INTRODUCTION:

Jaundice is one of the most common diseases affecting a large portion of citizens throughout the whole world. It is very much common disease especially in the developing countries. Jaundice is actually some sign and symptoms which are occurred due to various other diseases. During Jaundice the concentration of bilirubin in the blood becomes very high which may be due to haemolysis¹. Yellowish eyes and vomiting with yellowish fluid are commonly found to be the initial symptoms of Jaundice. Bilirubin is biosynthesized in the body. Liver cells produce bilirubin through a process called hemolysis. Jaundice may result due to different types of liver diseases which includes various types of hepatitis, liver cirrhosis, hemolytic anaemia, etc.²

Garlic is classified as a spice, herb, or vegetable. Together with onions, leeks, shallots, and chives, it is one of the main Allium foods consumed by humans. A garlic bulb consists of several individual pieces, also known as onions or cloves, weighing about 3g each. The actual intake of garlic is not known with certainty, mainly because they are not usually taken into account in dietary assessment surveys. However, income is assumed to vary from region to region and from individual to individual In 1981, the annual per capita retail consumption of fresh garlic was 0.5 pounds. According to In 1991, annual consumption increased to 1.2lb per person. After peaking at 3.1lb in 1999, retail consumption dropped to 2lb per person in 2001.9 Steinmetz et al.¹⁰ provided evidence that the average intake in parts of the US Midwest is around 0.6g per week or less, while intake in some parts of China can reach 20g per day. Data used in the colorectal and gastric meta-analysis cancer indicated mean intake (±SD) of raw and cooked garlic intake across all published reports was 18.3±14.2g per week or about 6 cloves of garlic per week. 11 Consumption ranged from none up to 3.5g per week (about 1 clove), with the highest intake exceeding 28.8g per week (about 9 up to 10 cloves).¹¹

Negative consequences are not always the result of excessive intake of garlic, but some individuals may be more susceptible to side effects than others. Although their incidence is low, a spectrum of adverse allergic reactions may occur after contact with garlic.¹² Although garlic is recognized as a strong irritant, there are relatively few reports of allergic contact dermatitis literature.¹³ Avoiding direct contact seems to be the most logical approach for food handlers who are sensitive, but this may be more difficult than expected as active diallyl disulfide (DADS). irritant penetrates most commercially available gloves.¹⁴

Excessive intake of garlic has also been reported to lead to hemolytic anemia. Gravity anemia correlates with reduced glutathione with reduced erythrocytes (GSH) and plasma ascorbic acid¹⁵ Incubation of canine erythrocytes with sodium 2-propanil thiosulfate from garlic was found to increase the concentration of methemoglobin and the occurrence of Heinz bodies, suggesting that this the compound may be the cause of oxidative damage to canine erythrocytes.¹⁶ Umar et al. found that ascorbic acid or vitamin E supplements prevented the garlic-induced decrease in GSH and plasma ascorbic acid, thereby providing greater protection to the erythrocyte membrane.

GARLIC COMPOSITION AND CHEMISTRY:

The use of garlic is usually centered on its unique flavor and aroma. Unlike other foods, garlic is characterized by the fact that about 1% of its dry weight is sulfur.¹⁷ Garlic is a somewhat limited nutritional value, as its total intake is usually low, even though it is more nutritious than onions based on fresh weight. A 3g serving of garlic provides about 4.5mg of potassium, 0.6g carbohydrates, and trace amounts of calcium, fiber, iron, and vitamin C. Table 1 lists some information on the composition of garlic. Carbohydrates make up about 33% of the weight of garlic, while protein makes up another 6.4%. While the many health benefits of garlic were attributed to its sulfur components, its other components, including arginine, selenium, oligosaccharides, and flavonoids, may influence the overall response.¹⁸ The chemistry of the sulfur compounds found in garlic is extremely complex and not complete^19-21 regardless, it is known that the primary sulfur-containing components in garlic bulbs are γ-glutamyl-S-alk(en)yl-L-cysteines and S-alk(en)yl-L-cysteine sulfoxides. Content S-alk(en)ylcysteine sulfoxide in garlic typically ranges between 0.53 to 1.3% fresh weight, with alliin (S-allyl cysteine sulfoxide) being the largest contributor²².This variation likely reflects environmental factors, including climate or growing conditions.^23,24 Similarly used can significantly affect the amount and types of individual sulfur compounds.²⁵ Alliin concentrations may increase during storage due to the transformation of γ-glutamyl cysteine. In addition to alliin, garlic cloves contain small amounts of (+)-S-methyl-L-cysteine sulfoxide (methiine) and (+)-S-(trans-1-propenyl)-L-cysteine sulfoxide, S-(2-carboxy propyl)glutathione, Yglutamyl-S-allyl-L-cysteine, γ-glutamyl-S-(trans-1-propenyl)-L-cysteine and γ-glutamyl-S-allyl mercapto-L-cysteine.^17,26

TABLE 1 Content* of Selected Components in Edible Garlic

Water	g 58.6
Energy	kcal 149.0
Protein	g 6.4
Total lipid (fat)	g 0.5
Carbohydrate	g 33.1
Fiber, total dietary	g 2.1
Calcium	mg 181.0
Magnesium	mg 25.0
Phosphorus	mg 153.0
Potassium	mg 401.0
Selenium	mcg 14.2
Vitamin C	mg 31.2
Folate	μg 3.1

*Component Amount/100 g

A USDA Nutrient Database for Standard Reference, Release 13 (November 1999)

Oil-soluble sulfur compounds formed when the bulb is crushed or damaged. This membrane destruction provides several organic sulfur degradation products as a result of the release of enzyme alliinase. This enzyme rapidly converts alliin to aromatic alkyl alkane thiosulfate, including allicin. Because allicin is unstable, it further breaks down into sulfides, ajoene, and dithiins.^27–29 Tamaki and Sonoki²⁹ reported that strong garlic flavor and aroma were associated with higher volatile sulfur content. Not surprisingly, heating garlic reduced allyl mercaptan (AM), methyl concentration of mercaptan, and allyl methyl sulfide (AMS) and reduced its odor perhaps because inactivation of alliinase activity.²⁹

Studies by Arnault et al.²⁰ provide evidence of the quality and stability of some preparations currently available on the market are worrying because different types of preparations cannot be considered equal. However, the stability of some of them seems to be acceptable to Lawson and Gardner.³⁰ They reported that allylthiosulfinates of mixed fresh garlic were stable for at least 2 years when stored at -80°C. Likewise, they found the dissolution of the release of thiosulfate from enteric-coated garlic tablets was nearly 95%, and bioavailability, as determined by breath allyl methyl sulfide, was virtually complete and equivalent to that found in crushed fresh garlic. S-allyl cysteine (SAC) was found in deodorized garlic preparations it is stable for 12 months when stored at ambient temperature.³⁰ Undoubtedly, more information on the composition should be provided for any garlic preparation available on the market, especially when claims are made about a specific preparation.³¹ Greater attention to types and the number of active compounds in different products will likely resolve some of the inconsistencies in the literature on the potential health benefits of garlic and commercially prepared garlic. extracts, solutions, or tablets. Arnault et al.²⁰ suggested high-pressure liquid chromatography. The profile can be a useful tool not only for understanding the composition of different garlic preparations but also for identifying the relative effectiveness of these preparations in slowing disease. However, standardization of different garlic preparations about one ingredient is not possible because different preparations available on the market probably have completely different active ingredients. The development of reference assays that can assess relative biological activity/efficacy across preparations may be one of the only solutions for comparing different preparations available on the market. Several studies have investigated the in vivo pharmacokinetics of allyl sulfur compounds. However, Lachmann et al.³² described the distribution of allicin and vinyldithiine in oil form macerate of 35S-labeled substances in the rat. Overall, absorption and elimination of 35S alliin were faster than other garlic components, with peak blood levels reached during the first 10 minutes after exposure. Elimination of alliin from the blood was almost complete after 6 hours.

The maximum concentrations of 35S-allicin in the blood were reached only 30 to 60 minutes after treatment, and for vinyldithiine, the maximum was reached only after 120min. Both allicin and vinyldithiine were present in the blood at the end of their 72-hour study. Urinary excretion indicated absorption at a rate of approximately 65% for allicin and 73% for vinyldithiins. However, Lawson and Wang 19 suggest that the absorption of allicin in humans is about 95%. accuracy was limited due to rapid metabolism and absence in blood after consumption. Allicin is known to be rapidly converted to DADS and allyl mercaptan (AM) in the liver.³³ DADS can also be further transformed into AM, allyl methyl sulfide, allyl methyl sulfoxide, and allyl methyl sulfone.³⁴ Teyssier et al.³⁵ provided evidence that DADS can be converted to diallylthiosulfinate (allicin) in tissues mainly by oxidation arising from cytochrome P450 monooxygenases and to a limited extent range by flavin-containing monooxygenases. Interestingly, their data suggest that DADS is preferentially metabolized in the human liver to allicin by cytochrome P450 2E1 (CYP2E1). How DADDY can it also cause auto-catalytic destruction of CYP2E1, it is not clear how much allicin may be formed under physiological conditions. Flavin-containing monooxygenases in the liver are likely responsible for the oxidation of S-allyl cysteine (SAC), among many other sulfur compounds.³⁶ P450 monooxygenases do not appear to be involved in SAC metabolism.

Comparisons of water- and oil-soluble compounds from garlic have rarely been investigated in the same study. However, the available evidence suggests that there are large differences in effectiveness between them extracts are not of primary importance.^37–42 While subtle differences between garlic preparations are likely to occur, the quantity rather than the source appears to be the key factor influencing the response.³⁷ The differences that occur between the preparations are very likely related to the content and effectiveness of individual sulfur components. The number of sulfur atoms present in the molecule appears to affect the response with diallyl trisulfide (DATS), which is generally considered more effective than DADS, which is superior to diallyl sulfide (DAS).^43–44 Likewise, the presence of an allyl group generally enhances the response over that provided by the propyl group.^45,46

IMPLICATION IN HEALTH:

Garlic and a number of its allyl sulfur compounds have been reported to have various health effects and benefits. Antimicrobial, Anticarcinogenic, and protective benefits are notable among them in cardiovascular disease. While long-term intervention studies are lacking, several laboratory and epidemiological studies suggest that key molecular targets involved in the risk of several diseases may be affected by these organosulfur compounds derived from garlic.

ANTIMICROBIAL EFFECTS:

Several plants are reported to act as antimicrobial agents. Those rich in tannins, terpenoids, alkaloids, flavonoids, and sulfur compounds are particularly effective. Historically, garlic extracts have been labeled as universal antibiotics.⁴⁷ There is considerable evidence to support this that garlic extracts can inhibit a variety of Gram-negative and Gram-positive bacteria and serve as antifungal.^48–50 In addition to allicin, various other sulfur compounds are used including DAS, DADS, E-ajoene, Z-ajoene, E-4,5,9-trithiadeca-1,6-dien-9-oxide (E-10-devinylajoene, E-10-DA), and E-4,5,9-trithiadeca-1,7-diene-9-oxide (iso-E-10-divinyl alone, iso-E-10-DA) may contribute on the antimicrobial properties of garlic.^51–53 For example, in vivo protection against methicillin Staphylococcus aureus infection in BALB/CA mice was demonstrated with orally administered DAS and DADS.⁵³ Although differences in potency between these compounds exist, they are relatively small amounts and are effective deterrents against microbial growth. However, not all microorganisms are the same and susceptible to the toxic effects of individual sulfur compounds.^54,55 Ruddock et al.⁵⁶ recently investigated the microbial activity of several garlic products found on the Canadian market and observed a general trend toward increased in vitro antibacterial activity for these products containing a higher amount of allicin. Those products with marginal antibacterial activity often contained lower concentrations of active ingredients than indicated on their labels, which suggests a need to standardize garlic preparations used in research Recently, a new protein in garlic, called allium in, has been identified that does both antimicrobial and antifungal activity.⁵⁷ It is noteworthy that the antifungal effect of allium in was preserved after exposure to 100°C for 1 h, indicating significant thermostability. As sure antifungal proteins that inhibit the proliferation of tumor cells, allium was found to be inhibitory L1210 cells; but interestingly it was shown to have no such activity against Hep G2 cells. Further characterization of allium is likely to shed light on its antifungal properties and may also provide further evidence of garlic's health-promoting activity. Colonization of the gastric mucosa by Helicobacter pylori is increasingly associated with gastritis. Likewise, new evidence links gastritis with a greater tendency to develop stomach cancer. Studies by Cellini et al.⁵⁸ provide fairly convincing evidence that aqueous extracts of garlic (2 to 5mg/ml) inhibit the proliferation of Helicobacter pylori. Reduced efficacy occurred when garlic was heated before extraction.⁵⁸ This decrease in activity indicates the need for decomposition products from Alliin to achieve maximum response. How both DAS and DADS are recognized to induce a dose-dependent depression of Helicobacter pylori proliferation in culture,⁵⁹ reduction of their formation may be the cause of the loss of efficiency caused by heating. Extracts from raw garlic and three commercially available garlic tablets have been found to vary in their effectiveness as indicated by minimum inhibitory concentration in the range of 10 to 17.5 μg dry weight/ml.^60\

Effect of garlic in vivo on H. pylori-induced gastritis in Mongolian gerbils reported⁶¹Although the number of viable H. pylori did not change with garlic extract treatment, garlic reduced the number of hemorrhagic spots in the glandular stomach and the microscopic score on gastritis compared to gerbils fed a control diet. These findings suggest that garlic and its active components may exhibit secondary or indirect effects, such as effects on inflammation or immunocompetence pathways, in addition to a direct effect on the viability of certain bacterial cells. The ability of garlic to reduce H. pylori infection in humans is inconclusive. Although an epidemiological study suggests an association between increased and decreased consumption of garlic H. pylori infection,⁶² two clinical trials testing different garlic preparations in H. pylori-infected patients subjects did not demonstrate efficacy.^63,64 None of these interventions resulted in the elimination of organisms, a change in the severity of gastritis, or a significant change in the symptom score. Both the studies were not randomized and had a small sample size, suggesting that this was a well-designed clinical trial a trial is still needed to determine the effectiveness of garlic consumption in reducing H. pylori infection and its symptoms. Allium foods, including garlic, are also effective in suppressing fungal growth.⁵⁰ Allicin has it has been reported to protect against Candida albicans and several other strains. These organisms were extremely sensitive to garlic extracts, some to a greater extent than to nystatin, which is known as an effective antibiotic.⁶⁵ Ajoene is also known for its antifungal activity in vitro and in vivo. AND a fungal infection of the skin known commonly as ringworm and medically as tinea corporis can also be affected by the sulfur compounds found in garlic. Ledezma et al.⁶⁶ found that treatment with ajoene (0.6% ajoene or 1% ajoene gel) was as effective as terbinafine (1% cream) in healing tinea corporis and tinea cruris in 70 soldiers with dermatophytosis. Like ajoene, it is easy to prepare garlic and may be particularly useful as a public health strategy, especially in developing countries. The primary antimicrobial effect of garlic may reflect chemical reactions that occur with selected thiol groups of various enzymes and/or a change in the overall redox state of the organism. Specifically, the antimicrobial action of allicin and its breakdown products were proposed are the result of its rapid interaction with SH-containing molecules, including amino acids and cellular proteins in microbial organisms.50 An example of such a putative reaction in vivo is the reaction between allicin and glutathione (GSH), which is considered the major intracellular mammalian thiol, and the investigators isolated the product of the reaction, determined its structure, and studied its interaction with thiol-containing proteins.⁶⁷ GSH was observed to react with allicin in the following method: 2GSH+ ZCH2-CH-CH2(SO)-S-CH2-CH=CH2(allicin) → 2GS-S-CH2-CH=CH2(S-allylmer captoglutathione) (GSSA) + H2O. As a proof of principle, it was found that in vitro GSSA reacted with proteins containing thiol papain and alcohol dehydrogenase from Thermoanaerobium brockii and inhibited their activity, while both proteins were reactivated using either reducing agent dithiothreitol or 2-mercaptoethanol. Simultaneous release of allyl mercaptan in both of these case reactions showed that the triallyl group binds to inactivated proteins in the same way as allicin has been shown to do. It is interesting to note that one enzyme that can be similarly affected by allicin breakdown products (ie DATS, SAC) is squalene monooxygenases.⁶⁸ Such activity can explain the antifungal properties of allicin because squalene monooxygenases are an important enzyme for the formation of the cell wall of the fungus.⁶⁹ Changes in the state of thiols have been proposed as one of the possibilities mechanisms by which garlic and related sulfur compounds might also suppress tumor proliferation.

CANCER:

Scientists, legislators, and consumers are increasingly aware that several foods can contribute to health, including reducing the risk of cancer.^70,71 Although there are some limitations in defining The exact role that garlic has in the cancer process, the probability of its importance is underlined by both epidemiological and laboratory investigations. Although there is epidemiological support for the association between increased intake of garlic and/or its active ingredients with certain cancer, data are very limited.^10,72,73 Results from the Iowa Women's Health Study, a prospective cohort study found the strongest association between fruits and vegetables for colon cancer risk reduction was related to the consumption of garlic with a reduced risk of approximately 50% in the distal colon cancer associated with high garlic consumption.¹⁰ In addition, a meta-analysis of data from seven epidemiological studies has found an inverse relationship between the consumption of raw and cooked garlic and the risk of stomach and colon, and rectal cancer.⁷² In addition, Hsing et al.⁷³ reported that decreased Prostate cancer risk in those consuming increasing amounts of allium vegetables was also independent of body size, intake of other foods, and total calorie intake. Several interventional studies have been conducted to investigate the effectiveness of garlic in the prevention of cancer treatment. In a double-blind, randomized trial of Japanese patients with colorectal adenoma, a higher dose of mature garlic extract was shown to reduce the risk of new colorectal adenomas compared to a lower dose of garlic extract.⁷⁴ Considering the observations of a case-control study of stomach cancer in Shandong, China, which showed that those in the highest quartile of allium-containing vegetable intake (including garlic, garlic scallions, scallions, chives, and onions) had only a 40% regarding risk in those in the lowest income quartile,⁷⁵ researchers included garlic supplementation arm (800 mg of garlic extract plus 4 mg of steam-distilled garlic oil daily) in a randomized multi-interventional trial to inhibit the progression of precancerous gastric lesions in the same area China.⁷⁶ The compliance rate after 39 months of treatment with garlic preparation was 92.9% measured by several pills;⁷⁷ study results were not yet available. Preclinical models (Table 3) provide some of the most compelling evidence that garlic and its related sulfur components suppress the risk of cancer and alter the biological behavior of tumors. Overall, garlic and its related sulfur components were found to suppress the incidence of carcinoma of the breast, colon, skin, uterus, esophagus, lung, kidney, foreskin, and liver.^38,78–85 Aberrant crypt foci (ACF) are a proposed early preneoplastic lesion of human adenocarcinoma and chemically induced colon cancer in rodents. In many preclinical studies, both water- and fat-soluble compounds of allyl sulfur were administered to animals through their diet inhibit ACF.^86–88 Protection against cancer may result from several mechanisms, including blockade of carcinogen formation, suppressed bioactivation of carcinogens, increased DNA repair, decreased cell proliferation, and/or induction of apoptosis. It is possible and quite likely that several of these cellular events are edited simultaneously

NITROSAMINE AND HETEROCYCLIC AMINE FORMATION:

Human beings are exposed to a complex array of substances that can contribute to cancer through food sources. Nitrosamines, heterocyclic amines, and polycyclic aromatic hydrocarbons are potential dietary carcinogens that are not normally found in foods but may appear during canning or cooking.⁸⁹ Human exposure to these suspected carcinogens occurs through ingestion or inhalation of preformed NOCs or ingestion of precursors that are endogenously combined.⁹⁰ Considerable evidence points to the ability of garlic to suppress the formation of several N-nitroso compounds (NOCs).^91,92 The ability of garlic to reduce NOCs may be secondary to the increase in the formation of nitrosothiols. Williams⁹³ suggested that several sulfur compounds could promote the formation of nitrosothiols, thereby reducing the amount of available nitrite NOC formation. Studies by Dion et al.⁵¹ revealed that not all allyl sulfur compounds are created equally effective in stopping NOC formation. The ability of SAC and its nominally analog S-propyl cysteine to slow NOC formation—but not DADS, dipropyl disulfide, and DAS-reveal the critical role played by the cysteine residue in this inhibition.⁵¹ Because the allyl sulfur content can vary among preparations, it is likely that not all sources of garlic are equal in the protection they provide against the formation of NOC. Part of the protection against NOC exposure may also be related to the antimicrobial properties associated with garlic and some of its components, as discussed above.

Some of the most convincing evidence that garlic suppresses nitrosamine formation in humans comes from studies by Mei et al.⁹⁴ In their studies, administration of 5g of garlic per day completely blocked increased urinary excretion of nitroso proline that occurred as a result of supplement ingestion nitrate and proline. The significance of this observation comes from the predictive value that nitroso proline has for the synthesis of potentially carcinogenic nitrosamines.⁹⁵ Evidence that the effect of garlic occurs with nitrosamines other than those excreted in the urine comes from the data of Lin et al.⁹⁶ Their studies provided evidence that garlic was effective in blocking liver and DNA adducts resulting from feeding NOC precursors. The anti-cancer benefits attributed to garlic are also linked to its allyl sulfur ability compounds to suppress carcinogen bioactivation. Evidence from various sources shows this garlic is effective in blocking DNA alkylation, which is the primary step in nitrosamine carcinogenesis.^82,97 Consistent with this reduction in biological activation, Dion et al.⁵¹ found that both water-soluble SAC and fat-soluble DADS were effective in retarding the mutagenicity of N-nitroso morpholine in Salmonella typhimurium TA100. Blockade of mutagenicity after exposure to aqueous garlic extract has also been reported after treatment with ionizing radiation, peroxides, adriamycin, and N-methyl-N-nitro-nitroso proline.⁹⁸

A block in nitrosamine bioactivation may reflect changes in several enzymes. However, substantial evidence points to the involvement of CYP2E1^99,100. Autocatalytic destruction of CYP2E1 may be responsible for some of the chemo-protective effects of DAS and possibly other allyl sulfur compounds.¹⁰¹ Differences in P4502E1 content and overall activity may be an important variable in the degree of protection provided by garlic and associated allyl sulfur components. In vivo bioactivation of heterocyclic amines to carcinogenic species is known to have been initiated by N-oxidation. This reaction occurs primarily in the liver and is catalyzed by cytochrome P4501A2 (CYP1A2) in humans. Davenport and Wargovich¹⁰² reported that in rats administer a single bolus of 200 mg/kg DAS and AMS increased hepatic CYP1A2 protein (but not mRNA) by 282 and 70% respectively. Acetylation or sulfation of N-hydroxy-HCA may also occur by the action of acetyltransferases (NAT) and sulfotransferases, which create N-acetoxy and N-sulfonyloxyesters, electrophiles that are much more reactive with DNA. Several studies provide evidence that garlic-derived organosulfur compounds can effectively reduce NAT activity. Recent studies by Yu et al.¹⁰³ demonstrated that suppression of NAT mRNA expression accounts for most of the reduction in activity.

CARCINOGEN ACTIVITY MODULATION:

Garlic and several of its allyl sulfur compounds can also effectively block the bioactivation of carcinogenicity of non-NOCs. This protection, which includes a diverse range of compounds and several target tissue sites, suggests either multiple mechanisms of action or an extended biological effect.

Garlic has also been found to reduce the incidence of tumors resulting from treatment methyl nitrosourea (MNU), a known direct-acting carcinogen.⁹⁶ Provision of water-soluble S-allyl cysteine and fat-soluble DADS at a dose of 57μmol/kg diet was reported to cause a comparable reduction in MNU-induced O6-methylguanine adducts bound to breast cell DNA.41 A study by Ludeke et al.¹⁰⁴ revealed that DAS reduced DNA hypermethylation of esophagus, liver, and nasal mucosa which was formed by the action of Nnitrosomethylbenzylamine This finding suggests that the bioactivation of several carcinogens known to affect DNA methylation patterns¹⁰⁵ may also be affected by garlic and its many sulfur components.⁹² However, not all evidence supports SAC as protection against MNU-induced mammary tumors.¹⁰⁶ The reason for this discrepancy is unknown but may be related to the number of lipids in the diet or the amount of carcinogen provided. If DADDY and/or SAC are potent blockers of MNU carcinogenesis, the mechanism(s) remain unresolved. Because many of these carcinogens are used in studies focused on when investigating the anticarcinogenic properties of garlic, phase I and II enzymes do likely plugged in. Recent observations show that the activity of several phases I enzymes, in addition to P450- 1A2 and -2E1, are modified after treatment with garlic or similar sulfur compounds.102,^107–109

The effect of organosulfur compounds (OSC) on phase I metabolizing enzymes is quite diverse. For example, previous studies have shown that DAS competitively inhibited CYP2E1 activity, however, significantly increased the transcriptional levels of CYP1A1, CYP2B1, and CYP3A1 in rat liver.^108,110. Therefore, the role of garlic OSCs in carcinogenic biotransformation may be substrate specific.

The significance of any mild induction of certain P450 activities is not clear, but some reports suggest that induction of P450 metabolic enzymes may increase the rate of clearance of toxicants metabolites.¹¹¹ Other enzymes and pathways are involved in the observed protection from garlic supplements in the bioactivation or removal of carcinogenic metabolites. Singh et al.¹¹² provided evidence that the efficacy of various organosulfides to suppress benzo(a)pyrene tumorigenesis correlates with their ability to induce NAD(P)H: quinone oxidoreductase (NQO), an enzyme that participates in the removal of quinones associated with this carcinogen. Investigators recently found that this inductive effect of organosulfur compounds appears to be mediated by resident antioxidant response enhancer (ARE) sequence bound by nuclear factor E2- related factor 2 (Nrf2) in the NQO1 and heme oxygenase 1 (HO1) gene promoters.¹¹³ organosulfur compounds – DAS, DADS, or DATS – were found to act differently at transcriptional levels of NQO1 and HO1. It appeared that the third sulfur in the OSC structure has a major contribution to this biological activity, and allyl-containing OSCs were more effective than OSC-containing propyl. The data also suggest that detoxification enzymes are up-regulated by garlic OSCs through Nrf2 protein accumulation and ARE activation may be partly due to stress signals originating from oxidative stress and/or calcium-dependent signaling pathways.¹¹³ Changes in glutathione concentration and specific glutathione-S-transferase activity, both factors involved in phase II detoxification may be important for the protection afforded by garlic. Both DADS and DATS have been shown to increase GST activity in various rat tissues.¹¹⁴ Preventive effects of garlic powders, containing different levels of sulfur compounds, on the development of preneoplastic foci initiated by aflatoxin B1 (AFB1) in rats were recently characterized.²⁴ The final metabolite of AFB1, AFBO, is conjugated to glutathione by GST and more specifically GST A5; Thus, GST has been investigated as the mechanism responsible for any chemo-protective properties of garlic against AFB1-induced carcinogenesis. Eating garlic was effective in protecting against AFB1 and GST protein carcinogenesis induced by DADS treatment levels and activities, especially GST A5. Thus, not all GST isoenzymes may be affected equally. Earlier evidence from Hu et al.46 provided support that induction of glutathione (GSH) S transferase pi (mGSTP1-1) may be particularly important in the anticarcinogenic properties associated with garlic and allyl sulfur components.

CELL CYCLE ARREST/APOPTOSIS:

Recent evidence suggests that garlic components (ie DADS, DATS, SAMC, ajoene) can suppress the proliferation of several different cancer cells by blocking cell cycle progression and/or causing apoptosis (also known as programmed cell death)^115–117 Current knowledge of the mechanisms by which these compounds cause apoptosis shows that garlic components target various molecules signaling apoptosis from initiation to execution, including MAPK (JNK, ERK1/2, and p38), P53, NF–kB, bcl-2 family, and caspases,¹¹⁶ but not all signaling molecules were affected by each of the garlic components. However, in many studies apoptotic effects components of garlic were triggered by increased intracellular production of reactive oxygen species (ROS), suggesting the importance of the intracellular redox environment for the induction of apoptosis. An example is the ability of DADS to induce apoptosis, as well as cell cycle arrest at the G2/M phase, in human A549 lung cancer cells in a time- and dose-dependent manner.¹¹⁷ Study, DADS caused not only a dose-dependent increase but also a time-dependent change in ROS.

Production and oxidation flare was found to be an early event, occurring less than 0.5 h after Treatment of DADS. These investigators hypothesized that increased ROS may also act on an important signaling molecule in the observed cell cycle arrest induced by DADS. Several mechanisms have been cited for the cell cycle arrest effect of garlic components, including reduced Cdk1/cyclin B kinase activity or extracellular signal-regulated activation kinases (ERK1/2).^115,118 Knowles and Milner¹¹⁹ showed that DADS-mediated suppression Cdk1 kinase activity during cell cycle arrest in G2/M was not due to direct interaction with protein, but was associated with (a) a transient and dose-dependent increase in cyclin B1 protein (b) reduction of Cdk1–cyclin B1 complex formation level, (c) inactivation of Cdk1 hyper phosphorylation and (d) reduction of Cdc25C protein level. Evidence suggests a complex and coordinated interaction of many factors for the observed DADS-induced cell cycle arrest. In addition, gene expression analysis indicated that changes in DNA repair and cellular adhesion factors may also be involved in the G2/M block after DADS exposure.¹²⁰

DNA REPAIR:

Exposure of cells to mutagens including intracellular by-products of cellular metabolism (ROS, endogenous alkylating agents) or extracellular influences (carcinogens, UV, or ionizing radiation) can cause DNA damage that manifests as genomic instability, cellular senescence, and/or cell death. Initially, the cell attempts to repair the damage, but if it is too extensive, a cascade of alternative cells is formed reactions including cell cycle arrest or induction of apoptosis may occur. There are three main mechanisms of DNA repair: base-excision, nucleotide excision, and mismatch correction. There is very little information about garlic or its organosulfur components such as a modifier of DNA repair, although there is evidence that pretreatment with garlic extracts was reported that stimulates DNA repair in human fibroblasts after treatment with cadmium chloride, gamma radiation, and 4-nitroquinoline-1-oxide.¹²¹ Regardless, several studies have shown that histone/chromatin modifications such as acetylation, methylation, and phosphorylation have a play a key role in DNA repair processes, and some evidence suggests that garlic might affect them or more of these repair determinants.

EPIGENETIC MODULATION:

Cancer progression is also likely to be highly dependent on epigenetic changes. Several regulatory proteins including DNA methyltransferases, methyl-cytosine guanine dinucleotide binding proteins, histone modifying enzymes, chromatin remodeling factors, and their multi-molecular complexes are involved in controlling the epigenetic process.¹²² Because epigenetic events can be influenced by several dietary components represents another possible site for intervention with bioactive substances and food components.¹²² As previously mentioned, there is evidence that some components of garlic can affect others aspect of epigenomics, namely histone homeostasis. Lea et al.¹²³ reported that at least part of the ability of DADS to induce differentiation in murine DS19 erythroleukemic cells may be related to its ability to increase histone acetylation. DADS caused a marked increase in H4 acetylation and histone H3 in human leukemia cells DS19 and K562. Consistent with other disulfide studies was found to be more effective than monosulfide. In a more recent paper, these investigators found that inhibition of cell proliferation by SAC and SAMC DS19, Caco-2 human colon cancer, and T47D human breast cancer cells were associated with increased histone acetylation.¹²⁴ More recently, Druesne et al.125 reported that DADS and AM effectively increased histone H3 acetylation in cultured Caco-2 and HT-29 cells. Hyperacetylation of histone H4 was found to occur preferentially on lysine residues 12 and 16. The reason for this hyperacetylation may be related to the observed decrease in histone deacetylase activity.125 This change in hyperacetylation was also accompanied by increasing p21(waf1/cip1) expression at the mRNA and protein levels, again demonstrating that epigenomic events can influence downstream patterns of gene expression and lead to accumulation cells in the G2 phase of the cell cycle.¹²⁵ DADS and AM are rather unique in that they join a relatively few food components, butyrate, and sulforaphane, as modifiers of histone homeostasis.¹²⁶

REDOX AND ANTIOXIDANT CAPACITY:

It is well-documented that ROS is involved in the etiology of various diseases. As a result, special attention was paid to the identification of antioxidants in human foods. Different Methods were used to evaluate the total antioxidant activity of available garlic preparations in the marketplace. Any single method is undeniably inadequate because the answer depends not only on its ability to reduce oxidative radicals but on its ability to chelate metals. Regardless both alliin and allicin are known to have antioxidant properties in the Fenton oxygen radical generating system [H₂O₂-Fe(II)].^67,127 In addition, the antioxidant effects of garlic and its components have been documented due to their ability to scavenge ROS, inhibit lipid peroxide formation, slow LDL oxidation, and by strengthening endogenous antioxidant systems.^6,128 Various organosulfur compounds, although not all, have been reported to exhibit antioxidant activity Properties. DADS, but not DAS, was found to inhibit dipropyl sulfide or dipropyl disulfide liver microsomal lipid peroxidation induced by NADPH, ascorbate, and doxorubicin.¹²⁹ The presence of allyl and sulfur groups appears to increase the antioxidant capacity molecule. Both the number of sulfur atoms and the oxidation state of the sulfur atoms can influence overall antioxidant potential.¹³⁰ While allicin is effective in retarding the oxidation of methyl linoleate, it is less than that caused by α-tocopherol.¹³¹ Organosulfur compounds such as SAC are recognized as powerful antioxidants and radical scavengers with a strong ability to minimize oxidation.¹²⁸ Garlic oil is also an effective antioxidant against oxidative damage caused by various agents suggesting that both water- and fat-soluble organosulfur compounds may be effective antioxidants. Although some garlic oil preparations on the market may contain about nine times more vinyl-dithiins and four times more ajoene, these preparations had no free radical scavenging properties, which again suggests that not all organosulfur components have antioxidant properties.¹³² It is also clear that heating garlic can not only denature proteins, but also its antioxidant properties.¹³³

IMMUNOCOMPETENCE/IMMUNONUTRITION:

It is increasingly recognized that diet plays an important role in the development and function of immunocompetent cells. Several dietary components, including garlic extracts and allyl sulfur compounds, may have physiologically important immunomodulatory effects.^7,134,135 the ethanol extract prepared from the garlic powder sample significantly stimulated the proliferation of rat spleen lymphocytes in culture, which correlated with up-regulation of interleukin 2- alpha receptor expression and increased IL-2 production.¹³⁵ These data also suggest that the potentiating effect of garlic extract on lymphocyte proliferation in vitro varied depending on specific stimulators of cell proliferation; speculate that the in vivo response would depend on the type of corresponding cells. These researchers also demonstrated that aqueous and ethanol extracts of two garlic powders significantly modulated the proliferation of rat thymocytes and splenocytes in vitro on concanavalin A.¹³⁶ Both garlic extracts significantly modulated lymphocyte proliferation, triggered by this potent T-cell mitogen, but the response was a type- and dilution-dependent extracts and concentrations of concanavalin A. Interestingly, at higher concentrations of extracts an inhibitory effect on T-cell proliferation was observed, while significant at lower concentrations there was an increase in T-cell proliferation. Ghazanfari et al.¹³⁷ found that garlic extract administered i.p. on BALB/c mice was effective in reducing Leishmania major infection and this response was associated with an enhanced TH1 immune response manifested by higher production of IFNg and IL-2. These results support the concept that garlic may be a potent modulator of T cell-mediated immune functions in vivo. In another in vivo study, DAS treatment of BALB/c mice was reported to block suppression of the antibody response caused by N-nitroso dimethylamine to T-cell-dependent antigens, and lymphoproliferative response to T-cell and B-cell mitogens.100 However, the effects are not limited to sulfur compounds as found in the protein fraction isolated from aged garlic extract enhance the cytotoxicity of human peripheral blood lymphocytes (PBLs) against the natural killer-sensitive K562 cell lines as well as the NK-resistant M14 cell lines.¹³⁸ A 14kDa glycoprotein was recently isolated in garlic and has been found to potentiate the delayed-type hypersensitivity reaction,¹³⁹ and also increase natural killer cell activity in BALB/c mice given i.p.¹⁴⁰ Mechanism(s) by which sulfur or non-sulfur components of garlic affect immunocompetence remains to be determined. Garlic compounds may also be modulators of inflammatory molecules, including cytokines which exhibit a wide range of regulatory functions in both adaptive and innate immunity. DADDY and AMS, in addition to DAS,¹⁴¹ demonstrated different effects on cytokine production in LPS-activated macrophages. DAS inhibited both pro-inflammatory and anti-inflammatory cytokines, including TNF- α, IL-β, IL-6, and IL-10 in stimulated macrophages. DADS enhanced pro-inflammatory cytokines IL-β and IL-6, but suppressed the anti-inflammatory cytokine IL-10, indicating the effect of DADS can lead more to inflammation. On the other hand, AMS decreased to a lesser extent production of NO and TNF-α in activated macrophages but significantly increased IL-10 production, suggesting that AMS may be a potent anti-inflammatory compound. Allicin and ajoene have been reported to cause dose-dependent inhibition of the inducible substance nitric oxide synthase system (iNOS) in RAW 264.7 macrophages¹⁴² stimulated with lipopolysaccharide (LPS). mRNA. Therefore, there may be changes in the amount or ratio of concentrations of NO and peroxynitrite significant in the observed reduction of inflammation by garlic and related sulfur components. Recently, DAS, DADS, and AMS had unique regulatory properties in suppressing NO in stimulated macrophages.¹⁴³ DAS was found to reduce the stimulated production of NO and PGE2 inhibiting the inducible expression of NO synthase and cyclooxygenase-2 and indirectly increasing NO clearance. DADS inhibited activated NO production by reducing the expression of inducible NO synthase and directly eliminating NO, while AMS suppressed NO mainly through its direct NO. clearing activity. These findings suggest that the antitumor effect of allyl sulfur may be related to its anti-inflammatory and immunostimulating properties.

COX/LOX PATHWAYS:

Smith et al.144 reported that prostaglandin H synthase can metabolize gulf region diol of benzo(a)pyrene to electrophilic diol epoxides that were capable of binding to DNA. Lately, Li et al.¹⁴⁵ reported that both cyclooxygenase and lipoxygenase are involved in DMBA bioactivation. Ali¹⁴⁶ provided evidence that garlic can block cyclooxygenase activity. McGrath and Milner¹⁴⁷ reported that lipoxygenase bioactivated DMBA at a rate that was about 10-fold greater than that caused by cyclooxygenase. Although limited, there is evidence that garlic and associated sulfur components can inhibit lipoxygenase activity.¹⁴⁸ Finally, evidence for the involvement of lipoxygenase in the bioactivation of DMBA comes from Song and Milner¹⁴⁹, who found that administration of a known lipoxygenase inhibitor, nor dihydro guaiaretic acid (NDGA), significantly reduced DNA adducts induced by DMBA in rat mammary gland tissue. About the effect of allyl sulfur compounds on lipoxygenase and cyclooxygenase Signaling pathways, DAS, DADS, and to a lesser extent AMS, were found to be differentially regulated NO and PGE2 production in LPS-stimulated RAW 264.7 murine macrophages.¹⁴³ In another In a recent study, ajoene was found to act similarly to several non-steroidal anti-inflammatory drugs that this garlic compound dose-dependently inhibited the release of PGE2 from LPS-activated RAW 264.7 cells, which was associated with dose-dependent inhibition of COX-2 enzyme activity¹⁵⁰ Taken together, these studies raise interesting questions about the role of both cyclooxygenases and lipoxygenases, not only in the formation of prostaglandins, and thus modulation of tumor cell proliferation and immunocompetence, but also their involvement in bioactivation carcinogens. Further attention is needed to clarify what role, if any, these enzymes have in determining the biological response to dietary garlic or its allyl sulfur components.

DIET AS A MODIFIER:

The effect of garlic on cancer processes cannot be assessed in isolation, as several components of the diet can influence the overall response. Recently, the effects of the combination of tomatoes and garlic were examined using several models of carcinogenesis.^151–153 The combination suppressed the incidence and mean tumor burden in hamster buccal pouch carcinomas more than either alone and appeared related to a decrease in phase I enzymes and an increase in phase II enzyme activities. Different individual food components can also affect the response to garlic. Notable are the changes made by the amount of fat, selenium, methionine, and vitamin A in the diet.^42,154,155 Amagase et al.¹⁵⁴ and Ip et al.¹⁵⁵ reported that selenium supplied either as a component diet or as a component of a garlic supplement increases protection against 7,12 dimethylbenz(a)anthracene (DMBA) mammary carcinogenesis beyond that provided by garlic alone. Carcinogen bioactivation may be suppressed, as indicated by a reduction in DNA adducts that are partially responsible for this combined benefit of garlic and selenium.⁴² Because both selenium and selenium allyl sulfur compounds are known to suppress tumor cell proliferation and induce apoptosis,^156–158 the synergistic response to allyl sulfur and selenium may relate to changes in cancer-related processes unrelated to carcinogen metabolism.

The supply of fatty acids in the diet can affect the bioactivation of DMBA and ultimately the metabolites of this carcinogen, which binds to the DNA of rat mammary cells. A significant part increase in mammary gland adducts caused by increased consumption of corn oil in the diet may be attributed to the intake of linoleic acid.¹⁵⁹ While excessive consumption of oleic acid is also increasing DMBA-induced DNA adducts, was found to be much less effective in promoting adduct formation than linoleic acid.

The variety of molecular targets that can be affected by different food components demonstrates the complexity of addressing nutrient–nutrient interactions. Although the effect of combining bioactive food components on garlic's ability to influence cell proliferation has not been sufficiently investigated, there are potentially several combinations that would produce more dramatic effects. For example, similar to information with chemical carcinogenesis, there is evidence of the greater effect of allyl sulfur in combination with selenium than when provided alone.¹⁶⁰ Similarly the combination of garlic and onion oil was more effective in blocking the proliferation of HL60 cells in culture than when used individually.¹⁶¹ Although the molecular basis for these enhanced effects needs to be explored in more detail, serves as evidence that food interactions When developing strategies to use the diet for cancer prevention, individual components must be considered.

HEART DISEASE:

Garlic may play a role in the genesis and progression of cardiovascular disease. These effects can be mediated through various biological responses including a reduction of total and LDL cholesterol, an increase of HDL-cholesterol, a reduction of serum triglyceride and fibrinogen concentrations, a reduction of arterial blood pressure, and/or inhibition of platelet aggregation.

CHOLESTEROL AND LIPOPROTEINS:

Several studies have attempted to clarify the exact role that garlic has on serum cholesterol, LDL, HDL, and triglycerides as these may signal protection.^162,163 While some studies reported that garlic reduced LDL concentrations,^164,165 others did not.^166,167 Inducing a true response is complicated by the use of different amounts of garlic, different preparations, and standardization and variation in treatment duration. Yet many provide evidence that garlic can lower cholesterol and triglyceride levels in some, but probably not all, patients. A recent systematic review by Adler et al.¹⁶³ showed that several studies provided evidence that garlic was effective in lowering cholesterol. Average drop in total cholesterol was 24.8 mg/dL (9.9%), LDL 15.3 mg/dL (11.4%), and triglycerides 38 mg/dL (9.9%). The overall mean Boyack and Lookinland Methodological Quality Index (MQI) score was 39.6% (18 to 70%). While cholesterol reductions in the range of 7 to 15% were fairly common it is a fairly large response variation. As shown in cancer models, it appears to be the response to cholesterol is dependent on the formation of bioactive sulfur compounds. Jabbari et al.¹⁶⁸ found that ingestion of intact garlic had little or no effect on lowering serum lipids but consumption of crushed garlic reduced cholesterol, triglycerides, malondialdehyde, and blood pressure. Therefore, the active substance arising from garlic, similar to other processes, requires time formation, and if it is not formed there is no biological reaction.¹⁴⁹

LDL oxidation is increasingly recognized as a contributor to the initiation and progression of atherosclerosis.¹⁶⁹ Munday et al.¹⁷⁰ found a slightly reduced susceptibility of LDL particles to Cu+2-mediated oxidation from subjects given 2.4 g of aged garlic extract (AGE) daily for 7 days. Interestingly, a similar response was not observed when subjects were given 6 g of raw garlic as a daily supplement for 7 days. Byrne et al.166 did not find that 900 mg of Kwai garlic powder (Lichtwer Pharma, Berlin) for 6 months affected the susceptibility of LDL to oxidation. It is not clear whether inconsistencies in the literature on garlic and LDL oxidation relate to the investigated subjects or preparations used. DADS has been reported to protect human LDL, erythrocyte membranes, and platelets from oxidation and/or glycation.¹⁷¹ Recently, the protective effects of six organosulfur compounds (DAS, DADS, SAC, S-acetylcysteine, S-methyl cysteine, and S-propylcysteine) tested for their ability to reduce further oxidation and glycation in already partially oxidized glycated samples from patients with non-insulin-dependent diabetes.¹⁷² Their studies revealed that DAS and DADS were superior in delaying LDL oxidation compared to four cysteine test compounds. However, agents containing cysteine were superior to DAS and DADS delaying glycation deterioration in already partially glycated LDL. Both responses were high concentration dependent. Thus, the content or potential for the formation of active intermediates is likely it explains much of the variability that has been observed in the published literature.

BLOOD PRESSURE:

Aortic stiffening is also an important risk factor for cardiovascular morbidity and mortality. This stiffness coincides with high systolic blood pressure and elevated pulse pressure. Extra diet Aortic stiffening is likely influenced by age, gender, hormonal status, and genetic factors. Increasing evidence suggests that garlic may be part of the diet with the ability to lower blood pressure and cause relaxation in the walls of the arteries. Garlic treatment has also been found to be dose-dependent vaso-relaxation in the endothelium intact and mechanically disturbed by the endothelium of the pulmonary system arterial rings.¹⁷³ This vasorelaxation was reduced by the administration of NG-nitro-L-arginine methyl ester, nitric oxide synthase inhibitor. It is known that inducible nitric oxide synthase occurs in human atherosclerotic lesions. Recent studies have shown that garlic has effects therapeutic effects by increasing the production of NO.¹⁷⁴ Relaxing effect on vascular smooth muscle It appears to be mediated by the reduction of cGMP and subsequent release of endothelium-derived relaxing factors, as well as depression of prostaglandins through suppression of cyclooxygenase activity.^175,176 ROS are known to counteract vasodilatory and antiproliferative effects of nitric oxide by its rapid degradation to peroxynitrites. Part of the blood pressure changes caused by garlic may be related to its ability to reduce the formation of radicals. Recently, garlic was found to induce a sustained depression of arterial blood pressure in the Goldblatt model of hypertension.¹⁷⁷ Garlic extract was reported to serve as an antihypertensive agent in this two-kidney, one-clip (2K-1C) renovascular rat model of hypertension. At least part of its Protection appears to be mediated by the normalization of prostaglandin E2 and thromboxane B2.¹⁷⁸ It may also be involved in altering Na/H exchanger (NHE) activity.¹⁷⁹

PLAQUE AND PLATELET AGGREGATION:

Acute coronary syndromes can occur when an unstable atherosclerotic plaque erodes or ruptures, thereby exposing the highly thermogenic material within the plaque to the circulating blood.¹⁸⁰ This exposure triggers the rapid formation of a thrombus that clogs the artery. Efendy et al.¹⁸¹ found that administration of a deodorized garlic preparation (Kyolic) reduced the formation of fatty streaks and cholesterol accumulation in the vessel wall in cholesterol-fed rabbits. A more recent Budoff et al.¹⁸² found in a pilot study that providing an AGE extract for one year inhibited the rate of progression of coronary calcification compared with a placebo. Regular aromas of garlic preparations were also reported to inhibit plaque formation in humans. Providing garlic powder (Lichtwer Pharma AG, Berlin, Germany) for 48 weeks in a randomized study reduced the volumes of arteriosclerotic plaques in carotid and femoral arteries by 5 to 18%.¹⁸³ Zahid et al.¹⁸⁴ suggest that garlic can act it's a beneficial effect on plaque formation by lowering cholesterol and maintaining NO-mediated endothelial function, probably secondary to the inhibition of LDL oxidation and increase in HDL. Aggregates of activated platelets are likely to have a key role in coronary syndromes. Garlic and some of its organosulfur components are potent platelet inhibitor aggregation in vitro.^{175,185–187} Some platelet inhibitory compounds derived from allium plants include ajoene, allicin, SAC, methyl allyl trisulfide, and alk(en)nylthiosulfates such as 2- propenyl thiosulfate and sodium n-propyl thiosulfate. Heating garlic by cooking slows down its potency to inhibit platelet aggregation.¹⁸⁵ Unfortunately, few studies have documented that garlic can inhibit platelet aggregation in vivo. Regardless, Steiner and Lin¹⁸⁸ provided evidence that consumption of aged garlic extract reduced adrenaline- and collagen-induced platelet aggregation, although it failed to affect aggregation induced by adenosine diphosphate. Their studies also provided evidence of this platelet adhesion to fibrinogen could be suppressed by consuming this garlic supplement. Overall, the ability of garlic to reduce hyperlipidemia, hypertension, sterol synthesis, and thrombus formation makes it a strong candidate for reducing the risk of heart disease and stroke. However, the literature provides evidence of considerable variability in responses. Additional studies are needed to clarify who might benefit most from added garlic.

CONCLUSIONS:

Garlic has significant physiological properties for health promotion. Although other allium foods may have similar health properties, several comparative studies have been conducted. Because garlic causes relatively few side effects, other than a possible lingering odor, it exists few reasons to avoid its use. However, the odor does not seem to be a necessary condition for many advantages as water-soluble SAC generally provides comparable advantages as these compounds are associated with smell. Although garlic and its bioactive components can affect a number of the key molecular events that are associated with health must reach an effective concentration to do so at the target site, be in the correct metabolic form and lead to changes in low molecular weight signals in the cellular environment (metabolomic effects). While most can enjoy the culinary experiences identified with garlic, some individuals may be particularly responsive to more excessive intake due to their genetic profile and/or environmental exposure.

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Received on 01.03.2023 Modified on 08.06.2023

Asian J. Res. Pharm. Sci. 2024; 14(1):92-106.

DOI: 10.52711/2231-5659.2024.00015