Abstract

The major garlic component, Allicin [diallylthiosulfinate, or (R, S)-diallyldissulfid-S-oxide] is known for its medicinal effects, such as antihypertensive activity, microbicidal activity, and antitumor activity. Allicin and diallyldisulfide, which is a converted form of allicin, inhibited the cholesterol level in hepatocytes, in vivo and in vitro. The metabolism of allicin reportedly occurs in the microsomes of hepatocytes, predominantly with the contribution of cytochrome P-450. However, little is known about how allicin affects the genes involved in the activity of hepatocytes in vivo. In the present study, we used the short-term intravenous injection of allicin to examine the in vivo genetic profile of hepatocytes. Allicin up-regulate ten genes in the hepatocytes. For example, the interferon regulator 1 (IRF-I), the wingless-related MMTV (mouse mammary tumor virus) integration site 4 (wnt-4), and the fatty acid binding protein 1. However, allicin down-regulated three genes: namely, glutathione S-transferase mu6, a-2-HS glycoprotein, and the corticosteroid binding globulin of hepatocytes. The up-regulated wnt-4, IRF-1, and mannose binding lectin genes can enhance the growth factors, cytokines, transcription activators and repressors that are involved in the immune defense mechanism. These primary data, which were generated with the aid of the Atlas Plastic Mouse 5 K Microarray, help to explain the mechanism which enables allicin to act as a therapeutic agent, to enhance immunity, and to prevent cancer. The data suggest that these benefits of allicin are partly caused by the up-regulated or down-regulated gene profiles of hepatocytes. To evaluate the genetic profile in more detail, we need to use a more extensive mouse genome array.

주제어

#Allicin   #DNA microarray   #Gene expression   #Gene profile   #Hepatocytes  

참고문헌 (21)

1. Ankri S, Miron T, Rabinkov A et al., Allicin from garlic strongly inhibits cysteine proteinases and cytopathic effects of Entamoeba histolytica. Antimicrob Agents Chemother 41(10):2286-2288, 1997 
2. Park RS. Effects of allicin on cytokine production genes of human peripheral blood mononuclear cells. Korean J Food Nutr 15(4):191-196, 2002 
3. Chua SC, Hennessey K, Zeitler P et al., The little (lit) mutation cosegregates with the growth hormone releasing factor receptor on mouse chromosome 6. Mamm Genome 4(10):555-559, 1993 
4. Ide N, Lau BH. Garlic compounds minimize intracellular oxidative stress and inhibit nuclear factor-kappa b activation. J Nutr 131 (3s): 1020S-1026S, 2001 
5. Hallstrom CK, Gardner AM, Gardner PR. Nitric oxide metabolism in mammalian cells: substrate and inhibitor pro­files of a NADPH-cytochrome P450 oxidoreductase-coupled microsomal nitric oxide dioxygenase. Free Radic Biol Med 37(2):216-228, 2004 
6. Teyssier C, Guenot L, Suschetet M et al., Metabolism of diallyl disulfide by human liver microsomal cytochromes P-450 and flavin-containing monooxygenases. Drug Metab Dispos 27(7):835-841, 1999 
7. Feldberg RS, Chang SC, Kotik AN et al., In vitro mechanism of inhibition of bacterial cell growth by allicin. Antimicrob Agents Chemother 32(12): 1763-1768, 1988 
8. Knowles LM, Milner JA. Diallyl disulfide induces ERK phosphorylation and alters gene expression profiles in human colon tumor cells. J Nutr 133(9):2901-2906, 2003 
9. Gebhardt R. Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes. Lipids 28(7):613-619, 1993 
10. Hodge G, Hodge S, Han P. Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: potential therapeutic use in the treatment of inflammatory bowel disease. Cytometry 48(4):209-215, 2002 
11. Eilat S, Oestraicher Y, Rabinkov A, et al., Alteration of lipid profile in hyperlipidemic rabbits by allicin, an active consti­tuent of garlic. Coron Artery Dis 6(12):985-990, 1995 
12. Patya M, Zahalka MA, Vanichkin A et al., Allicin stimulates lymphocytes and elicits an antitumor effect: a possible role of p21ras. Int Immunol 16(2):275-281, 2004 
13. Germain E, Auger J, Ginies C et al., In vivo metabolism of diallyl disulphide in the rat: identification of two new metabolites. Xenobiotica 32(12):1127-1138, 2002 
14. Harris JC, Cottrell SL, Plummer S et al., Antimicrobial properties of Allium sativum (garlic). Appl Microbiol Biotechnol 57(3):282-286, 2001 
15. Xu X, Zhang HG, Liu ZY et al., Defective clearance of adenovirus in IRF-1 mice associated with defects in NK and T cells but not macrophages. Scand J Immunol 60(1-2):89-99, 2004 
16. Jaruga B, Hong F, Kim WH et al., IFN-gamma/STAT1 acts as a proinflammatory signal in T cell-mediated hepatitis via induction of multiple chemokines and adhesion molecules: a critical role of IRF-1. Am J Physiol Gastrointest Liver Physiol 287(5):G 1044-1052, 2004 
17. Kim EJ, Lee JM, Namkoong SE et al., Interferon regulatory factor-1 mediates interferon-gamma-induced apoptosis in ovarian carcinoma cells. J Cell Biochem 85(2):369-380, 2002 
18. Dornan D, Eckert M, Wallace M et al., Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53. Mol Cell Biol 24(22): 10083-10098, 2004 
19. Shadkchan Y, Shemesh E, Mirelman D et al., Efficacy of allicin, the reactive molecule of garlic, in inhibiting Aspergillus spp. in vitro, and in a murine model of disseminated aspergillosis. J Antimicrob Chemother 53(5):832-836, 2004 
20. Gebhardt R, Beck H, Wagner KG. Inhibition of cholesterol biosynthesis by allicin and ajoene in rat hepatocytes and HepG2 cells. Biochim Biophys Acta 1213(1):57-62, 1994 
21. Dirsch VM, Kiemer AK, Wagner H et al.. Effect of allicin and ajoene, two compounds of garlic, on inducible nitric oxide synthase. Atherosclerosis 139(2):333-339, 1998 

이 논문을 인용한 문헌 (0)

1. 이 논문을 인용한 문헌 없음