Garlic Biological Activities

Garlic-Protection of the cardiovascular system

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Garlic Biological Activities–Protection of cardiovascular system

The factors affecting human cardiovascular health are complex and diverse. The biological activity of garlic for cardiovascular  healthcare is mainly manifested in the following five ways

 

Inhibition of cholesterol synthesis

Garlic and garlic-derived organosulfur compounds have been found to decrease the synthesis of cholesterol by hepatocytes. Several garlic-derived organosulfur compounds, including S-allylcysteine and ajoene, have been found to inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), a critical enzyme in the cholesterol biosynthesis pathway. Garlic-derived compounds may also inhibit other enzymes in this pathway, including sterol 4α-methyl oxidase.

 

Inhibition of platelet aggregation

An increase in the ability of platelets to aggregate has been linked to the narrowing of blood vessels and the occurrence of acute thrombotic events. A variety of garlic-derived organosulfur compounds have been found to inhibit platelet aggregation in the test tube. Aged garlic extract was found to inhibit chemically stimulated platelet aggregation by downregulating the fibrinogen binding activity of glycoprotein IIb/IIIa fibrinogen receptor found on platelets and/or by preventing intraplatelet calcium mobilization.

 

Inhibition of vascular smooth muscle cell (VSMC) proliferation

The proliferation and migration of normally quiescent VSMCs are central features of vascular diseases, including atherosclerosis and coronary restenosis (when treated arteries become blocked again). Although the significance of these findings for human cardiovascular disease is not yet clear, limited cell culture research suggested that organosulfur compounds from garlic could inhibit the proliferation and migration of VSMCs .

 

Inhibition of vascular cell adhesion molecules

An elevation of oxidized low-density lipoprotein (LDL) concentration in plasma has been involved in the pathogenesis of atherosclerosis. Oxidized LDL may stimulate the recruitment of inflammatory white blood cells from the blood to the arterial wall by inducing the expression of vascular cell adhesion molecules. DADS and DATS inhibited the expression of adhesion molecules, E-selectin and vascular cell adhesion molecule-1 (VCAM-1), on endothelial cell surface by reversing oxidized LDL-induced inhibition of PI3K/Akt and cAMP responsive element binding protein (CREB) signaling pathways.

 

Hydrogen sulfide-mediated vasodilatory activity

The preservation of normal arterial function plays an important role in cardiovascular disease prevention. Hydrogen sulfide (H2S), a gaseous signaling molecule produced by some cells within the body, acts as a vasodilator (relaxes blood vessels) and thus may have cardioprotective properties. H2S production may be involved in vascular smooth muscle cell relaxation through regulating the opening/closing of potassium channels and/or enhancing NO-dependent signaling pathway. A study found that garlic-derived compounds are converted to hydrogen sulfide by red blood cells in vitro. However, human consumption of a high dose of raw garlic does not increase breath hydrogen sulfide levels, suggesting that significant metabolism of garlic compounds to hydrogen sulfide does not occur in vivo.

Note that the potential benefits of garlic consumption/supplementation on cardiovascular health may also be attributed to antioxidant and anti-inflammatory activities described above.

 


Reference:

1. Gebhardt R, Beck H. Differential inhibitory effects of garlic-derived organosulfur compounds on cholesterol biosynthesis in primary rat hepatocyte cultures. Lipids. 1996;31(12):1269-1276. (PubMed)

2. Ferri N, Yokoyama K, Sadilek M, et al. Ajoene, a garlic compound, inhibits protein prenylation and arterial smooth muscle cell proliferation. Br J Pharmacol. 2003;138(5):811-818. (PubMed)

3. Liu L, Yeh YY. S-alk(en)yl cysteines of garlic inhibit cholesterol synthesis by deactivating HMG-CoA reductase in cultured rat hepatocytes. J Nutr. 2002;132(6):1129-1134. (PubMed)

4. Singh DK, Porter TD. Inhibition of sterol 4α-methyl oxidase is the principal mechanism by which garlic decreases cholesterol synthesis. J Nutr. 2006;136(3 Suppl):759S-764S. (PubMed)

5. Allison GL, Lowe GM, Rahman K. Aged garlic extract may inhibit aggregation in human platelets by suppressing calcium mobilization. J Nutr. 2006;136(3 Suppl):789S-792S. (PubMed)

6. Chan KC, Hsu CC, Yin MC. Protective effect of three diallyl sulphides against glucose-induced erythrocyte and platelet oxidation, and ADP-induced platelet aggregation. Thromb Res. 2002;108(5-6):317-322. (PubMed)

7. Lawson LD, Ransom DK, Hughes BG. Inhibition of whole blood platelet-aggregation by compounds in garlic clove extracts and commercial garlic products. Thromb Res. 1992;65(2):141-156. (PubMed)

8. Allison GL, Lowe GM, Rahman K. Aged garlic extract inhibits platelet activation by increasing intracellular cAMP and reducing the interaction of GPIIb/IIIa receptor with fibrinogen. Life Sci. 2012;91(25-26):1275-1280. (PubMed)

9. Rahman K, Lowe GM, Smith S. Aged garlic extract inhibits human platelet aggregation by altering intracellular signaling and platelet shape change. J Nutr. 2016;146(2):410S-415S. (PubMed)

10. Hedin U, Roy J, Tran PK. Control of smooth muscle cell proliferation in vascular disease. Curr Opin Lipidol. 2004;15(5):559-565. (PubMed)

11. Campbell JH, Efendy JL, Smith NJ, Campbell GR. Molecular basis by which garlic suppresses atherosclerosis. J Nutr. 2001;131(3s):1006S-1009S. (PubMed)

12. Golovchenko I, Yang CH, Goalstone ML, Draznin B. Garlic extract methylallyl thiosulfinate blocks insulin potentiation of platelet-derived growth factor-stimulated migration of vascular smooth muscle cells. Metabolism. 2003;52(2):254-259. (PubMed)

13. Lei YP, Chen HW, Sheen LY, Lii CK. Diallyl disulfide and diallyl trisulfide suppress oxidized LDL-induced vascular cell adhesion molecule and E-selectin expression through protein kinase A- and B-dependent signaling pathways. J Nutr. 2008;138(6):996-1003. (PubMed)

14. Pryor WA, Houk KN, Foote CS, et al. Free radical biology and medicine: it’s a gas, man! Am J Physiol Regul Integr Comp Physiol. 2006;291(3):R491-511. (PubMed)

15. Lefer DJ. A new gaseous signaling molecule emerges: cardioprotective role of hydrogen sulfide. Proc Natl Acad Sci U S A. 2007;104(46):17907-17908. (PubMed)

16. Ried K, Fakler P. Potential of garlic (Allium sativum) in lowering high blood pressure: mechanisms of action and clinical relevance. Integr Blood Press Control. 2014;7:71-82. (PubMed)

17. Benavides GA, Squadrito GL, Mills RW, et al. Hydrogen sulfide mediates the vasoactivity of garlic. Proc Natl Acad Sci U S A. 2007;104(46):17977-17982. (PubMed)

Antibiotic Effect- Allicin, Natural Antibacterial Agent

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Antibiotic Effect

Allicin, Natural Antibacterial Agent

 

Garlic has been used for centuries in various societies to combat infectious disease. Historically, it is believed that Louis Pasteur described the antibacterial effect of garlic in 1858 for the first time, and in World War I extracts of garlic were used in antibacterial and antiseptic therapeutics. Numerous scientific studies concerning the antibacterial potential of garlic have been published.

Garlic has been proven to be effective against a plethora of gram-positive, gram-negative, and acid-fast bacteria. These include Salmonella, Escherichia coli (Adler and Beuchat, 2002), Pseudomonas, Proteus, Staphylococcus aureus (Cavallito, 1944), Escherichia coli, Salmonella (Johnson and Vaughn, 1969), Klebsiella (Jezowa and Rafinski, 1966), Micrococcus, Bacillus subtulis (Sharma et al., 1977 ), Clostridium (De Witt et al., 1979 ), Mycobacterium (Delaha and Garagusi, 1985 ), and Helicobacter (O’Gara et al., 2000 ). It has been documented that garlic exerts a differential inhibition between beneficial intestinal microflora and potentially harmful enterobacteria (Ress et al., 1993).

 

Allicin is almost Exclusively Responsible for the Antimicrobial Activity of Freshly Crushed Garlic.

The antibacterial properties are shown in Table 1. Corresponding studies have shown that allicin is effective against numerous bacteria (2, 5), among others against helicobacter (6) and Salmonella flexneri Y. In the rabbit experiment, allicin was active against Shigella.

Allicin is effective against numerous fungi. The antifungal effect is shown in Table 2 (7, 8, 9, 10).

 

Tab 1; Antibacterial effect of allicin on various bacteria

Bacteria Type Allicin concentration
(LD 50 μg / ml)
annotation
Escherichia coli   15 Antibiotic sensitive
Escherichia coli   15 Antibiotic-resistant
Staphylococcus   12 Antibiotic-sensitive
Aureus Staphylococcus aureus   12 Methicillin-resistant
Streptococcus pyogenes   3 Antibiotic-sensitive
Streptococcus β hemolyticus > 100 Antibiotic-resistant
Proteus mirabilis   15 Antibiotic-sensitive
Proteus mirabilis > 30 Antibiotic-resistant
Pseudomonas   15 Antibiotic-sensitive
Aeruginosa Pseudomonas > 100 Antibiotic-resistant
Aeruginosa Acinetobacterbaumanii   15 Clinical isolates
Klebsiella pneumoniae   8 Clinical isolates
Enterococcusfaecium > 100 Antibiotic-resistant

LD 50: dose that kills 50% of bacteria

 

Tab. 2 Antifungal activity of allicin on various types of fungi

Mushroom Type Allicin concentration
MIC (μg / ml)
annotation
Candida albicans 0.3
Candida albicans 0.8 Clinical isolates
Candida neoformans 0.3
Candida parapsilosis 0.15
Candida tropicalis 0.3
Candida krusei 0.3
Torulopsis 0.3
Glabrata Torulopsis glabrata 1.9 Clinical isolates

MIC: Minimal inhibitory concentration, ie minimum dose that prevents growth of the fungi

Garlic-Anticancer activity

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Garlic Biological Activities- Anticancer activity

Summary

Cancer Cancer is one of the main causes of deaths worldwide. Based on National Cancer Database and the Surveillance, Epidemiology, and End Results, about 16.9 million people were identified with cancer in 2019 and this number will probably rise to more than 22.1 million in 2030. The Food and Drug Administration’s evidence-based review system for the scientific evaluation of health showed no reliable evidence for the relation between garlic and a reduced risk of gastric, breast, and lung cancer. However, credible evidence for an association between garlic intake and colon, prostate, esophageal, larynx, oral, ovary, and renal cell cancers has been reported, even if all studies were observational and the number of such trials that are scientifically considered valid in this analysis is remarkably few and the number of subjects involved generally small. As a result, relations between garlic and reduction of risk of cancers are still uncertain.

 

Effects on carcinogen metabolism

Inhibition of metabolic activation of carcinogens: Some chemical carcinogens do not become active carcinogens until they have been metabolized by Phase I biotransformation enzymes, such as those belonging to the cytochrome P450 (CYP) family. Inhibition of specific CYP enzymes involved in carcinogen activation inhibits the development of cancer in some animal models. In particular, DAS and its metabolites have been found to inhibit CYP2E1 activity in vitro. and when administered orally at high doses to animals. Oral administration of garlic oil and DAS to humans has also resulted in evidence of decreased CYP2E1 activity.

Induction of Phase II detoxifying enzymes: Reactions catalyzed by phase II detoxifying enzymes generally promote the elimination of drugs, toxins, and carcinogens from the body. Consequently, increasing the activity of phase II enzymes, such as glutathione S-transferases (GSTs) and NQO-1, may help prevent cancer by enhancing the elimination of potential carcinogens (see the Nrf2-dependent antioxidant pathway).In animal studies, oral administration of garlic preparations and organosulfur compounds was found to increase the expression and activity of phase II enzymes in a variety of tissues. For example, DADS protected rodent liver against carbon tetrachloride (CCl4; an environmental pollutant)-induced lipid peroxidation and cell necrosis by blocking CYP2E1-mediated CCL4 metabolic activation and by upregulating Nrf2 downstream genes for NQO-1, HO-1, GCL, GST, and superoxide dismutase (SOD1).

Induction of cell cycle arrest

In normal cells, the cell cycle is tightly regulated to ensure faithful DNA replication and chromosomal segregation prior to cell division. When defects occur during DNA replication or chromosomal segregation and in case of DNA damage, the cell cycle can be transiently arrested at check points to allow for repair. Apoptosis is triggered when repair fails. Defective check points and evasion of apoptosis allow the unregulated division of cancer cells. Organosulfur compounds, including allicin, DAS, DADS, DATS, ajoene, and SAMC, have been found to induce cell cycle arrest when added to cancer cells in cell culture experiments. DATS reduced the incidence of poorly differentiated prostate tumors and limited the number of metastatic lesions in the lungs of mice genetically modified to develop prostate adenocarcinomas. DATS was shown to inhibit cancer cell proliferation, as well as neuroendocrine differentiation — a hallmark of prostate cancer malignancy — but had no effect on apoptosis and markers of invasion.In a rat model of chemically induced colon cancer, inhibition of cell proliferation by aged garlic extract was associated with a reduction in the incidence of precancerous lesions and dysplastic adenomas, but not of adenocarcinomas.

Induction of apoptosis

Apoptosis is a physiological process of programmed death of cells that are genetically damaged or no longer necessary. Precancerous and cancerous cells are resistant to signals that induce apoptosis. Garlic-derived organosulfur compounds, including allicin, ajoene, DAS, DADS, DATS, and SAMC, have been found to induce apoptosis when added to various cancer cell lines grown in culture. Oral administration of aqueous garlic extract and S-allylcysteine has been reported to enhance apoptosis in an animal model of oral cancer. Garlic oil reduced the incidence of N-nitrosodiethylamine-induced liver nodules by preventing oxidative damage to lipids and DNA and by promoting apoptosis. Garlic oil upregulated the activity of various antioxidant enzymes and expression of pro-apoptotic effectors like Bax and Caspase-3 and downregulated the expression of the anti-apoptotic genes β-arrestin-2, Bcl-2, and Bcl-X.

Inhibition of angiogenesis

To fuel their rapid growth, invasive tumors must develop new blood vessels by a process known as angiogenesis. Anti-angiogenic properties of several organosulfur compounds, including alliin, DATS, and ajoene, have been observed in in vitro or ex vivo experiments. In human breast cancer cells, DADS inhibited TNF-α-induced release of MCP-1, a chemokine that promotes tissue remodeling, angiogenesis, and metastasis. Aged garlic extract was also found to suppress in vitro angiogenesis by inhibiting endothelial cell proliferation, loss of adhesion, motility, and tube formation.

 

  1. Yang CS, Chhabra SK, Hong JY, Smith TJ. Mechanisms of inhibition of chemical toxicity and carcinogenesis by diallyl sulfide (DAS) and related compounds from garlic. J Nutr. 2001;131(3s):1041S-1045S. (PubMed)
  2. Brady JF, Ishizaki H, Fukuto JM, et al. Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolites. Chem Res Toxicol. 1991;4(6):642-647. (PubMed)
  3. Taubert D, Glockner R, Muller D, Schomig E. The garlic ingredient diallyl sulfide inhibits cytochrome P450 2E1 dependent bioactivation of acrylamide to glycidamide. Toxicol Lett. 2006;164(1):1-5. (PubMed)
  4. Jeong HG, Lee YW. Protective effects of diallyl sulfide on N-nitrosodimethylamine-induced immunosuppression in mice. Cancer Lett. 1998;134(1):73-79. (PubMed)
  5. Park KA, Kweon S, Choi H. Anticarcinogenic effect and modification of cytochrome P450 2E1 by dietary garlic powder in diethylnitrosamine-initiated rat hepatocarcinogenesis. J Biochem Mol Biol. 2002;35(6):615-622. (PubMed)
  6. Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther. 2002;72(3):276-287. (PubMed)
  7. Gurley BJ, Gardner SF, Hubbard MA, et al. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John’s wort, garlic oil, Panax ginseng and Ginkgo biloba. Drugs Aging. 2005;22(6):525-539. (PubMed)
  8. Loizou GD, Cocker J. The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazone. Hum Exp Toxicol. 2001;20(7):321-327. (PubMed)
  9. Munday R, Munday CM. Induction of phase II enzymes by aliphatic sulfides derived from garlic and onions: an overview. Methods Enzymol. 2004;382:449-456. (PubMed)
  10. Andorfer JH, Tchaikovskaya T, Listowsky I. Selective expression of glutathione S-transferase genes in the murine gastrointestinal tract in response to dietary organosulfur compounds. Carcinogenesis. 2004;25(3):359-367. (PubMed)
  11. Hatono S, Jimenez A, Wargovich MJ. Chemopreventive effect of S-allylcysteine and its relationship to the detoxification enzyme glutathione S-transferase. Carcinogenesis. 1996;17(5):1041-1044. (PubMed)
  12. Munday R, Munday CM. Relative activities of organosulfur compounds derived from onions and garlic in increasing tissue activities of quinone reductase and glutathione transferase in rat tissues. Nutr Cancer. 2001;40(2):205-210. (PubMed)
  13. Lee IC, Kim SH, Baek HS, et al. The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats. Food Chem Toxicol. 2014;63:174-185. (PubMed)
  14. Lee IC, Kim SH, Baek HS, et al. Protective effects of diallyl disulfide on carbon tetrachloride-induced hepatotoxicity through activation of Nrf2. Environ Toxicol. 2015;30(5):538-548. (PubMed)
  15. Stewart ZA, Westfall MD, Pietenpol JA. Cell-cycle dysregulation and anticancer therapy. Trends Pharmacol Sci. 2003;24(3):139-145. (PubMed)
  16. Powolny AA, Singh SV. Multitargeted prevention and therapy of cancer by diallyl trisulfide and related Allium vegetable-derived organosulfur compounds. Cancer Lett. 2008;269(2):305-314. (PubMed)
  17. Singh SV, Powolny AA, Stan SD, et al. Garlic constituent diallyl trisulfide prevents development of poorly differentiated prostate cancer and pulmonary metastasis multiplicity in TRAMP mice. Cancer Res. 2008;68(22):9503-9511. (PubMed)
  18. Jikihara H, Qi G, Nozoe K, et al. Aged garlic extract inhibits 1,2-dimethylhydrazine-induced colon tumor development by suppressing cell proliferation. Oncol Rep. 2015;33(3):1131-1140. (PubMed)
  19. Wu X, Kassie F, Mersch-Sundermann V. Induction of apoptosis in tumor cells by naturally occurring sulfur-containing compounds. Mutat Res. 2005;589(2):81-102. (PubMed)
  20. Balasenthil S, Rao KS, Nagini S. Apoptosis induction by S-allylcysteine, a garlic constituent, during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Cell Biochem Funct. 2002;20(3):263-268. (PubMed)
  21. Balasenthil S, Rao KS, Nagini S. Garlic induces apoptosis during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Oral Oncol. 2002;38(5):431-436. (PubMed)
  22. Zhang CL, Zeng T, Zhao XL, Yu LH, Zhu ZP, Xie KQ. Protective effects of garlic oil on hepatocarcinoma induced by N-nitrosodiethylamine in rats. Int J Biol Sci. 2012;8(3):363-374. (PubMed)
  23. Bauer D, Redmon N, Mazzio E, et al. Diallyl disulfide inhibits TNFα induced CCL2 release through MAPK/ERK and NF-Kappa-B signaling. Cytokine. 2015;75(1):117-126. (PubMed)
  24. Matsuura N, Miyamae Y, Yamane K, et al. Aged garlic extract inhibits angiogenesis and proliferation of colorectal carcinoma cells. J Nutr. 2006;136(3 Suppl):842S-846S. (PubMed)

Garlic-Antioxidant activity

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Garlic Antioxidant activity

Garlic has strong antioxidant properties due to its organosulfur compounds and Non-sulfur garlic phytochemicals. Mainly through the following three mechanisms.

Glutathione

Low cellular concentrations of glutathione, a major intracellular antioxidant, and/or overproduction of reactive oxygen species (ROS) can lead to oxidative stress-induced damage to biological macromolecules and contribute to the development and progression of pathological conditions. In endothelial cells (that line the inner wall of blood vessels), garlic-derived allicin lowered ROS production and increased the concentration of glutathione. Oral administration of allicin to mice lowered ROS production and prevented ROS-induced cardiac hypertrophy by inhibiting pro-inflammatory pathways like mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β) signaling pathways. It is thought that, upon crossing cell membranes, allicin interacts with glutathione and forms SAMG, which could prolong the antioxidant activity of allicin.

Nrf2-dependent antioxidant pathway

Allicin was also found to upregulate the expression of glutamate-cysteine ligase (GCL), the rate-limiting enzyme in glutathione synthesis, and other Phase II detoxifying/antioxidant enzymes, likely via the activation of the nuclear factor E2-related factor 2 (Nrf2)-dependent pathway. Briefly, Nrf2 is a transcription factor that is bound to the protein Kelch-like ECH-associated protein 1 (Keap1) in the cytosol. Keap1 responds to oxidative stress signals by freeing Nrf2. Upon release, Nrf2 translocates to the nucleus and binds to the antioxidant response element (ARE) located in the promoter of genes coding for antioxidant/detoxifying enzymes and scavengers. Nrf2/ARE-dependent genes code for numerous mediators of the antioxidant response, including GCL, glutathione S-transferases (GSTs), thioredoxin, NAD(P)H quinone oxidoreductase 1 (NQO-1), and heme oxygenase 1 (HO-1). Like allicin, oil-soluble organosulfides, DADS and DATS, have been shown to stimulate Nrf2-dependent antioxidant pathway. For example, antioxidant and cytoprotective effects of DADS against acute ethanol-induced liver damage in mice were associated with the ability to trigger Nrf2-dependent HO-1 activation. DATS protected cardiac cells in vitro and in experimental diabetic rats from high glucose-induced oxidative stress and apoptosis by inducing PI3K/Akt-dependent Nrf2 antioxidant signaling .

Aged garlic extract have also been shown to increase expression of antioxidant enzymes via the Nrf2/ARE pathway. SAC, a major organosulfur compound in aged garlic extract, prevented renal damage caused by ROS in cisplatin-treated rats, by limiting cisplatin-induced reduction of glutathione level, Nrf2 expression, and activity of several antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase). SAC also protected neurons from oxidative damage and apoptosis in wild-type mice but not in mice without a functional Nrf2 signaling pathway.

 

Nitric oxide (NO) signaling cascade

The generation of nitric oxide (NO) catalyzed by endothelial nitric oxide synthase (eNOS) plays a critical role in protecting the vascular endothelium from oxidative and inflammatory insults. ROS-induced NO inactivation can impair vascular endothelial function, contributing to various pathologies like atherosclerosis, hypertension, cardiovascular disease, and central nervous system disorders. Interestingly, ingestion of 2 g of fresh garlic was found to increase NO plasma concentrations within two to four hours in healthy volunteers. DADS and DATS protected eNOS activity and NO bioavailability in cultured endothelial cells challenged with oxidized low-density lipoprotein (LDL). In a model of traumatic brain injury in rats, allicin attenuated brain edema, neurological deficits, and apoptotic neuronal death, and exhibited antioxidant and anti-inflammatory effects, partly by increasing Akt-mediated eNOS activation. Aged garlic extract and SAC were also found to stimulate NO production in different experimental settings. In a model of erectile dysfunction in diabetic rats, SAC restored electrically-induced penile erection by stimulating eNOS activity and inhibiting the expression of NADPH oxidase (Nox) responsible for ROS overproduction.

 


Reference

1. Horev-Azaria L, Eliav S, Izigov N, et al. Allicin up-regulates cellular glutathione level in vascular endothelial cells. Eur J Nutr. 2009;48(2):67-74. (PubMed)

2. Liu C, Cao F, Tang QZ, et al. Allicin protects against cardiac hypertrophy and fibrosis via attenuating reactive oxygen species-dependent signaling pathways. J Nutr Biochem. 2010;21(12):1238-1250. (PubMed)

3. Chen C, Kong AN. Dietary chemopreventive compounds and ARE/EpRE signaling. Free Radic Biol Med. 2004;36(12):1505-1516. (PubMed)

4. Zeng T, Zhang CL, Song FY, et al. The activation of HO-1/Nrf-2 contributes to the protective effects of diallyl disulfide (DADS) against ethanol-induced oxidative stress. Biochim Biophys Acta. 2013;1830(10):4848-4859. (PubMed)

5. Tsai CY, Wang CC, Lai TY, et al. Antioxidant effects of diallyl trisulfide on high glucose-induced apoptosis are mediated by the PI3K/Akt-dependent activation of Nrf2 in cardiomyocytes. Int J Cardiol. 2013;168(2):1286-1297. (PubMed)

6. Hiramatsu K, Tsuneyoshi T, Ogawa T, Morihara N. Aged garlic extract enhances heme oxygenase-1 and glutamate-cysteine ligase modifier subunit expression via the nuclear factor erythroid 2-related factor 2-antioxidant response element signaling pathway in human endothelial cells. Nutr Res. 2016;36(2):143-149. (PubMed)

7. Gomez-Sierra T, Molina-Jijon E, Tapia E, et al. S-allylcysteine prevents cisplatin-induced nephrotoxicity and oxidative stress. J Pharm Pharmacol. 2014;66(9):1271-1281. (PubMed)

8. Shi H, Jing X, Wei X, et al. S-allyl cysteine activates the Nrf2-dependent antioxidant response and protects neurons against ischemic injury in vitro and in vivo. J Neurochem. 2015;133(2):298-308. (PubMed)

9. Higashi Y, Noma K, Yoshizumi M, Kihara Y. Endothelial function and oxidative stress in cardiovascular diseases. Circ J. 2009;73(3):411-418. (PubMed)

10. Lundblad C, Grande PO, Bentzer P. Hemodynamic and histological effects of traumatic brain injury in eNOS-deficient mice. J Neurotrauma. 2009;26(11):1953-1962. (PubMed)

11. Bhattacharyya M, Girish GV, Karmohapatra SK, Samad SA, Sinha AK. Systemic production of IFN-α by garlic (Allium sativum) in humans. J Interferon Cytokine Res. 2007;27(5):377-382. (PubMed)

12. Lei YP, Liu CT, Sheen LY, Chen HW, Lii CK. Diallyl disulfide and diallyl trisulfide protect endothelial nitric oxide synthase against damage by oxidized low-density lipoprotein. Mol Nutr Food Res. 2010;54 Suppl 1:S42-52. (PubMed)

13. Chen W, Qi J, Feng F, et al. Neuroprotective effect of allicin against traumatic brain injury via Akt/endothelial nitric oxide synthase pathway-mediated anti-inflammatory and anti-oxidative activities. Neurochem Int. 2014;68:28-37. (PubMed)

14. Shouk R, Abdou A, Shetty K, Sarkar D, Eid AH. Mechanisms underlying the antihypertensive effects of garlic bioactives. Nutr Res. 2014;34(2):106-115. (PubMed)

15. Yang J, Wang T, Yang J, et al. S-allyl cysteine restores erectile function through inhibition of reactive oxygen species generation in diabetic rats. Andrology. 2013;1(3):487-494. (PubMed)

16. Ho SC, Su MS. Evaluating the anti-neuroinflammatory capacity of raw and steamed garlic as well as five organosulfur compounds. Molecules. 2014;19(11):17697-17714. (PubMed)

17. Liu KL, Chen HW, Wang RY, Lei YP, Sheen LY, Lii CK. DATS reduces LPS-induced iNOS expression, NO production, oxidative stress, and NF-κB activation in RAW 264.7 macrophages. J Agric Food Chem. 2006;54(9):3472-3478. (PubMed)

18. You S, Nakanishi E, Kuwata H, et al. Inhibitory effects and molecular mechanisms of garlic organosulfur compounds on the production of inflammatory mediators. Mol Nutr Food Res. 2013;57(11):2049-2060. (PubMed)

19. Lee HH, Han MH, Hwang HJ, et al. Diallyl trisulfide exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 macrophages by suppressing the Toll-like receptor 4/nuclear factor-κB pathway. Int J Mol Med. 2015;35(2):487-495. (PubMed)

Garlic-Antiviral properties

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Garlic Antiviral properties

 

In comparison with the antibacterial action of garlic, very little work has been done to investigate its antiviral properties.
But garlic (Allium sativum) has been shown to have antiviral activity, but the compounds responsible have not been identified. Using direct pre-infection incubation assays, we determined the in vitro virucidal effects of fresh garlic extract, its polar fraction, and the following garlic associated compounds: diallyl thiosulfinate (allicin), allyl methyl thiosulfinate, methyl allyl thiosulfinate, ajoene, alliin, deoxyalliin, diallyl disulfide, and diallyl trisulfide. Activity was determined against selected viruses including, herpes simplex virus type 1, herpes simplex virus type 2, parainfluenza virus type 3, vaccinia virus, vesicular stomatitis virus, and human rhinovirus type 2. The order for virucidal activity generally was: ajoene > allicin > allyl methyl thiosulfinate > methyl allyl thiosulfinate. Ajoene was found in oil-macerates of garlic but not in fresh garlic extracts. No activity was found for the garlic polar fraction, alliin, deoxyalliin, diallyl disulfide, or diallyl trisulfide.

 

Fresh garlic extract, in which thiosulfinates appeared to be the active components, was virucidal to each virus tested. The predominant thiosulfinate in fresh garlic extract was allicin. Lack of reduction in yields of infectious virus indicated undetectable levels of intracellular antiviral activity for either allicin or fresh garlic extract. Furthermore, concentrations that were virucidal were also toxic to HeLa and Vero cells. Virucidal assay results were not influenced by cytotoxicity since the compounds were diluted below toxic levels prior to assaying for infectious virus. These results indicate that virucidal activity and cytotoxicity may have depended upon the viral envelope and cell membrane, respectively. However, activity against non-enveloped virus may have been due to inhibition of viral adsorption or penetration.

 

The few studies have reported that garlic extract showed in vitro activity against influenza A and B (Fenwick and Hanley, 1985 ), cytomegalovirus (Meng et al., 1993 ; Nai-Lan et al., 1993), rhinovirus, HIV, herpes simplex virus 1 (Tsai et al., 1985 ), herpes simplex virus 2 (Weber et al., 1992 ), viral pneumonia, and rotavirus. Allicin, diallyl trisulfide and ajoene have all been shown to be active (Hughes et al., 1989 ; Weber., 1992 ).

 

In the case of HIV, it is thought that ajoene acts by inhibiting the integrin dependent processes (Tatarintsev et al., 1992 ). Allyl alcohol and diallyl disulfide have also proven effective against HIV-infected cells (Shoji et al., 1993 ). No activity has been observed with allicin or S-allyl cysteine. It appears that only allicin and allicin-derived substances are active. Taken together, the beneficial effects of garlic extract make it useful in medicine. There are insufficient clinical trials regarding the effects of garlic in preventing or treating the common cold. A single trial suggested that garlic may prevent occurrences of the common cold, but more studies are needed to validate this finding. This trial randomly assigned 146 participants to either a daily garlic supplement (with 180 mg of allicin content) or a placebo for 12 weeks.

 

The investigation revealed 24 occurrences of the common cold in the garlic group compared with 65 in the placebo group, resulting in fewer days of illness in the garlic group compared with the placebo group. However, claims of effectiveness of garlic on common cold appear to rely largely on poor quality evidence (Lissiman et al., 2012 ). Many countries have used garlic extract for clinical treatments, but the untoward actions of garlic following long-term administration should be fully noted. Even though many studies on garlic and its derivatives have been performed, the exact biological mechanism of garlic extract still remains to be elucidated.

 

Additionally the composition of various commercial garlic products. Including garlic powder tablets and capsules, oil-macerated garlic. Steam-distilled garlic oils, garlic aged in anqueos alcohol. And fermented garlic oil was determined as well ass the virucidal activated of the products against herpes simplex virus type 1. and parainfluenza virus type 3. virucidal activities of commercial products were de-pendent upon their preparation process. Those products producing the highest level of allicin and other thiosulfinates has the best virucidal activities.

 

In Vitro Virucidal Effects of Allium Sativum (Garlic)

In Vitro Virucidal Effects of Allium Sativum (Garlic)-Allicin Pharm

Garlic-Anti-inflammatory activity

Allicin Pharm No Comments

Garlic Biological Activities

Anti-inflammatory activity

 

Garlic-derived organosulfur compounds have been found to inhibit mediators of the inflammatory response, including cytokines, chemokines, adhesion molecules, and enzymes like cyclooxygenase (COX), lipoxygenase (LOX), and inducible nitric oxide synthase (iNOS). Nuclear factor-kappa B (NF-κB) is a transcription factor that binds DNA and induces the transcription of the COX-2 gene, other pro-inflammatory genes, as well as genes involved in cell proliferation, adhesion, survival, and differentiation. The anti-inflammatory effects of organosulfur compounds result from their ability to counteract the activation of pro-inflammatory pathways — like NF-κB-, MAPK-, and PI3K/Akt-dependent signaling pathways — by pro-inflammatory stimuli. DATS inhibited bacterial lipopolysaccharide (LPS)-induced macrophage activation by limiting LPS binding to toll-like receptor 4 (TLR4) and blocking the upregulation of TLR4 and TLR4-associated molecule MyoD88 expression. DATS also inhibited LPS-induced NF-κB-dependent expression of COX-2, iNOS, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). In a mouse model of inflammation, the decrease of LPS-induced paw edema by DATS was associated with reduced serum concentrations of the pro-inflammatory cytokines, TNF-α, IL-6, and monocyte chemotactic protein-1 (MCP-1).

 

Various chronic diseases, such as cancer and cardiovascular diseases, are related with inflammatory processes; in these conditions, different types of therapeutic and natural tools have been used to prevent them. In this context, garlic has shown to exert potent anti-inflammatory effects by decreasing the inflammatory biomarkers in end-stage renal disease and adult patients. A double-blind randomized clinical trial showed a significant reduction of inflammatory cytokines, such as interleukin 6 (IL-6), C-reactive protein (CRP), and erythrocyte sedimentation rate when standardized GE was administered at 400 mg twice a day for eight weeks in peritoneal dialysis patients. In addition, a meta-analysis revealed that garlic supplementation, including AGE, garlic powder and garlic capsule, reduced serum concentrations of tumor necrosis factor alpha (TNF-α), and CRP, but did not affect serum adiponectin and leptin in healthy adults.

 

Immune cells are responsible for the anti-inflammation effect; aged garlic contains various compounds that can improve immune systems by modulating cytokine production. For example, the consumption of aged garlic supplementation at a dose of 2.56 g per day for 90 days increased the activity of immune cells, such as γδ-T and natural killer (NK) cells and decreased inflammation by reducing TNF-α and IL-6 in obese adults. Interestingly, the same dose of GE boosted immune cell function, decreasing the severity of cough and flu [48] and increasing urinary cytokine IL-12 excretion, even if no significant effect on IL-8 and TNF-α were found. In addition, a negative correlation has been found between organosulfur compounds of AGE and obesity-induced inflammation in a randomized, double-blind, placebo-controlled clinical trial. After taking AGE supplement at a dose of 3.6 g per day for six weeks, SAC reduced obesity-induced inflammation by releasing hydrogen sulfide (H2S) via increasing its endogenous products. Moreover, garlic supplementation increased microbial richness and diversity and improved inflammation condition, in patients with uncontrolled hypertension, while no significant effects have been found after garlic consumption at 2.1 g per day for 12 weeks, on inflammation in overweight subjects and type 2 diabetes patients with high cardiovascular risk.

 


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