• Clinical data 90%
  • Efficacy 80%
  • Security 70%
  • Toxicity 30%

Allium sativum
Bulbus Allii Sativi

Synonyms

Porvium sativum Rehb.

General appearance

Bulbus Allii Sativi consists of several outer layers of thin sheathing protective leaves which surround an inner sheath. The latter enclose the swollen storage leaves called “cloves”. Typically, the bulb possesses a dozen sterile sheathing leaves within which are 6–8 cloves bearing buds making a total of 10–20 cloves and 20–40 well-developed but short and embedded roots. The cloves are asymmetric in shape, except for those
near the centre.

Major chemical constituents

The most important chemical constituents reported from Bulbus Allii Sativi are the sulfur compounds. It has been estimated that cysteine sulfoxides and the non-volatile γ glutamylcysteine peptides make up more than 82% of the total sulfur content of garlic. The thiosulfinates, ajoenes, vinyldithiins, and sulfides, however, are not naturally occurring compounds. Rather, they are degradation products from the naturally occurring cysteine sulfoxide, alliin. When the garlic]bulb is crushed, minced, or otherwise processed, alliin is released from compartments and interacts with the enzyme alliinase in adjacent vacuoles. Hydrolysis and immediate condensation of the reactive intermediate (allylsulfenic acid) forms allicin. One milligram of alliin is considered to be equivalent to 0.45 mg of allicin. Allicin itself is an unstable product and will undergo additional reactions to form other derivatives, depending on environmental and processing conditions. Extraction of garlic cloves with ethanol at _0°C gave alliin; extraction with ethanol and water at 25 °C led to allicin and no alliin; and steam distillation (100 °C) converted the alliin totally to diallyl sulfides. Sulfur chemical profiles of Bulbus Allii Sativi products reflected the processing procedure: bulb, mainly alliin, allicin; dry powder, mainly alliin, allicin; volatile oil, almost entirely diallyl sulfide, diallyl disulfide, diallyl trisulfide, and diallyl tetrasulfide; oil macerate, mainly 2-vinyl-[4H]-1,3-dithiin, 3-vinyl-[4H]-1,3-dithiin, E-ajoene, and Z-ajoene. The content of alliin was also affected by processing treatment: whole garlic cloves (fresh) contained 0.25–1.15% alliin, while material carefully dried under mild conditions contained 0.7 1.7% alliin. Gamma-glutamylcysteine peptides are not acted on by alliinase. On prolonged storage or during germination, these peptides are acted on by γ-glutamyl transpeptidase to form thiosulfinates.

Medicinal uses of Allium sativum

Uses supported by clinical data
Allium sativum as an adjuvant to dietetic management in the treatment of hyperlipidaemia, and in the prevention of atherosclerotic (age-dependent) vascular changes. The drug may be useful in the treatment of mild hypertension.

Uses described in pharmacopoeias and in traditional systems of medicine
The treatment of respiratory and urinary tract infections, ringworm and rheumatic conditions. The herb has been used as a carminative in the treatment of dyspepsia.

 Uses described in folk medicine, not supported by experimental or clinical data
As an aphrodisiac, antipyretic, diuretic, emmenagogue, expectorant, and sedative, to treat asthma and bronchitis, and to promote hair growth.

Pharmacology

Experimental pharmacology

Bulbus Allii Sativi has a broad range of antibacterial and antifungal activity.

The essential oil, water, and ethanol extracts, and the juice inhibit the in vitro growth of Bacillus species, Staphylococcus aureus, Shigella sonnei, Erwinia carotovora, Mycobacterium tuberculosis, Escherichia coli, Pasteurella multocida, Proteus species, Streptococcus faecalis, Pseudomonas aeruginosa, Candida species, Cryptococcus species, Rhodotorula rubra, Toruloposis species, Trichosporon pullulans, and Aspergillus niger. Its antimicrobial activity has been attributed to allicin, one of the active constituents of the drug. However, allicin is a relatively unstable and highly reactive compound and may not have antibacterial activity in vivo. Ajoene and diallyl trisulfide also have antibacterial and antifungal activities. Garlic has been used in the treatment of roundworm (Ascaris strongyloides) and hookworm (Ancylostoma caninum and Necator americanus). Allicin appears to be the active anthelminthic constituent, and diallyl disulfide was not effective. Fresh garlic, garlic juice, aged garlic extracts, or the volatile oil all lowered cholesterol and plasma lipids, lipid metabolism, and atherogenesis both in vitro and in vivo. In vitro studies with isolated primary rat hepatocytes and human HepG2 cells have shown that water-soluble garlic extracts inhibited cholesterol biosynthesis in a dose-dependent manner. Antihypercholesterolaemic and antihyperlipidaemic effects were observed in various animal models (rat, rabbit, chicken, pig) after oral (in feed) or intragastric administration of minced garlic bulbs; water, ethanol, petroleum ether, or methanol extracts; the essential oil; aged garlic extracts and the fixed oil. Oral administration of allicin to rats during a 2-month period lowered serum and liver levels of total lipids, phospholipids, triglycerides, and total cholesterol. Total plasma lipids and cholesterol in rats were reduced after intraperitoneal injection of a mixture of diallyl disulfide and diallyl trisulfide. The mechanism of garlic’s antihypercholesterolaemic and antihyperlipidaemic activity appears to involve the inhibition of hepatic hydroxymethylglutaryl-CoA (HMG-CoA) reductase and remodelling of plasma lipoproteins and cell membranes. At low concentrations (0.5 mg/ml), garlic extracts inhibited the activity of hepatic HMG-CoA reductase, but at higher concentrations (0.5 mg/ml) cholesterol biosynthesis was inhibited in the later stages of the biosynthetic pathway (68). Alliin was not effective, but allicin and ajoene both inhibited HMG-CoA reductase in vitro (IC50  7 and 9mmol/l respectively). Because both allicin and ajoene are converted to allyl mercaptan in the blood and never reach the liver to affect cholesterol biosynthesis, this mechanism may not be applicable in vivo. In addition to allicin and ajoene, allyl mercaptan (50 mmol/l) and diallyl disulfide (5mmol/l) enhanced palmitate induced inhibition of cholesterol biosynthesis in vitro. It should be noted that water extracts of garlic probably do not contain any of these compounds; therefore other constituents of garlic, such as nicotinic acid and adenosine, which also inhibit HMG-CoA reductase activity and cholesterol biosynthesis, may be involved.

The antihypertensive activity of garlic has been demonstrated in vivo.

Oral or intragastric administration of minced garlic bulbs, or alcohol or water extracts of the drug, lowered blood pressure in dogs, guinea-pigs, rabbits, and rats. The drug appeared to decrease vascular resistance by directly relaxing smooth muscle. The drug appears to change the physical state functions of the membrane potentials of vascular smooth muscle cells. Both aqueous garlic and ajoene induced membrane hyperpolarization in the cells of isolated vessel strips. The potassium channels opened frequently causing hyperpolarization, which resulted in vasodilation because the calcium channels were closed. The compounds that produce the hypotensive activity of the drug are uncertain. Allicin does not appear to be involved, and adenosine has been postulated as being associated with the activity of the drug. Adenosine enlarges the peripheral blood vessels, allowing the blood pressure to decrease, and is also involved in the regulation of blood flow in the coronary arteries; however, adenosine is not active when administered orally.

Bulbus Allii Sativi may increase production of nitric oxide, which is associated with a decrease in blood pressure.

In vitro studies using water or alcohol extracts of garlic or garlic powde  activated nitric-oxide synthase, and these results have been confirmed by in vivo studies. Aqueous garlic extracts and garlic oil have been shown in vivo to alter the plasma fibrinogen level, coagulation time, and fibrinolytic activity. Serum fibrinolytic activity increased after administration of dry garlic or garlic extracts to animals that were artificially rendered arteriosclerotic. Although adenosine was thought to be the active constituent, it did not affect whole blood. Garlic inhibited platelet aggregation in both in vitro and in vivo studies. A water, chloroform, or methanol extract of the drug inhibited collagen-, ADP-, arachidonic acid-, epinephrine-, and thrombin-induced platelet aggregation in vitro. Prolonged administration (intragastric, 3 months) of the essential oil or a chloroform extract of Bulbus Allii Sativi inhibited platelet aggregation in rabbits. Adenosine, alliin, allicin, and the transformation products of allicin, the ajoenes; the vinyldithiins; and the dialkyloligosulfides are responsible for inhibition of platelet adhesion and aggregation. In addition methyl allyl trisulfide, a minor constituent of garlic oil, inhibited platelet aggregation at least 10 times as effectively than allicin. Inhibition of the arachidonic acid cascade appears to be one of the mechanisms by which the various constituents and their metabolites affect platelet aggregation.

Inhibitionof platelet cyclic AMP phosphodiesterase may also be involved.

Ajoene, one of the transformation products of allicin, inhibited in vitro platelet aggregation induced by the platelet stimulators—ADP, arachidonic acid, calcium ionophore A23187, collagen, epinephrine, platelet activating factor, and thrombin. Ajoene inhibited platelet aggregation in cows, dogs, guineapigs, horses, monkeys, pigs, rabbits, and rats. The antiplatelet activity of ajoene is potentiated by prostacyclin, forskolin, indometacin, and dipyridamole. The mechanism of action involves the inhibition of the metabolism of arachidonic acid by both cyclooxygenase and lipoxygenase, thereby inhibiting the formation of thromboxane A2 and 12- hydroxyeicosatetraenoic acid. Two mechanisms have been suggested for ajoene’s antiplatelet activity. First, ajoene may interact with the primar agonist–receptor complex with the exposure of fibrinogen receptors through specific G-proteins involved in the signal transduction system on the platelet membrane. Or it may interact with a haemoprotein involved in platelet activation that modifies the binding of the protein to its ligands.

Hypoglycaemic effects of Bulbus Allii Sativi have been demonstrated in vivo.

Oral administration of an aqueous, ethanol, petroleum ether, or chloroform extract, or the essential oil of garlic, lowered blood glucose levels in rabbits and rats. However, three similar studies reported negative results. In one study, garlic bulbs administered orally (in feed) to normal or streptozotocin-diabetic mice reduced hyperphagia and polydipsia but had no effect on hyperglycaemia or hypoinsulinaemia. Allicin administered orally to alloxan-diabetic rats lowered blood glucose levels and increased insulin activity in a dose-dependent manner. Garlic extract’s hypoglycaemic action appears to enhance insulin production, and allicin has been shown to protect insulin against inactivation. Intragastric administration of an ethanol extract of Bulbus Allii Sativi decreased carrageenin-induced rat paw oedema at a dose of 100 mg/kg.

The antiinflammatory activity of the drug appears to be due to its antiprostaglandin activity.

A water or ethanol extract of the drug showed antispasmodic activity against acetylcholine, prostaglandin E2 and barium-induced contractions in guinea-pig small intestine and rat stomach. The juice of the drug relaxed smooth muscle of guinea-pig ileum, rabbit heart and jejunum, and rat colon and fundus. The juice also inhibited norepinephrine-, acetylcholine- and histamine-induced contractions in guinea-pig and rat aorta, and in rabbit trachea.

Contraindications

Bulbus Allii Sativi is contraindicated in patients with a known allergy to the drug. The level of safety for Bulbus Allii Sativi is reflected by its worldwide use as a seasoning in food.

Warnings

Consumption of large amounts of garlic may increase the risk of postoperative bleeding.

News and Journals

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