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Sulfur-containing compounds, such as cyclic compounds with a vinyl sulfane structure, exhibit a wide range of biological activities including anticancer activity. Therefore, the development of efficient strategies to synthesize such compounds is a remarkable achievement. We have developed a unique approach for the rapid and modular preparation of nature-inspired cyclic and acyclic sulfur-containing compounds using thioacrolein, a naturally occurring chemically unstable intermediate. We constructed thiopyranone derivatives through the regioselective sequential double Diels-Alder reaction of thioacrolein produced by allicin, a major component in garlic, and two molecules of silyl enol ether as the diene partner. The cytotoxicity toward cancer stem cells of the thiopyranones was equal to or higher than that of (Z)-ajoene (positive control) derived from garlic, and the thiopyranones had higher chemical stability than (Z)-ajoene.

Malaria is an infectious disease with a high morbidity and mortality rate caused by Plasmodium and is transmitted through the Anopheles mosquito. Garlic (Allium sativum) has active substances that can be used as medicinal ingredients. Several active substances, namely allicin, ajoene, and quercetin contained in garlic have the potential to act as an effective and safe anti plasmodium for the host. This writing is a literature review using relevant literature. The results of the study concluded that the active ingredients in garlic have potential to be a new antimalarial agent, and it is hoped that it can be a cheaper and more effective malaria treatment so that drug resistance and morbidity and mortality from malaria can be reduced.

Ever-growing research efforts are demonstrating the potential of medicinal plants and their phytochemicals to prevent and manage obesity, either individually or synergistically. Multiple combinations of phytochemicals can result in a synergistic activity that increases their beneficial effects at molecular, cellular, metabolic, and temporal levels, offering advantages over chemically synthesized drug-based treatments. Herbs and their derived compounds have the potential for controlling appetite, inhibiting pancreatic lipase activity, stimulating thermogenesis and lipid metabolism, increasing satiety, promoting lipolysis, regulating adipogenesis, and inducing apoptosis in adipocytes. Furthermore, targeting adipocyte life cycle using various dietary bioactives that affect different stages of adipocyte life cycle represents also an important target in the development of new antiobesity drugs. In this regard, different stages of adipocyte development that are targeted by antiobesity drugs can include preadipocytes, maturing preadipocytes, and mature adipocytes. Various herbal-derived active compounds, such as capsaicin, genistein, apigenin, luteolin, kaempferol, myricetin, quercetin, docosahexaenoic acid, quercetin, resveratrol, and ajoene, affect adipocytes during specific stages of development, resulting in either inhibition of adipogenesis or induction of apoptosis. Although numerous molecular targets that can be used for both treatment and prevention of obesity have been identified, targeted single cellular receptor or pathway has resulted in limited success. In this review, we discuss the state-of-the-art knowledge about antiobesity medicinal plants and their active compounds and their effects on several cellular, molecular, and metabolic pathways simultaneously with multiple phytochemicals through synergistic functioning which might be an appropriate approach to better management of obesity. In addition, epigenetic mechanisms (acetylation, methylation, miRNAs, ubiquitylation, phosphorylation, and chromatin packaging) of phytochemicals and their preventive and therapeutic perspective are explored in this review.

Ajoene is a compound found in garlic extracts exhibiting a large range of biological activity. Novel ajoene analogues have been prepared in the search of compounds with superior bioactivity. Modifications include the alteration of the sulfoxide, the central alkene and the terminal allyl groups.

Significance: Sulfur has a critical role in protein structure/function and redox status/signaling in all living organisms. Although hydrogen sulfide (H2S) and sulfane sulfur (SS) are now recognized as central players in physiology and pathophysiology, the full scope and depth of sulfur metabolome's impact on human health and healthy longevity has been vastly underestimated and is only starting to be grasped. Since many pathological conditions have been related to abnormally low levels of H2S/SS in blood and/or tissues, and are amenable to treatment by H2S supplementation, development of safe and efficacious H2S donors deserves to be undertaken with a sense of urgency; these prodrugs also hold the promise of becoming widely used for disease prevention and as antiaging agents. Recent Advances: Supramolecular tuning of the properties of well-known molecules comprising chains of sulfur atoms (diallyl trisulfide [DATS], S8) was shown to lead to improved donors such as DATS-loaded polymeric nanoparticles and SG1002. Encouraging results in animal models have been obtained with SG1002 in heart failure, atherosclerosis, ischemic damage, and Duchenne muscular dystrophy; with TC-2153 in Alzheimer's disease, schizophrenia, age-related memory decline, fragile X syndrome, and cocaine addiction; and with DATS in brain, colon, gastric, and breast cancer. Critical Issues: Mode-of-action studies on allyl polysulfides, benzyl polysulfides, ajoene, and 12 ring-substituted organic disulfides and thiosulfonates led several groups of researchers to conclude that the anticancer effect of these compounds is not mediated by H2S and is only modulated by reactive oxygen species, and that their central model of action is selective protein S-thiolation. Future Directions: SG1002 is likely to emerge as the H2S donor of choice for acquiring knowledge on this gasotransmitter's effects in animal models, on account of its unique ability to efficiently generate H2S without byproducts and in a slow and sustained mode that is dose independent and enzyme independent. Efficient tuning of H2S donation characteristics of DATS, dibenzyl trisulfide, and other hydrophobic H2S prodrugs for both oral and parenteral administration will be achieved not only by conventional structural modification of a lead molecule but also through the new “supramolecular tuning” paradigm.

Aged black garlic (BG) is a functional food in global markets; however, very few studies have ventured into comprehensive profiling of BG metabolomes during the aging process. Herein, we exploited UHPLC-Orbitrap HRMS for a comparative metabolomics analysis. During the heat treatment, organosulfur compounds such as allicin, diallyl disulfide, ajoene, S-allyl-l-cysteine (SAC), and γ-glutamyl-SAC were downregulated. Plenty of glycerophospholipids together with shikimate, aromatic amino acids, and vitamin B6 vitamers were significantly augmented; tryptophan was however consumed to generate downstream products manifested in nicotinate metabolism and aminobenzoate degradation. These secondary metabolites serve as signaling mediators or protectants against extreme thermal exposure. Besides, Heyns compounds and Amadori-rearrangement byproducts with potential mutagenic effects were concentrated. Together, our findings expand the known metabolome space of BG processing and better elucidate the reactivities of the key metabolites. We provide in-depth insights into the biochemical changes of BG that enable further functional or toxicological investigations of this popular food.

Introduction: Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The leading cause of death worldwide is responsible for 1.5 million deaths each year. The cause of tuberculosis infection is the tubercle bacillus discovered by Robert Koch in 1882. The organism causing it is Mycobacterium tuberculosis.The spread of new cases is divided in several regions including Southeast Asia and Africa, which are the regions that have the biggest contribution to the prevalence of tuberculosis. So it takes pillars and components of TB control that cover all lines. Method: This study aims to discuss the potential of herbal plants spread in Indonesia as herbal medicines that have the potential to treat tuberculosis infection. This study uses a literature study method which prepares the same as other research, but the sources and methods of data collection are by taking data from the library, reading, taking notes, and processing research materials. Result: One of the components that are currently being developed in TB infection intervention methods is the development of herbal medicines for tuberculosis control. The herbal medicines used come from garlic (Allium sativum), Centellaasiatica, beluntas leaves, Hibiscus rosasinensis L., Boechmeria virgate (Forst) Guill, tobacco leaves, Morindacitrifolia L., Javanese wood bark, Spondiaspinnata (Lf)Kurz. Conclusion: The herbal medicinal ingredients contain major chemicals such as alicin, ajoene, asiaticoside, asiatic acid, madecassic acid, and madecassoside, alkaloids, flavonoids, tannins, saponins, phenolic, and triterpenoids which have the ability to have a bactericidal effect to kill the Mycobacterium tuberculosis bacteria.

Gentamicin can induce damage to the kidney because of the accumulation of epithelial cells in the cortex. This accumulation can cause an increase in Reactive Oxygen Species (ROS), which in turn can trigger an increase in free radicals which causes a decrease in kidney function, which can be seen with Blood Urea Nitrogen (BUN) and sCr (serum creatinine) parameters. Garlic (Allium sativum L.) contains several bioactive compounds, including alliin, allisin, ajoene, and allil cysteine. The content of allisin has activity as an antioxidant. This study used a nephrotoxic mouse modelling method with 100 mg/kgBW of gentamicin induction intraperitoneally, then BUN and sCr levels were checked 24 hours after the 10th day induction. This study aimed to determine the effect of garlic ethanol extract in preventing the decline of renal function in rats induced by gentamicin with a parameter of BUN and sCr. The animal test were divided into 5 treatment groups, normal control group, negative controls, and three treatment groups at a dose of 50, 120, and 300 mg/kgBW for 10 days of concurrent treatment between extracts with gentamicin. The results of the study showed that garlic ethanol extract with a dose of 50, 120, 300 mg/kgBW was able to prevent a decrease in kidney function due to the administration of gentamicin significantly when compared with negative controls (p 0,05).

A short total synthesis of ajoene, (E,Z )‐4,5,9‐trithiadodeca‐1,6,11‐triene 9‐oxide, has been achieved over six steps. In addition, a continuous flow synthesis under mild reaction conditions to (E,Z )‐4,5,9‐trithiadodeca‐1,7,11‐triene is described starting from simple and easily accessible starting materials. Over four steps including propargylation, radical addition of thioacetate, deprotection, and disulfide formation/ allylation, the target product can be obtained at a rate of 0.26 g h−1 in an overall yield of 12 %.

espanolGeneralmente, los chefs utilizan el ajo como un ingrediente que mejora las cualidades sensoriales de los alimentos. Sin embargo, estudios recientes han demostrado que el ajo contiene compuestos de azufre, que proporcionan un beneficio para la salud. Esta revision identifica y describe los componentes del ajo responsables de sus propiedades antimicrobianas, antioxidantes, antiinflamatorias y, en algunos casos, anticancerigenas. Ademas, se informa sobre el contenido quimico y nutricional del ajo (Allium sativumL.) y muestra sus beneficios para la salud humana. En la literatura se encontro una gran variabilidad y diversidad en el contenido nutricional del ajo, incluyendo propiedades funcionales (antioxidantes, antimicrobianas, antimicrobianas, antimicoticas e inmunologicas), y muchos componentes beneficiosos para la salud, tales como antihipertensivos, hipolipidemicos, antiaterogenicos, anticancerigenos, antitumorales, antiagregantes, fibrinoliticos, inmunomoduladores y antianemicos. La alicina y el ajoene se identificaron entre algunos de los compuestos del ajo que son beneficiosos para la salud humana, las que varian dependiendo de la madurez del bulbo y de la ubicacion de la cosecha, y los valores oscilan entre aproximadamente 1 mg/g y9 mg/g para la alicina y 0,12 mg/g a 0,22 mg/g de aceite de ajo macerado para el ajoene EnglishGenerally, chefs use garlic as an ingredient that enhances the sensory qualities of foods. However, recent studies have shown that garlic contains Sulphur compounds, which provide a health benefit. This review identifies and describes those constituents in garlic responsible for their anti-microbial, antioxidant, anti-inflammatory, and in some cases anti-cancer properties. Also, this review reports the chemical and nutritional contents of garlic (Allium sativum L.) and shows its health benefits for humans. A large variability and diversity in the nutritional content of garlic was found in the literature, including functional properties (antioxidant, antimicrobial, antifungal, and immunological), and many health benefit components, such as antihypertensive, hypolipidemic, antiatherogenic, anticarcinogenic, antitumor, antiaggregant, fibrinolytic, immunomodulatory, and antianemic. Allicin and ajoene were identified among some of the compounds in garlic which are beneficial for human health. Quantity varies depending on bulb maturity and harvest location, and values range between approximately 1mg/g and 9mg/g for allicin and 0.12 mg/g to 0.22 mg/g of garlic oil macerate for ajoene.

Prenatal screening in pregnant women between 35 and 37 weeks of gestation and intrapartum antibiotic prophylaxis has successfully reduced the incidence of neonatal morbidity and mortality related to Streptococcus agalactiae. However, the contamination rates of newborns are still considerable. In traditional and folk medicines, it has been observed that garlic has been effective in treating S. agalactiae infection. The aim of this study was to isolate and identify the active compounds from garlic that have antimicrobial activity against S. agalactiae. In order to do this, SP80 (Sep-Pak 80%) obtained from crude garlic extract (CGE) was fractionated by reverse-phase ultrafast liquid chromatography with UV (RP-UFLC-UV) using a Shim-pack PREP-ODS column. All fractions obtained were tested using a microbial growth inhibition test against the S. agalactiae strain (ATCC 12386). Five clinical isolates were used to confirm the action of the fractions with antimicrobial activity, and the bacterial growth curve was determined. Identification of the antimicrobial compounds was carried out through liquid chromatography coupled with mass spectrometry (LC/MS) and nuclear magnetic resonance (NMR). The active compounds found to exhibit antimicrobial activity were Ƴ-glutamyl-S-allyl-cysteine (fraction 18), Ƴ-glutamyl-phenylalanine (fraction 20), and the two stereoisomers (E and Z) of ajoene (fraction 42). The MICs of these fractions were 5.41 mg/ml, 4.60 mg/ml, and 0.16 mg/ml, respectively, and they inhibited the growth of the clinical isolates tested. Antimicrobial compounds from garlic may be a promising source in the search for new drugs against S. agalactiae. IMPORTANCE Invasive disease due to group B streptococcal (GBS) infection results in a wide spectrum of clinical disease in neonates. Maternal colonization by GBS is the primary risk factor for disease. The strategy recommended by the Centers for Disease Control to reduce neonatal GBS infection is the culture-based screening of all pregnant women at 35 to 37 weeks of gestation and intrapartum antibiotic prophylaxis (IAP). However, indiscriminate use of antibiotics favors the selection and spread of resistant bacteria. The global scenario of antibacterial resistance has been of great concern for public health, and natural products can be a source of new substances to help us grapple with this problem.

Antibiotics in poultry as growth promoters have the perspective of products acceptability and human health concern. Plant extracts have been used as alternatives to antibiotics but dosage varies and reducing agents in the chicken gut in-activates most of the potential compounds. This research aimed to determine the antibacterial activity, acute toxicity in mice and the effect of Garlic and Onion Chitosan Nanoparticles on growth indices in Rainbow Rooster Chicken. Study involved two treatments, treatment 1 consisted of Chitosan Nanoparticles prepared from aqueous of Garlic (Allium sativum) and Onion (Allium cepa L.) (CHIAGO) whilst treatment 2 was Chitosan Nanoparticles prepared from total Phenol and Ajoene rich extract (CHITPA). Products were characterized by pH sensitivity, Fourier Transform Infrared Spectroscopy (FTIR) and Field Emission Scanning Electron Microscopy (SEM). Disc diffusion method was used to test for activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) with Fosbac as the positive control. Acute toxicity in mice through oral administration of the nanoparticles solution at dosage of 5% and 10%. Nanoparticles and chitosan solution were administered orally to chicken at dosage of 5% and 10%. The treatments against E. coli gave resistance zone of inhibition (≤ 12), an intermediate zone of inhibition (13 to 15) while against S. aureus gave resistance zone of inhibition (≤ 12), an intermediate zone of inhibition (13 to 15) and susceptible zone of inhibition (≥ 16). Alanine aminotransferase and urea had no significant changes (p > 0.05) but significant differences in PCV in mice (p 0.05) observed in crypt depth and PCV% when compared with the contolled chicken. Garlic and Onion Chitosan Nanoparticles can act as alternative to antibiotics as growth promoters in poultry.

In the current scenario, pharmaceutical industry is dependent on chemical based drugs to treat viral infection. However, these drugs are known to induce many side effects in human body. There is pressing need to promote safe alternative to chemical based antiviral drugs. Onion and garlic are natural sources which are known to possess antiviral properties. It is well known that onion and garlic are rich source of organosulfur compounds. Organosulfur compounds like quercetin and allicin are associated with inhibition of viral infection. These chemicals can hinder virus attachment to host cell, alter transcription and translation of viral genome in host cell and also affect viral assembly. Quercetin can affect entry and attachment of Enterovirus and Influenza virus on host cell. This compound also has ability to inhibit RNA polymerase which is necessary for viral replication. Quercetin also inhibit process by which virus alter signalling pathway in host cell. Organosulfur compounds like allicin, diallyl trisulfide and ajoene are main chemicals which impart antiviral property to garlic. It is known that allicin can pass through phospholipid membrane of cell and can further contribute in inhibiting viral multiplication. Considering numerous studies which corroborate antiviral effect of onion and garlic, this paper recommends consumption of these plants as a safe alternative to prevent virus infection.

Background:Cancer is a multi-factorial disease including alterations in the cell signalling pathways. Currently, several drugs are in use to treat cancer but such drugs show negative side effects on normal cells and cause severe toxicity.Methods:The current research is mainly focused on medicinal plants with potential therapeutic efficacy in the treatment of cancer without any adverse effects on normal cells. In this regard, garlic and its active compounds including diallyl sulfide, diallyl trisulfide, ajoene, and allicin have been established to suppress the growth of cancer and killing of cancer cells.Result:The review focuses on garlic and its active compounds chemopreventive effect through modulating various cell signalling pathways. Additionally, garlic and its active compound were established to induce cell cycle arrest at the G0/G1 phase and G2/M phases in cancer cells, increase the expression of tumor suppressor genes, inhibit the angiogenesis process, induction of apoptosis and modulation of various other genetic pathways.Conclusion:This review sketches the diverse chemopreventive activities of garlic and their active ingredients in the management of cancer mainly focusing on cell signalling pathways.

Currently, viral infection is the most serious health issue which causing unexpected higher rate of death globally. Many viruses are not yet curable, such as corona virus-2 (SARS-CoV-2), human immunodeficiency virus (HIV), hepatitis virus, human papilloma virus and so others. Furthermore, the toxicities and ineffective responses to resistant strains of synthetic antiviral drugs have reinforced the search of effective and alternative treatment options, such as plant-derived antiviral drug molecules. Therefore, in the present review, an attempt has been taken to summarize the medicinal plants reported for exhibiting antiviral activities available in Bangladesh along with discussing the mechanistic insights into their bioactive components against three most hazardous viruses, namely SARS-CoV-2, HIV, and HBV. The review covers 46 medicinal plants with antiviral activity from 25 families. Among the reported 79 bioactive compounds having antiviral activities isolated from these plants, about 37 of them have been reported for significant activities against varieties of viruses. Hesperidin, apigenin, luteolin, seselin, 6-gingerol, humulene epoxide, quercetin, kaempferol, curcumin, and epigallocatechin-3-gallate (EGCG) have been reported to inhibit multiple molecular targets of SARS-CoV-2 viral replication in a number of in silico investigations. Besides, numerous in silico, in vitro, and in vivo bioassays have been demonstrated that EGCG, anolignan-A, and B, ajoene, curcumin, and oleanolic acid exhibit anti-HIV activity while piperine, ursolic acid, oleanolic acid, (+)-cycloolivil-4′-O-β-d-glucopyranoside, quercetin, EGCG, kaempferol, aloin, apigenin, rosmarinic acid, andrographolide, and hesperidin possess anti-HBV activity. Thus, the antiviral medicinal plants and the isolated bioactive compounds may be considered for further advanced investigations with the aim of the development of effective and affordable antiviral drugs.

Garlic, a member of the Allium family, widely used in cooking for many centuries, displays well described antioxidant and anti-inflammatory properties, as a result of its constituent organosulfur compounds, such as alliin, allicin, ajoene S-allyl-cysteine, diallyl sulfide and diallyl disulfide, among others. Although garlic has demonstrated beneficial effects in cardiovascular disease, diabetes, and cancer, its efficacy as a therapeutic intervention in chronic kidney disease remains to be proven. This review thus focuses on the potential benefits of garlic as a treatment option in chronic kidney disease. and its ability to mitigate associated cardiovascular complications and gut dysbiosis.

Non-alcoholic fatty liver disease (NAFLD) occurs when triglycerides inside hepatocytes are swollen. A single bulb garlic extract containing allicin components, S-allyl-l-cysteine, Ajoene (E-Ajoene and Z-Ajoene) are thought to inhibit fat biosynthesis and reduce triglycerides in blood serum. This study aimed to analyze single bulb garlic extract in NAFLD due to a high-fat diet (HFD) in mice. Twenty male Balb/C mice were divided into five groups: normal, HFD, HFD + Single Bulb Garlic Extract (SBGE) 100 mg kg BW−1, HFD + SBGE 200 mg kg BW−1, and HFD + SBGE 400 mg kg BW−1. The administration of SBGE orally altogether with HFD for 30 days. On the last day of treatment, the mice were sacrificed. The liver was collected to make a micro-anatomic slide and stained by Hematoxylin Eosin. Liver microanatomy slides were observed under a light microscope and scoring to count fatty liver cells. The results of this study indicated that administration of SBGE affected the average liver weight (p < 0.05). Treating SBGE with dose of 100 mg kg BW−1, 200 mg kg BW−1, and 400 mg kg BW−1 decreased hepatic steatosis (p < 0.05). SBGE could prevent non-alcoholic fatty liver disease in mice fed with HFD.

Gliomas are a group of malignant brain tumors. Despite significant efforts to optimize treatment options for patients with high-grade glioma, the prognosis of the overwhelming majority of patients remain poor. This bleak prognosis despite treatment of the glioma, is partly due to the tendency of therapeutics to diffusely penetrate into the neighboring brain tissues, but also due to the innate resistance of these tumors to chemotherapy and radiation. Garlic contains water-soluble and oil-soluble sulfur compounds. The oil-soluble compounds, including diallyl sulfide, diallyl disulfide (DADS), diallyl trisulfide and ajoene, are more effective potential anti-cancer treatments than the water-soluble compounds. There are several studies examining the effects of oil-soluble compounds on various types of cancer cells, although, to the best of our knowledge, there are no studies examining the effects of these compounds on glioma cells. The aim of the present study was to investigate the potential anti-glioma properties of DAD and garlic oil on proliferation and induction of apoptosis in four different types of glioma cell lines representative of different grades of the disease. The results showed that garlic oil exhibits favorable anti-cancer potential towards gliomas of various degrees of differentiation.

We re-examined the antioxidative mechanism of allicin as a radical scavenger on the basis of the reactivity toward 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and peroxyl radicals. Initially, it was found that allicin decomposed more rapidly in n-hexane and chlorobenzene than in acetonitrile, ethanol, and ethanol/water solutions and decomposed into ajoene and vinyldithiins in these solvents. Furthermore, the decomposition of allicin and the following formations of ajoene and vinyldithiins from allicin were accelerated by the reaction of allicin with DPPH and peroxyl radicals. These results show that 2-propenesulfenic acid, which arises by Cope elimination from allicin, is proposed to contribute to scavenge these radicals because ajoene and vinyldithiins were produced from allicin through the use of 2-propenesulfenic acid. Next, allicin was more effective at inhibiting the linoleic acid oxidation at 50 °C than at 30 °C and in cyclohexane than in acetonitrile. These results indicate that allicin decomposed rapidly at high temperatures in a hydrogen-bond-acceptor solution to 2-propenesulfenic acid. In addition, 2-propene-1-sulfinothionic acid S-methyl ester, which does not produce sulfenic acid through Cope elimination, has no activity against the radicals. On the other hand, methanesulfinothionic acid S-2-propenyl ester, which produces methanesulfenic acid through Cope elimination, has the same or increased activity as its allicin against the radicals. Based on these results, the Cope elimination product, sulfenic acid, from thiosulfinates with an α-sulfenyl proton was found to make a larger contribution to the radical scavenger than that of allicin itself. PRACTICAL APPLICATION We examined the antioxidant activity of allicin on the oxidation of cumene and linoleic acid in homogeneous solutions. It is obvious from these results that 2-propenesulfenic acid was found to make a larger contribution to the radical scavenger than that of allicin itself.

Garlic (Allium sativum) is an essential vegetable that has been widely utilized as seasoning, flavoring, culinary and in herbal remedies. Garlic contains several characteristic organosulfur compounds, such as diallyl sulfide, allicin (diallyl thiosulphate), γ-glutamylcysteine, and S-allyl cysteine (alliin) and ajoene, which garlic has beneficial effects on inflammation, oxidative stress markers, hypertension, hyperlipidaemia and endothelial functionin vitroor in animal model. These bioactive molecules are also playing pivotal role in livestock and fisheries production apart from its application in humans. Supplementation of animal feed with garlic and its related products is consistent with the modern agricultural concept of organic animal husbandry. This review compiles the information describing the effects of feeding garlic and its extracts on selected performance parameters in animals (chicken, rabbits, ruminants, pigs and fish). This review may provide reference for scientists and entrepreneurs to investigate the applications of feeds added with garlic and allicin by-products for the improvement of animal husbandry and aquatic production.

Ajoene, a garlic-derived sulfur-containing compound, has broad-spectrum antimicrobial activity. To assess the potential of ajoene for treating tuberculosis (TB), we determined whether it induces the stress response of the endoplasmic reticulum (ER), which plays an important role in TB. We showed that ajoene stimulation induced the production of ER stress sensor molecules and reactive oxygen species (ROS) levels. Ajoene-induced ROS production was dependent on c-Jun N-terminal kinase (JNK) activation. Interestingly, the inhibition of JNK activity and suppression of ROS production reduced ajoene-induced CHOP production in macrophages. Because ER stress activates autophagy, the activation of which suppresses the growth of mycobacteria, we investigated the ajoene-induced production of autophagy-related factors, including LC3-II, P62 and Beclin-1. As expected, ajoene treatment increased the levels of these factors in RAW 264.7 cells. Remarkably, the total amount of Mycobacterium tuberculosis (Mtb) H37Rv was significantly reduced in ajoene-treated RAW 264.7 cells. The treatment of macrophages with ajoene resulted in the activation of JNK, induction of ROS synthesis and accumulation of ROS, possibly leading to the activation of ER stress and autophagy. These results reveal the mechanism of the antimycobacterial effects of ajoene against Mtb H37Rv. Our findings might facilitate the development of novel therapies for patients with TB.

Fil: Ramirez, Daniela Andrea. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mendoza. Instituto Argentino de Nivologia, Glaciologia y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivologia, Glaciologia y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivologia, Glaciologia y Ciencias Ambientales; Argentina

Allium vegetables are highly nutritional, its dietary use improves digestion and mental health and lower down cholesterol level. Use of onions, garlic, scallions, chives and leeks show therapeutic efficacy against cardiovascular disease, hyperglycemia, and stomach cancer, Onions contain allylsulfides and flavonoids particularly quercetin that is an important anti-oxidative and reduces hepatocytes apoptosis in streptozotocin-induced diabetic rat. Steroid saponins and sapogenins present in garlic bulbs are used to prepare soft soaps. I²-chlorogenin is a characteristic steroid sapogenin from garlic that is used for skin ointment and as a shiner. Both garlic paste and soft garlic preparations are used for flavoring the food items. Garlic products that contain the most safe, effective, stable, and odorless components are the most valuable as dietary supplements. Garlic also contains non sulfur compounds such as steroid saponins. Alliums showed antimicrobial, antithrombotic, antitumor, anti-hyperlipidaemic, antiarthritic, anti-hyperglycemic anticarcinogenic potential. Allium vegetables contain organosulfur compounds, including DATS, diallyl disulfide (DADS), ajoene, and S-allylmercaptocysteine (SAMC), have been found to induce cell cycle arrest in cancer cells. Alliums have great ethnomedicinal importance as these are used as native remedies against wide spectrum of diseases including diabetes. Allium origin natural products are of great therapeutic and dietary use. These are most preferred items used by nutritionists, physicians, food technologists, food chemists. Green allium vegetables are good source of natural pharmaceutics which are good for health and act against nutritionally induced acute and chronic diseases. Their possible inclusion in diets could explore new therapeutic avenues to enhance immunity against diseases.

The Ebers papyrus mentions external application of garlic for indurations. Hippocrates prescribed eating garlic as treatment for uterine tumors, and Dioscorides as official physician of the Roman army specified garlic for intestinal and lung disorders occurring among Roman troops in Asia. A preparation of garlic and vinegar known as the Four Thieves was credited with protecting citizens of Marseilles when plague struck in 1722. Louis Pasteur reported antibacterial activity of garlic in 1858. The Hindus consider it to be tonic, hot, digestive, aperients, cholagogue, and alterative; useful in cough, and phlegmatic affections, fever, swellings, gonorrhea, piles, leprosy, colic, rheumatism and worms. In the Raja Nirgantha it is described under the name of Rasona, and bears many synonyms indicative of its properties, such as Ugra-gandha (strong smelling), Mahanshadha (panacea), and Bhuta-ghna (destroying demons), and Lasuna. Epidemiological studies indicate that consumption of garlic is inversely associated with cancer risk. In Chinese medicine, garlic, known as Dasuan, is credited as vital-energy-stimulant, spleen- and stomach-warming, digestant, anti-inflammatory, detoxicant, and anthelmintic. Sulfur-containing compounds, the odoriferous substances in garlic are principally made of diallyl disulphide, together with smaller quantities of diallyl trisulphide and diallyl polysulphide. Allin serves as the precursor of alliin, allicin, diallylsulphide and ajoene. When garlic bulb is crushed, alliin present in fresh garlic is converted by the enzyme alliin lyase or alliinase into allicin. Allicin and diallyl disulphide combine to form ajoene, the diallyl disulphide being formed from allicin by heat. Allicin, a water-soluble substance, is responsible for the strong characteristic odor of garlic, is the major potent platelet antiaggregator, and is active against Gram-positive and Gram-negative bacteria, as well as against acid fast organisms. Garlic extracts have shown anticancer, antiatherogenic, antibacterial, blood cholesterol lowering, fibrinolytic, and platelet antiaggregation activities. Garlic oil inhibits human platelet aggregation by interfering with TXB2 synthesis. Meta-analyses of clinical studies agree that garlic supplementation, especially aged garlic, reduces both SBP and DBP in hypertensive patients, reduces TC and LDL-C, decreases platelet aggregation, prevents LPO of oxidized erythrocytes and LDL, increases antioxidant status, stimulates immune system, and exhibits anticancer activity.

Obesity is a chronic condition of excess body fat accumulated, which can cause interference healthy. Indonesian prevalence of obesity in 2018 is 31% and is predicted to increase annually. Obesity is caused by excess calories and sugar, which affect high 11β-HSD1 activity in sugar metabolism regulated by glucocorticoids; however, that activity can be inhibited by providing an 11β-HSD1 inhibitor. Alliin, allicin, and ajoene from single bulb garlic (Allium sativum) can inhibit 11β-HSD1. The present research aims to predict alliin, allicin, and ajoene as an 11β-HSD1 inhibitor for obesity drugs candidate using in silico method. The research was done by using physicochemical properties analysis, PA test, pharmacokinetics test, and molecular docking of alliin, allicin, ajoene, and control drug BVT-2733. The results showed that alliin, allicin, and ajoene have good oral bioavailability, antioxidant potential, lipoprotein disorders treatment, and lipid metabolism regulator. Based on pharmacokinetics test absorption, distribution and excretion are high, and the toxicity is low. The molecular docking shows the same binding site and amino acid residue with control drug BVT-2733. The type of bond formed is hydrogen and hydrophobic bond. This research concluded that single bulb garlic has the potential to be an oral drug candidate for treating obesity.

Allium plants, such as garlic, onion and leek have long been known to be effective in the therapy of infectious diseases. In particular, garlic has a greater antimicrobial activity than other Allium plants as it contains several hydrophobic antimicrobial compounds, such as allicin, vinyldithiins, ajoenes and diallyl polysulfides. Allicin is a characteristic sulfur-containing compound found in raw garlic produced from alliin and exhibits antimicrobial activity against both Gram-positive and Gram-negative bacteria. In addition, allicin has been reported to inhibit the biofilm formation of bacteria, which is a major cause of bacterial resistance to the antibiotic treatment of infections, by regulating quorum sensing in microorganisms. Other hydrophobic compounds also have similar inhibitory effects on bacteria as allicin. These biological properties of garlic-derived hydrophobic compounds can be used to enhance the effects of existing drugs and may thus be used in the treatment of infections, such as by preventing drug resistance through the inhibition of biofilm formation. In this review, we summarize the effects of hydrophobic compounds of garlic on bacteria.

Storey onion (Allium cepa L. var. proliferum Regel) is a variety of onion commonly grown in northern China that has not been researched in detail. This study aimed to identify the chemical compositions of storey onion aqueous extracts by UPLC-ESI-MS/MS, as well as characterize the antioxidant, antibacterial and cytotoxic activities, compared with welsh onion and onion. A total of 42 compounds were identified, among which the contents of organosulfur compounds (962.20 ± 34.55 μg/g), polyphenols (100.40 ± 12.55 μg/g) and organic acids (54.04 ± 2.69 μg/g) in storey onion were higher than those in welsh onion and onion. Additionally, the contents of cycloalliin (551.74 ± 8.12 μg/g), ajoene (159.31 ± 5.30 μg/g) and (E)-1-propene-1-sulfenic acid (72.12 ± 2.98 μg/g) in storey onion were the highest. Storey onion had pronounced DPPH• (IC50 = 1.24 ± 0.52 mg/mL) and OH• scavenging activities (IC50 = 14.45 ± 1.29 mg/mL) as well as ferric ion reducing power (absorbance from 0.32 to 2.21). Onion had the highest ABTS•+ scavenging activity (IC50 = 1.64 ± 0.64 mg/mL), while welsh onion had the lowest antioxidant activity. Storey onion had the strongest inhibitory effect on all the tested strains (MIC 31.3–125 mg/mL), and cell viability assays against human liver (HepG2) cancer cell lines also illustrated that aqueous extracts from storey onion significantly inhibited cell proliferation (when incubated for 24 h, IC50 = 33.21 ± 1.12 mg/mL) and induced cell apoptosis. Welsh onion and onion also had weaker antibacterial and anticancer activites, with those of onion being the weakest. The results showed that storey onion with excellent biological activity may benefit to human health and can be developed into functional foods.

Scope Garlic (Allium sativum) has been used for centuries as both a prophylactic and therapeutic medicinal agent to control inflammation-associated pathologies. To investigate the underlying mechanisms, we established an in vitro inflammatory model using RAW264.7 murine macrophages exposed to low-doses of lipopolysaccharide (LPS) in the presence of the garlic compounds allicin and Z-ajoene, mimicking regular garlic consumption. Methods and results Both allicin and Z-ajoene dampened both transcript and protein expression of the pro-inflammatory cytokines IL1β, IL6 and IL12β, and upregulated the expression of the anti-inflammatory cytokine IL10. Protein arrays of selected secreted inflammatory mediators confirmed that Z-ajoene has a pronounced down-regulatory effect on LPS-induced inflammatory cytokines and chemokines. Many of these proteins are known targets of the transcription factor STAT3; and indeed, Z-ajoene or its analogue dansyl-ajoene (DP) was found to decrease the phosphorylation and nuclear translocation of STAT3, and to covalently modify the protein by S-thiolation at Cys108, Cys367 and Cys687. It was further found that Z-ajoene dose-dependently and non-competitively inhibited the activity of COX2, possibly attributed to S-thiolation at Cys9 and Cys299. Conclusion The characterisation of Z-ajoene's activity of targeting and covalently modifying STAT3 and COX2, both important regulators of inflammation, may contribute to the health benefits of regular dietary garlic consumption. This article is protected by copyright. All rights reserved.

Allium sativum (garlic) is widely known and is consumed as a natural prophylactic worldwide. It produces more than 200 identified chemical compounds, with more than 20 different kinds of sulfide compounds. The sulfide compounds particularly are proven to contribute to its various biological roles and pharmacological properties such as antimicrobial, antithrombotic, hypoglycemic, antitumour, and hypolipidemic. Therefore, it is often referred as disease-preventive food. Sulphur-containing compounds from A. sativum are derivatives of S-alkenyl-l-cysteine sulfoxides, ajoene molecules, thiosulfinates, sulfides, and S-allylcysteine. This review presents an overview of the water-soluble and oil-soluble sulphur based phytochemical compounds present in garlic, highlighting their mechanism of action in treating various health conditions. However, its role as a therapeutic agent should be extensively studied as it depends on factors such as the effective dosage and the suitable method of preparation.

Natural resources such as plants are an upright curing option in treating cancers and reducing the side effects of current therapeutic modalities. Allium genus vegetables are of the most interesting herbs in restricting cancers that includes garlic, onions, leeks, chives, and shallots. These plants have been exploited in folk medicine because of their beneficial health effects in improving numerous diseases. The phytochemical analysis of various Allium genus members showed that, to date, 16 species have proved potential anticancer properties due to the accumulation of various sulfur and organic compounds like S-allyl mercaptocysteine, quercetin, flavonoids, and ajoene. These compounds with various mechanisms such as hindering cell cycle, inhibiting signaling pathways, inducing apoptosis, and antioxidant activity interfere with diverse stages of formation, growth, differentiation, and metastasis of cancer cells. Similar to garlic and onion, other species have exhibited anticancer activities, so that active natural molecules extracted from them might serve as possible anticancer agents. Therefore, evaluating the main ingredients and studying their anticancer mechanisms are of great importance. In this review, we aim to summarize the available data on anticancer mechanisms of 16 species of Allium genus and their major compounds to assist further researches on the treatment and prevention of cancers.

Garlic (Allium sativum Linn), a member of Liliaceae family has been used in different cultures as foodstuffs and medicine. It possesses potent biological activities, i.e., anti-inflammatory, antidiabetic, anticancer, and anti-atherosclerotic properties that are accredited to the organosulfur compound (OSCs) as well as other phytochemicals content of garlic, viz., phenolic acids, flavonoids, thiosulfinates, and anthocyanins that either work alone or synergistically by complex mechanisms. Among all the dietary phytochemicals from A. sativum Linn, OSCs have been found to show greater effects against various metabolic disorders. Major OSCs from garlic owing to its high therapeutic and pharmacological properties are allicin, diallyl trisulfide (DAT), allyl methyl trisulfide, diallyl disulfide (DAD), ajoene, and many others. The current chapter summarizes the therapeutic efficacy of garlic and its bio-active OSCs against risk factor-mediated atherosclerotic cardiovascular diseases (ASCVD) via modulation of distinct molecular mechanisms, i.e., antioxidant potential, lipid and lipoprotein metabolism, HDL functionality through paraoxonase-1 (PON-1) activity, HMG-CoA reductase (HMG-R) expression and functionality, LDL-receptor (LDL-R), LDL oxidation status, effects on macrophage, foam cell formation and plaque stabilization, inflammatory signalling pathways and hypertension, etc. We also hypothesized that garlic and its OSCs could be beneficial in targeting proprotein convertase subtilisin/kexin type-9 (PCSK-9) and LDL-R pathway in order to treat and manage hypercholesterolemia especially for the patients facing inadequate lipid lowering with classical HMG-R inhibitors (statins) and statin intolerance. Finally to sum up the whole, we conclude that the garlic and its OSCs may be promoted from alternative to mainstream medicine in targeting risk factor-mediated ASCVD.

Aberrant activation of a Wnt/β-catenin pathway results in nuclear accumulation of β-catenin in colon cancer. Inhibiting β-catenin is one strategy for treating colon cancer. Here, we identified Z-ajoene, a sulfur containing compound isolated from crushed garlic, as an inhibitor of colon cancer cell growth. Z-Ajoene repressed β-catenin response transcriptional activity, intracellular β-catenin levels, and its representative target protein levels (c-Myc and cyclin D1) in SW480 colon cancer cells. To clarify the regulatory mechanism of decreased β-catenin levels, we examined the effect of Z-ajoene on β-catenin phosphorylation, which is involved in β-catenin degradation. Z-Ajoene promoted the phosphorylation of β-catenin at Ser45 in a casein kinase 1α (CK1α)-dependent manner, which is an essential step in β-catenin degradation in the cytosol. These findings indicate that Z-ajoene from garlic may be a potential chemotherapeutic agent by modulating CK1α activity and the Wnt/β-catenin signaling pathway.

Sulfur-containing compounds, allicin and ajoene, etc., were isolated from Allium species. In a recent study, some sulfur-containing cyclic compounds were isolated from A. sativum, A. cepa, and A. fistulosum. Four new compounds with multiple rings with methyl disulfide or propyl disulfide at the side chain of the 7-position, kujounins A3 (1), B1 (2), B2 (3) and B3 (4), and two new thiolane type compounds with methoxy and methyl sulfoxide moiety at the 2- and 5-positions, and allium sulfoxides A2 (5) and A3 (6), were isolated from the acetone extract of the fresh white parts of Allium fistulosum 'Kujou' with three known compounds, kujounin A1 (7) and A2 (8), and allium sulfoxide A1 (9). The chemical structures of the new compounds were elucidated on the basis of physicochemical evidence. The kujounins had a rare molecular skeleton, which was tetrahydro-2H-difuro[3,2-b:2',3'-c]furan-5(5aH)-one.

Ajoene, a garlic-derived organosulfur compound, exerts anti-tumorigenic effect against various cancers. However, little is known about the biological effect of ajoene on lung adenocarcinoma, an aggressive malignancy with dismal prognosis. We investigated the biological effect of ajoene on lung adenocarcinoma and the underlying pathway. Lung adenocarcinoma cells A549, NCI-H1373, and NCI-H1395, along with the noncancerous lung bronchus cells BEAS-2B, were used. MTT test showed that ajoene (25 μM) reduces viability of lung adenocarcinoma cells but not the noncancerous BEAS-2B cells. Bromodeoxyuridine incorporation assay revealed that ajoene inhibits proliferation of lung adenocarcinoma cells. Treatment of lung adenocarcinoma cells with ajoene enhances apoptosis and ROS generation in a time- and dose-dependent fashion. Abrogation of caspase activation by zVAD-fmk completely prevents the ajoene-induced apoptosis; whereas block of ROS generation by N-acetylcysteine partly abolishes the ajoene-induced apoptosis. ROS-mediated induction of apoptosis contributes partially to the anti-tumorigenic property of ajoene observed, a phenomenon also confirmed by xenograft tumor study. Mitogen activated protein kinases (MAPKs), pivots of ROS-mediated signaling pathway, are activated upon ajoene treatment; Jun-N-terminal kinase (JNK)/p38 activations are required for signaling pathway underlying the ajoene-induced apoptosis. Our results suggest that ROS-mediated activation of JNK/p38 contributes partially to the pro-apoptotic action of ajoene on cells of lung adenocarcinoma. Ajoene may be a promising chemotherapeutic agent for lung adenocarcinoma.

Ajoene is a natural allylsulfur compound found in crushed garlic that arrests growth and induces apoptosis in cancer cells. To gain mechanistic insights into the cytotoxicity of ajoene in cancer cells, two fluorescently labelled ajoene analogs with dansyl- (DP) and fluorescein- (FOX) tags were synthesized. The tagged ajoenes were found to retain their activity at inhibiting proliferation and inducing apoptosis in MDA-MB-231 human breast-cancer and WHCO1 human esophageal-cancer cells. Both tagged ajoenes localized to the endoplasmic reticulum (ER) in MDA-MB-231 cells as observed by live cell confocal laser scanning microscopy (CLSM) and confirmed by generating an MDA-MB-231 cell line expressing yellow fluorescent protein (YFP) in the ER. DP appears to S-thiolate multiple protein targets in MDA-MB-231 cells as observed by immunoblotting under non-reducing conditions only; and a competition assay demonstrated that DP and Z-ajoene in fact share the same target. Ajoene S-thiolation interfered with protein folding and led to an accumulation of misfolded protein aggregates and activated the unfolded protein response (UPR). Consistent with this mechanism, increased levels of GRP78 and total ubiquitinated proteins were observed; and an ER-folded protein, type-1 collagen, was tracked to the proteasome following ajoene treatment. The intracellular protein aggregates were observed by CLSM and transmission electron microscopy (TEM). This is the first time that ajoene has been shown to target protein folding in the ER of cancer cells. © 2015 Wiley Periodicals, Inc.

Allium sativum (garlic) is well-known plant throughout the world as a food or flavor additive but also for its medicinal properties. Validating ethnobotanical uses of a plant is vital in understanding the mechanism of the plant extract and compounds, it is also important in the development of the plant into medicinal products. Multiple in vitro and in vivo studies have been conducted. In this chapter, the authors summarize some of the various results obtained, related to the biological activities associated with garlic. These studies are linked to all kinds of diseases and ailments. Garlic is chemically diverse with many compounds being isolated from it and tested. Allicin, diallyl sulfides, and ajoene are probably the most studied compounds from garlic. These compounds have shown great antibacterial activities against Gram-positive and Gram-negative bacteria. This chapter discusses the beneficial effect of garlic's nutritional value, antibacterial activity, cardiovascular effect, immune stimulation, as well as its effect on cancer.

For the last decade, chemical control of bacterial virulence has received considerable attention. Ajoene, a sulfur-rich molecule from garlic has been shown to reduce expression of key quorum sensing regulated virulence factors in the opportunistic pathogen Pseudomonas aeruginosa. Here we show that the repressing effect of ajoene on quorum sensing occurs by inhibition of small regulatory RNAs (sRNA) in P. aeruginosa as well as in Staphylococcus aureus, another important human pathogen that employs quorum sensing to control virulence gene expression. Using various reporter constructs, we found that ajoene lowered expression of the sRNAs RsmY and RsmZ in P. aeruginosa and the small dual-function regulatory RNA, RNAIII in S. aureus, that controls expression of key virulence factors. We confirmed the modulation of RNAIII by RNA sequencing and found that the expression of many QS regulated genes encoding virulence factors such as hemolysins and proteases were lowered in the presence of ajoene in S. aureus. Importantly, our findings show that sRNAs across bacterial species potentially may qualify as targets of anti-virulence therapy and that ajoene could be a lead structure in search of broad-spectrum compounds transcending the Gram negative-positive borderline.

Garlic is a food and medicinal plant that has been used in folk medicine since ancient times for its beneficial health effects, which include protection against cancer. Crushed garlic cloves contain an array of small sulfur-rich compounds such as ajoene. Ajoene is able to interfere with biological processes and is cytotoxic to cancer cells in the low micromolar range. BisPMB is a synthetic ajoene analogue that has been shown in our laboratory to have superior cytotoxicity to ajoene. In the current study we have performed a DNA microarray analysis of bisPMB-treated WHCO1 oesophageal cancer cells to identify pathways and processes that are affected by bisPMB. The most significantly enriched biological pathways as assessed by gene ontology, KEGG and ingenuity pathway analysis were those involving protein processing in the endoplasmic reticulum (ER) and the unfolded protein response. In support of these pathways, bisPMB was found to inhibit global protein synthesis and lead to increased levels of ubiquitinated proteins. BisPMB also induced alternate splicing of the transcription factor XBP-1; increased the expression of the ER stress sensor GRP78 and induced expression of the ER stress marker CHOP/GADD153. CHOP expression was found to be central to the cytotoxicity of bisPMB as its silencing with siRNA rendered the cells resistant to bisPMB. The MAPK proteins, JNK and ERK1/2 were activated following bisPMB treatment. However JNK activation was not critical in the cytotoxicity of bisPMB, and ERK1/2 activation was found to play a pro-survival role. Overall the ajoene analogue bisPMB appears to induce cytotoxicity in WHCO1 cells by activating the unfolded protein response through CHOP/GADD153.

The optimum conditions for the formation of E- and Z-ajoene from garlic juice mixed with soybean oil were determined using response surface methodology. A central composite design was used to investigate the effects of three independent variables temperature (°C, X 1), reaction time (hours, X 2), and oil volume (multiplied by weight, X 3). The dependent variables were Z-ajoene (Y 1) and E-ajoene (Y 2) in oil-macerated garlic. The optimal conditions for E- and Z-ajoene using ridge analysis were 98.80°C, 6.87 h, and weight multiplied by weight 2.57, and 42.24°C, 9.71 h, and weight multiplied by weight 3.08, respectively. These conditions resulted in E- and Z-ajoene compound predicted values of 234.17 and 752.62 μg/g from garlic juice, respectively. The experimental values of E- and Z-ajoene were 222.75 and 833.59 μg/g, respectively. The estimated maximum values at the predicted optimum conditions were in good agreement with experimental values.

Numerous gram-negative phytopathogenic and zoopathogenic bacteria utilise acylated homoserine lactone (AHL) in communication systems, referred to as quorum sensing (QS), for induction of virulence factors and biofilm development. This phenomenon positions AHL-mediated QS as an attractive target for anti-infective therapy. This review focused on the most significant groups of plant-derived QS inhibitors and well-studied individual compounds for which in silico, in vitro and in vivo studies provide substantial knowledge about their modes of anti-QS activity. The current data about sulfur-containing compounds, monoterpenes and monoterpenoids, phenylpropanoids, benzoic acid derivatives, diarylheptanoids, coumarins, flavonoids and tannins were summarized; their plant sources, anti-QS effects and bioactivity mechanisms have also been summarized and discussed. Three variants of plant-derived molecules anti-QS strategies are proposed: (i) specific, via binding with LuxI-type AHL synthases and/or LuxR-type AHL receptor proteins, which have been shown for terpenes (carvacrol and l-carvone), phenylpropanoids (cinnamaldehyde and eugenol), flavonoid quercetin and ellagitannins; (ii) non-specific, by affecting the QS-related intracellular regulatory pathways by lowering regulatory small RNA expression (sulphur-containing compounds ajoene and iberin) or c-di-GMP metabolism reduction (coumarin); and (iii) indirect, via alteration of metabolic pathways involved in QS-dependent processes (vanillic acid and curcumin).

The presentation discusses two themes of current interest in my research group in conjunction with a garlic mimics program. The first involves a new one-pot methodology for preparing unsymmetrical disulfides in high yield using 1-chlorobenzotriazole (BtCl) as oxidant, which can be applied to a range of functional types. The second part of the lecture will discuss the synthesis of derivatives of the garlic-derived natural product ajoene, in conjunction with an anti-cancer screening program. The synthesis has been used to prepare a fluorescently tagged derivative of the natural product that has been used to investigate localization and mode of action within the cancer cell using confocal laser scanning microscopy.

The DataChip is a universal platform for three-dimensional (3D) cell cultures on a micropillar chip, which can be applicable to a variety of human cells to simulate organ-specific toxicity. In addition, the MetaChip is developed for various combinations of drug metabolizing enzymes that can be spotted into the microwell chip and incubated with 3D human cells to simulate systematic compound metabolism in the human liver on a microscale format. Ajoenes have been known for various therapeutics activities, including anticancer effects, but there was limited information available in regard to their metabolism and cytotoxicity. In the present work, the metabolism-mediated toxicity of ajoenes was evaluated on a DataChip/MetaChip platform. In detail, we tested cytotoxicity of E- and Z-ajoene on 3D cultured Hep3B human hepatoma cells coupled with mixtures of drug metabolizing enzymes. Metabolic profiles of ajoenes were assessed with 23 representative drug metabolizing enzymes on the MetaChip. As a result, cytotoxicity of E-ajoene was significantly augmented in the presence of cytochrome P450 (CYP) isoforms, such as CYP2E1 and CYP3A5. Both E- and Z-ajoene were drastically detoxified in the presence of Phase II enzymes, including major UGTs, SULTs, NATs, and GSTs. Interestingly, All Mix, an artificial human liver microsome containing representative P450 mixture and phase II enzyme mixture, attenuated P450-induced cytotoxicity of ajoenes. Conclusively, we were able to confirm the metabolism-medicated toxicity of ajoenes on the chip.

Garlic is a commonly known vegetable, which is used for preparing various dishes around the world. This plant is widely used as a herb in medicine. Garlic contains many bioactive compounds mainly sulfur derivatives allicin, ajoene, diallyl sulfide, diallyl disulfide and diallyl trisulfide but is also a source of vitamins E, C, minerals and polyphenols. Its chemical composition and antioxidant properties are still under research. Numerous scientific studies have shown that garlic may be used in the prevention and treatment of many diseases e.g.: atherosclerosis, myocardial infarction, cancer, bacterial, viral and fungal infections, and as a treatment for colds and digestive problems. Unlike antibiotics, garlic does not weaken the immune system but promotes it. It stimulates humoral and cell responses of the immune system. Its healthy properties are mainly due to strong antioxidant activity. The aim of this review is to present recent data on the healthy properties of garlic.

Recent researches demonstrated the potential of phytochemicals to prevent and to counteract obesity. Multiple combinations of phytochemicals can result in a synergistic activity that increases their bioavailability and action on multiple molecular targets, offering advantages over chemical treatments. Herbal-derived compounds have potential for controlling appetite, inhibiting pancreatic lipase activity, stimulating thermogenesis and lipid metabolism, promoting lipolysis and adipogenesis, and inducing apoptosis in adipocytes. Appetite reduction and inhibiting pancreatic lipase activity represent the first line in the regulation of body weight. Stimulating lipolysis and thermogenesis represents an essential target for the development of anti-obesity drugs. Furthermore, targeting adipocyte life cycle using various dietary bioactives that affects different stages of adipocyte life cycle represents also an important target for the development of new anti-obesity drugs. In this regard, different stages of adipocyte development that are targeted by anti-obesity drugs can include preadipocytes, maturing preadipocytes, and mature adipocytes. Various herbal-derived active compounds, such as genistein, daidzein, cyanidin, proanthocyanidin, xanthohumol, apigenin and luteolin, kaempferol, myricetin, quercetin, epigallocatechin gallate, conjugated linoleic acid, docosahexaenoic acid, quercetin, resveratrol, and ajoene, affect adipocytes during specific stages of development, resulting in either the induction of apoptosis or inhibition of adipogenesis. Although numerous molecular targets that can be used for both treatment and prevention of obesity have been identified, targeted single cellular receptor or pathway has resulted in limited success. Therefore, targeting several cellular pathways simultaneously with multiple phytochemicals to achieve synergistic effects might be an appropriate approach in the management of obesity.

Multidrug resistance (MDR) caused by P-glycoprotein (P-gp) overexpression impedes successful cancer chemotherapy. In this study, we investigated the anticancer effects of SPA3015, a synthetic ajoene analog, in P-gp-overexpressing MDR cancer cells (KBV20C and MES-SA/DX5). Treatment with SPA3015 caused a dramatic decrease in the cell viabilities of both KBV20C and MES-SA/DX5 cells. This decrease was accompanied by apoptotic cell death without affecting the expression level or drug efflux function of P-gp. SPA3015 selectively suppressed NF-κB reporter gene activity, which led to decreased expression of NF-κB target genes such as CIAP1, CIAP2, XIAP, and Bcl-XL. Surprisingly, nuclear localization and DNA binding affinity of the p65 subunit were not affected by SPA3015, suggesting that SPA3015 inhibits the transcriptional activity of NF-κB at the nucleus. Indeed, SPA3015 treatment led to an increase in the physical interaction of p65 with PPARγ, which resulted in the inhibition of NF-κB activity. Our findings support the hypothesis that SPA3015 inhibits NF-κB transcriptional activity by facilitating the physical interaction of the p65 subunit and PPARγ, which leads to apoptotic cell death in MDR cancer cells.