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In vivo hydroxylation of the neurotoxin, 1-methyl-4-phenylpyridinium, and the effect of monoamine oxidase inhibitors: electrospray-MS analysis of intra-striatal microdialysates.

The neurotoxin 1-methyl-4-phenylpyridinium (MPP+) has been shown to increase hydroxyl radical formation in the striatum. The production of hydroxyl radicals correlates with the MPP(+)-driven dopamine release which presumably leads to increased metabolism via monoamine oxidase or increased dopamine autoxidation. Both processes result in enhanced production of hydrogen peroxide, which in the presence of iron(II) ions decomposes to the hydroxyl radical. Monoamine oxidase inhibitors decrease the production of hydroxyl radicals as measured by salicylate and 4-hydroxybenzoate trapping. As both MPP+ and monoamine oxidase inhibitors, such as deprenyl and MDL-72,974A, possess aromatic rings, hydroxyl radical adduct formation was investigated in vitro in defined Fenton systems and also in vivo using intra-striatal microdialysis to infuse MPP+ to rats pretreated systemically with either deprenyl or MDL-72,974A. Electrospray mass spectrometric analysis, using full-scan, fragment ion and constant neutral loss spectra, demonstrated ring hydroxylation of all three compounds in the Fenton systems. Spectral comparison of microdialysis samples with spectra from the Fenton reactions indicated the in vivo hydroxyl radical adduct attachment to MPP+, deprenyl and possibly MDL-72,974A.

1-Methyl-4-phenylpyridinium↗

Photodynamic properties of pyridoxal phosphate bound to cystathionase-gamma-lyase.

The cofactor pyridoxal phosphate bound through an aldimine linkage to lysine residues of the enzyme cystathionase (L-Cystathione cysteine-lyase (deaminating), EC 4.4.1.1) is very stable to irradiation with light of 420 nm. The catalytic function of the enzyme remains unaffected indicating that the cofactor is not an efficient photosensitizer of essential amino acid residues. This unusual stability of the cofactor to irradiation can be ascribed to the presence of aldimine linkages as demonstrated by studies conducted on model compounds. The binding of a reversible inhibitor (L-allylglycine) to the catalytic site of the enzyme does not facilitate photooxidation of the cofactor. On the contrary, irradiation of the cofactor in the presence of the inhibitor results in photodestruction of the inhibitor.

Allyl Compounds↗

Neuroprotective activity of honokiol and magnolol in cerebellar granule cell damage.

The aim of the present study was to investigate the neuroprotective effects of honokiol and magnolol, two major bioactive constituents of the bark of Magnolia officinalis, against neuron toxicity induced by glucose deprivation, excitatory amino acids and hydrogen peroxide (H(2)O(2)) in cultured rat cerebellar granule cells. Cell membrane damage was measured with a lactate dehydrogenase (LDH) release assay and 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to assess mitochondrial activity, reflecting cell survival. Results showed that honokiol and magnolol alone did not affect mitochondrial function and cell damage, but significantly reversed glucose deprivation-induced mitochondrial dysfunction and cell damage. The glutamate receptor blocker MK-801 and antioxidant vitamin E also provided protection against this damage. Furthermore, honokiol was more potent than magnolol in protecting against glutamate-, N-methyl-D-aspartate (NMDA)- and H(2)O(2)-induced mitochondrial dysfunction. These results demonstrated that the neuroprotective effects of honokiol and magnolol may be related to their anti-oxidative actions and antagonism of excitotoxicity induced by excitatory amino acids, suggesting that both compounds may be potential therapeutic agents for neurodegenerative diseases.

Animals↗

Improvement of scopolamine-induced memory impairment by Z-ajoene in the water maze in mice.

Z-ajoene, a major compound containing sulfur in oil-macerated garlic products, exhibited inhibitory effects against scopolamine-induced memory impairment in mice using the Morris water maze test. The effects of Z-ajoene were observed dose-dependently (0.25-25 mg/kg). At the highest dosage, the memory performance of mice was improved compared to normal mice. The acetylcholinesterase (AChE) activity in the brain was reduced by administration of Z-ajoene dose-dependently. However, alliin and diallyl disulfide, organosulfur compounds from garlic, did not improve memory performance nor AChE inhibitory effect. These results suggest that Z-ajoene may act on the cholinergic system and on memory impairment caused by excess activity of AChE.

Acetylcholinesterase↗

Effects of garlic oil on postmenopausal osteoporosis using ovariectomized rats: comparison with the effects of lovastatin and 17beta-estradiol.

The purpose of this study was to examine the antiosteoporosis effects of garlic oil in an ovariectomized (Ovx) rat model of osteoporosis and to compare its efficacy with lovastatin (a synthetic hypocholesterolemic drug) and 17beta-estradiol (a potent antiosteoporotic agent). Animals were divided into five groups: sham-operated control, ovariectomized, ovariectomized supplemented with lovastatin, ovariectomized supplemented with garlic oil and ovariectomized supplemented with 17beta-estradiol. In our study, the development of a high rate of bone turnover and osteoporosis in the ovariectomized animals were confirmed by significant alterations of serum alkaline phosphatase activity, serum tartrate-resistant acid phosphatase activity, urinary excretion of calcium, phosphate, hydroxyproline and urinary calcium to creatinine ratio, when compared with the sham-operated control group. Supplementation of these animals with either garlic oil or lovastatin or 17beta-estradiol, in addition to their hypocholesterolemic effect, could counterbalance all these changes. The results revealed that all three compounds significantly protected the hypogonadal bone loss as reflected by higher bone densities and higher bone mineral contents than the ovariectomized group of animals. The results emphasize that, like 17beta-estradiol, the hypocholesterolemic compounds garlic oil and lovastatin are also effective in suppressing bone loss owing to estrogen deficiency and their efficacy in the order of lower to higher is garlic < lovastatin < 17beta-estradiol.

Acid Phosphatase↗

Behavioural pharmacological characteristics of honokiol, an anxiolytic agent present in extracts of Magnolia bark, evaluated by an elevated plus-maze test in mice.

Honokiol, a neolignane derivative of Magnolia bark, has central depressant action and, at much lower doses, anxiolytic activity. We have investigated the characteristics of the behavioural effects of honokiol by means of an elevated plus-maze test. In the plus-maze test a single oral dose of 20 mg kg(-1) honokiol significantly prolonged the time spent in the open arms of the maze, suggesting anxiolytic effect. Moreover, when honokiol was administered daily for seven days and the plus-maze test was conducted 3 or 24 h after the last administration, significant prolongation of the time in the open arms was manifested even for doses of 0.2 mg kg(-1). The maximum effect was observed for doses of 0.5 mg kg(-1). Honokiol at any dose in both single and repeated administration schedules caused neither change in motor activity nor disruption of traction performance. Orally administered diazepam, 0.5-2 mg kg(-1), caused dose-dependent prolongation of the time spent in the open arms of the maze with a significant increase in motor activity at 1 mg kg(-1), and dose-dependent disruption of traction performance. The changes in the plus-maze performance after treatment for seven days with 0.2 mg kg(-1) honokiol and after a single treatment with 1 mg kg(-1) diazepam were almost equivalent. The effect of honokiol (0.2 mg kg(-1), treatment for seven days) was inhibited by subcutaneous flumazenil (0.3 mg kg(-1)) and (+)-bicuculline (0.1 mg kg(-1)) and by intraperitoneal CCK-4 (50 microg kg(-1)) and caffeine (30 mg kg(-1)). The anxiolytic effect of diazepam (1 mg kg(-1)) was also inhibited by flumazenil and bicuculline. However, the combined administration of diazepam with caffeine enhanced the effect, and diazepam completely reversed the effect of CCK-4. These results suggest that, in contrast with diazepam, honokiol selectively induces an anxiolytic effect with less liability of eliciting motor dysfunction and sedation or disinhibition. The combined effects of the drug also revealed that the mechanism of anxiolytic effect of honokiol is partially different from that of diazepam.

Administration, Oral↗

Oxyaniliniums as acetylcholinesterase inhibitors for the reversal of neuromuscular block.

A series of oxyanilinium-based AChE inhibitors have been synthesised and tested for the reversal of vecuronium-induced neuromuscular block. Several compounds, for example 2-hydroxy- and 2-methoxy-N,N-dimethyl-N-allylanilinium bromide (3 and 6) showed comparable reversal potencies to edrophonium and clean in vivo cardiovascular profiles.

Acetylcholinesterase↗

Garlic organosulfur compounds upregulate the expression of the pi class of glutathione S-transferase in rat primary hepatocytes.

The chemopreventive property of garlic is related in part to its induction of phase II detoxification enzymes. In the present study, we investigated the modulatory effect of 3 garlic organosulfur compounds, i.e., diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), which differ in their number of sulfur atoms, on the gene expression of the pi class of glutathione S-transferase (GSTP). Hepatocytes isolated from male Sprague-Dawley rats were cultured with 50-200 micromol/L of DAS, DADS, or DATS for 24 h. DADS and DATS increased GST activity toward ethacrynic acid by 40 and 66%, respectively (P < 0.05). Moreover, both garlic allyl sulfides dose dependently induced GSTP mRNA and protein expression. DATS increased the protein level more than DADS (P < 0.05). In contrast, DAS did not affect the activity or the protein or mRNA levels of this phase II drug-metabolizing enzyme. In Clone 9 liver cells, the pTA-luciferase reporter assay showed that luciferase activity in DADS- and DATS-treated cells was 2.8- and 3.9-fold higher than that in control cells, respectively (P < 0.05). Again, luciferase activity was not affected by treatment with DAS. Deletion of -2.7 to -2.6 kb in the GSTP promoter region, which contains the GSTP enhancer (GPE) I element, abolished the upregulation of GSTP transcription by DADS and DATS. Deletion of GPE II, however, did not affect the induction of reporter activity. In conclusion, the effectiveness of 3 garlic allyl sulfides on GSTP expression was related to the number of sulfur atoms in the molecules, and GPE I was responsible for this upregulation.

Allyl Compounds↗

Honokiol up-regulates prostacyclin synthease protein expression and inhibits endothelial cell apoptosis.

Honokiol is a bioactive compound extracted from the Chinese medicinal herb Magnolia officinalis. We recently demonstrated that honokiol inhibited arterial thrombosis through stimulation of prostacyclin (PGI2) generation and endothelial cell protection. The current study is designed to investigate its mechanism of stimulation of PGI2 generation and cell protection. 6-keto-PGF1alpha, the stable metabolite of PGI2, in the media of rat aortic endothelial cells was measured with radioimmunoassay kits. Indomethacin, an inhibitor of cyclooxygenase (COX) and tranylcypromine, a prostacyclin synthease inhibitor were used to ascertain the target enzyme affected by honokiol. Prostacyclin synthease protein levels in endothelial cells were determined by Western blot analysis using an anti-PGI2 synthease rabbit polyclonal antibody. Flow cytometry was used to quantify the apoptotic cells and spectrophotometry was used to test the caspase-3 activity. Honokiol (0.376-37.6 microM) increased the level of 6-keto-PGF1alpha in the media of normal endothelial cells. It counteracted the inhibitory effect of tranylcypromine on the PGI2 generation, but did not influence the effect of indomethacin; evidently, honokiol up-regulated the expression of prostacyclin synthease in the endothelial cells. These effects showed perfect concentration-dependent behavior. In addition, at lower concentration (0.376-3.76 microM), honokiol significantly decreased the percentage of apoptotic endothelial cells induced by oxidized low-density lipoprotein (ox-LDL) and significantly lowered the activity of caspase-3 stimulated by ox-LDL. A high dose of honokiol (37.6 microM), however, failed to influence either of them. In conclusion, honokiol augments PGI2 generation in normal endothelial cells; its effect on PGI2 generation attributes to up-regulation of prostacyclin synthease expression; its cell protection may be correlated with its inhibition on apoptosis of endothelial cells. These findings have partly revealed the molecular mechanism of honokiol on inhibiting arterial thrombosis.

Animals↗

Honokiol, a small molecular weight natural product, alleviates experimental mesangial proliferative glomerulonephritis.

Glomerulonephritis (GN) is still the most common cause of end-stage renal disease. Accumulation of glomerular macrophages, proliferation of mesangial cells, and deposition of extracellular matrix proteins are pathobiological hallmarks of GN. Pharmacological interventions that can inhibit these insults may be beneficial in the retardation of the progression of GN. Honokiol originally isolated from Magnolia officinalis, shows antioxidative, anti-inflammatory, and antiproliferative activities in a variety of inflammation models. In this study, we first investigated the in vivo effects of honokiol on rat anti-Thy1 nephritis. Anti-Thy1 nephritis was induced in Wistar rats by injecting mouse anti-rat Thy1 antibodies intravenously. Nephritic rats were randomly assigned to receive honokiol (2.5 mg/kg, twice a day) or vehicle and were killed at various time points. Glomerular histology and immunohistopathology and urine protein excretion were studied. Western blotting was conducted for markers of proliferation. Adhesion molecules, chemokine, and extracellular matrix gene expression were evaluated by Northern blotting. Honokiol-treated nephritic rats excreted less urinary protein and had lower glomerular cellularity and sclerosis. The increased intraglomerular proliferating cell nuclear antigen and Akt phosphorylation in nephritic rats could be abolished by the treatment of honokiol. Honokiol also alleviated glomerular monocyte chemoattractant protein-1 and intracellular adhesion molecule-1, similar to type I (alpha1) collagen and fibronectin mRNA levels of nephritic rats. These results indicate that honokiol may have therapeutic potential in mesangial proliferative GN.

Animals↗

Chemical release at the airport and lessons learned from the medical perspective.

The risk of massive exposure to toxic chemical substances including chemical weapons or industrial chemicals has increased especially during the last century due to the development in industry and chemistry science. This paper aims to describe a real chemical release event and further exposures to personnel working at the Esenboğa Airport, Ankara, Turkey, and to give lessons learned. This chemical release was noticed firstly by airport staff giving symptoms including nausea, vomiting, irritation of eyes, itching and rinorrhea. First responders from civil defense unit and a group of health staff including NBC First-aid and Rescue Team gave response to the incident. The increasing number of exposed or suspected cases transferred to hospital were isolated in Emergency Department (ED) following the decontamination at the airport. Due to the characteristic odour and the growing number of the victims, the releasing agent was considered to be likely cyanide or sulfur mustard. Because of the panic amongst the workers, the number of the exposed (real or suspected) people increased up to about 40 and were kept under observation in ED of the hospital. The chromotographic analysis revealed that the agent contained diallyl disulfide, an organo-sulfur compound present at very high concentrations in pure garlic oil. Blood results showed no cyanide and the isolation were terminated. Along with the lessons learned, incident showed that the health facilities should be prepared against such deliberate or accidental mass casualties.

Accidents↗

Abolition of the diethylstilbestrol reduction of enzyme leakage from muscle by a 3,3' diallyl substitution.

Diethylstilbestrol (DES) lowers enzyme efflux from isolated mouse skeletal muscle. It also lowers the high serum enzyme activities in Duchenne's muscular dystrophy. We have begun a systematic study of DES congeners, to identify those portions of the DES molecule which are critical to these effects, and to tailor a molecule which might have fewer feminizing effects. The first compound tested was the 3,3' diallyl derivative of DES (DAS). It was selected because previous reports indicated that it was as anabolic as DES, but only 1/10 to 1/30 as estrogenic. Doses of 20, 100 and 250 microgram/mouse/day were administered in 0.05 ml sesame seed oil vehicle to C57BL/6 mice. Control animals received only the vehicle. In contrast to DES which has consistently reduced muscle enzyme efflux 30-50%, DAS was inert. The substitution of the two allyl groups in the 3 and 3' positions blocks access to the neighboring ethyl groups and partially covers the two phenolic hydroxyl groups of DES. This suggests that these molecular sites have pertinence to the reduction of enzyme efflux from mouse skeletal muscle by DES, and possibly the reduction of the high serum enzyme activities in Duchenne's muscular dystrophy.

Allyl Compounds↗

Diallyl disulfide, a chemopreventive agent in garlic, induces multidrug resistance-associated protein 2 expression.

The organosulfur compounds (OSCs), present in garlic, are studied for their protective effect against human cancers. P-glycoprotein (P-gp) and multidrug resistance protein 2 (Mrp2) are two transporters involved in the defense of cells and in the development of multidrug resistance. Whereas OSCs increase glutathione S-transferase activity (GST), Mrp2 plays a role in the transport of glutathione (GSH)-conjugates. In this study, we have investigated the effect of two OSCs, diallyl disulfide (DADS) and S-allyl cysteine (SAC), on P-gp and Mrp2 expression in renal brush-border membranes. By Western blot analysis, our results show that DADS induces Mrp2 expression (by 7-fold), which correlates with the rise of GST activity and GSH levels. Surprisingly, a co-administration of OSC with cisplatin, an anticancer drug, significantly increased Mrp2 gene and protein expression (by 30-fold), suggesting that DADS could potentiate the effects of cisplatin. Interestingly, SAC and cisplatin in co-treatment decreased P-gp protein expression and mdr1b isoform mRNA levels. In addition, modulation of the mdr1b isoform and Mrp2 by cisplatin was completely abolished by a glutathione precursor, N-acetyl cysteine. These results indicate that OSCs present in a garlic-rich diet might alter chemotherapeutic treatments using P-gp or Mrp2 substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Cytosolic and microsomal epoxide hydrolases: differential properties in mammalian liver.

The epoxide hydrolase activities of the 100,000 g pellet (microsomal) and 100,00 g soluble (cystosolic) fractions of mouse, rat, and guinea pig liver were measured with three closely related compounds used as substrates. Differences between the species in the distribution of the cytosolic and microsomal hydrolases and in their substrate specificities and pH optima demonstrate why epoxide hydrolase activity in the cytosolic fraction was not detected earlier in spie of intensive work on the microsomal epoxide hydrolase.

Allyl Compounds↗

Protective effects of honokiol against oxidized LDL-induced cytotoxicity and adhesion molecule expression in endothelial cells.

Honokiol, a compound extracted from Chinese medicinal herb Magnolia officinalis, has several biological effects. However, its protective effects against endothelial injury remain unclarified. In this study, we examined whether honokiol prevented oxidized low-density lipoprotein (oxLDL)-induced vascular endothelial dysfunction. Incubation of oxLDL with honokiol (2.5-20 microM) inhibited copper-induced oxidative modification as demonstrated by diene formation, thiobarbituric acid reactive substances (TBARS) assay and electrophoretic mobility assay. Expression of adhesion molecules (ICAM, VCAM and E-selectin) and endothelial NO synthase (eNOS) affected by oxLDL was investigated by flow cytometry and Western blot. We also measured the production of reactive oxygen species (ROS) using the fluorescent probe 2',7'-dichlorofluorescein acetoxymethyl ester (DCF-AM). Furthermore, several apoptotic phenomena including increased cytosolic calcium, alteration of mitochondrial membrane potential, cytochrome c release and activation of caspase-3 were also investigated. Apoptotic cell death was characterized by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) stain. The results showed that honokiol prevented the copper-induced oxidative modification of LDL. Honokiol also ameliorated the oxLDL-diminished eNOS protein expression and reduced the oxLDL-induced adhesion molecules and the adherence of THP-1 cells to HUVECs. Furthermore, honokiol attenuated the oxLDL-induced cytotoxicity, apoptotic features, ROS generation, intracellular calcium accumulation and the subsequent mitochondrial membrane potential collapse, cytochrome c release and activation of caspase-3. Our results suggest that honokiol may have clinical implications in the prevention of atherosclerotic vascular disease.

Antioxidants↗

Honokiol causes the p21WAF1-mediated G(1)-phase arrest of the cell cycle through inducing p38 mitogen activated protein kinase in vascular smooth muscle cells.

Honokiol, an active component in extracts of Magnolia officinalis, has been proposed to play a role in anti-inflammatory, antioxidant activity, anti-angiogenic and anti-tumor activity. Although honokiol has a variety of pharmacological effects on certain cell types, its effects on vascular smooth muscle cells (VSMC) are unclear. This issue was investigated in the present study, honokiol was found to inhibit cell viability and DNA synthesis in cultured VSMC. These inhibitory effects were associated with G1 cell cycle arrest. Treatment with honokiol blocks the cell cycle in the G1 phase, down-regulates the expression of cyclins and CDKs and up-regulates the expression of p21WAF1, a CDK inhibitor. While honokiol did not up-regulate p27, it caused an increase in the promoter activity of the p21WAF1 gene. Immunoblot and deletion analysis of the p21WAF1 promoter showed that honokiol induced the expression of p21WAF1 and that this expression was independent of the p53 pathway. Furthermore, the honokiol-mediated signaling pathway involved in VSMC growth inhibition was examined. Among the relevant pathways, honokiol induced a marked activation of p38 MAP kinase and JNK. The expression of dominant negative p38 MAP kinase and SB203580, a p38 MAP kinase specific inhibitor, blocked the expression of honokiol-dependent p38 MAP kinase and p21WAF1. Consistently, blockade of p38 MAPK kinase function reversed honokiol-induced VSMC proliferation and cell cycle proteins. These data demonstrate that the p38 MAP kinase pathway participates in p21WAF1 induction, subsequently leading to a decrease in the levels of cyclin D1/CDK4 and cyclin E/CDK2 complexes and honokiol-dependent VSMC growth inhibition. In conclusion, these findings concerning the molecular mechanisms of honokiol in VSMC provides a theoretical basis for clinical approaches to the use therapeutic agents in treating atherosclerosis.

Antineoplastic Agents, Phytogenic↗

Regulation of cytochrome P450 2B1/2 genes by diallyl sulfone, disulfiram, and other organosulfur compounds in primary cultures of rat hepatocytes.

Our previous study demonstrated that diallyl sulfide (DAS), a compound derived from garlic, transcriptionally activated the P450 2B1/2 genes in rat liver. In the present study, rat primary hepatocytes were used to determine the effects of DAS and its metabolite, diallyl sulfone (DASO2), on the expression of the P450 2B1/2 genes. Freshly isolated adult rat hepatocytes were cultured in a serum-free medium on a reconstituted basement membrane matrix "matrigel" that enabled the hepatocytes to maintain expression of numerous liver-specific genes for more than 1 week. After 48-hr of acclimation, 0.1, 0.5, and 2.0 mM concentrations of DAS or DASO2 were added to the culture medium and the cells were harvested at 4, 12, 24, or 36 hr after the treatment for the preparation of microsomes and RNA. Cytotoxicity was not observed by morphological examinations after DAS and DASO2 treatments. In contrast to the in vivo results, there was only a slight increase in the levels of P450 2B1/2 mRNA and protein in DAS-treated cells. However, DASO2 treatment (2 mM) resulted in 11-, 21-, and 22-fold increases in P450 2B1/2 mRNA levels at 12, 24, and 36 hr after the treatment, respectively. P450 2B1/2 protein levels were also increased markedly in DASO2-treated cells. Co-incubation of the rat hepatocyte cultures with a physiological concentration of growth hormone significantly blocked the induction of P450 2B1/2 mRNA by DASO2. Northern blot analysis using oligonucleotide probes specific for 2B1 and 2B2 demonstrated that DASO2 induced mRNA levels of both 2B1 and 2B2, with a greater induction of 2B1 mRNA. For comparison, the effects of disulfiram (DSF) and its metabolite, diethyldithiocarbamate (DDTC), on P450 2B1/2 mRNA expression were also examined in the cultured rat hepatocytes. Both DSF and DDTC caused a significant increase in P450 2B1/2 mRNA level with the highest induction at 0.5 mM. Addition of growth hormone to the culture effectively suppressed the P450 2B1/2 mRNA induction by DSF but had little effect on the induction by DDTC. Neither mRNA nor protein levels of P450 2E1 in cultured hepatocytes were affected by all the organosulfur compounds tested. These results suggest that DASO2, DSF and DDTC selectively modulate P450 isozymes in cultured rat primary hepatocytes and that the induction of P450 2B1/2 by DAS in rat liver may be mediated by its metabolite, DASO2.

Allyl Compounds↗

Intake of garlic and its bioactive components.

The health benefits of garlic likely arise from a wide variety of components, possibly working synergistically. The complex chemistry of garlic makes it plausible that variations in processing can yield quite different preparations. Highly unstable thiosulfinates, such as allicin, disappear during processing and are quickly transformed into a variety of organosulfur components. The efficacy and safety of these preparations in preparing dietary supplements based on garlic are also contingent on the processing methods employed. Although there are many garlic supplements commercially available, they fall into one of four categories, i.e., dehydrated garlic powder, garlic oil, garlic oil macerate and aged garlic extract (AGE). Garlic and garlic supplements are consumed in many cultures for their hypolipidemic, antiplatelet and procirculatory effects. In addition to these proclaimed beneficial effects, some garlic preparations also appear to possess hepatoprotective, immune-enhancing, anticancer and chemopreventive activities. Some preparations appear to be antioxidative, whereas others may stimulate oxidation. These additional biological effects attributed to AGE may be due to compounds, such as S-allylcysteine, S-allylmercaptocysteine, N(alpha)-fructosyl arginine and others, formed during the extraction process. Although not all of the active ingredients are known, ample research suggests that several bioavailable components likely contribute to the observed beneficial effects of garlic.

Allyl Compounds↗