539-86-6Relevant articles and documents
Analysis of responses of allicin, a compound from garlic, in the pulmonary vascular bed of the cat and in the rat
Kaye, Alan D.,Nossaman, Bobby D.,Ibrahim, Ikhlass N.,Feng, Chang J.,McNamara, Dennis B.,et al.
, p. 21 - 26 (1995)
Allicin, diallyl disulfide-oxide, an active ingredient released from garlic is a systemic vasodilator that acts by an unknown mechanism. In the present experiments, pulmonary vascular responses to allicin (0.1-1.0 mg) were studied in the intact-chest anesthetized cat and in the isolated lung of the rat under constant flow conditions. When baseline tone in the pulmonary vascular bed of the cat was raised with U46619 (11α,9α-epoxymethano-9α,11β-dideoxyprostaglandin F2α), intralobar injections of allicin produced dose-related decreases in pulmonary arterial pressure without changing left atrial pressure indicating that allicin had significant vasodilator activity in the pulmonary vascular bed when tone was increased experimentally. Allicin also decreased systemic arterial pressure in a dose-related manner. In terms of relative vasodilator activity in the cat, allicin was 100-fold less potent than sodium nitroprusside and many orders of magnitude less potent than isoproterenol. In the cat, vasodilator responses to allicin were unchanged by methylene blue or Nω-nitro-L-arginine methyl ester. Allicin also significantly diminished the pulmonary pressor response to ventilatory hypoxia in the isolated perfused rat lung. These data show that allicin has significant vasodilator activity in the pulmonary vascular bed of the cat and the rat. The present data suggest that pulmonary vasodilator responses to allicin are independent of the synthesis of endothelial-derived relaxing factor or the activation of soluble guanylate cyclase.
An optimized facile procedure to synthesize and purify allicin
Albrecht, Frank,Leontiev, Roman,Jacob, Claus,Slusarenko, Alan J.
, (2017)
Allicin is a reactive sulfur species (RSS) and defence substance from garlic (Allium sativum L.). The compound is a broad-spectrum antibiotic that is also effective against multiple drug resistant (MDR) strains. A detailed protocol for allicin synthesis based on diallyl-disulfide (DADS) oxidation by H2O2 using acetic acid as a catalyst was published in 2001 by Lawson and Wang. Here we report on improvements to this basic method, clarify the mechanism of the reaction and show that it is zero-order with respect to DADS and first-order with respect to the concentration of H2O2. The progress of allicin synthesis and the reaction mechanism were analyzsd by high-performance liquid chromatography (HPLC) and the identity and purity of the products was verified with LC-MS and 1H-NMR. We were able to obtain allicin of high purity (>98%) and >91% yield, with standard equipment available in any reasonable biological laboratory. This protocol will enable researchers to prepare and work with easily and cheaply prepared allicin of high quality.
Therapeutic effect and mechanism study of L-cysteine derivative 5P39 on LPS-induced acute lung injury in mice
He, Yanting,Zhao, Yalei,Feng, Yuchen,Ren, Anqi,Zhang, Yunyi,Wang, Yang,Li, Hong
, (2020)
Organosulfur compounds, such as L-cysteine, allicin and other sulfur-containing organic compounds in Allium species, have been proposed to possess many important physiological and pharmacological functions. A novel L-cysteine derivative, t-Butyl S-allylthio-L-cysteinate (5P39), was designed and synthesized by combining L-cysteine derivative and allicin pharmacophore through a disulfide bond. This study aimed to explore the effects and mechanisms of 5P39 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. At the experimental concentration (5, 10 and 20 μM), 5P39 suppressed the excessive secretion of nitric oxide (NO) and interleukin-6 (IL-6) in mice peritoneal macrophages stimulated by LPS. A mouse model of ALI was established by tracheal instillation of LPS for 2 h before 5P39 (30 and 60 mg/kg) administration. The results showed that 5P39 treatment down-regulated the wet/dry weight ratio (W/D ratio) of lungs and reduced the protein concentration, the number of total cells as well as the myeloperoxidase (MPO) activity in bronchoalveolar lavage fluid (BALF). 5P39 administration improved the histopathological changes of lungs in ALI mice with the decreased levels of pro-inflammatory cytokines in BALF. The inhibitory effects of 5P39 on the toll-like receptor 4 (TLR4) expression and macrophages accumulation in lung tissues were observed by immunohistochemistry. Additionally, 5P39 significantly attenuated the LPS-activated high expression of key proteins in TLR4/MyD88 signaling pathway. Taken together, the present study showed that 5P39 effectively alleviate the severity of ALI, and its mechanism might relate to the inhibition of LPS-activated TLR4/MyD88 signaling pathway, demonstrating a promising potential for further development into an anti-inflammatory drug candidate.
The beneficial effects of Allicin in chronic kidney disease are comparable to Losartan
García Trejo, Ehécatl Miguel ángel,Buendía, Abraham Said Arellano,Reyes, Omegar Sánchez,Arroyo, Fernando Enrique García,García, Raúl Arguello,Mendoza, María Lilia Loredo,Tapia, Edilia,Lozada, Laura Gabriela Sánchez,Alonso, Horacio Osorio
, (2017)
Recent studies suggest that allicin may play a role in chronic kidney disease (CKD), reducing hypertension and oxidative stress and improving renal dysfunction. In the present study, CKD was induced by 5/6 nephrectomy and the animals were divided into four treatment groups as follows: control (C), CKD, CKD+allicin (40 mg/kg pathway oral) (CKDA), and CKD+Losartan (20 mg/kg) (CKDL). After CKD induction, the rats developed hypertension from week 3 to the end of the study. This was associated with increased creatinine and blood urea nitrogen (BUN) levels in serum, increased albuminuria, increased urinary excretion of N-acetyl-β-D-glucosaminidase (NAG), increased nephrin expression, and incrased histological alterations in the cortex. The levels of angiotensin receptors and endothelial nitric oxide synthase (eNOS) were decreased in the renal cortex from the CKD group. Otherwise, lipid and protein oxidation were higher in the CKD group than in the control group. A disturbance was observed in the expression levels of the nuclear factor erythroid 2-related factor 2/Kelch ECH associating protein 1 system (Nrf2/keap1) and the antioxidant enzymes catalase, superoxide dismutase, and heme oxygenase-1. Allicin or losartan treatments relieved renal dysfunction, hypertension, and oxidative stress. In addition, both treatments showed the same efficacy on the expression of angiotensin receptors, the nephrin, Nrf2/keap1 pathway, and eNOS. Further in silico analyses suggest that allicin and losartan could have a common mechanism involving interaction with AT1 receptors. Allicin showed antihypertensive, antioxidant, and nephroprotective effects. The beneficial effects showed by allicin are similar, or even better, than those of losartan. In fact, the effect of allicin on blood pressure and renal function is comparable to reductions seen with losartan, a prescription drug commonly used as a first-line therapy.
Hypochlorous acid scavenging activities of thioallyl compounds from garlic
Argueello-Garcia, Raul,Medina-Campos, Omar N.,Perez-Hernandez, Nury,Pedraza-Chaverri, Jose,Ortega-Pierres, Guadalupe
, p. 11226 - 11233 (2010)
The hypochlorous acid (HOCl) scavenging capacities of 10 garlic compounds containing modifications in the thioallyl group (-S-CH2CH=CH 2) were determined by a catalase protection assay, and the corresponding structure-activity relationships using molecular descriptors were calculated. This scavenging activity was enhanced by increasing the number of S atoms or by the alanyl group (-CH2CH-NH2-COOH) and decreased in the absence of the C=C bond or in the presence of a sulfoxide group in the thioallyl group. Interestingly, S-allylcysteine and its corresponding sulfoxide (alliin) showed the highest and lowest HOCl-scavenging capacities, respectively. Quantitative modeling by multiple regression analysis and partial least-squares projections showed that the topological descriptor polar surface area and two electronic properties, namely, highest occupied molecular orbital and total energy, contributed mainly to variations in the HOCl scavenging activity of thioallyl compounds. These observations provide new insights on the antioxidant mechanism of garlic derivatives in processes involving HOCl production.
Garlic Chemistry: Stability of S-(2-Propenyl) 2-Propene-1-sulfinothioate (Allicin) in Blood, Solvents, and Simulated Physiological Fluids
Freeman, Fillmore,Kodera, Yukihiro
, p. 2332 - 2338 (1995)
S-(2-Propenyl) 2-propene-1-sulfinothioate (allicin), which is one of the constituents of freshly crushed garlic (garlic homogenate), was synthesized, and its stability in blood, ethyl acetate, methanol, simulated gastric fluid (SGF, pH 1.2), simulated intestinal fluid (SIF, pH 7.5), and water (pH 1.2 and 7.5) and under simulated digestive conditions (sequential combination of SGF and SIF) was investigated by HPLC.Although neat allicin decomposes rapidly at 37 deg C, it is more stable in protic polar methanol than in aprotic polar ethyl acetate.Approximately 90percent of the allicin remained after incubation at 37 deg C for 5 h in water at pH 1.2 and 7.5.Only traces of allicin could be detected after it was incubated in blood for 5 min.The allicin content and allicin-producing potential of commercial garlic preparations were also analyzed.The allicin contents in these garlic preparations were less than 1 ppm, and the allicin-producing potential was severely suppressed under simulated digestive conditions (sequential combination of SGF and SIF).The transformation products of allicin were identified.Keywords: (E)-Ajoene; allicin; allicin content; allicin-producing potential; allicin stability; garlic preparations; 2-ethenyl-4H-1,3-dithiin, diallyl disulfide; garlic products
Allium sativum extract chemical composition, antioxidant activity and antifungal effect against meyerozyma guilliermondii and rhodotorula mucilaginosa causing onychomycosis
Parvu, Marcel,Mo?, C?t?lin A.,Parvu, Alina E.,Mircea, Cristina,Stoeber, Leander,Ro?ca-Casian, Oana,?igu, Adrian B.
, (2019)
Onychomycosis is a major health problem due to its chronicity and resistance to therapy. Because some cases associate paronychia, any therapy must target the fungus and the inflammation. Medicinal plants represent an alternative for onychomycosis control. In the present work the antifungal and antioxidant activities of Alium sativum extract against Meyerozyma guilliermondii (Wick.) Kurtzman & M. Suzuki and Rhodotorula mucilaginosa (A. J?rg.) F.C. Harrison, isolated for the first time from a toenail onychomycosis case, were investigated. The fungal species were confirmed by DNA molecular analysis. A. sativum minimum inhibitory concentration (MIC) and ultrastructural effects were examined. At the MIC concentration (120 mg/mL) the micrographs indicated severe structural alterations with cell death. The antioxidant properties of the A. sativum extract were evaluated is a rat turpentine oil induced inflammation, and compared to an anti-inflammatory drug, diclofenac, and the main compound from the extract, allicin. A. sativum reduced serum total oxidative status, malondialdehyde and nitric oxide production, and increased total thiols. The effects were comparable to those of allicin and diclofenac. In conclusion, the garlic extract had antifungal effects against M. guilliermondii and R. mucilaginosa, and antioxidant effect in turpentine-induced inflammation. Together, the antifungal and antioxidant activities support that A. sativum is a potential alternative treatment in onychomycosis.
Antimalarial activity of allicin, a biologically active compound from garlic cloves
Coppi, Alida,Cabinian, Melissa,Mirelman, David,Sinnis, Photini
, p. 1731 - 1737 (2006)
The incidence of malaria is increasing, and there is an urgent need to identify new drug targets for both prophylaxis and chemotherapy. Potential new drug targets include Plasmodium proteases that play critical roles in the parasite life cycle. We have previously shown that the major surface protein of Plasmodium sporozoites, the circumsporozoite protein (CSP), is proteolytically processed by a parasite-derived cysteine protease, and this processing event is temporally associated with sporozoite invasion of host cells. E-64, a cysteine protease inhibitor, inhibits CSP processing and prevents invasion of host cells in vitro and in vivo. Here we tested allicin, a cysteine protease inhibitor found in garlic extracts, for its ability to inhibit malaria infection. At low concentrations, allicin was not toxic to either sporozoites or mammalian cells. At these concentrations, allicin inhibited CSP processing and prevented sporozoite invasion of host cells in vitro. In vivo, mice injected with allicin had decreased Plasmodium infections compared to controls. When sporozoites were treated with allicin before injection into mice, malaria infection was completely prevented. We also tested allicin on erythrocytic stages and found that a 4-day regimen of allicin administered either orally or intravenously significantly decreased parasitemias and increased the survival of infected mice by 10 days. Together, these experiments demonstrate that the same cysteine protease inhibitor can target two different life cycle stages in the vertebrate host. Copyright
Allicin induces thiol stress in bacteria through S-allylmercapto modification of protein cysteines
Müller, Alexandra,Eller, Jakob,Albrecht, Frank,Prochnow, Pascal,Kuhlmann, Katja,Bandow, Julia Elisabeth,Slusarenko, Alan John,Leichert, Lars Ingo Ole
, p. 11477 - 11490 (2016)
Allicin (diallyl thiosulfinate) from garlic is a highly potent natural antimicrobial substance. It inhibits growth of a variety of microorganisms, among them antibiotic-resistant strains. However, the precise mode of action of allicin is unknown. Here, we show that growth inhibition of Escherichia coli during allicin exposure coincides with a depletion of the glutathione pool and S-allylmercapto modification of proteins, resulting in overall decreased total sulfhydryl levels. This is accompanied by the induction of the oxidative and heat stress response. We identified and quantified the allicin-induced modification S-allylmercaptocysteine for a set of cytoplasmic proteins by using a combination of label-free mass spectrometry and differential isotope-coded affinity tag labeling of reduced and oxidized thiol residues. Activity of isocitrate lyase AceA, an S-allylmercapto-modified candidate protein, is largely inhibited by allicin treatment in vivo. Allicin-induced protein modifications trigger protein aggregation, which largely stabilizes RpoH and thereby induces the heat stress response. At sublethal concentrations, the heat stress response is crucial to overcome allicin stress. Our results indicate that the mode of action of allicin is a combination of a decrease of glutathione levels, unfolding stress, and inactivation of crucial metabolic enzymes through S-allylmercapto modification of cysteines.
Garlic: Source of the ultimate antioxidants - Sulfenic acids
Vaidya, Vipraja,Ingold, Keith U.,Pratt, Derek A.
, p. 157 - 160 (2009)
(Chemical Equation Presented) The medicinal properties of garlic, thought to derive at least in part from the antioxidant activity of its sulfur-containing secondary metabolites, have been recognized for hundreds of years. The ability of garlic to scavenge peroxyl radicals can be accounted for in terms of the action of transient sulfenic acids, which are predicted to react by diffusion-controlled five-center proton-coupled electron transfer (see scheme and transition state).
