INTRODUCTION:

Garlic belongs to the genus Allium which also includes onion, leek, chives and shallot. The plants belonging to this genus contain a variety of sulfur-based natural products which are responsible for their pungency as well as spicy aroma (1). Allicin and other thiocyanates are short lived in aqueous solutions and they yield organosulfur biproducts like diallyl sulfides (DAS), ajoene and dithiines (2). So, the characteristic pungencies of various Allium bulbs depend on distinctive mixtures of organosulfur compounds which they produce (2, 3). Surprisingly, these compounds bears structural similarity to isothiocyanates and the pungent ingredients of wasabi, yellow mustard and other Brassica plants (4). Though there is well-known culinary and medical use of garlic, very little is known abou their cellular and molecular mechanisms through which garlic extracts exert their physiological effects. Sensory nerve endings which innervate the skin, mucous membrane and the vascular smooth muscle are the likely targets which are given the irritant and vasodilatory actions of these pungent extracts.

AGED GARLIC EXTRACT: (AGE):

Aged Garlic Extract is an odourless product which is produced as a result of prolonged extraction of fresh garlic at room temperature. It exerts its biological activity in animals and humans. In Aged Garlic Extract, garlic is aged for 20 months in stainless steel tanks. This extract is then filtered and concentrated at low temperature (5). S-Allylcysteine is formed from γ-glutamyl- S-allylcysteine catabolism which is used to standardize commercial Aged Garlic Extract (6). Under acidic conditions, C-S bond cleavage is not observed which suggest that S-Allylcysteine can be absorbed in the gastrointestinal tract after oral administration without any changes (7).

GARLIC AND HELICOBACTER PYLORI:

Helicobacter pylori is now found to be the causal agent of gastritis (8) and gastric and duodenal ulcers (9). It is believed that garlic materials may provide a suitable basis for new anti Helicobacter pylori therapies as they possess well-established anti-microbial actions (10, 11).

Garlic components were accurately quantified with the use of established high performance liquid chromatography methods for the allyl thiosulfinate (12) and sulfide (13) constituents of garlic. Direct intragastric effects are feasible since gastric antimicrobials are least affected by acid environments (14) and gastric juice enhances the antimicrobial activity of garlic constituents(15). Garlic oil is produced commercially by heating crushed garlic cloves at 100 degree Celsius and the vapour is collected as a distillate (12). This process which has effects similar to that of cooking crushed garlic, allicin converts to diaalyl sulfide (DADS) and other garlic sulfides. Recently, reports have provided invitro evidence for anti- Helicobacter pylori activities of aqueous garlic extracts (16, 17, 18).

Studies by Cavallito and Bailey (19) and Stoll and Seebeck (20) have shown that the compound allicin is the main active antimicrobial agent provided by garlic. Allicin is formed catalytically when garlic cloves are crushed and the substrate of he bundle sheath cells mixes with the enzyme allinase (13). The main reason for seeking new therapies using garlic is that the wide spread use of antibiotics is associated with increased drug resistance problems like metro-nidazole and clarithromycin-resistant Helicobacter pylori strains have been reported (21).

Garlic materials may provide a required basis for new anti Helicobacter pylori therapies as they possess well-established anti-microbial actions (19,22). The chemical complexity of garlic materials along with their broad spectrum effectiveness suggest that the acquired antibiotic resistance would be unlikely. Helicobacter pylori infections are treated with potent combination therapies and these are found to have a success rate of 80-90% (23) but problems such as those of undesirable side effects (24,25) and poor patient compliance are are associated with treatment failure and contraindications for some patients. Also, the cost of this therapy is significant and nearly 90% of the cases have been reported in developing countries (26).

ANTIOXIDANT MECHANISM ASSOCIATED WITH AGED GARLIC EXTRACT:

S-Allylcysteine is the most important component studied under Aged Garlic Extract and has many antioxidant properties. S-Allylcysteine is known to have increased glutathione levels in kidney and liver and has enhanced catalase and glutathione peroxidase activities in kidney and liver (27). S-Allyl cysteine is also known to inhibit NO production in LPS/cytokine stimulated macrophages and hepatocytes through the suppression of iNOS gene expression (28).

NEUROPROTECTIVE EFFECTS OF S-ALLYLCYSTEINE:

Moriguchi et al. had reported that the positive actions of garlic compounds in rat hippocampal neuron culture with a thioallyl group. It was found that S-Allylcysteine increased the survival and axonal branching from neurons. From this, it was concluded that thioallyl group is important for neutrotrophic activity (29).

S-ALLYLCYSTEINE AND ALZHEIMER’S DISEASE:

Alzheimer’s disease is a devastating neurodegenerative disorder which leads to progressive loss of cognitive abilities, leads to accumulation of Aβ deposits in the basal forebrain, hippocampus and cortex (30). Some studies show that Alzheimer’s disease causes an overstimulation of the N-methyl-D-aspartate receptor at some points of the disease progress (31). This state is reproduced through Aβ and ibotenic acid administrations that has a feature which S-Allylcysteine significantly attenuates in the CA3 area (32).

S-ALLYLCYSTEINE IN ISCHAEMIC BRAIN DAMAGE:

Hypertension is believed to be the most important risk factor in the development of ischemic cerebral infarction in humans. Kim et al. studied this effect of S-Allylcysteine in stroke-prone hypertensive rats and demonstrated that S-Allylcysteine reduced mortality and the overall stroke related behavioural score (33). It has also been reported that the positive actions of S-Allylcysteine which is seen in the cerebral ischemia-induced damage to the hippocampus maybe due to possible modulation of mitochondrial dysfunctions.

S-ALLYLCYSTEINE IN HUNTINGTON’S DISEASE:

Huntington’s disease is an autosomal dominant neurodegenerative disorder which is characterized by gradual loss of neurons particularly in the striatum. This is due o the mutation in the huntington gene. Major clinical manifestations include chorea, psychiatric disorders most of which are related to striatal and cotical atrophy. In recent days, there is no treatment to prevent or to reduce the morphological and functional alterations which are seen in the brains of Huntington’s patients (34). S-Allylcysteine has been studied in two animal models such as 3-nitropropionic acid and quinolinic acid and its administration to rats infused with 3-nitropropionic acid showed prevention of behavioural alterations, increased copper or zinc superoxide dismutase activities and mitochondrial dysfunction (35).

S-ALLYLCYSTEINE IN PARKINSON’S DISEASE:

Parkinson’s disease is the progressive degeneration of dopaminergic neurons in the Substantia nigra pars compacta, along with a concomitant formation of intaneuronal fibrillar inclusions and depletion of noradrenaline and serotonin from the nuclei of the brain stem (36). In this, it was found that S-Allylcysteine protected dopamine levels, decreased ROS production, lipid peroxidation along with increased manganese and copper superoxide dismutase activity in a mice injected with MPP+ (37). Other Parkinsonian model is produced by 6-hydroxydopamine in which S-Allylcysteine is blocked by oxidative damage, prevents dopamine depletion and returned behavioural patterns to basal level in rats.

ROLE OF AGED GARLIC EXTRACT IN ATHEROSCLEROTIC PATIENTS:

Atherosclerosis is a multifactorial disease and a leading cause of mortality all over the world. Lipid peroxidation, LDL oxidation which is produced by free radicals and end-aldehyde products of lipid hydroperoxide breakdown play a major role in atherosclerosis. Munday et al; reported that LDLs which are isolated from subjects receiving 2.4g of Aged Garlic Extract daily for a week are found to be more resistant to oxidation than those LDL isolated from subjects receiving no supplementation which suggests that Aged Garlic Extract could be useful in preventing oxidative stress in atherosclerotic disease (38). Currently, there is no evidence whether antioxidants can reduce atherogenesis or not but it is viewed that Aged Garlic Extract and serum cholesterol lowing therapies maybe useful in the reduction of progression of atherosclerosis in humans.

ROLE OF AGED GARLIC EXTRACT IN SICKLE CELL ANAEMIA PATIENTS:

Sickle cell anemia is the prevalent inherited disorders with prominent morbidity and mortality. Reports show that oxidative stress plays a major role in the pathophysiology of this disease and hence contributes to the sicklng process with the formation of Heinz bodies which are aggregates of insoluble hemochromes (39). It is reported that Aged Garlic Extract reduced the number of Heinz bodies in sickle-cell anaemia patients and Aged Garlic Extract is viewed as a potential therapeutic agent to ameliorate the complications of sickle cell anemia (40).

CONCLUSION:

Many beneficial aspects have been attributed to garlic and it is capable of reducing the risk of stroke and neurodegenerative damage. S-Allylcysteine is a main antioxidant agent and also a water soluble compound which is less toxic than other antioxidants and is easily absorbed in the gastrointestinal tract. Plants saponins are known to inhibit cholesterol absorption from the intestinal lumen. Saponins contribute to the cholesterol lowering effect of garlic. Many steroid saponins occur in Aged Garlic Extract and garlic. So, further attention and research in the study of garlic may give rise to various medically valuable arenas.

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Received on 27.06.2017 Modified on 24.07.2017

Research J. Pharm. and Tech. 2018; 11(1): 393-396.

DOI: 10.5958/0974-360X.2018.00072.0