Bulbus Allii Sativi
Plant material of interest: fresh or dried bulbs
Organoleptic propertiesOdour strong, characteristic alliaceous ( 1, ('I ,)); taste very persistcntly pungent and acrid (1, 6, 8).
The thiosulfinates (e.g. allicin ), ajoenes (e.g. E-ajoene , Z-ajoene ). vinyldithiins (e.g. 2-vinyl-(4H)-1,8-dithiin , 8-vinyl-(4H)-1.2-dithiin ), and sulfides (e.g.diallyl disulfide , diallyl trisulfide ), however, are not naturally occurring compounds,. Rather, they are degradation products from the naturally occurring cysteeine sulfoxide, alliin . When the garlic bulb is crushed, minced, or otherwise processed, alliin is released from compartments and interacts with th eoenzyme alliinase in adjacent vacuoles. Hydrolysis and immediate condensation of the reactive intermediate (allylsulfenic acid) forms alicin . One milligram of alliin is considered to be equivalent to 0.45mg of allicin (26). Allicin itself is an usntable product and will undergo additional reactions to form otherderivatives (e.g. products -), depending on environemntal and processing condition (24-26). Extraction of grlic cloves with ethanol at <0 o C gave alliin ; extraction with ethanol and water at 25o C led to allicin  and no allin; and steam distillation (100o C) converted the alliin totally to diallyl sulfides .  (24,25). 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 tisul fide, and diallyl tetrasulfide; oil macerate, mainly 2-vinyl-[4H]-1.8-dithiin, 8-vinyl-[4H]-1,8-dithiin, E-ajoene, and Z-ajoene (18-22,24). 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 (18-21).
Gamma-glutamylcysteine peptides are not acted on by alliinase. On prolonged storage or during germination, these peptides are acted on by y-glutamyl transpeptidase to forn1 thiosilfinates (25).
The juice is the most unstable dosage form. Alliin and allicin decompose rapidly, and those products must be used promptly (18).
Dried Bulbus Allii Sativi products should be stored in well-closed containers, protected from light, moisture, and elevated temperature.
described in pharmacopoeias and in traditional systems of medicine
described in folk medicine, not supported by experimental or clinical
Fresh garlic, garlic juice, aged garlic extracts, or the volatile oil all lowered chlesterol and plasma lipids, lipid metabolism, and athero9genesis both in vitro and in vivo (18, 43, 47-64). 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 (48-50). Antihyperchlesterolaemic and antihyperlipidameic 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 (51-64). Oral administration of allicin to rats during a 2-month period lowered serum and liver levels of total lipids, phospholipids, triglycerides, and total cholesterol (65). Total plasma lipids and cholesterol in rats were reduced after intraperitoneal injection of a mixture of diallyl disulfide and diallyl trisulfide (66). The mchanism 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 (67). At low concentrations (<0.5mg/ml), garlic extracts inhibited the activity of hepatic HMG-CoA reductase, but at higher concentrations (>0.5mg/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 (IC 50 = 7 and 9 mmol/l respectively) (49). 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 (50mmol/l) and diallyl disulfide (5mmol/l) enhanced palmitate-inducedinhibition of chgolesterol biosynthesis in vitro (50). It should be noted that water extracts of garlic probably do not contain any of these compunds; therefore other contituents of garlic, such as nicotinic acid and adenosine, which also inhibit HmG-CoA reductase activity and cholesterol biosynthesis, may be involved (69,70).
The antihypertensive activity of garlic has bee demonstrated in vivo. Oral or intragastric administration of minced garlic bulbs, or alcohol or water extracts o fthe drug, lowered blood pressured in dogs, guineapigs, rabbits, and rats (52, 71-73). The drug appeared to dcecrease vascular resistance by directly relaxing smooth muscle (74). The durg 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 (75, 76). The compounds that produce the hypotensive activity of the drug are uncertain. Allicin does not appear to be involved (43), 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 powder activated nitric-oxide synthase (77), and these results have been confirmed by in vivo studies (78).
Aqueous garlic extracts and garlic oil have been shown in vivo to alter the plasma fibrinogen level, coagulation time, and fibrinolytic activity (43). Serum fibrinolytic activity increased after administration of dry garlic or garlic extracts to animals that were artificially rendered arteriosclerotic (79, 80). Although adenosine was thought to be the active constituent, it did not affect whole blood (43).
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 (81-87). Prolonged administration (intragastric, 3 months) of the essential oil or a chloroform extract of Bulbus Allii Sativi inhibited platelet aggregation in rabbits (88-90). 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 (4, 42, 9.1-93). In addition methyl allyl trisulfide, a minor constituent of garlic oil, inhibited platelet aggregation at least 10 times as effectively than allicin (94). Inhibition of the arachidonic acid cascade appears to be one of the mechanisms by which the various constituents and their metabolites affect platelet aggregation. Inhibition of platelet cyclic AMP phosphodiesterase may also be involved (91).
Ajoene, one of the transformation products of allicin, inhibited in vitro plate-let aggregation induced by the platelet stimulators-ADP, arachidonic acid, calcium ionophore A28187, collagen, epinephrine, platelet activating factor, and thrombin (95, 96). Ajoene inhibited platelet aggregation in cows, dogs, guinea- pigs, horses, monkeys, pigs, rabbits, and rats (95, 96). The antiplatelet activity of ajoene is potentiated by prostacyclin, forskolin, indometacin, and dipyridamole (95). The mechanism of action involves the inhibition of tllc metabolism of arachidonic acid by both cyclooxygenase and lipoxygenase, thereby inhibiting the formation of thromboxane A2 and 12- . hydroxyeicosatetraenoic acid (95). Two mechanisms have been suggested for ajoene's antiplatelet activity. First, ajoene may interact with the primary agonist-receptor complex with the exposure of fibrinogen receptors through specific G-proteins involved in the signal transduction system on the platelet membrane (92). Or it may interact with a haemoprotein involved in platelet activation that modifies the binding of the protein to its ligands (96).
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 (24, 97-104). However, three similar studies reported negative results (105 - 107), 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 orhypoinsulinaemia (107). Allicin administered orally to alloxan-diabetic rats lowered blood glucose levels and increased insulin activity in a dose-dependent manner (24), Garlic extract's hypoglycaemic action appears to enhance insulin production, and allicin has been shown to protect insulin against inactivation ( 108).
Intragastric administration of an ethanol extract of Bulbus Allii Sativi decreased carrageenin-induced rat paw oedema at a dose of 100 mg/k,g, The anti-inflammatory activity of the drug appears to be due to its antiprostilglanlin activity (109,110).
A water or ethanol extract of the drug showed antispasmodic activity against acetylcholine, prostaglandin E2 and barium-induced contractions in guinca-pig small intestine and rat stomach (111). The juice of the drug relaxed smooth muscle of guineapig ileum, rabbit heart and jejunum, and rat colon and fundus(112, 113). The juice also inhibited norepinephrine-. acetylcholine- and histamine-induced contractions in guineapig and rat aorta, and in rabbit trachea (112,113).
A meta-analysis of the effect of Bulbus Allii Sativi on blood pressure re- viewed a total of 11 randomized, controlled trials (published and unpublished) (113, 114). Each of the trials used dried garlic powder (tablets) at a dose of 600- 900mg daily (equivalent to 1.8-2.7 g/day fresh garlic). The median duration of the trials was 12 weeks. Eight of the trials with data from 415 subjects were included in the analysis; three trials were excluded owing to a lack of data. Only, three of the trials specifically used hypertensive subjects, and many of the studies suffered from methodological flaws. Of the seven studies that compared garlic with placebo, three reported a decrease in systolic blood pressure, and four studies reported a decrease in diastolic blood pressure ( 115). The results of the meta-analysis led to the conclusion that garlic may have some clinical usefulness in mild hypertension, but there is still insufficient evidence to recommend the drug as a routine clinical therapy for the treatment of hypertension ( 115).
A meta-analysis of the effects of Bulbus Allii Sativi on serum lipids and lipoproteins reviewed 25 randomized, controlled trials (published and unpub- lished) (116) and selected 16 with data from 952 subjects to include in the analysis. Fourteen of the trials used a parallel group design, and the remaining two were cross-over studies. Two of the studies were conducted in an open- label fashion, two others were single-blind, and the remainder were double- blind. The total daily dose of garlic was 600-900 mg of dried garlic powder, or 10 g of raw garlic, or 18 mg of garlic oil, or aged garlic extracts (dosage not stated). The median duration of the therapy was 12 weeks. Overall, the subjects receiving garlic supplementation (powder or non-powder) showed a 12% re- duction (average) in total cholesterol, and a 13% reduction (powder only) in serum triglycerides. Meta-analysis of the clinical studies confirmed the lipid-lowering action of garlic. However, the authors concluded that the overall quality of the clinical trials was poor and that favourable results of better- designed clinical studies should be available before garlic can be routinely recommended as a lipid-lowering agent. However, current available data support the hypothesis that garlic therapy is at least beneficial (116). Another meta- analysis of the controlled trials of garlic effects on total serum cholesterol reached similar conclusions (117). A systematic review of the lipid-lowering potential of a dried garlic powder preparation in eight studies with 500 subjects had similar findings (-1-18). In seven of the eight studies reviewed, a daily dose of 600-900 mg of garlic powder reduced serum cholesterol and triglyceride levels by 5-20%. The review concluded that garlic powder preparations do have lipid-lowering potential ( 118).
An increase in fibrinolytic activity in the serum of patients suffering from atherosclerosis was observed after administration of aqueous garlic extracts, the essential oil, and garlic powder (119, 120). Clinical studies have demonstrated that garlic activates endogenous fibrinolysis, that the effect is detectable for several hours after administration of the drug, and that the effect increases as the drug is taken regularly for several months (43, -121). Investigations of the acute haemorheological (blood flow) effect of 600-1200mg of dry garlic pow- der demonstrated that the drug decreased plasma viscosity, tissue plasminogen activator activity and the haematocrit level (118).
The effects of the drug on haemorheology in conjunctival vessels was determined in a randomized, placebo-controlled, double-blind, cross-over trial. Garlic powder (900 mg) significantly increascd the mean diameter of the arterioles (by 4.2%) and venules (by 5.90;0) as compared with controls (122). In another double-blind, placebo-controlled study, patients with stage II peripheral arterial occlusive disease were given a daily dose of 800 mg of garlic powder for 4 weeks (-123,124). Increased capillary erythrocyte flow rate and decreased plasma viscosity and plasma fibrinogen levels were observed in the group treated with the drug ( 123, 124). Determinations of platelet aggregation ex vivo after ingestion of garlic and garlic preparations by humans, suffers from methodological difficulties that may account for the negative results in some studies(24). In one study in patients with hypercholesterolinaemia trcated with a garlic-oil macerate for 3 months, platelet adhesion and aggregation decreased significantly (125). In a 3-year intervention study, 482 patients with myocardial infarction were treated with either an ether-extracted garlic oil (0.1 mg/kg/day, corresponding to 2g fresh garlic dailyy ora placebo (126). In the group treated with garlic, there were 35%, fewer new heart attacks and 45% fewer deaths than in the control group. The serum lipid concentrations of the treated patients were also reduced ( .'26).
The acute and chronic effects of garlic on fibrinolysis and platelet aggregation in 12 healthy patients in a randomized, double-blind, placebo-controlled cross-over study were investigated (30). A daily dose of 900 mg of garlic powdcr for 14 days significantly increased tissue plasminogen activator activity as compared with placebo (30). Furthermore, platelet aggregation induced h}, adenosine diphosphate and collagen was significantly inhibited 2 and 4 hours after garlic ingestion and remained lower for 7 to 14 days after treatment (30). Another randomized, double-blind, placebo-controlled study investigated thc effects of garlic on platelet aggregation in 60 subjects with increased risk of juvenile ischaemic attack (29). Daily ingestion of 800mg of powdered garlic for 4 weeks significantly decreased the percentage of circulating platelet aggregates and spontaneous platelet aggregation as compared with the placebo group (29).
Oral administration of garlic powder (800mg/day) to 120 patients for 4 weeks in a double-blind, placebo-controlled study decreased the average blood glucose by 11.6% (30). Another study found no such activity after dosing non- insulin-dependent patients with 700mg/day of a spray-dried garlic preparation for 1 month (127).
mutagenesis, impairment of fertility
Bulbus Allii Sativi should be taken with food to prevent gastrointestinal upset.