Introduction

Allicin (diallylthiosulfinate; Figure 1) is a defence molecule from garlic (Allium sativum L.)with a broad range of biological activities. Allicin is produced upon tissue damage from the non-proteinogenic amino acid alliin (S-allylcysteine sulfoxide) in a reaction that is catalyzed by the enzyme alliinase. Current understanding of the allicin biosynthetic pathway will be presented in this review. Being a thiosulfinate, allicin is a reactive sulfur species (RSS) and undergoes a redox-reaction with thiol groups in glutathione and proteins that is thought to be essential for its biological activity. Allicin is physiologically active in microbial, plant and mammalian cells. In a dose-dependent manner allicin can inhibit the proliferation of both bacteria and fungi or kill cells outright, including antibiotic-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, in mammalian cell lines, including cancer cells, allicin induces cell-death and inhibits cell proliferation. In plants allicin inhibits seed germination and attenuates root-development.The majority of allicin’s effects are believed to be mediated via redox-dependent mechanisms. In sub-lethal concentrations, allicin has a variety of health-promoting properties, for example cholesterol-and blood pressure-lowering effects that are advantageous for the cardio-vascular system. Clearly, allicin has wide-ranging and interesting applications in medicine and (green) agriculture, hence the detailed discussion of its enormous potential in this review. Taken together, allicin is a fascinating biologically active compound whose properties are a direct consequence of the molecule's chemistry.[1]

Antibacterial activity of allicin

Cavallito and Bailey were the first to demonstrate that the antibacterial action of garlic is mainly due to allicin. The sensitivity of various bacterial and clinical isolates to pure preparations of allicin is very significant. In most cases the 50% lethal dose concentrations were somewhat higher than those required for some of the newer antibiotics. Interestingly, various bacterial strains resistant to antibiotics such as methicillin-resistant Staphylococcus aureus as well as other multidrug-resistant enterotoxicogenic strains of Escherichia coli, Enterococcus, Shigella dysenteriae,S. flexneri, and S. sonnei cells were all found to be sensitive to allicin. Allicin also had an in vivo antibacterial activity against S. flexneri Y when tested in the rabbitmodel of experimental shigellosis. On the otherhand, other bacterial strains such as the mucoid strains of Pseudomonas aeruginosa, Streptococcus hemolyticusand Enterococcus faecium were found to be resistant tothe action of allicin. The reasons for this resistance areunclear. It is assumed that hydrophilic capsular or mucoidlayers prevent the penetration of the allicin into the bacteria, but this has to be studied more in depth.

A synergistic effect of allicin against M. tuberculosis was also found with antibiotics such as streptomycin or chloramphenicol. A very interesting aspect of the antibacterial activity of allicin is the apparent inability of most bacteria to develop resistance to it because the mode of action is completely different from that of other antibiotic substances (see below). It has been proposed that the development of resistance to beta-lactam antibiotics is 1000-fold easier than development of resistance to allicin.

Antifungal activity of allicin

Allicin was assumed to be the main component responsible for the inhibition of fungal growth. A concentrated garlic extract containing 34% allicin, 44% total thiosulfinates, and 20% vinyldithiins possessed potent in vitro fungistatic and fungicidal activity against three different isolates of Cryptococcus neoformans. The minimum inhibitory concentration of the concentrated garlic extract against 1 × 105 organisms of C. neoformans ranged from 6 to 12 μg/mL. In addition, in vitro synergistic fungistatic activity with amphotericin Bwas demonstrated against all isolates of C. neoformans. Pure allicin was found to have a high anticandidal activity with a minimum inhibitory concentration of 7 μg/mL.

Antiparasitic properties of allicin

Several years ago the researchers found out that Entamoeba histolytica, the human intestinal protozoan parasite, is very sensitive to allicin, as only 30 μg/mL of allicin totally inhibits the growth ofamoeba cultures. More recently they have found that at lower concentrations (5 μg/mL), allicin inhibited by90% the virulence of trophozoites of E. histolytica asdetermined by their inability to destroy monolayers of tissue-cultured mammalian cells in vitro.Allicin (30 μg/mL) also very efficiently inhibited the growth of other protozoan parasites such as Giardia lamblia, Leishmania major, Leptomonas colosoma, and Crithidia fasciculata. Some allicin toxicity towards tissue-cultured mammalian cells was observed at concentrations above 100μM. Interestingly however, at these high allicin concentrations no damage to the mammalian cells was seen if the incubations were done in the presence of amoebic trophozoites, suggesting that the affinity of the allicin molecules is towards the parasite targets. The reason formicrobial cells’higher sensitivity to allicin than that of mammalian cells is that most of the microbial cells do not have, or have very small amounts of, glutathione (or its equivalent thiol molecules such as trypanothione) and thus lack the ability to reactivate the essential SH-enzymesthat are thiolated by allicin.

Antiviral activity of allicin

The allicin condensation product, ajoene, seems to have in general more antiviral activity than allicin. Ajoene was found to block the integrin-dependent processes in ahuman immunodeficiency virus-infected cell system.Interestingly, there are some viruses like the garlic plant virus X which are resistant to the antiviral effects of garlic extracts.[1]

Anticancer activity of allicin

There is a link between the functioning of the immune system and cancer. In an early study (1960), explants of mouse-tumours were incubated in allicin before implantation into healthy mice. In contrast to the control group (where the explants were not allicin-treated), mice with tumour explants incubated in allicin showed no further growth of the explant.[2] How allicin affects cancer cells has been examined at the molecular level. It became clear that the induction of apoptosis was crucial for the anti-cancer effect of allicin. Allicin has garnered significant attention for its potential role in modulating Fas-FasL, Bcl2-Bax, PI3K-Akt-mTOR, autophagy, and miRNA pathways. At the molecular level, allicin induces the release of cytochrome c from the mitochondria and enhances the activation of caspases-3, -8, and -9. This is accompanied by the simultaneous upregulation of Bax and Fas expression in tumor cells. Allicin can inhibit excessive autophagy by activating the PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways. Allicin-loaded nano-formulations efficiently induce apoptosis in cancer cells while minimizing toxicity to normal cells.[3]

References

[1]Borlinghaus J, Albrecht F, Gruhlke MC, Nwachukwu ID, Slusarenko AJ. Allicin: chemistry and biological properties. Molecules. 2014;19(8):12591-12618. Published 2014 Aug 19. doi:10.3390/molecules190812591

[2]Ankri S, Mirelman D. Antimicrobial properties of allicin from garlic. Microbes Infect. 1999;1(2):125-129. doi:10.1016/s1286-4579(99)80003-3

[3]Bhuker S, Kaur A, Rajauria K, et al. Allicin: a promising modulator of apoptosis and survival signaling in cancer. Med Oncol. 2024;41(9):210. Published 2024 Jul 26. doi:10.1007/s12032-024-02459-6