The subject of this article is garlic and our health. Yes, this is a purely scientific material, but if you want to deal specifically with this favorite product, then you are here.
Garlic (Allium sativum L.) is a particularly rich source of organic sulfonic compounds, which are currently being studied for their potential for the prevention and treatment of diseases. Also if you use Garlic For Weight Loss, you will see miracle benefits within a week.
The two main classes of organosulfonic compounds found in whole garlic cloves are L-cysteine? sulfoxides and glutamyl-L-cysteine? peptides.
Crushing or grinding garlic releases an enzyme called alliinase, which catalyzes the formation of allicin from S-allyl-L-cysteine? sulfoxide (Allin). Allicin is rapidly destroyed, forming various organosulfonic compounds.
In vivo studies show that sulfur-containing compounds derived from allicin can be poorly bioavailable, whereas water-soluble derivatives of glutamyl-L-cysteine? peptides were detected in plasma, liver, and kidneys after oral consumption.
Several different types of garlic supplements are commercially available, and each class provides a different profile of organosulfonic compounds depending on how it was processed.
Numerous preclinical studies have reported that organosulfur compounds from garlic can exert antioxidant, anti-inflammatory, antimicrobial, antitumor, and cardioprotective activity under various experimental conditions.
Results from randomized controlled trials have shown that adding garlic moderately improves serum lipid profiles in people with elevated serum cholesterol and lower blood pressure fast in hypertensive patients, at least in the short term. It is not known whether adding garlic can help prevent cardiovascular diseases.
Current observational studies do not confirm the link between high consumption of garlic and cancer prevention, including stomach and colorectal cancer.
It is not known whether compounds of sulfur-containing compounds obtained from garlic are effective in preventing or treating human cancer.
Garlic has been used for culinary and medicinal purposes in many cultures for centuries. Garlic is a particularly rich source of organosulfonic compounds, which are thought to be responsible for its flavor, as well as its potential health benefits.
Consumer interest in the benefits of garlic is strong enough to place it among the best-selling medicinal herbs in the United States. Scientists are interested in the opportunities in garlic-derived organosulfur compounds for preventing and treating chronic diseases such as cancer and cardiovascular diseases.
Organosulfur Compounds From Garlic
Two classes of organosulfide compounds are found in whole garlic cloves: L-cysteine sulfoxides and glutamyl-L-cysteine peptides.
S-allyl-L-cysteine sulfoxide (alliin) is about 80% of cysteine sulfoxides in garlic. When raw garlic cloves are crushed, cut, or chewed merely, an enzyme known as alliinase is released. Alliinase catalyzes the formation of sulfenic acids from L-cysteine sulfoxides. Sulfenic acids react spontaneously with each other to form unstable compounds called thiosulfins.
In the case of allyin, the resulting sulfinic acids react with each other to form thiosulfinate, known as allicin (the half-life in chopped garlic at 23 ° C is 2.5 days). The formation of thiosulfinates occurs very quickly and, as has been established, is completed within 10-60 seconds after chopping garlic.
Allicin is destroyed in vitro to form various fat-soluble sulfur-containing compounds, including diallyl trisulfide (DATS), diallyl disulfide (DADS) and diallyl sulfide (DAS) or in the presence of oil or organic solvents, ajoene and vinyldithiine.
In vivo, allicin can interact with glutathione and L-cysteine ? to form S-ally-mercapto glutathione (SAMG) and S-ally-mercapto cysteine? (SAMC), respectively.
Crushing garlic does not change the peptide glutamyl-L-cysteine content. Y-glutamyl-L-cysteine peptides include a set of water-soluble dipeptides, including glutamyl-S-allyl-L-cysteine, glutamylmethylcysteine, and glutamylpropylcysteine.
Water-soluble organosulfur compounds, such as S-allyl cysteine and SAMC, are formed from glutamyl-S-allyl-L-cysteine during prolonged incubation of chopped garlic in aqueous solutions, as in the production of long-infused garlic extracts.
Non-sulfur Phytochemicals Garlic
Although little is known about their bioavailability and biological activity, sulfur-free phytochemicals, including flavonoids, steroid saponins, organic compounds, and allicin, probably work in synergy with organic sulfur compounds.
Metabolism And Bioavailability
S-Allyl-L-cysteine sulfoxide (Alliin)
In studies conducted in rodents, it was found that alliin, administered orally, is wholly absorbed and reaches the plasma and liver, not turning into allicin. Insulins (for example, allicin) is not present in the natural garlic teeth, and none of them can be grown in the stomach because alliinase is irreversibly inhibited under acidic conditions.
Allicin And Derivatives
Absorption and metabolism of compounds derived from allicin and allicin are only partially understood. In humans, allicin was not detected in serum or urine for up to 24 hours after ingestion of 25 g of raw garlic containing significant amounts of allicin.
Before use in garlic preparations and after ingestion of the stomach, allicin is likely to be destroyed to release many volatile compounds, including DAS and DADS. These organosulfonic compounds are metabolized to allyl mercaptan, allyl methyl sulfide, and allyl methyl disulfide, which were found during human respiration after garlic consumption.
Although some biological activities have been attributed to various compounds derived from allicin, it is not yet clear which of these compounds or metabolites reaches the target tissues. Allyl methyl sulfide - but not allyl mercaptan - was detected in the urine within four hours after ingestion of garlic, which indicates that this compound is absorbed into the circulation and quickly excreted from the body.
Other compounds derived from allicin, including diallyl sulfides, agencies, and vinyl dithiins, were not found in human blood, urine, or stools even after consuming up to 25 g of fresh garlic or 60 mg of pure allicin. These data suggest that, if they are absorbed, the compounds obtained by allicin and allicin are rapidly metabolized.
Glutamyl-S-Allyl-L-Cysteine? And Derivatives
It is assumed that? glutamyl-S-allyl-L-cysteine ? is absorbed intact and hydrolyzed to S-allyl-L-cysteine?( SAC) and trans-S-1-propenyl-L-cysteine since the metabolites of these compounds were measured in urine human after consumption of garlic.
Consumption of aged garlic extract, a commercial garlic preparation containing SAC, has been found to increase plasma SAC concentrations in humans. SAC is located in the plasma, liver, and kidneys of animals feeding SAC. Water-soluble organosulfur compounds, such as SAC and its metabolites, N-acetyl-S-allyl-L-cysteine, can be used as reliable markers of compliance in clinical trials involving garlic.
Low cellular concentrations of glutathione, an important intracellular antioxidant, and overproduction of reactive oxygen species (ROS) can damage biological macromolecules caused by oxidative stress, and contribute to the development and progression of pathological conditions.
In endothelial cells (which lined the inner wall of blood vessels), allicin, obtained from garlic, lowered ROS production and increased the concentration of glutathione.
Oral administration of allicin to mice reduced ROS production and prevented ROS-induced cardiac hypertrophy by inhibiting pro-inflammatory pathways, such as mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase (PI3K) / protein kinase B (Akt) / glycogen synthase 3az kinase 3 kinases. Ways. When crossing the cell membrane, it is believed that allicin interacts with glutathione and forms SAMG, which can prolong the antioxidant activity of allicin.
Garlic-derived organosulfide compounds were found to inhibit inflammatory response mediators, including cytokines, chemokines, adhesion molecules, and enzymes, such as cyclooxygenase (COX), lipoxygenase (LOX), and inducible nitric oxide synthase (iNOS), Nuclear Kappa B factor (NF-?B) is a transcription factor that binds DNA and induces the transcription of the COX-2 gene, other pro-inflammatory genes, as well as genes involved in proliferation, adhesion, survival and cell differentiation.
The anti-inflammatory effect of organosulfonic compounds is a consequence of their ability to counteract the activation of pro-inflammatory pathways, such as NF-?B-, MAPK- and PI3K / Akt-dependent signaling pathways - by pro-inflammatory stimuli. DATS inhibited macrophage activation induced by bacterial lipopolysaccharide (LPS) by restricting the binding of LPS to toll-like receptor 4 (TLR4) and blocking the regulation of expression of TLO4 and TLR4 MyoD88.
DATS also inhibits LPS-induced NF-?B-dependent expression of COX-2, iNOS, tumor necrosis factor-a (TNF-a) and interleukin-1 (IL-1). In a mouse model of inflammation, a decrease in LPS-induced paw edema with DATS was associated with a reduction in serum concentrations of pro-inflammatory cytokines, TNF-a, IL-6, and monocytic chemotactic protein-1 (MCP-1).
Inhibition of cholesterol synthesis
Garlic and garlic derivatives of sulfur-containing compounds have been found to reduce cholesterol synthesis by hepatocytes. Some of the organo-sulfur compounds derived from garlic, including S-allyl cysteine and Agen, were found to inhibit 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), a critical enzyme in the cholesterol biosynthesis pathway. Compounds derived from garlic can also inhibit other proteins in this pathway, including sterol 4a-methyl oxidase.
Inhibition Of Platelet Aggregation:
An increase in the ability of platelet aggregation is associated with narrowing of the blood vessels and the occurrence of acute thrombotic events. It was found that various organo-sulfur compounds obtained from garlic inhibit platelet aggregation in vitro.
Aged garlic extract was found to inhibit chemically stimulated platelet aggregation, inhibiting fibrinogen binding activity of glycoprotein IIb / IIIa found on platelets and by preventing interplanetary mobilization of calcium.
Inhibition Of Vascular Smooth Muscle Cell Proliferation (VSMC)
The spread and migration of usually resting VSMCs are significant features of vascular diseases, including atherosclerosis and coronary restenosis (when the treated arteries are blocked again).
Although the significance of this data for human cardiovascular diseases is not yet clear, limited cell culture research suggests that organosulfide compounds from garlic can inhibit the proliferation and migration of VSMC.
Inhibition Of Adhesion Molecules Of Vascular Cells:
An increase in the concentration of low-density oxidized lipoprotein (LDL) in plasma is involved in the pathogenesis of atherosclerosis. Oxidized LDL can stimulate the recruitment of inflammatory leukocytes from the blood into the arterial wall by inducing the expression of vascular cell adhesion molecules. DADS and DATS inhibited the expression of adhesion molecules, E-selectin and vascular cell-1 adhesion molecules (VCAM-1) on the surface of endothelial cells by reverse oxidation of LDL-induced inhibition of PI3K / Akt and cAMP-binding protein (CREB) signaling pathways.
Hydrogen-associated Vasodilating Activity:
Maintaining normal arterial function plays an essential role in the prevention of cardiovascular diseases. Hydrogen sulfide (H 2 S), a gas signaling molecule produced by some cells in the body, acts as a vasodilator (relaxes blood vessels) and, therefore, can have cardioprotective properties.
Production of H 2 S can participate in the relaxation of vascular smooth muscle cells by regulating the opening/closing of potassium channels and enhancing the NO-dependent signaling pathway. The study found that compounds derived from garlic are converted to hydrogen sulfide by red blood cells in vitro.
However, human consumption of high doses of raw garlic does not increase the levels of hydrogen sulfide in the airways, indicating that significant metabolism of garlic compounds to hydrogen sulfide does not occur in vivo.
Please note that the potential benefits of garlic consumption/supplements on cardiovascular health may also be associated with the antioxidant and anti-inflammatory activity described above.
Impact On The Metabolism Of Carcinogens
Inhibition of metabolic activation of carcinogens: some chemical carcinogens do not become active carcinogens until they are metabolized by phase I biotransformation enzymes, such as those belonging to the cytochrome P450 (CYP) family. Inhibition of specific CYP enzymes involved in the activation of carcinogens inhibits the development of cancer in some animal models.
In particular, it was found that DAS and its metabolites inhibit CYP2E1 activity in vitro and when administered orally in high doses to animals. Oral administration of garlic oil and DAS for humans also led to evidence of a decrease in CYP2E1 activity.
Phase II Detoxifying Enzymes Induction: Reactions catalyzed by Phase II detoxification enzymes usually contribute to the elimination of drugs, toxins, and carcinogens from the body. Therefore, increasing the activity of phase II enzymes, such as glutathione S-transferase (GST) and NQO-1, can help prevent cancer by increasing the elimination of potential carcinogens (see Nrf2-dependent antioxidant pathway).
In animal studies, it was found that oral administration of garlic preparations and organosulfonic compounds increases the expression and activity of phase II enzymes in various tissues. For example, DADS protected the liver of rodents from liver insufficiency of carbon tetrachloride (CCl 4, an environmental pollutant) induced by lipid peroxidation and cell necrosis, blocking the metabolic activation of CYP2E1 CCL 4 and activating Nrf2 genes downstream for NQO-1, HO-1, GCL, GST and superoxide dismutase (SOD1).
Several different types of garlic preparations are commercially available, and each category provides a different profile of organosulfonic compounds depending on how it was processed (see Table 1). Not all garlic preparations are standardized, and even standardized brands can vary depending on the amount and bioavailability of the organosulfonic compounds contained in them.
Powdered Garlic (dehydrated)
Powdered or dehydrated garlic is made from garlic cloves, which are usually cut and dried at low temperature to prevent inactivation of the alliinase. Dried garlic is crushed and often turned into tablets.
To meet the standards of the American Pharmacopoeia Convention (USP), powdered garlic supplements must contain at least 0.1% ?-glutamyl-S-allyl-L-cysteine? and at least 0.3% alliin (dry weight).
Although garlic powder supplements do not contain allicin, a manufacturer can provide the value of the “allicin potential” or “allicin yield” supplement on the label. These values? represent the maximum achievable yield of allicin supplement. It is determined by dissolving powdered garlic in water at room temperature and measuring the allicin content after 30 minutes.
Since the acidic pH of the stomach inactivates alliinase, most powdered garlic tablets have an enteric coating to prevent them from dissolving until the neutral pH of the small intestine is reached. It was argued that it would be more appropriate to measure “allicin release” using the USP method to assess drug release from enteric-coated tablets under conditions that mimic the stomachs and intestines. It was shown that allicin release by this method is parallel to the true bioavailability.
It was found that the majority of tablet pills under these conditions emit little allicins, mainly due to low alliinase activity and long disintegration time. Many manufacturers provide information on the “allicin potential” of their garlic powder supplements, but few provide information on the “allicin release.”
Some controlled clinical trials have examined the effect of powdered or dehydrated garlic supplements on cardiovascular risk factors (see Cardiovascular Diseases). The most commonly used doses ranged from 600 to 900 mg/day and provided 3.6–5.4 mg/day of potential allicin.
When garlic cloves are incubated in a solution of ethanol and water for up to 20 months, allicin is mainly converted to allyl sulfides, which are lost during evaporation or converted to other compounds. The resulting extract contains primarily water-soluble organosulfur compounds, such as SAC and SAMC.
Extracts from garlic liquid, including aged garlic extracts, are standardized by their S-allyl-L-cysteine?content. In controlled clinical trials, daily intake of garlic extract from 1.2 g to 2.4 g (containing from 1.2 to 2.4 mg of S-allyl-L-cysteine) consistently resulted in a reduction in the GARDEN of 9 mm Hg. Art. - 10 mm Hg. Art. Also, a decrease in DBP of 4 mm Hg-8 mm Hg. Technique. in most patients with uncontrolled hypertension.
Also, sustained garlic extract in doses of 2.4 to 7.2 g / day resulted in a short-term reduction of ex vivo platelet aggregation and a decrease in serum cholesterol concentration to 12 weeks.