Garlic, the Spice of Life-(Part –I) Kishu Tripathi Surya College of Pharmacy, Lucknow

Asian J. Research Chem. 2(1): Jan.-March, 2009 ,

ISSN 0974-4169 www.ajrconline.org

REVIEW ARTICLE

A Review –Garlic, the Spice of Life-(Part –I) Kishu Tripathi Surya College of Pharmacy, Lucknow

ABSTRACT Garlic [Allium sativum] is among the oldest of all cultivated plants. It has been used as a medicinal agent for thousands of years. It is a remarkable plant, which has multiple beneficial effects such as antimicrobial, antithrombotic, hypolipidemic, antiarthritic, hypoglycemic and antitumor activity etc

KEY WORDS Garlic,Allium

INTRODUCTION: Garlic has played an important dietary and medicinal role Preparations of garlic are available as tablets, capsules, throughout the history of mankind. Garlic is a nature’s boon to syrup, tinctures and oil. In ointment form, garlic has been mankind. For over 5000 years garlic has been consumed both used externally for treatment of ring worm; boiled with as food and used for medicine by ancient scholars. Garlic, vinegar and sugar for treatment of asthma; made into an Allium sativum L. is a member of the Alliaceae family, has infusion for treatment of epilepsy; pounded with honey for been widely recognized as a valuable spice and a popular use against rheumatism; and mixed with milk for use as a remedy for various ailments and physiological disorders. The vermifuge. Garlic is commonly used in Europe and Asia for name garlic may have originated from the Celtic word 'all' medicinal benefits in healing wounds, etc.In Germany, sale meaning pungent. As one of the earliest cultivated plants, of garlic preparations competes with sales of leading garlic is mentioned in the Bible and in the literature of Ancient drugs.Garlic produces a variety of volatile sulfur-based Israel (The Talmud), Egypt (Codex Ebers) and India (Vedas compounds which are effective as insect repellents and and Purans, Charak Sanghita).Chinese strongly believe that insecticides. Diallyl disulfide is one of such compounds garlic prolongs longevity and is useful in treating most human which has a strong odor and acts as a powerful diseases, including infections, cancer and heart diseases. In insecticide.Commercial preparations of garlic are certified historical writings of India and in literature like Vedas and as insecticide against mites, nematodes and mosquito larvae Purans, garlic is reported to have medicinal as well as nutritive affecting a variety of crops. value in food items. Clinical indications of garlic include It has been used as a medicinal agent for thousands of years. hemorrhoids, rheumatism, dermatitis, abdominal pain, It is a remarkable plant, which has multiple beneficial cough,loss of appetite and loss of weight. effects such as antimicrobial, antithrombotic, hypolipidemic, antiarthritic, hypoglycemic and antitumor The medicinal qualities of garlic were described by Pliny the activity. Allicin has antibacterial and antioxidant activity. It Elder, Aristophanes, and Galen. may possibly increase blood levels of catylase and glutathione peroxidase activity. Ajoene decreases the Hippocrates, the Father of Medicine, observed that garlic was activity of factors needed for lipid synthesis by reducing the excellent for curing tumors and is an effective diuretic. thiol group in coenzyme A and HMG CoA reductase and Aristotle attributed garlic as a cure for rabies, and the Prophet also by oxidizing NADPH. Ajoene has antiplatelet activity Mohammad recommended it for treating scorpion stings. In and interferes with thromboxane synthesis and decreases Historia Naturalis by Pliny, garlic was recommended for platelet aggregation1. gastro-intestinal disorders as well as dog and snake bites. Desired medicinal results of garlic are obtained when bulbs So where do we stand today on this issue of garlic? Is garlic are chewed and swallowed or mixed with food and eaten. always good for health? How safe is it? Is it necessary to isolate the antioxidant compounds for its medicinal use in a more effective way?

8 Asian J. Research Chem. 2(1): Jan.-March, 2009 , CHEMISTRY water are diallyltrisulfide, diallyl disulfide and allyl methyl Intact garlic cloves contain only a few medicinally active. The trisulfide. Incubation of allicin or allyl methane thiosulfinate main chemical constituent of intact garlic is the amino acid in low polarity solvents (or without solvent) primarily alliin, an alkyl derivative of cysteine alkyl sulfoxide, which produces 1, 3-vinyldithiin (2-vinyl-4H-, 3-dithiin) (51% of may varies from 0.2 to 2.0% fresh weight. The efficacy of total), 1,2-vinyldithiin (3-vinyl-4H-1,2-dithiin) (19% of chemical constituents of garlic chiefly depends on the mode of total) and lesser amounts of ajoene (E,Z-4,5,9-trithiododeca- preparation of its extract. Crushing, chewing or cutting (or 1,6,11-trien 9-oxide) (12% of total) and sulfides (18% of exposing dehydrated, pulverized garlic to water) of garlic total).Incubation of pure allicin in methanol yields 8% cloves release the vacular enzyme allinase that rapidly lyses diallyl trisulfide and about equal amounts (20-25% of total) the cytosolic cysteine sulfoxide to form sulfenic acid (R- of ajoene and the vinyldithiins. Steam distillation of garlic SOH). Which immediately condenses to form allicin: the bulbs yields a garlic oil that consists of diallyl (57% of oil), compound which produces the odor of freshcut garlic? Garlic allyl methyl (37% of oil), and dimethyl (mono to hexa contains at least 100 sulfur-containing compounds basic to sulfides; 6% of oil of total). The essential oil content of medicinal uses. Allicin represents 70-80 % of the total fresh garlic bulbs is between 0.09 to 0.352. thiosulfinates formed (Fig. 1). Other thiosulfinates formed include allyl-ss(o)-methyl (6-16% of total), methyl-ss(o)-allyl BIOLOGICAL EFFECTS (3-9% of total), trans-1-propenyl (0.2-0.4% of total), trans-1- The biological activity of an extract of garlic depends on the propenyl-ss (o)-methyl+methyl-ss(o)-trans-1-propenyl (0.1- mode of its preparation. The extract prepared at room 2.5% of total) and methyl-ss(o)methyl (2% of total) temperature contains mainly allicin, which has a powerful thiosulfinates. The formation of allicin (allyl 2-propene antibacterial property and a strong smell. Besides allicin, thiosulfinate or diallyl thiosulfinate) is complete in 0.2 to 0.5 small amounts of several other thiosulfinates and complex min at room temperature. Formation of the methyl sulphinyl components, including the antithrombotic ajoenes, thiosulfinate takes 1.5 to 5.0 min. All possible combinations of are also present. The enzyme allinase responsible for 2-propene, 1-propene and methane sulfenic acids result in converting alliin to allicin is inactivated by heat. The water thiosulfinates extract of heat-treated garlic mainly contains alliin, which is odour-free. Garlic powder is a simply dehydrated, pulverized garlic clove. The allinase activity of garlic powder is identical to that of fresh garlic. It may be emphasized here that dehydration temperature should not exceed 60 ºC, above which allinase is inactivated.

When distilled in steam, garlic yields an oily mass consisting of diallyl, methyl allyl, dimethyl, all originating from the thiosulfinates.Garlic oil has been shown to possess biological properties such as antitumor and antioxidant effects.Another widely studied garlic preparation is aged garlic extract (AGE). When garlic is subjected to cold aging process, organosulphur compounds, such as s-allyl cysteine, s-allyl mercaptocysteine, and several sulphur-containing amino acids, are produced. S-allyl cysteine and s-allyl mercaptocysteine have been shown to be anticarcinogenic and provides protection against liver damage.

Garlic is one of the most investigated medicinal plants. During 1960 to 2007, more than three thousand research papers have been published on the chemistry and biological effects of garlic and garlic preparations. These studies mainly focus on the cardiovascular, anti-microbial and anti- cancer effects of garlic and, to a lesser extent, on the therapeutic indications for the treatment of hypoglycemia, The thiosulfinates released from crushed garlic are reactive heavy metal poisoning and liver dysfunction and molecules and undergo a number of transformations, hyperthyroidism. depending on the temperature, pH and solvent conditions. Allyl-s- thiosulfinates (allicin) are the least stable of the eight Sickle cell anemia thiosulfinates. The half-life of allicin (concentration of 0.1- Sickle cell anaemia is a life threatening hereditary disease, 0.4mg/ml) at room temperature is 10 days in 1mM citric acid in which oxidative stress plays a prominent role. AGE with (pH 3), 4 days in water, 48 h in methanol or chloroform, 24 h its high antioxidant activity, has therapeutic effects on the in ethanol, 24 h in hexane and 3 h in ether. The principal disease. In a 4 week study 5 patients with sickle cell transformation products after incubation of thiosulfinate in anaemia ingested AGE at 5 ml a day. The results showed 9 Asian J. Research Chem. 2(1): Jan.-March, 2009 , antioxidant protection of the red blood cells and a significant activity after acute and chronic garlic powder intake. reduction in the sickle cell markers3,4. Chutani and Bordia (1981) designed one study to show that both raw and fried garlic significantly enhance FA. Frying Potential effect of aged garlic extract (AGE) as an anti-oxidant removes the strong acrid smell of garlic, but preserves it in sickle RBC. Previously, AGE has been shown to useful effects on FA. The rise in FA has been observed significantly improve erythrocyte deformability through within 6 hours of garlic administration, which showed that stabilization of erythrocyte membranes in non-sickle RBC. garlic has a rapid onset of action and the effect is well These phenomenons were attributed to the anti-oxidant maintained as long as garlic is being taken. Recently Bordia activities of AGE .At baseline, erythrocyte deformability is (1998) found that intake (3 months) of ethyl acetate extract further altered in sickle RBC due to abnormal membrane that of crushed raw garlic also increased FA6. is highly permeable. This abnormality is thought to be contributory, at least partially, in formation of dense cells. The An increase in plasma cholesterol and fibrinogen and a dense cells, in turn, react with inflammatory cells and decrease in blood fibrinolytic activity (BFA) was observed endothelial cells leading to vasoocclusive changes. Perhaps during alimentary lipaentia produced by an ingestion of a AGE may also improve erythrocyte membrane stability in fatty breakfast by healthy volunteers. Addition of garlic in sickle RBC with anti-oxidant activities as suggested that there its both raw and boiled forms to fatty breakfast was found to was reduction of Heinz bodies in sickle RBC with daily AGE prevent the rise in cholesterol end fibrinogen in blood and to 5 administration . produce an enhancement of BFA. Fibrinolytic enhancing effect of garlic seems to be mediated through an increase in Garlic and cardiovascular diseases blood activator of fibrinolysis. A decrease in blood Garlic has been used for millennia in folk medicine of many cholesterol may also contribute to this action indirectly as cultures to treat cardiovascular diseases and other disorders. increased concentration of this lipid was found to decrease The medicinal effect of garlic and garlic extracts on the BFA7. cardiovascular diseases has been widely studied. Preparations of garlic and chemical constituents of garlic have been Fibrinolysis occurring in the body maintains the fluidity of investigated for possible effects on cardiovascular diseases the circulating blood by dissolving and removing deposits of such as hyperlipidemia, hypertension, platelet aggregation and fibrin. Perhaps an important function of fibrinolysis is to blood fibrinolytic activity. It is a great challenge for scientists remove very minute clots from tiny peripheral vessels that all over the world to make a proper use of garlic and enjoy its eventually would become occluded were there no way to maximum beneficial effect as it is the cheapest way to prevent cleanse them. Defects in coagulation and fibrinolytic cardiovascular disease6. activity are main factors for the development of thrombus. Garlic, when used continuously produces constant lytic Fibrinolytic activity (FA) activity, probably due to decrease in cholesterol and an Inhibition of fibrinolytic activity (FA) or deficiency of the increase in the plasminogen activity. Fibrinolysis of fibrin, factors involved might upset the hemostatic balance and allow releases fibrin degradation products which have excessive fibrin deposition. In diabetes, hypertension, anticoagulant activity. Increased plasmin may lower factor hypercholesterolemia etc, it is possible that disturbance in the V, VIII, IX and can cause increase in clotting time. These coagulation-fibrinolytic system may be an important factor 8,9 drawbacks are absent with garlic therapy . leading to the development of thrombosis and ischemia. Accordingly, the greater the FA, the more favorable is the antithrombic effect. FA is generally determined by euglobulin Platelet aggregation lysis time. The patients who died with acute or old myocardial The antiplatelet mechanism of garlic is much more infarction showed the highest values of plasma fibrinogen, established than its any other biological effects. Aqueous euglobulin lysis time and antiplasmin. This suggests that extract of garlic inhibited platelet aggregation induced by prognosis in myocardial infarction is partly influenced by the ADP, collagen, arachidonate, epinephrine and calcium degree to which plasma fibrinolysis is impaired. ionophore A23187 in a dose-dependent manner. Garlic reduced the formation of thromboxane, inhibited the phospholipase activity and lipoxygenase products formed in Almost all human studies on fibrinolytic activity of garlic have platelets. These effects may explain, in part, inhibition of been found to have positive effect. Acute as well as chronic platelet aggregation. Further, since garlic was also effective intake of garlic oil and raw garlic increased fibrinolytic in inhibiting aggregation induced by calcium ionophore activity (FA). In 1975, Bordia first demonstrated that garlic oil A23187 it may be suggested that the antiaggregation effect increased FA after 3 hours of administration. Bordia also may be related to intraplatelet mobilization of calcium. reported that chronic (3 weeks to 3 months) administration of Inhibition of epinephrine-induced aggregation by garlic garlic oil (dose: equivalent to 1 gm/kg of fresh garlic) extract may suggest that it may be inhibiting uptake of increased FA significantly ranging from 36% to 130% in calcium into platelets thereby lowering cytosolic calcium healthy as well as acute myocardial infarction patients. Dried concentrations.Ajoene strongly inhibits the metabolism of garlic powder has been also tested for its fribinolytic activity. arachidonic acid by both cyclooxygenase and lipoxygenase While two studies showed no difference in FA, one study pathways ,thus inhibiting the synthesis of thromboxane A2 showed increased FA as well as tissue plasminogen activator and 12-HETE. Antiaggregatory effect of ajoene may also be 10 Asian J. Research Chem. 2(1): Jan.-March, 2009 , causally related to its direct interaction with the putative fibrinolytic activity and blood coagulation time. Garlic can fibrinogen receptor (GPIIb/IIa).Ajoene interacts with a lead to a decrease in thrombocyte aggregation in blood. purified hemoprotein implicated in platelet activation.Ajoene Srivastava and Mustafa(1993) reported that several modifies the binding of the hemoprotein with ligands deemed mechanisms are involved in garlic-induced inhibition of to be physiologically relevant as effectors. Allicin inhibits platelet aggregation.These effects are the modification of human platelet aggregation in vitro without affecting platelet membrane properties, inhibition of calcium cyclooxygenase or thromboxane synthase activity or cyclic mobilization,and inhibition of several steps of the adenosine monophosphate (AMP) levels. Allicin also inhibits arachidonic acid cascade in platelets. In fact, a direct platelet aggregation but does not alter the activity of vascular inhibitory effect of garlic extracts and its components on the prostacyclin synthase. However, it inhibits ionophore A23187- enzymes of the arachidonic acid cascade have been stimulated human neutrophil lysosomal enzyme release. Thus reported. Kiesewetter et al. (1991) observed that intake of garlic appears to be in possession of components which might 800 mg of garlic powder over a period of 4 weeks caused exert their effects at various stages involved in the process of disappearance of thrombocyte aggregation, increased platelet aggregation6. microcirculation of the skin by 47.6% and decreased plasma viscosity by 3.2%; decreases in diastolic blood pressure by Garlic extracts, synthesized thiosulfinates, and the garlic 9.5% and blood glucose concentration by 11.6% were also derivative ajoene inhibited platelet aggregation in vitro in observed. Five hours after intake of 900mg garlic powder platelet-rich plasma and whole blood .Our in vitro experiments caused a significant increase in capillary skin perfusion by confirm that the whole blood point-of-care platelet function 55%. It causes minimal vasodilation and significant tests we used (Multiplate, PFA-100, and Platelet Mapping reduction in haematocrit and plasma viscosity6. assay) permit the detection of platelet dysfunction induced by garlic extracts. Platelet inhibition induced by garlic can be Hypotensive effect detected by using the agonists arachidonic acid, collagen, and Two Allimin tablets containing 4.75 g of garlic concentrate epinephrine used in our study. The PFA-100 has been (equivalent to about 0.31 g of desiccated garlic and 2.375 g recommended for preoperative platelet function screening of desiccated parsley) to 26 hypertensive patients three because it sensitively detects aspirin's effects as well as times daily for three days. Blood pressure reduction was defects, e.g., due to von Willebrand syndrome. Whole blood observed in 85% of the patients: the average decline in platelet aggregometry (Multiplate, Platelet Mapping assay) systolic and diastolic blood pressure was 12.3 mm Hg and permits detection of aspirin and clopidogrel's effects (when 6.5 mm Hg, respectively. Hypotensive action of garlic juice using adenosine diphosphate as agonist)10. may be due to a direct relaxant effect on smooth muscles. Allicor treatment of 600 mg/day produced reduction in both Platelet aggregation and subsequent thrombus formation are systolic and diastolic blood pressure2. significantly reduced by garlic and its constituents. Chloroform/ acetone extracts of fresh garlic have been shown Antihypertensive action of garlic is due to its prostaglandin to inhibit cyclooxygenase activity directly in cell-free assays, like effects, which decreases peripheral vascular resistance. with the acetone extract being more effective. The chloroform The gamma-glutamylcysteines are the compounds in garlic extract of garlic was a more effective inhibitor of ADP- and that may lower blood pressure, as indicated by their ability platelet-activating factor (PAF)-induced platelet aggregation. to inhibit angiotensin-converting enzyme in in vitro .Garlic Ajone, another garlic derivative, has also been shown to modulates the production and function of both endothelium inhibit platelet aggregation in vitro. A recent study has also derived relaxing and constricting factors and this may found another garlic component, sodium 2-propenyl contribute to its protective effect against hypoxic pulmonary thiosulfate, to modulate cyclooxygenase activity in canine vasoconstriction. Garlic elicits nitric-oxide-dependent platelets, thus preventing their aggregation11. relaxation in pulmonary arteries. This hypothesis was explained by the fact that NG-nitro-L-arginine methyl ester Bordia (1978) first showed the dose-dependent inhibition of (L-NAME, a NOS inhibitor) abolished the vasodilatory platelet aggregation by garlic. Raw garlic, garlic oil and other effect of garlic. But another study reported that pulmonary extract of garlic have been shown to inhibit platelet vasodilatory effect of allicin are independent of the synthesis of NO, ATP-sensitive (K+) channel, activation of aggregation in in vitro induced by ADP, collagen, 6 arachidonate, epinephrine and calcium ionophore. Chronic cyclooxygenase enzyme . intake of garlic powder and garlic oil also inhibits platelet aggregation. Single dose of garlic has also been shown to A garlic extract has been shown to modulate the production inhibit platelet aggregation6. and function of both endothelium-derived relaxing factor (NO) and constricting factors (endothelin-1) in isolated rat Lutomski (1987) demonstrated that adenosine, a compound in pulmonary arteries (24). Garlic juice has also been shown to high concentration (0.056%) in garlic, inhibits aggregation of have some beneficial effect on heart rate; however, at higher platelet and improves blood flow in the coronary vessels. dosages it exerts undesirable effects (25). -lutamylcysteines Investigations have shown that garlic oil could inhibit platelet are compounds found in garlic, and these may lower blood pressure, as indicated by their ability to inhibit aggregation and ether extract of garlic juice taken with a fatty 11 diet could decrease cholesterol and fibrinogen and increase angiotension-converting enzyme in vitro . 11 Asian J. Research Chem. 2(1): Jan.-March, 2009 , garlic was also suggested by Martin et al . The positive inotropism and chronotorpism induced by isoproterenol were partially antagonized by preincubation of the rat atria with the garlic dialysate. The ECG showed a regular sinus bradycardic rhythm in garlic dialysate fed anaesthetized rat.Direct relaxant effect of cardiac muscles was reported by Aqel et al. Garlic juice inhibited norepinephrine-induced contractions of rabbit and guinea pig aortic rings. It also inhibited the force of contraction of isolated rabbit heart in a concentration-dependent manner. Only one study showed that aqueous garlic extract increased the amplitudes of atrial complex 'p' wave and the ventricular complex 'QRS' of the rat ECG. This is suggestive of increase in voltage output of the atria and ventricles probably in accordance with positive inotropism6.

Antihyperlipidemic effect Hyperlipidemia is the major risk factor of atherosclerosis and the lowering of its level together with increase in plasma anticoagulant and antioxidant activities decreases the morbidity and mortality from this disease. In all these experiments the same protocol was used: (i) Wistar male rats were randomly divided into control and experimental groups; (ii) the rats of the control group were fed basal diet (BD) that included wheat starch, casein, soybean oil, cellulose,mineral, and vitamin mixtures; (iii) raw or boiled garlic was administered orally; (iv) the duration of the experiments was 28–30 days. To the BD of the experimental groups, 25 mg of lyophilized garlic (equivalent to 500 mg raw garlic/kg body weight) or garlic boiled for 20, 40 and 60 min and 1% of cholesterol was added. After the trial in the groups of rats, whose diets were supplemented with raw or boiled for 20 min garlic a significant hindering in the rise in plasma lipids was registered: total cholesterol (TC),20.1– 26.8%, LDL-C, 39.3–54.2% and triglycerides, 8.6–17.3%, and TC in liver, 27.2–35.7%. No significant changes were The effect of garlic preparations on SBP/DBP are comparable found in the level of HDL-C. Addition of garlic boiled for to the hypotensive effects of commonly-prescribed blood 40 and 60 min did not affect plasma and liver lipid pressure drugs, e.g. beta-blockers of 5 mm Hg for SBP, levels.From it is concluded that only raw or boiled for 20 angiotension converting enzyme inhibitors (ACEI) of 8 mm min garlic possesses plasma lipid-lowering properties. Hg for SBP, and angiotensin II type 1 receptor antagonists of

10.3 mm Hg for DBP and observed a reduction of 4 to 5 mm Raw and boiled aqueous extracts of garlic with a low dose Hg in SBP and 2 to 3 mm Hg in DBP has been estimated to (50 mg/kg) were administered daily to normal rats both reduce the risk of cardiovascular morbidity and mortality by orally and intraperitoneally for 4 weeks showed a significant 8–20%. Garlic powder dosages of 600–900 mg per day, reduction in triglyceride levels (38%). When the rats were providing potentially 3.6–5.4 mg of allicin, the active treated with a high dose (500 mg/kg) of raw garlic then compound in garlic12. triglyceride levels were significantly affected. Russian investigators studied effects of allicor (a long-acting garlic Antiarrhythmic effect drug) on the risk of coronary artery disease (CAD). They Garlic has a significant antiarrhythmic effect in both examined 167 patients with hyperlipidemia free of CAD. In ventricular and supraventricular arrhythmias. Garlic powder men,intake of allicor for 12 months resulted in a 10.7% (1% added to a standard chow for an 8 week period) reduction of a 10-year absolute risk to develop CAD (p a significantly reduced ischemia reperfusion-induced ventricular 0.05) and decreased a 10-year absolute risk of acute fibrillation (VF) in isolated perfused rat heart. Garlic dialysate myocardial infarction and sudden death by 22.7% (p a 0.05). suppressed premature ventricular contractions and ventricular In women,allicor prevented age-related cardiovascular risk tachycardia in ouabain-intoxicated dogs as well as ectopic (p a 0.05).Among lipid parameters, the greatest decrease rhythms induced by isoprenaline and aconitine on electrically was observed for total and LDL-C cholesterol (p a 0.05) by driven left rat atria . Garlic dialysate decreased the positive 27.9 and 22.5 and 11.4 and 10.8 mg/dL for men and inotropic and chronotropic effects of isoproterenol in a women,respectively. concentration dependent manner. -receptor blocking action of 12 Asian J. Research Chem. 2(1): Jan.-March, 2009 , A clinical trial was performed in a group of 50 type 2 diabetic lanosterol synthesis, and identical results were obtained with patients (39 women, 11 men, cholesterol concentration greater 14C-acetate and 14C-mevalonate, confirming that 3- than or equal to 220 mg/dL) to assess the effect of garlic hydroxy-3-methylglutaryl-CoA reductase activity was not powder tablet on blood glucose, lipid profiles and blood affected in these short-term studies. Several methylsterols pressure. Each patient received tablets containing 300 mg of that accumulated in the presence of garlic were identified by garlic powder three times per day for 6 weeks. In the coupled GC–MS as 4, 49-dimethylzymosterol and a beginning of the study and after 6 weeks supplementation of possible metabolite of 4-methylzymosterol; both are garlic powder tablets, blood pressure, fasting blood glucose, substrates for sterol 4a-methyl oxidase, pointing to this glycated hemoglobin and lipid profiles were measured.After enzyme as the principal site of inhibition in the the trial, the following results were registered: a significant cholesterolgenic pathway by garlic. Of nine garlic-derived decrease in TC (p a 0.01), LDL-C (p a 0.001),systolic blood compounds tested for their ability to inhibit cholesterol pressure (p a 0.03) and a significant increase (p a 0.02) in synthesis, only diallyl disulfide, diallyl trisulfide, and allyl HDL-C. No significant changes in diastolic blood pressure, mercaptan proved inhibitory. The results of this fasting blood sugar, serum triglycerides and HbA1c were investigation indicate that compounds containing an allyl- found. disulfide or allyl-sulfhydryl group are most likely responsible for the inhibition of cholesterol synthesis In a randomized, double-blind, placebo-controlled intervention by garlic and that this inhibition is likely mediated at sterol study, these authors showed that AGE supplementation was 4 -methyl oxidase13. effective in lowering plasma concentration of TC by 7% and LDL-C by 10% in hypercholesterolemic men compared with subjects consuming placebo. Supplementation of AGE to REFERENCES: animal diets similarly reduced plasma concentrations of TC 1. Laura Shane-McWhorter. Diabetes Spectrum 14:199-208, and triglycerides by 15 and 30%, respectively. In subsequent 2001 experiments using cultured rat hepatocytes, they found 44– 2. Vinay K Singh, Dinesh K Singh. ARBS Annual Rev Biomed 87% inhibition of cholesterol synthesis by the water- Sci 2008;10:6-26 extractable fraction (WEF), methanol-extractable fraction 3. Takasu J. et al. Aged garlic extract therapy for sickle cell (MEF) and petroleum ether extractable fraction (PEF) of fresh anemia patients. BMC Blood Disorders, 2: 3 2002 4. Shah Biren N, Nayak Bhavesh. S, Patel Manish A, Mishra garlic, and Kyolic (liquid form of AGE).They observed that Ashish D and Seth Avinash K. Pharmacognosy Magazine, hydrophilic and hydrophobic compounds of garlic are Vol 2, Issue 6, Apr-Jun, 2006 inhibitory to cholesterol synthesis. Because S-allylcysteine 5. Junichiro Takasu, Rolando Uykimpang, Maria Alenor Sunga, (SAC) alone was less potent than Kyolic, which contains SAC Harunobu Amagase and Yutaka Niihara. BMC Blood and other sulfur compounds, a maximal inhibition appears to Disorders.2002, 2:3 require a concerted action of multiple compounds of garlic. In 6. Sanjay K Banerjee and Subir K Maulik. 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Principal mechanism by which garlic decreases cholesterol levels: garlic decreases cholesterol by inhibition of sterol 4 - methyl oxidase. In order to identify the principal site of inhibition in the cholesterolgenic pathway and the active components of garlic, they have treated with aqueous garlic extract or its chemical derivatives cultured hepatoma cells and identified and quantified radiolabeled cholesterol and intermediates. The used extract reduced cholesterol synthesis by up to 75% without evidence of cellular toxicity. Levels of squalene and 2, 3-oxidosqualene were not altered by garlic, indicating that the site of inhibition was downstream of 13