Major Organosulfur Compounds Research Articles

Profiling of organosulfur compounds and amino acids in novel variety of Allium sativum (Hisar garlic 17) by HR-LCMS-QTOF

Over the past few years, the biological properties of garlic have been utilized as an attractive natural alternative to many therapeutic drugs. The biological effects of garlic have been ascribed to organosulfur compounds, secondary metabolites derived from amino acids. The present study aimed to investigate the extracts of a novel garlic variety (Hisar garlic 17) after processing it as fresh, dry, heated, and aged in different solvents and then analyzed with highly sensitive and rapid technique i.e., High resolution liquid chromatograph mass spectrometer quadrupole time of flight (HR-LCMS-QTOF) Mass spectrometer to study the amino acids and organosulfur compounds. 47 amino acids and 11 organosulfur compounds were detected out of which 8 organosulfur compounds were found as secondary metabolites of amino acids. Among the 22 crucial α-amino acids, garlic extracts revealed the presence of 18 amino acids, either in their native state or associated with various complex compounds. The study reported major organosulfur compounds, including Alliin, S-allyl cysteine, S-methyl cysteine, N-gamma-Glutamyl-S-allylcysteine, and 2-Propenyl 1-(2- propenylsulfinyl)propyl disulfide. This study demonstrated that HG17 garlic is abundant in amino acids and organosulfur compounds, suggesting its potential utilization as a supplement in nutraceuticals.

Diallyl Trisulfide attenuates alcohol-induced hepatocyte pyroptosis via elevation of hydrogen sulfide.

Garlic is a popular culinary herb for the prevention and treatment of alcoholic liver disease (ALD). Diallyl Trisulfide (DATS) is the major organosulfur compound of garlic. Latest studies indicated that the hepatocyte pyroptosis serves a primary role in the pathogenesis of ALD. The present study aims to assess the inhibitory effect of DATS on alcohol-induced hepatocyte pyroptosis, and to elucidate the potential mechanism by using the hepatocyte cell line HL-7702. Our study found that DATS inhibited alcohol-induced pyroptosis by decreasing gasdermin D (GSDMD) activation. Results illuminated that DATS inhibited alcohol-induced (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation by reducing intracellular reactive oxygen species (ROS) accumulation. Furthermore, DATS upregulated hydrogen sulfide (H2S) to resist ROS overproduction. The present study demonstrated that DATS mitigated alcohol-induced hepatocyte pyroptosis by increasing the intracellular level of H2S.

Diallyl Disulfide: A Bioactive Garlic Compound with Anticancer Potential.

Cancer is a life-threatening disease caused by the uncontrolled division of cells, which culminates in a solid mass of cells known as a tumor or liquid cancer. It is the leading cause of mortality worldwide, and the number of cancer patients has been increasing at an alarming rate, with an estimated 20 million cases expected by 2030. Thus, the use of complementary or alternative therapeutic techniques that can help prevent cancer has been the subject of increased attention. Garlic, the most widely used plant medicinal product, exhibits a wide spectrum of biological activities, including antibacterial, hypo-lipidemic, antithrombotic, and anticancer effects. Diallyl disulfide (DADS) is a major organosulfur compound contained within garlic. Recently, several experimental studies have demonstrated that DADS exhibits anti-tumor activity against many types of tumor cells, including gynecological cancers (cervical cancer, ovarian cancer), hematological cancers (leukemia, lymphoma), lung cancer, neural cancer, skin cancer, prostate cancer, gastrointestinal tract and associated cancers (esophageal cancer, gastric cancer, colorectal cancer), hepatocellular cancer cell line, etc. The mechanisms behind the anticancer action of DADS include epithelial-mesenchymal transition (EMT), invasion, and migration. This article aims to review the available information regarding the anti-cancer potential of DADS, as well as summarize its mechanisms of action, bioavailability, and pharmacokinetics from published clinical and toxicity studies.

Nutraceutical and multi-element profiles of elephant garlic (Allium ampeloprasum L.) and common garlic (Allium sativus L.) from Slovenia

Bulbous Allium spp. such as “big-headed” elephant garlic (Allium ampeloprasum L.) and common garlic (Allium sativus L.) contain a wide range of bioactive compounds with health-promoting properties and are most commonly used as food seasonings. The objective of the present study is to verify if there is a difference in selected nutraceuticals (dry matter, TPC, and allicin) and elemental profiles (macro- and micro-elements) of the two Allium species produced in two growing seasons in Jablje, Slovenia (a sub-Alpine region). The total phenolic content (TPC) was determined spectrophotometrically, the organosulfur compound allicin was determined by the HPLC analysis and the multi-element profiles by an inductively coupled plasma-mass spectrometry (ICP-MS). The results show that elephant garlic bulbs had slightly lower TPC and about six times less allicin, a major organosulfur compound. The content of macro- (Mg, P, S, K, and Ca) and micro-elements (Cr, Mn, Fe, Co, Cu, Zn, and Mo) varied considerably among the Allium samples studied. The greatest differences between bulbs of elephant garlic and common garlic were observed for P, Ca, S, and Fe. Our results confirm different nutritional characteristics of the bulbs and cloves of the two Allium species.

Onion (Allium cepa L.) bioactives: Chemistry, pharmacotherapeutic functions, and industrial applications

AbstractBioactive compounds possess different health benefits. Onion contains various bioactive compounds, such as organosulfur compounds, flavonols, ascorbic acids, and carbohydrate prebiotics, and its by‐products have more content of flavonoids than the bulb. Diallyl monosulfide, diallyl disulfide, diallyl trisulfide, and diallyl tetrasulfide are the major organosulfur compounds, whereas quercetin, kaempferol, anthocyanin, and luteolin are considered as main flavonoids. Ascorbic acid and fructooligosaccharides are also regarded as bioactive compounds. Onion bioactive compounds have the strong antioxidant potential for neutralizing oxidative stress of the cells. These bioactive components are beneficial as anticarcinogenic, antibiotic, anti‐inflammatory, antiplatelet, antidiabetic, and cardioprotective agents along with other nutritional benefits. However, various postharvest practices have an impact on these bioactive compounds, for example, curing mostly enhances the bioactive level and processing temperature generally decreases the concentration of many of them, whereas storage studies suggest an increase of others under optimized conditions. Additionally, conventional extraction techniques showed a negative impact on bioactive compounds of onion, whereas innovative methods yielded a higher amount of bioactive components. There is a need for innovative and integrated procedures in the postharvest sector to maintain or enhance the level of bioactive compounds without compromising the quality of onions. The present review comprehensively describes different bioactive compounds of onion, their chemistry, and their pharmacotherapeutic roles. Moreover, it also explores the effects of various postharvest factors, such as temperature, storage duration, and extraction conditions on the level of the bioactive components. It also suggests industrial applications of onion waste and its bioactive compounds in the food sector.

Identification of a pro-elongation effect of diallyl disulfide, a major organosulfur compound in garlic oil, on microglial process

Microglia are the innate immune cells in the nervous system. In the resting state, they display a ramified morphology, while upon disease stimulation their processes would be retracted, along with pro-inflammatory cytokine overproduction. Reversing microglial process retraction may help reduce pro-inflammatory cytokine production and restore microglia's ability to scan surrounding environments, rendering brain function regulation to be more effective. We found that diallyl disulfide (DADS), a major organosulfur compound in garlic oil, administered at different doses and time points, promoted microglial process elongation in both cultured systems and prefrontal cortexes in mice in a reversible manner. Lipopolysaccharide (LPS), a classical activator of microglia, did not affect this pro-elongation effect of DADS at conditions in vitro and in vivo. Functional studies revealed that DADS pre-treatment attenuated LPS-induced decreases in levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA as well as LPS-induced increases in levels of IL-10 and CD206 mRNA in both cultured microglia and prefrontal cortexes in mice. Protein kinase B (Akt) inhibition attenuated the pro-elongation effect of DADS on microglial process and blocked the regulatory effects of DADS on LPS-induced inflammatory responses in both cultured microglia and prefrontal cortexes in mice. In an in vivo model of neuroinflammation, DADS pre-treatment prevented LPS-induced retraction of microglial process in the prefrontal cortex in mice and attenuated LPS-induced increase in immobility time in the tail suspension test and forced swim test. These results indicate that DADS induces an Akt-dependent elongation of microglia process, along with the induction of an anti-inflammatory phenotype.

Bioactivities of Allicin and Related Organosulfur Compounds from Garlic: Overview of the Literature Since 2010

The medical values of garlic, a traditionally used allium vegetable, were recognized as early as 3000 BC. Allicin, one of the major organosulfur compounds present in garlic, is associated with a wide variety of benificial activities like anticancer, anti-inflammatory, antiarthritic, antimicrobial, anti-diabetic, cholesterol-lowering, the potential to lower cardiovascular disorders, ameliorating neuron functions, etc. In this article, we have reviewed biological activities of allicin and related organosulfur compounds since the year 2010, using various scientific websites like Pub med, Google Scholar, Science Direct etc. Our literature review has highlighted many organo sulphur components of garlic and their possible mechanisms in curing different diseases. The information provided in this review will provide strategies for efficient organosulfur-based treatments of several diseases in future. Further research efforts are needed for a clear understanding of the interconnection between these functional components and various chronic diseases.

Kinetic Studies of 2‐(2′‐hydroxyphenyl)benzenesulfinate desulfinase substrate analogs

2‐(2′‐hydroxyphenyl)benzenesulfinate desulfinase (DszB) is an enzyme that catalyzes the cleavage of the carbon‐sulfur bond as the final step of the desulfurization of 2‐(2′‐hydroxyphenyl)benzenesulfinate (HPBS) producing sulfite and 2‐hydroxybiphenyl (HBP). This reaction is used to study the biodesulfurization of dibenzothiophene, the major organosulfur compound found in fossil fuels/petroleum. Previous studies in the Watkins lab suggested that halogenated analogs of HPBS are competitive inhibitors of DszB, so a coupled assay was used to test their effect on kinetic activity. The relative activity of these analogs was tested measure both products of the reaction. The rate of HBP formation was monitored using a fluorometric assay with an excitation at 288 nm and measuring emission at 414 nm. The rate of sulfite product formation was measured in the coupled assay with Sulfite Oxidase (SOX) by analyzing a change in absorbance at 540 nm. When testing the analogs HPBS‐Cl and HPBS‐Br for activity, no product was detected. When measuring enzyme activity in the presence of the halogenated analogs and the substrate HPBS, an increase in DszB activity was observed, with HPBS‐Cl and HPBS‐Br showing an increase product formation of 475% and 213%, respectively. Individually these HPBS analogs did not act as catalytic substrates or competitive inhibitors, however when coupled with HPBS the analogs acted as activators. Based on these results, we are exploring the structure of DszB to further understand how HPBS analogs can affect the desulfinase kinetics.Support or Funding InformationNSF CHE‐1757874This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

PO-105 Diallyl disulfide enhances high-LET carbon beams -induced apoptotic cell death in human cervical cancer cells via regulating balance between Tap73 and ΔNp73

IntroductionDADS, a major organosulfur compound derived from garlic, induces cell death in various cancer cells. However, the effect of diallyl disulfide on high-LET carbon beams - induced cell death is currently unknown.Material and methodsHere we showed that the magnitude of radiation effects evoked by high-LET carbon beam was marked by inhibition of cell viability, cell cycle arrest, significant rise of apoptotic cells, upregulation of pro-apoptotic Tap73, downregulation of anti-apoptotic ΔNp73, as well as alterations of crucial mediator of the apoptosis pathway.Additionally, when combined with high-LET carbon beams, pretreatment of 10 µM DADS resulted in more significant decrease in cell viability, weaker G2/M phase arrest, more significant increase in apoptosis were observed in comparison with HeLa cells exposed to radiation group alone. Furthermore, combination DADS and high-LET carbon beams exacerbated the activation of apoptosis pathways through up-regulated ration of pro-apoptotic Tap73 to anti-apoptotic ΔNp73, and its downstream protein such as FASLG, and APAF1 in contrast to radiation group alone.Results and discussionsThese observations indicate that DADS is a very promising candidate as radio sensitive agent for cervical cancer and the ratio of pro-apoptotic Tap73 to anti-apoptotic ΔNp73 might be a molecular predictor of tumour responsiveness to radiation in s p53-independent manner. This study highlights a potential role of DADS and the ratio of Tap73/ΔNp73 in radiotherapy.Taken together, our results strongly suggest that DADS enhances high-LET carbon beams -induced apoptotic cell death in human cervical cancer cells via regulating balance between Tap73 and ΔNp73. We propose that DADS could be an a very promising candidate as radio sensitive agent for cervical cancer and the ratio of pro-apoptotic Tap73 to anti-apoptotic ΔNp73 might be a molecular predictor of tumour responsiveness to radiation in s p53-independent manner. However, this would require further investigation using tumor-bearing animal model and clinical trials to understand the effects of the DADS.ConclusionThese observations indicate that DADS is a very promising candidate as radio sensitive agent for cervical cancer and the ratio of pro-apoptotic Tap73 to anti-apoptotic ΔNp73 might be a molecular predictor of tumour responsiveness to radiation in s p53-independent manner. This study highlights a potential role of DADS and the ratio of Tap73/ΔNp73 in radiotherapy.

Initial Characterization of DszA, a Monooxygenase from the Rhodococcus Biodesulfurization Pathway

Sulfur dioxide is a pollutant found in our atmosphere that affects our health, environment, and economy. The most common source of sulfur dioxide pollution is the combustion of fossil fuels. To control pollution, it is important to remove sulfur from these fuels. The current sulfur removal method, hydrodesulfurization, is inefficient because it cannot remove sulfur from refractory organosulfur compounds. There are multiple bacterial species, including Rhodococcus erythropolis, that can remove sulfur from aromatic compounds, such as dibenzothiophene (DBT). DBT is a major organosulfur compound found in crude petroleum. The biodesulfurization pathway in Rhodococcus erythropolis can successfully remove sulfur from DBT to produce hydroxybiphenyl and sulfite. Our study focuses on an enzyme in this biodesulfurization pathway, the DBT sulfone monooxygenase, DszA that catalyzes the conversion of DBT sulfone to 2′‐hydroxybiphenyl 2‐sulfinate. Our goal was to obtain pure, active, and soluble protein for initial characterization of DszA. Thus far, we have determined the optimal parameters for expression of DszA by various expression and pH trials. The optimal temperature and pH for enzyme expression were 18°C and 7.5, respectively. DszA was successfully overexpressed in Escherichia coli and will be ready to purify by nickel affinity chromatography to take advantage of the His tag found in our protein. Our future steps are to apply steady‐state and transient‐kinetics to determine the kinetic parameters and study the mechanism of this important reaction step in the Rhodococcus biodesulfurization pathway. We will also analyze the substrate and product by high‐performance liquid chromatography to determine substrate specificity. These initial studies will provide a greater understanding towards the biodesulfurization mechanism for industrial purposes and pollution control.Support or Funding InformationThis research was supported by the Research Corporation (CCSA 22672) and by the National Institutes of Health (NIH) Grant 5SC2AI109500.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The application of compound-specific sulfur isotopes to the oil–source rock correlation of Kurdistan petroleum

The concentrations and δ34S values of thioaromatic compounds of a suite of oils from several major oil fields in Kurdistan and their corresponding regional Type II-S source rocks have been measured to investigate their source relationship. The oils of three fields (Khabbaz, Jambur, Ajeel) and the bitumen extracted from specific rock formations (Alan, Sargelu, Naokelekan, Chia Gara) showed particularly high abundances of thioaromatics consistent with a carbonate source deposited in a restricted sulfate-rich marine platform setting. The δ34S [V-CDT] values of the major organosulfur compounds (OSCs) in these petroleum samples were measured with a gas chromatograph coupled to a multi-collector inductively coupled plasma mass spectrometer. δ34S values of dibenzothiophenes and methyldibenzothiophenes were consistently in the range −4‰ to −12‰ and −9‰ to −18‰ for the oils and rocks, respectively. Separate groupings of oils and rocks were distinguishable by > 2‰ difference, given an analytical reproducibility of < 0.8‰. OSCs from rocks were consistently ∼2–4‰ depleted than in oils, reflecting a similar trend to previous bulk δ34S studies from which an initial evolution of 34S depleted H2S during diagenesis and thermal maturation had been proposed. Distinctive δ34SOSC data of the oils and rocks with particularly high thioaromatic abundances did suggest several oils–source rock relationships: the Ajeel and Jambur oils and sediments from the Chia Gara formation yielded relatively enriched δ34SOSC values, whereas consistently depleted δ34SOSC values were observed for the Khabbaz oil and Naokelekan source rocks. Results suggest that compound-specific S isotope analysis can help establish oil–source rock relationships of S-rich petroleum.

Specificity studies of the aromatic desulfinase, 2‐(2′‐hydroxyphenyl)benzenesulfinate desulfinase (DszB) from Nocardia asteroides A3H1

2‐(2′‐hydroxyphenyl)benzenesulfinate desulfinase (DszB) is a desulfinating enzyme that catalyzes the final carbon‐sulfur bond cleavage reaction in the biodesulfurization (BDS) of dibenzothiophene (DBT), a major organosulfur compound in fossil fuels. Homology studies suggest that Alanine 195 and Alanine 200 are important in determining the specificity of the active site. Point mutations were created to determine the effect of switching A200 to an Arginine (A200R), as well as switching A195 to an Arginine (A195R) and switching both A195 and A200 to Arginine (A195/200R). By altering amino acids in the active site of DszB, the effects of amino acid A195 and A200 on the active site specificity can be determined. Codon optimized DszB was cloned into pTAC‐MAT‐Tag‐2, overexpressed in E. coli, and purified using a Ni2+ column. Enzyme stored in aliquots containing 15% DMSO was stable at −80 °C for several weeks. The natural substrate 2‐(2′‐hydroxyphenyl)benzenesulfinate (HPBS) was tested, along with the smaller ring analogs 2‐(2′‐hydroxyphenyl)enthen‐1‐sulfinate (HPES) and benzenesulfinate (BS), in order to test whether the active site prefers one, two or three rings. The kinetic data of the codon optimized DszB showed a Km of 3.71 ± 0.60 μM and kcat of 52.8 ± 5.49 hr−1. The specificity of DszB‐A3H1‐A200R showed a change in specificity, preferring HPES over BS.Support or Funding InformationNational Science Foundation (CHE 1062629)

The Progress of Diallyl Disulfide in Anti-Cancer

Considerable evidence in recent years suggests that garlic has anti-proliferative effects on various types of cancer. Garlic contains water-soluble and oil-soluble sulfur compounds. Oil-soluble compounds (OSCs), such as diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS) and ajoene are more effective than watersoluble compounds in protection against cancer. DADS, a major organosulfur compound derived from garlic, can reduce carcinogen-induced cancers in experimental animals and inhibit the proliferation of various types of cancer cells. The mechanisms of these action of DADS include activation of metabolic enzymes that detoxify carcinogens, suppression of the formation of DNA adducts, antioxidant effects, regulation of cell-cycle progression, induction of apoptosis, and inhibition of angiogenesis and metastasis. These topics are discussed in depth in this review.

Evaluation of the Effects of &lt;i&gt;S&lt;/i&gt;-Allyl-L-cysteine, &lt;i&gt;S&lt;/i&gt;-Methyl-L-cysteine, &lt;i&gt;trans&lt;/i&gt;-&lt;i&gt;S&lt;/i&gt;-1-Propenyl-L-cysteine, and Their &lt;i&gt;N&lt;/i&gt;-Acetylated and &lt;i&gt;S&lt;/i&gt;-Oxidized Metabolites on Human CYP Activities

Three major organosulfur compounds of aged garlic extract, S-allyl-L-cysteine (SAC), S-methyl-L-cysteine (SMC), and trans-S-1-propenyl-L-cysteine (S1PC), were examined for their effects on the activities of five major isoforms of human CYP enzymes: CYP1A2, 2C9, 2C19, 2D6, and 3A4. The metabolite formation from probe substrates for the CYP isoforms was examined in human liver microsomes in the presence of organosulfur compounds at 0.01-1 mM by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Allicin, a major component of garlic, inhibited CYP1A2 and CYP3A4 activity by 21-45% at 0.03 mM. In contrast, a CYP2C9-catalyzed reaction was enhanced by up to 1.9 times in the presence of allicin at 0.003-0.3 mM. SAC, SMC, and S1PC had no effect on the activities of the five isoforms, except that S1PC inhibited CYP3A4-catalyzed midazolam 1'-hydroxylation by 31% at 1 mM. The N-acetylated metabolites of the three compounds inhibited the activities of several isoforms to a varying degree at 1 mM. N-Acetyl-S-allyl-L-cysteine and N-acetyl-S-methyl-L-cysteine inhibited the reactions catalyzed by CYP2D6 and CYP1A2, by 19 and 26%, respectively, whereas trans-N-acetyl-S-1-propenyl-L-cysteine showed weak to moderate inhibition (19-49%) of CYP1A2, 2C19, 2D6, and 3A4 activities. On the other hand, both the N-acetylated and S-oxidized metabolites of SAC, SMC, and S1PC had little effect on the reactions catalyzed by the five isoforms. These results indicated that SAC, SMC, and S1PC have little potential to cause drug-drug interaction due to CYP inhibition or activation in vivo, as judged by their minimal effects (IC50>1 mM) on the activities of five major isoforms of human CYP in vitro.

Diallyl disulfide attenuated carbon ion irradiation-induced apoptosis in mouse testis through changing the ratio of Tap73/ΔNp73 via mitochondrial pathway.

Diallyl disulfide (DADS), a major organosulfur compound derived from garlic, has various biological properties, including anti-cancer effects. However, the protective mechanism of DADS against radiation-induced mouse testis cell apoptosis has not been elucidated. In this study, the magnitude of radiation effects evoked by carbon ion irradiation was marked by morphology changes, significant rise in apoptotic cells, activation expression of p53, up regulation the ratio of pro-apoptotic Tap73/anti-apoptotic ΔNp73, as well as alterations of crucial mediator of the mitochondrial pathway. Interestingly, pretreatment with DADS attenuated carbon ion irradiation-induced morphology damages and apoptotic cells. Additionally, DADS elevated radiation-induced p53 and p21 expression, suggesting that p53 might be involved in the inhibition of cell cycle progression through up regulation of p21. Furthermore, administration with DADS prevented radiation-induced Tap73/ΔNp73 expression and consequently down regulated Bax/Bcl-2 ratio, cytochrome c release and caspase-3 expression, indicating that the balance between Tap73 and ΔNp73 had potential to activate p53 responsive genes. Thus, our results showed that radio protection effect of DADS on mouse testis is mediated by blocking apoptosis through changing the ratio of Tap73/ΔNp73 via mitochondrial pathway, suggesting that DADS could be used as a potential radio protection agent for the testis against heavy-ion radiation.

Acute toxicological studies of the main organosulfur compound derived from Allium sp. intended to be used in active food packaging

Some plant extracts have been proposed as potential alternative to the use of synthetic preservatives in the food industry. Among those, extracts from Allium species exhibit interesting antimicrobial and antioxidant properties for the food packaging industry. The present work aims to assess the usefulness and potential safety of the major organosulfur compound present in a commercial Allium sp. extract (PROALLIUM AP®), namely propyl thiosulfinate oxide (PTSO). For this purpose, its antimicrobial activity was studied in a wide range of microorganisms. Moreover, cytotoxicity and ultrastructural cellular damages caused by PTSO were studied in two human cell lines, Caco-2 and HepG2, being the colonic cells more sensitive to this compound. Finally, the protective role of PTSO against an induced oxidative situation was evaluated in the human intestinal Caco-2 cells. The results revealed damage at high concentration, although no significant adverse effects were recorded for the concentration to be used in food packaging. Moreover, the in vivo study also revealed the potential safety use at the established concentrations. In addition, the antimicrobial properties and the antioxidant role of PTSO were confirmed. Therefore, this compound could be considered as a good natural alternative to synthetic preservatives used in the food packaging industry.

Diallyl Disulphide Protects against Colon Cancer in vitro, of HT-29 Cells and in Male Rabbits of Colon Cancer Model: An Analysis of Genetic and Epigenetic Variations

Diet and dietary habits are currently accused of being among cancer causing agents. The present study was carried out in a trial to point at the beneficial anti-cancer properties of one the most Egyptian traditional food components (Garlic). We studied the anti-cancerous properties of Diallyl disulphide (DADS), a major organosulfur compound in garlic oil, on HT29 colon cancer cell line and in vivo of male rabbits (Oryctolagus cuniculus) as an animal model of colon cancer. DADS showed differential effect on the expression of a group of genes, as it down-regulated the expression of oncogenes (e.g., CTNNB1, CCDN1, BIRC5, MYC and AKT), while up-regulated the expression of tumour suppressor gene (TP53) and apoptosis regulator gene (BAX). DADS apoptotic effect was also seen via inducing the expression of cytochrome c and activation of caspase-3. Moreover, DADS induced chromatin configuration changes through increasing histone acetylation of histone-3 and -4. Examination of 1,2 dimethyl hydrazine (DMH) induced cancer in vivo model (O. cuniculus) showed histological changes characteristic for colon tumorigenesis such as, hyperplastic intraepithelial lesions, neoplastic changes and lymphocytes infiltration, which were strongly attenuated in animals coinjected with both DADS and DMH and were not observed in the animals that received DADS prior to DMH treatment. This study suggested the protective properties of DADS against colon cancer in vitro and in vivo.

Diallyl-disulfide, an organosulfur compound of garlic, attenuates airway inflammation via activation of the Nrf-2/HO-1 pathway and NF-kappaB suppression

Diallyl disulfide (DADS) is a major organosulfur compound found in garlic oil that is widely used as a flavoring agent. In this study, we evaluated the effects of DADS on airway inflammation using an ovalbumin-induced model of allergic asthma and RAW264.7 cells. DADS decreased nitric oxide production with a reduction in the levels of interleukins (IL)-1β and IL-6 in RAW264.7 cells stimulated with LPS. DADS also reduced the expression of proinflammatory proteins including inducible nitric oxide synthase (iNOS), nuclear factor (NF)-κB, and matrix metalloproteinase (MMP)-9, and it enhanced the expression of antioxidant proteins including Nrf-2 and hemeoxygenase (HO)-1. In in vivo experiments, DADS decreased the inflammatory cell count in the bronchoalveolar lavage fluid (BALF) with IL-4, IL-5, IL-13, and immunoglobulin (Ig) E. These results were consistent with the histological analysis. DADS attenuated the airway inflammation and mucus hypersecretion induced by OVA challenge. In addition, DADS induced the activation of Nrf-2 and the expression of HO-1. In contrast, DADS reduced the activation of NF-κB, iNOS and MMP-9. In conclusion, DADS reduced the airway inflammation via regulation of Nrf-2/HO-1 and NF-κB. These results suggest that DADS might represent a useful new oral therapy to treat allergic asthma.

Molecular mechanisms for the anti-cancer effects of diallyl disulfide

Considerable evidence in recent years suggests that garlic has anti-proliferative effects against various types of cancer. Garlic contains water-soluble and oil-soluble sulfur compounds. Oil-soluble compounds such as diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS) and ajoene are more effective than water-soluble compounds in protection against cancer. DADS, a major organosulfur compound derived from garlic, can decrease carcinogen-induced cancers in experimental animals and inhibit the proliferation of various types of cancer cells. Its mechanisms of action include: the activation of metabolizing enzymes that detoxify carcinogens; suppression of the formation of DNA adducts; antioxidant effects; regulation of cell-cycle arrest; induction of apoptosis and differentiation; histone modification; and inhibition of angiogenesis and invasion. These topics are discussed in depth in this review.

Dose-dependent effects of diallyl disulfide on plasma glucose and free fatty acid levels in rats

The acute effects of oral administration of diallyl disulfide (DADS), the major organosulfur compound of garlic, on plasma glucose and free fatty acid (FFA) concentrations were examined in rats. Male, 10-week-old Sprague-Dawley rats were divided into DADS-free and DADS-administered (dose = 10, 20, and 40 mg/kg body weight [BW]) groups. Plasma samples were prepared from whole blood drawn from the tail vein 0, 1, 2, 4, and 6 hr after administration. The stomachs were isolated, and the contents were measured 8 hr after administration. In DADS-administered groups, plasma glucose concentrations were increased in a dose-dependent manner 1 hr after the administration. The increase was transient, except in groups administered 40 mg/kg BW of DADS, in which plasma glucose levels remained significantly higher than the DADS-free levels throughout the experimental period. Similar patterns were observed in the plasma FFA concentrations, although the significant differences were lower than those observed in the plasma glucose concentrations. The gastric contents were dose-dependently elevated after DADS administration. The increase was significant when 20 or 40 mg/kg BW of DADS was administered. These results suggest that oral administration of DADS can mobilize energy substrates into the blood, although a higher dose of DADS slows gastric emptying.