garlic in Mice

Allium sativum (garlic) is used as food additives and medicines. Its health benefits are well known, which are mainly contributed by the active organosulfur compounds present in it. Though garlic widely used, but limited is known about preclinical acute toxicity of its organosulfur compounds in mice. The present study aimed at toxicity evaluation of diallyl sulfide (DAS) in C57BL/6 mice following oral administration at range of concentrations (40 mg/kg, 400 mg/kg, 800 mg/kg and 1600 mg/kg). Survival, hematological, organ coefficients, and histopathology studies were performed to establish the DAS toxicity in mice. Stability studies performed in vitro by HPLC showed rapid and time dependent changes in DAS area. A single oral dose upto 1600 mg/kg was well tolerated in mice without any significant changes in standard toxicological parameters. No death was recorded at the tested concentrations. Also no significant changes in the organ coefficient were observed when compared to vehicle treated and sham control. Mild alterations in liver pathology and hematological changes were observed post 1600 mg/kg DAS administration orally. This study demonstrates that single oral administration (upto 1600 mg/kg) of DAS is within the safe limits with no observable adverse effects in mice. Based on the safety profile of DAS, we conclude that DAS can be further explored for use in humans as a potential radiomitigator.

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

The conformational landscapes of diallyl ether (DAE) and diallyl sulfide (DAS) were investigated for the first time using rotational spectroscopy from 6-20 GHz supported by quantum mechanical calculations. A significant difference in the conformational distribution of these chalcogen-bridged compounds is predicted by theory at the B3LYP-D3(BJ)/aug-cc-pVTZ level as DAS has only one low energy conformer while DAE has up to 12 energy minima within 5 kJ mol-1. This was confirmed by rotational spectroscopy as only transitions corresponding to the global minimum of DAS were observed while the spectrum of DAE was much richer and composed of features from the nine lowest energy conformers. To understand the effects that govern the conformational preferences of DAE and DAS, natural bond orbital and non-covalent interaction analyses were done. These show that unique orbital interactions stabilize several conformers of the ether making its conformational landscape more competitive than that of the sulfide. This is consistent with a bonding model involving decreased hybridization of the bridging atom as one moves down the periodic table which is confirmed by the experimental ground state structures of the lowest energy forms of DAE and DAS, derived using spectra of the 13C and 34S substituted species in natural abundance.

Antioxidant Activities of Eremurus spectabilis M. Bieb. Extracts and Sulfur Compounds

Objective: Eremurus spectabilis M. Bieb. is grown in East and Southeast Mediterranean regions of Turkey, and is commonly used as an edible plant in these regions. The aim of the current study was to determine the antioxidant activities of different E. spectabilis M. Bieb. extracts and some sulfur compounds. Materials and Methods: In this study, the antioxidant activities of aqueous, ethanolic, and ethyl acetate extracts of E. spectabilis M. Bieb. and sulfur compounds (α-lipoic acid, cysteamine, cysteine, diallyl sulfide, glutathione, homocysteine, N-acetyl cysteine, vitamin U and 1,4-dithioerythritol) were assessed in several antioxidant tests. These tests included reducing power, cupric ion reducing antioxidant capacity, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, N,N-dimethyl-4-phenylenediamine dihydrochloride radical scavenging, superoxide anion radical scavenging, hydroxyl radical scavenging, metal chelating activities and ferric ion reducing antioxidant power. The phytochemical profiles and total phenolic and flavonoid contents of all extracts were investigated. Results: It was found out that the antioxidant activities of all the extracts and sulfur compounds generally increased with concentration increases, the highest antioxidant activity was found in ethyl acetate extract, while the aqueous extract was found to have the lowest antioxidant activity. Diallyl sulfide was found to have the highest antioxidant activity, whereas vitamin U had the lowest antioxidant activity. It was observed that all extracts of E. spectabilis M. Bieb. and the sulfur compounds showed antioxidant activity. Conclusion: The E. spectabilis M. Bieb. and sulfur compounds investigated in this study could be considered as a source of antioxidants.

Tobacco carcinogen 4-[methyl(nitroso)amino]-1-(3-pyridinyl)-1-butanone (NNK) drives metabolic rewiring and epigenetic reprograming in A/J mice lung cancer model and prevention with diallyl sulphide (DAS).

Early detection of biomarkers in lung cancer is one of the best preventive strategies. Although many attempts have been made to understand the early events of lung carcinogenesis including cigarette smoking (CS) induced lung carcinogenesis, the integrative metabolomics and next-generation sequencing approaches are lacking. In this study, we treated the female A/J mice with CS carcinogen 4-[methyl(nitroso)amino]-1-(3-pyridinyl)-1-butanone (NNK) and naturally occurring organosulphur compound, diallyl sulphide (DAS) for 2 and 4 weeks after NNK injection and examined the metabolomic and DNA CpG methylomic and RNA transcriptomic profiles in the lung tissues. NNK drives metabolic changes including mitochondrial tricarboxylic acid (TCA) metabolites and pathways including Nicotine and its derivatives like nicotinamide and nicotinic acid. RNA-seq analysis and Reactome pathway analysis demonstrated metabolism pathways including Phase I and II drug metabolizing enzymes, mitochondrial oxidation and signaling kinase activation pathways modulated in a sequential manner. DNA CpG methyl-seq analyses showed differential global methylation patterns of lung tissues from week 2 versus week 4 in A/J mice including Adenylate Cyclase 6 (ADCY6), Ras-related C3 botulinum toxin substrate 3 (Rac3). Oral DAS treatment partially reversed some of the mitochondrial metabolic pathways, global methylation and transcriptomic changes during this early lung carcinogenesis stage. In summary, our result provides insights into CS carcinogen NNK's effects on driving alterations of metabolomics, epigenomics and transcriptomics and the chemopreventive effect of DAS in early stages of sequential lung carcinogenesis in A/J mouse model.

Diallyl Trisulfide, the Antifungal Component of Garlic Essential Oil and the Bioactivity of Its Nanoemulsions Formed by Spontaneous Emulsification.

The aim of this study was to evaluate the chemical compounds of garlic essential oil (EO), and determine the antifungal efficacy of garlic EO and its major components, diallyl trisulfide and its nanoemulsions against wood-rotting fungi, Trametes hirsuta and Laetiporus sulphureus. GC-MS analysis revealed that the major constituents of garlic EO were diallyl trisulfide (39.79%), diallyl disulfide (32.91%), and diallyl sulfide (7.02%). In antifungal activity, the IC50 value of garlic EO against T. hirsuta and L. sulphureus were 137.3 and 44.6 μg/mL, respectively. Results from the antifungal tests demonstrated that the three major constituents were shown to have good antifungal activity, in which, diallyl trisulfide was the most effective against T. hirsuta and L. sulphureus, with the IC50 values of 56.1 and 31.6 μg/mL, respectively. The diallyl trisulfide nanoemulsions showed high antifungal efficacy against the examined wood-rotting fungi, and as the amount of diallyl trisulfide in the lipid phase increases, the antifungal efficacy of the nanoemulsions increases. These results showed that the nanoemulsions and normal emulsion of diallyl trisulfide have potential to develop into a natural wood preservative.

Garlic (Allium sativum L.) Bioactives and Its Role in Alleviating Oral Pathologies.

Garlic (Allium sativa L.) is a bulbous flowering plant belongs to the family of Amaryllidaceae and is a predominant horticultural crop originating from central Asia. Garlic and its products are chiefly used for culinary and therapeutic purposes in many countries. Bulbs of raw garlic have been investigated for their role in oral health, which are ascribed to a myriad of biologically active compounds such as alliin, allicin, methiin, S-allylcysteine (SAC), diallyl sulfide (DAS), S-ally-mercapto cysteine (SAMC), diallyl disulphide (DADS), diallyl trisulfide (DATS) and methyl allyl disulphide. A systematic review was conducted following the PRISMA statement. Scopus, PubMed, Clinicaltrials.gov, and Science direct databases were searched between 12 April 2021 to 4 September 2021. A total of 148 studies were included and the qualitative synthesis phytochemical profile of GE, biological activities, therapeutic applications of garlic extract (GE) in oral health care system, and its mechanism of action in curing various oral pathologies have been discussed. Furthermore, the safety of incorporation of GE as food supplements is also critically discussed. To conclude, GE could conceivably make a treatment recourse for patients suffering from diverse oral diseases.

Toxicity and physiological effects of diallyl sulfide and dialyl disulfide on Tuta absoluta Meyrick

Toxicity and physiological effects of the two components within garlic essential oil, diallyl sulfide, and diallyl disulfide, were studied against the larvae of Tuta absoluta. The larvae treated by dially sulfide showed the LC50 of 0.518% while it was observed 0.390% in those treated by diallyl disulfide. The LT50 values of diallyl sulfide and diallyl disulfide were calculated 9.65 and 7.18 h, respectively. The binary mixture of the given compounds in the different ratios revealed the higher expected mortality than the observed one implying antagonistic interaction against the larvae of T. absoluta. Diallyl sulfide and diallyl disulfide in both LC30 and LC50 concentrations significantly decreased the activities of larval α-amylase, glucosidases, and lipase. The LC50 concentration of diallyl sulfide caused the lower activity of general protease than LC30 concentration but the least activity of general protease was recorded in the larvae treated by both concentrations of diallyl disulfide. Treatment of T. absoluta larvae by both concentrations of dially sulfide and diallyl disulfide significantly decreased the activities trypsin, chymotrypsin, and elastase as well as amino- and carboxypeptidases compared to control. The larval treatment with two concentrations of diallyl sulfide and diallyl disulfide significantly decreased the activity of acetylcholine esterase compared to control in both in vivo and in vitro assays. Diallyl sulfide and diallyl disulfide significantly decreased the activity of alanine aminotransferase compared to control while the highest activity of aspartate aminotransferase was recorded in the larvae treated by LC50 concentration of diallyl disulfide. Dially sulfide and diallyl disulfide significantly decreased the amounts of triglyceride, glycogen, and protein as storage macromolecules compared to control.

Estrogen receptor-α36 is involved in diallyl sulfide-induced inhibition of malignant growth of HepG2 and Huh7 hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a highly malignant disease that currently lacks effective treatment. Epidemiological studies have suggested the preventive role of raw garlic intake in different tumors, such as HCC. Although diallyl sulfide (DAS), the main component of garlic extracts, has been reported to inhibit the growth of HCC cells, the underlying mechanism remains elusive. This study aimed to investigate the inhibitory effect of DAS on the growth of HepG2 and Huh7 hepatocellular carcinoma cells and its underlying mechanism. HepG2 and Huh7 cells were treated with DAS and nude mice were intrahepatically injected with human HCC HepG2 cells and maintained with or without DAS administration for 28 days. MTS and clonogenic assays revealed that DAS inhibited the growth and clonogenicity of HepG2 and Huh7 hepatocellular carcinoma cells. Furthermore, DAS inhibited the growth of xenograft tumors accompanied by a decreased rate of pathological karyomitosis as observed by H&E staining. The expression levels of estrogen receptor-α36 (ER-α36) and epidermal growth factor receptor (EGFR) in HepG2 and Huh7 cells and in xenograft tumors derived from HepG2 cells after DAS treatment were detected by immunohistochemistry and western blotting. We found that DAS disrupted the positive regulatory loop between ER-α36 and EGFR, and decreased the phosphorylation of AKT at Ser 473 both in vivo and in vitro. DAS also induced cell apoptosis, as evidenced by Hoechst and TUNEL staining. Western blotting revealed activation of caspase3, increased BAX and decreased Bcl-2 expression. However, the ER-α36 expression knockdown attenuated DAS-induced ERK and AKT phosphorylation in HCC cells. DAS was also able to inhibit ER-α36-mediated activation of the MAPK/ERK signaling induced by estrogen. Thus, our results indicate that ER-α36 signaling is involved in DAS-induced inhibition of HCC cell growth both in vitro and in vivo.

Identification of NSP3 (SH2D3C) as a Prognostic Biomarker of Tumor Progression and Immune Evasion for Lung Cancer and Evaluation of Organosulfur Compounds from Allium sativum L. as Therapeutic Candidates.

The multi-domain non-structural protein 3 (NSP3) is an oncogenic molecule that has been concomitantly implicated in the progression of coronavirus infection. However, its oncological role in lung cancer and whether it plays a role in modulating the tumor immune microenvironment is not properly understood. In the present in silico study, we demonstrated that NSP3 (SH2D3C) is associated with advanced stage and poor prognoses of lung cancer cohorts. Genetic alterations of NSP3 (SH2D3C) co-occurred inversely with Epidermal Growth Factor Receptor (EGFR) alterations and elicited its pathological role via modulation of various components of the immune and inflammatory pathways in lung cancer. Our correlation analysis suggested that NSP3 (SH2D3C) promotes tumor immune evasion via dysfunctional T-cell phenotypes and T-cell exclusion mechanisms in lung cancer patients. NSP3 (SH2D3C) demonstrated a high predictive value and association with therapy resistance in lung cancer, hence serving as an attractive target for therapy exploration. We evaluated the in silico drug-likeness and NSP3 (SH2D3C) target efficacy of six organosulfur small molecules from Allium sativum using a molecular docking study. We found that the six organosulfur compounds demonstrated selective cytotoxic potential against cancer cell lines and good predictions for ADMET properties, drug-likeness, and safety profile. E-ajoene, alliin, diallyl sulfide, 2-vinyl-4H-1,3-dithiin, allicin, and S-allyl-cysteine docked well into the NSP3 (SH2D3C)-binding cavity with binding affinities ranging from –4.3~–6.70 Ă and random forest (RF) scores ranging from 4.31~5.26 pKd. However, S-allyl-cysteine interaction with NSP3 (SH2D3C) is unfavorable and hence less susceptible to NSP3 ligandability. In conclusion, our study revealed that NSP3 is an important onco-immunological biomarker encompassing the tumor microenvironment, disease staging and prognosis in lung cancer and could serve as an attractive target for cancer therapy. The organosulfur compounds from A. sativum have molecular properties to efficiently interact with the binding site of NSP3 and are currently under vigorous preclinical study in our laboratory.

Antioxidant and protective effects of extra virgin olive oil incorporated with diallyl sulfide against CCl4-induced acute liver injury in mice.

The present study delineates the effects of incorporation of 1% diallyl sulfide (DAS) into extra virgin olive oil (EVOO) on the physico‐chemical characteristics, in vitro antioxidant, and in vivo hepatoprotective properties in CCl4‐induced acute liver injury in mice. Results showed that the DAS‐rich EVOO exhibited good oxidative stability over one‐month storage and preserved its original quality‐related parameters including major components (oleic acid, linoleic acid, and palmitic acid), and minor components (tocopherols, chlorophylls and carotenoids, tyrosol, hydroxytyrosol, elenolic acid, oleuropein and its aglycone, pinoresinol, vanilic acid, cinnamic acid, ferulic acid, luteolin, apigenin, and sterols). Compared with EVOO or DAS, the DAS‐rich EVOO displayed the highest DPPH and ABTS‐radical scavenging activities and showed the strongest cellular antioxidant activity (CAA). In connection with its free radical scavenging activity and CAA, DAS‐rich EVOO significantly normalized the serum ALT and AST levels and prevented the increase in interleukin‐6 in CCl4‐intoxicated mice. The manifest anti‐inflammatory and hepatoprotective effects of DAS‐rich EVOO were further supported by liver histopathological examinations. Overall, the EVOO enrichment with DAS could open up opportunities for the development of novel functional food with improved antioxidant and hepatoprotective properties.

Potential drug interactions with garlic

Every drug may cause central nervous system, gastrointestinal tract or cardiovascular system adverse drugs reactions (ADRs). At the same time, doctors often do not have sufficient information about possible food-drug interactions, in particular, garlic. But this spice is shown to increase the risks of developing ADRs. From the beginning of the 20th century to the present, garlic has been the subject of many chemical studies, which have revealed some differences in the chemical composition of the studied preparation (fresh or stored garlic). The most important chemical ingredients found in garlic are divided into two groups: sulfur-containing (allicin [diallyl thiosulfinate], allyl methanesulfinate, alliin [S-allyl-L-cysteine sulfoxide, diallyl disulfide, DADS], S-allylmethyl cysteine, diallyl trisulfide [diallyl trisulfide, DATS], allyl methyl trisulfide, allyl methyl disulfide, diallyl tetrasulfide, allyl methyl tetrasulfide, dimethyl trisulfide, diallyl sulfide, 2-vinyl-4-H1,3-dithiine, 3-vinyl-4.-H1,2-dithiin) and sulfur-free compounds. Most of the pharmacological effects of garlic are due to sulfur compounds, in particular allicin. In animal, in vitro and clinical studies, it has been shown that garlic can interact with various drug througt pharmacokinetic or pharmacodynamic way. For example, garlic extract has shown to inhibit the metabolic activity of CYP2C9*1, 2C19, 3A4, 3A5, 3A7, but not CYP2D6. It has also been shown that garlic can affect the function thrombocyte and blood clotting, which leads to an increased risk of bleeding, which is especially important in the case of its simultaneous use with antiplatelet agents and/or anticoagulants. This article provides an overview of the open literature on the risks and benefits of the simultaneous use of drugs and products containing garlic.

Diallyl sulfide protects against dilated cardiomyopathy via inhibition of oxidative stress and apoptosis in mice

Cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a member of the cytochrome P450 enzyme family and catalyzes the metabolism of various substrates. CYP2E1 is upregulated in multiple heart diseases and causes damage mainly via the production of reactive oxygen species (ROS). In mice, increased CYP2E1 expression induces cardiac myocyte apoptosis, and knockdown of endogenous CYP2E1 can attenuate the pathological development of dilated cardiomyopathy (DCM). Nevertheless, targeted inhibition of CYP2E1 via the administration of drugs for the treatment of DCM remains elusive. Therefore, the present study aimed to investigate whether diallyl sulfide (DAS), a competitive inhibitor of CYP2E1, can be used to inhibit the development of the pathological process of DCM and identify its possible mechanism. Here, cTnTR141W transgenic mice, which developed typical DCM phenotypes, were used. Following treatment with DAS for 6 weeks, echocardiography, histological analysis and molecular marker detection were conducted to investigate the DAS-induced improvement on myocardial function and morphology. Biochemical analysis, western blotting and TUNEL assays were used to detected ROS production and myocyte apoptosis. It was found that DAS improved the typical DCM phenotypes, including chamber dilation, wall thinning, fibrosis, poor myofibril organization and decreased ventricular blood ejection, as determined using echocardiographic and histopathological analyses. Furthermore, the regulatory mechanisms, including inhibition both of the oxidative stress levels and the mitochondria-dependent apoptosis pathways, were involved in the effects of DAS. In particular, DAS showed advantages in terms of improved chamber dilation and dysfunction in model mice, and the improvement occurred in the early stage of the treatment compared with enalaprilat, an angiotensin-converting enzyme inhibitor that has been widely used in the clinical treatment of DCM and HF. The current results demonstrated that DAS could protect against DCM via inhibition of oxidative stress and apoptosis. These findings also suggest that inhibition of CYP2E1 may be a valuable therapeutic strategy to control the development of heart diseases, especially those associated with CYP2E1 upregulation. Moreover, the development of DAS analogues with lower cytotoxicity and metabolic rate for CYP2E1 may be beneficial.

Effects of Black Garlic Extract and Nanoemulsion on the Deoxy Corticosterone Acetate-Salt Induced Hypertension and Its Associated Mild Cognitive Impairment in Rats.

Organosulfur compounds, phenolic acids and flavonoids in raw and black garlic were determined, and followed by preparation of black garlic nanoemulsion for studying their effects on deoxycorticosterone acetate-salt-induced hypertension and associated mild cognitive impairment in rats. Three organosulfur compounds, including diallyl sulfide (87.8 μg/g), diallyl disulfide (203.9 μg/g) and diallyl trisulfide (282.6 μg/g) were detected in black garlic by GC-MS, while gallic acid (19.19 μg/g), p-coumaric acid (27.03 μg/g) and quercetin (22.77 μg/g) were detected by UPLC-MS/MS. High doses of both black garlic extract and nanoemulsion prepared using Tween-80, glycerol, grapeseed oil and water could decrease systolic blood pressure through the elevation of bradykinin and nitric oxide levels as well as diminish aldosterone and angiotensin II levels in rats. In Morris water maze test, they could significantly decrease escape latency and swimming distance and increase the time spent in the target quadrant, accompanied by a decline of acetylcholinesterase activity and malondialdehyde level in the hippocampus as well as a rise in glutathione level and activities of superoxide dismutase, catalase and glutathione peroxidase. In addition, the levels of tumor necrosis factor, interleukin-6 and interleukin-1β were reduced. Effects of lowering blood pressure and improving learning/memory ability in rats followed the order: lisinopril > black garlic nanoemulsion > black garlic extract.

Chemical Profiling, Larvicidal Activity and Antihemolytic Property of Allium sativum L. and Allium cepa L. Essential Oil

Essential oils are plant derived concentrates of the secondary metabolites responsible for the aromatic flavor attributing to its various medicinal properties. Fresh Allium sativum (A. sativum) and Allium cepa (A. cepa) were subjected to steam distillation for isolation of essential oil characterized by performing Gas Chromatography – Mass Spectroscopy (GC-MS). Chromatogram of the essential oil depicted the presence diallyl sulfide (5.35%), 2-(2’-carbamoylphenoxy)-butanoic acid (2.64%), 2-ethyl-5-methylthiophene (0.42%), diallyl disulphide (18.76%), 3-(2-thia-4-pentenyl)-1-thia-cyclohex-5-ene (1.09%) and dimethyl tetrasulphide (0.15%), 2,4-dimethylpyrido[2,3-d]pyrimidin-5-one (47.91%), 2,4-Thiazolidinedione (0.01%), 5-chloro-2-hydroxy-1,3-dinitrobenzene (5.93%), 6-Methoxy-1-methyl-3,4-dihydroisoquinoline (47.91%) in A. sativum and A.cepa respectively. Larvicidal activity against third instar larvae of Anopheles stephensi (A. Stephensi) was assessed by following the standard protocol of World Health Organization. The 50% lethality (LC50) of A. stephensi larvae was observed at 265.96 ± 1.88 ppm and 357.14 ± 2.36 ppm of A. sativum and A. cepa essential oil correspondingly. The mortality rate of the larvae was both time and dose dependent. Besides, the in vitro antihemolytic activity of the essential oil was also assessed using Sheep erythrocytes. The erythrocyte lysis was inhibited by the essential oils of both A. sativum and A. cepa in a concentration dependent manner with an IC50 of 427.35 ± 1.23 μl and 549.45 ± 1.38 μl respectively. On a comparative assessment between the essential oils of A. sativum and A. cepa, the former exhibited better larvicidal activity against the disease-causing vector, A. stephensi. Still, both could serve as potent insecticidal agents after further identification of the responsible chemical compound and its mode of action.

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.