|Year : 2014 | Volume
| Issue : 4 | Page : 577-581
Garlic: Review of literature
Shridevi Adaki1, Raghavendra Adaki2, Kaushal Shah1, Amol Karagir1
1 Department of Oral Medicine and Radiology, Bharati Vidyapeeth University Dental College, Sangli, Maharashtra, India
2 Department of Prosthodontics, Bharati Vidyapeeth University Dental College, Sangli, Maharashtra, India
|Date of Web Publication||1-Feb-2016|
Department of Oral Medicine and Radiology, Bharati Vidyapeeth University Dental College, Sangli, Maharashtra
Source of Support: None, Conflict of Interest: None
Garlic is one of the components, which have effects on reducing the risk of cancer. Including garlic in the diet helps for the betterment of the health. Medicinal effects of the garlic were known since 5,000 years. Recently, studies were carried out to known its effect on the cancer cell lines. Many studies have shown its effects not only on carcinomas, but also on the cardiovascular system and immune system. Functions of the each component of the garlic were studied to know exactly, which component has got beneficial effect. So this review has been carried out to know about the component, functions of each component, mode of action, and beneficial effects of the garlic.
Keywords: Anticancer effects, antioxidant, chemoprevention, immunomodulation, Rocambole
|How to cite this article:|
Adaki S, Adaki R, Shah K, Karagir A. Garlic: Review of literature. Indian J Cancer 2014;51:577-81
| » Introduction|| |
The contribution of diet and nutrition status to cancer risk has been a major focus of research as well as public health policy. Diet plays a significant role in cancer etiology and its prevention. Interestingly, various studies carried out have shown that the incidence of cancer can be reduced substantially by means of dietary modification. Different types of epidemiological designs have been employed to obtain sufficient proof of causal relationships between dietary modification and cancer. This offers the prospect for initiating primary and secondary prevention measures for control and prevention of cancers.
Many dietary supplements reduce the risk of cancer and garlic is one among them. The recorded use of garlic in the treatment of tumors dates all the way back to 1,550 BC when Egyptians realized the benefits of garlic as a remedy for a variety of diseases, and administered it orally and topically; the modern era, however, begins in the 1950s when demonstrated in vitro and in vivo that thiosulfinate extracts of garlic inhibited the growth of malignant cells and prevented growth of sarcoma 180 ascites tumor.
The use of garlic for medicinal purposes dates to antiquity. The Bible mentions garlic with regard to the Jew's flight from Egypt. Garlic bulbs were found in tombs of the pharaohs, in Crete, and in ancient cultures throughout the world. Indeed, Hippocrates considered garlic to be a vital part of therapeutic armamentarium.
Garlic (Allium sativum) is a bulbous perennial plant with a powerful onion such as aroma and pungent taste that has been used as a flavoring agent, condiment, and for medicinal purposes for over 5,000 years. Garlic benefits have been greatly recognized for many years by numerous health authorities and enthusiasts for its effects on promoting better health. Garlic is also known as Rocambole, ajo, Allium, stinking rose, rustic treacle, nectar of the gods, camphor of the poor, poor man's treacle, and clove garlic.
| » Contents of Garlic|| |
Fresh garlic contains various organosulfur compounds, trace elements and compounds of phenolic and steroidal origin, along with carbohydrates, proteins and fiber., Based on the solubility the contents are divided into two groups. One group is the lipid-soluble allyl sulfur compounds such as diallyl disulfide (DADS) and diallyl trisulfide (DATS), and the other one is the water-soluble compounds g-glutamyl S-allylcysteine (SAC) group such as SAC and S-allylmercaptocysteine (SAMC).
Garlic is characterized by a high content of organosulfur. In the bulb, the sulfur is primarily g-glutamyl peptides and allylcysteine sulfoxides. When the bulb is cut, chopped or squeezed, alliin, the main allylcysteine sulfoxide is metabolized to allicin through the action of alliinase. Allicin is a self-reactive constituent and it is converted readily to more stable compounds such as polysulfides.
| » Functions of the Components|| |
Diallylsulfide, a powerful garlic component, has been reported to inhibit oxidative stress caused by testosterone and to accelerate testosterone metabolism. It has been postulated that in the early stages of prostate cancer, when sensitivity to testosterone is retained, the predominant effect of Allium derivatives is to stimulate testosterone degradation and in the later stages, to interfere with signal transduction. Furthermore, garlic is a seleniferous plant, accumulating selenium from the soil against a concentration gradient. Selenium has many anticancer actions, particularly in control of genes involved in carcinogenesis. In addition to inhibiting primary cancer, Allium derivatives from garlic may further inhibit metastatic processes. In an androgenin-dependent prostate cancer mouse model, the water-soluble Allium derivative, S-allyllmercaptocysteine, inhibited metastases to the lung and adrenal gland by 90%.
Some anoctedent studies have even demonstrated garlic to be particularly effective in inhibiting persistent yeast infections and in treating ear infections. The allicin in garlic can help shield the stomach from the proliferation of Helicobacter pylori, a bacterium directly related to gastrointestinal cancer. Allicin is further broken down to a compound called ajoene. Ajoene contributes to the anticoagulant action of garlic. It may be the compound that prevents the clogging of blood vessels, which can lead to atherosclerosis.
| » Beneficial Effects|| |
Garlic possesses a variety of beneficial pharmacological properties affecting most notably the cardiovascular system (lipid management, decreased blood pressure, platelet inhibition, and decreased fibrinolytic activity), and the immune system as an antineoplastic and immunostimulant agent and it is also a potent antioxidant. Garlic was shown to be used more than twice as much as any other natural supplement. Garlic is promoted to lower cholesterol and blood pressure, delay the progression of atherosclerosis, prevent heart disease, improve circulation, prevent cancer, and is used topically for tinea infections.
Animal studies have shown that garlic can unclog arteries by reducing the size of existing plaque deposits. Garlic also helps prevent breast, colon, and esophageal cancer. Garlic supplements may also be beneficial to patients undergoing chemotherapy, especially those being administered with doxorubicin, by preventing the depletion of glutathione and the increased free radical activity that is associated chemotherapy, which can damage heart, liver, and other vital organs and tissues. Garlic possesses antibiotic, antiviral, and antifungal, antihistamine, anticoagulant, expectorant, antibacterial, anti-parasitic, diaphoretic, diuretic, expectorant, stimulant, and antispasmodic properties.
| » Modes of Action|| |
Several modes of action have been proposed. These include: (i) Effect on drug metabolising enzymes (that is induction of phase II detoxification enzymes, including glutathione transferases, quinine reductase, epoxide hydrolase and glucuronosyl transferase that inactivate toxic substances and facilitate their excretion); (ii) antioxidant activity (garlic preparations exhibit radical scavenging activity and decrease lipid peroxidation, which is relevant in the light of the observation that tumor promotion may involve oxygen radicals); (iii) tumor growth inhibition that has been documented in several carcinoma cell lines, including prostate carcinoma cells; (iv) induction of apoptosis, which coincides with an increase in the percentage of cells blocked in the G2/M phase of the cell cycle (possibly through a depression in p34cdc2 kinase); and (v) effective stimulation of the immune response (Organosulfurcompounds (OSC) stimulates proliferation of lymphocytes and macrophage phagocytosis, induce the infiltration of macrophages and lymphocytes in transplanted tumors, induce splenic hypertrophy, stimulate the release of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ, enhance natural killer cell, killer cell and lymphokine-activated killer cell activity).
| » Types of Garlic Preparations|| |
Four types of garlic preparations are currently available: Garlic essential oils, garlic oil macerate, garlic powder, and aged garlic extract (AGE). Most garlic preparations report allicin yield potentials, whereas AGE products standardize to SAC amounts. Some products have been shown to release differing amounts of active components depending on when the product was made. Allicin is extremely unstable and further breaks down to produce hundreds of organosulfur compounds such as diallyl sulfide (DAS), DADS, DATS, ajoenes and trisulfides, vinyl dithiins, and other sulfur compounds, depending on how the garlic is prepared.
| » Anticancer Effect|| |
Both in vivo and in vitro studies have shown that these individual compounds are not only able to suppress the skin, esophageal, stomach, colon, liver, lung, and breast cancer growth in animal models, but also directly inhibit proliferation of a variety of cancer cell lines derived from colon, lung, leukemia, skin, breast, and prostate cancers (PCa) in vitro. For example, intra-peritoneally injecting nude mice with DADS significantly inhibited the growth of colon cancer xenograft by 69% compared to the control group (P < 0.05). In addition, DATS is able to inhibit proliferation of PCa cell lines by induction of apoptosis through down regulation of Bcl-2 protein and activation of extracellular signal-regulated kinase 1/2 (ERK) extracellular signal regulated kinease 1/2 and c-Jun N-terminal kinase (JNK) pathways. Recently, SAMC has been shown to exert anti-proliferation effects on colon cancer cells through disrupting the microtubule assembly that triggers JNK1 and caspase 3 signaling pathways leading to apoptosis. These lines of evidence suggest that in addition to their cancer preventive effect, the garlic derivatives may also be used as effective agents in the treatment of human primary cancers.
Garlic together with vitamins E and C reduced the incidence of precancerous gastric lesions in a large population in China. Garlic derivatives have been found to influence an increasing number of molecular mechanisms in carcinogenesis, including DNA adduct formation, scavenging of free radicals, mutagenesis, cell proliferation, and differentiation and angiogenesis. The growth rate of cancer cells is reduced by garlic, with cell cycle blockade that occurs particularly in the G2/M phase. Apoptosis is stimulated by garlic.
Garlic has been demonstrated in epidemiologic studies to be associated with a reduced risk of stomach cancer and in animal models, to have antitumor activity in sarcoma, mammary carcinoma, hepatoma, colon cancer, and squamous cell carcinoma of the skin and esophagus. These effects appear to be mediated by various mechanisms. Prevention of malignant transformation after the administration of chemical carcinogens may result from inhibition of the activation of procarcinogens by garlic's effect on cytochrome P450 enzymes, antioxidant activity, or detoxification by binding to sulfur compounds in garlic. Direct inhibition of cancer cell growth in tissue culture has been documented in sarcoma as well as gastric, colon, bladder, and prostate carcinoma cell lines.
A case-control study was conducted to evaluate the association between garlic intake and several cancer sites. They analyzed the relation between garlic intake and different cancers. They reported that a high use of garlic was positively associated with a reduction of cancer in the following subjects: 395 patients with esophageal cancer compared to 1066 control subjects, 527 patients with larynx cancer compared with 1297 control subjects; 749 patients with oral cancer compared to 1772 control subjects; 1031 patients with ovarian cancer compared to 2411 control subjects; and 767 patients with renal cell cancer compared to 1534 control subjects.
Evidence for immunologic antitumor action of garlic 
What evidence supports immune stimulation as an important antitumor effect of garlic? One approach is to compare the reported effects of garlic with clinically useful cancer immunotherapy such as BCG.
The effects of garlic on murine transitional cell carcinoma are remarkably similar to those of BCG. Both inhibit tumor growth, and microscopic examination of the site of tumor transplantation reveals infiltration with macrophages and lymphocytes. BCG, but not garlic, induces granuloma formation. In animal models, both BCG and garlic induce hypertrophy of the reticuloendothelial system as measured by splenic hypertrophy. Garlic, like BCG, increases NK cell activity.
Intravesical BCG administration results in the release of cytokines in the urine, and elevation of urinary cytokines, particularly IL-2, TNF-α, and INF-g (interferon), is associated with antitumor activity. In animal studies, AGE is reported to induce the release of IL-2, TNF-α, and INF-g. Enhanced phagocytosis, one of the first immunostimulatory actions reported with BCG, is seen with garlic administration (Kyo et al. 1998). Additional activities seen with both BCG and garlic include enhanced killer cell activity and immune-proliferation of lymphocytes in response to mitogen stimulation (Kyo et al. 1998). These effects, particularly the pattern of cytokine release, suggest that garlic, like BCG, stimulates a Th1 cellular immune response that is characteristic of effective antitumor immunotherapies.
The component in garlic that is responsible for the effective immune stimulation is not known conclusively, and it is likely that multiple ingredients are immunologically active. A protein fraction from garlic is known to augment in vitro macrophage cytotoxicity and phagocytosis as well as stimulate lymphocyte proliferation. The protein fraction 4 (F4) from garlic has been demonstrated to enhance the cytotoxicity of human peripheral blood lymphocytes against NK-sensitive (K562) and NK-resistant (M14) cell lines. These effects were markedly augmented by the addition of low doses of IL-2. The combination was also more effective in inducing lymphokine-activated killer cell activity. F4 enhanced IL-2 or conconavalin A–induced proliferation of lymphocytes and IL-2 receptor expression. The enhanced cytotoxicity induced by F4 and F4 plus IL-2 was abolished by anti-IL-2 antibody, suggesting that the activity of F4 is mediated by IL-2 (Morioka et al. 1993). These data suggest that the F4 fraction of garlic is an efficient immunopotentiator that may be effective in cancer immunotherapy.
Although the F4 fraction of garlic is clearly an immune stimulant, it is not the only immunologically active ingredient in garlic. Therefore, F4 may not be entirely responsible for the observed beneficial response in transplanted tumors. In studies of the effect of DADS on the growth of transplanted human colon carcinoma cell lines in immunologically compromised nude mice, Sundaram and Milner (1996) found DADS to be as effective as 5-fluorouracil (5-FU) in inhibiting tumor growth. Combining the DADS and 5-FU did not increase the effect, but concurrent DADS treatment did significantly reduce the depression of leukocyte counts and splenic weight associated with chemotherapy administration (Sundaram and Milner 1996). In another study, the effects of S-allyl cysteine, a water-soluble constituent of garlic that inhibits chemical carcinogen-induced colon and mammary tumors in animals and inhibits the growth of neuroblastoma and melanoma in vitro. In studies of human T cells, S-allyl cysteine was found to inhibit activation of the nuclear protein of the Rel oncogene family (nuclear factor-kB). This protein, which is induced by TNF-α or H2O2, regulates immune function, inflammation and cellular growth (Geng et al. 1997). These studies suggest that low-molecular-weight compounds as well as proteins found in garlic have antitumor and immune effects.
Prevention of immune suppression
Immune surveillance offers protection from cancer and from impairment of immune defenses as occurs with conditions ranging from abnormalities such as acquired immunodeficiency syndrome (AIDS) to the normal aging process. In addition to enhancing NK function in AIDS patients, garlic is reported to improve age-related deterioration of learning behavior and impairment of immune response in a mouse model. The most common carcinogen, ultraviolet irradiation, appears to be inhibited by garlic. UV irradiation damages DNA and induces a specific defect in T-cell immunity, impairing the recognition of UV-induced malignancy. Most interestingly, oral garlic administration is found to protect from photo-immuno-suppression. Induction of an impaired immune response by the tumor itself is an effective means to escape destruction by host surveillance mechanisms. It is not known whether garlic can reduce the inhibition of immune response induced by tumor, but the observed responses are certainly compatible with this hypothesis. Protection from immune suppression is potentially an important mechanism in preventing the development of malignancy. In a study of the effect of garlic on the neuroendocrine and immunomodulation network, Zhang et al. (1997) reported that AGE improves age-related deterioration of learning behavior as well as impaired immune response in a mouse model. Garlic increased not only lymphocyte proliferation, as seen in other studies, but antibody production as well (Zhang et al. 1997).
Data now suggest that low molecular-weight sulfur compounds and F4 have immune stimulating properties and also that garlic can detoxify chemical carcinogens to prevent carcinogenesis and directly inhibit the growth of cancer cells. Garlic appears to stimulate immunity including macrophage activity, NK and killer cells, and lymphokine activated killer cells, and it increases production of IL-2, TNF, and INF-γ. These cytokines are associated with the beneficial Th1 antitumor response, which is characteristic of effective cancer immuno-therapies. Like BCG, garlic stimulates proliferation of macrophages and lymphocytes and also protects against suppression of immunity by chemotherapy and UV radiation.
| » Chemoprevention|| |
Many epidemiological studies support the protective role of garlic and related Allium foods against the development of certain human cancers. Natural garlic and garlic cultivated with selenium fertilization have been shown in animals to have protective roles in cancer prevention. Certain organoselenium compounds and their sulfur analogs have been identified in plants. Organoselenium compounds synthesized in our laboratory were compared to their sulfur analogs for chemopreventive efficacy. Diallyl selenide was at least 300-fold more effective than DAS in protecting against 7, 12-dimethylbenz (a) anthracene (DMBA)-induced mammary adenocarcinomas in rats. In addition, benzyl selenocyanate inhibited the development of DMBA-induced mammary adenocarcinomas and azoxymethane-induced colon cancer in rats and benzo (a) pyrene-induced forestomach tumors in mice. Garlic extracts inhibited the oxidative modification of lipids, thus protecting cells from injury by the oxidized molecules. The best chemopreventive action of garlic was observed in mice in which garlic treatment was performed before and after the induction of skin carcinogenesis. Garlic ingestion delayed formation of skin papillomas in animals and simultaneously decreased the size and number of papillomas, which was also reflected in the skin histology of the mice treated.
Several mechanisms have been presented to explain cancer chemopreventive effects of garlic-derived products. These include modulation in activity of several metabolizing enzymes that activate and detoxify carcinogens and inhibit DNA adduct formation, anti-oxidative and free radicals scavenging properties and regulation of cell proliferation, apoptosis and immune responses. Recent data show that garlic-derived products modulate cell-signaling pathways in a fashion that controls the unwanted proliferation of cells thereby imparting strong cancer chemopreventive as well as a cancer therapeutic effects.
The compounds of garlic can cause G2/M phase arrest in the proliferation of cancer cells, induction of apoptosis by altering the ratio of the Bcl-2 family of proteins and anti-angiogenic activity. Collectively, pre-clinical investigations demonstrated consistently that cancer chemoprevention by garlic and related sulfur compounds is clearly evident and appears to be independent of the organ site or the carcinogen employed.
| » Antioxidant Effects|| |
AGE, but not fresh garlic, has been shown to have antioxidant effects. Garlic exerts antioxidant effects by scavenging free radicals, enhancing superoxide dismutase, catalase and glutathione peroxidase, and increasing cellular glutathione. These effects of garlic may play a role in the cardiovascular, antineoplastic, and cognitive effects of garlic. AGE has been shown in vitro and animal studies to protect against liver toxicity from environmental substances, such as bromobenzene, protect against cardiotoxicity from doxorubicin, and improve age-related spatial memory deficits.
The antioxidants available in garlic contribute to this effect by shielding against the cell damage by cancer-causing free radicals. Antioxidants can neutralize the harmful effects of free radicals and may minimize or even help eliminate some if not most of the damage they cause over time.
| » Immunomodulation|| |
Garlic extract has been shown to enhance cytotoxicity of human peripheral blood lymphocytes against both NK cell sensitive and resistant cell lines. Lau et al. have demonstrated that garlic may augment macrophage (oxidative burst) and T lymphocyte (blastogenesis) functions. Reeve et al. have shown that garlic extract protect from UV induced suppression of contact hypersensitivity.
Garlic lowered IL-6 in an in vitro human model. Besides the hypocholesterolemic, antioxidant, and ACE-inhibition activity of garlic, the effect on IL-6 may offer further insight into garlic's well-known cardiovascular activity. In the same model, garlic also lowered the pro-inflammatory cytokine IL-1. IL-1 has been postulated to be involved in the destruction of pancreatic ß-cells and garlic demonstrates hypoglycemic action and amelioration of alloxan-induced diabetes in murine models. IL-1 inhibition may be partially responsible for this activity.
Because of the potential for garlic to reduce the pro-inflammatory cytokines IL-1, TNF, and IL-8, and stimulate IL-10 sretion (an antagonist of proinflammatory cytokines), Hodge et al. concluded that this effect, along with garlic's antimicrobial activity, may provide potential mechanisms for garlic's use in inflammatory bowel disease. IL-10 demonstrates modulation of the immuno-pathology of brain inflammatory diseases such as Alzheimer's disease, providing another potential use for garlic as a cytokine modulator.
| » Conclusion|| |
This review includes the actions of garlic and its components on the cardiovascular system, immune system, and carcinomas. It also includes in vitro and in vivo studies to confirm the beneficial effects. However, until now, no studies have been carried out to know its effects on the oral mucosal lesions and oral cancer. Further studies are required to confirm these effects on the oral cells and to identify the active ingredients in garlic that are responsible for the observed antitumor activity and immune stimulation. Garlic is clearly not a panacea for cancer, but its broad range of beneficial effects warrants serious consideration in clinical trials for the prevention and treatment of cancer.
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