Revitalizing allicin for cancer therapy: advances in formulation strategies to enhance bioavailability, stability, and clinical efficacy.

The main objective of this review is to highlight the therapeutic potential of allicin, a defense molecule in garlic known for its diverse health benefits, and address the key challenges of its bioavailability and stability. The research further aims to evaluate various formulation strategies and nanotechnology-based delivery systems that can resolve these issues and improve allicin's clinical efficacy, especially in cancer therapy. We conducted a comprehensive review of the available literature and previous studies, focusing on the therapeutic properties of allicin, its bioavailability, stability issues, and novel formulation strategies. We assessed the mechanism of action of allicin in cancer, including its effects on signaling pathways, cell cycle, apoptosis, autophagy, and tumor development. We also evaluated the outcomes of both in vitro and in vivo studies on different types of cancers, such as breast, cervical, colon, lung, and gastric cancer. Despite allicin's significant therapeutic benefits, including cardiovascular, antihypertensive, cholesterol-lowering, antimicrobial, antifungal, anticancer, and immune-modulatory activity, its clinical utility is limited due to poor stability and unpredictable bioavailability. Allicin's bioavailability in the gastrointestinal tract is dependent on the activity of the enzyme alliinase, and its stability can be affected by various conditions like gastric acid and intestinal enzyme proteases. Recent advances in formulation strategies and nanotechnology-based drug delivery systems show promise in addressing these challenges, potentially improving allicin's solubility, stability, and bioavailability. Allicin offers substantial potential for cancer therapy, yet its application is hindered by its instability and poor bioavailability. Novel formulation strategies and nanotechnology-based delivery systems can significantly overcome these limitations, enhancing the therapeutic efficacy of allicin. Future research should focus on refining these formulation strategies and delivery systems, ensuring the safety and efficacy of these new allicin formulations. Clinical trials and long-term studies should be carried out to determine the optimal dosage, assess potential side effects, and evaluate their real-world applicability. The comparative analysis of different drug delivery approaches and the development of targeted delivery systems can also provide further insight into enhancing the therapeutic potential of allicin.

Allicin, the Odor of Freshly Crushed Garlic: A Review of Recent Progress in Understanding Allicin's Effects on Cells.

The volatile organic sulfur compound allicin (diallyl thiosulfinate) is produced as a defense substance when garlic (Allium sativum) tissues are damaged, for example by the activities of pathogens or pests. Allicin gives crushed garlic its characteristic odor, is membrane permeable and readily taken up by exposed cells. It is a reactive thiol-trapping sulfur compound that S-thioallylates accessible cysteine residues in proteins and low molecular weight thiols including the cellular redox buffer glutathione (GSH) in eukaryotes and Gram-negative bacteria, as well as bacillithiol (BSH) in Gram-positive firmicutes. Allicin shows dose-dependent antimicrobial activity. At higher doses in eukaryotes allicin can induce apoptosis or necrosis, whereas lower, biocompatible amounts can modulate the activity of redox-sensitive proteins and affect cellular signaling. This review summarizes our current knowledge of how bacterial and eukaryotic cells are specifically affected by, and respond to, allicin.

Effect of physicochemical parameters on the stability and activity of garlic alliinase and its use for in-situ allicin synthesis.

Garlic is a well-known example of natural self-defence system consisting of an inactive substrate (alliin) and enzyme (alliinase) which, when combined, produce highly antimicrobial allicin. Increase of alliinase stability and its activity are of paramount importance in various applications relying on its use for in-situ synthesis of allicin or its analogues, e.g., pulmonary drug delivery, treatment of superficial injuries, or urease inhibitors in fertilizers. Here, we discuss the effect of temperature, pH, buffers, salts, and additives, i.e. antioxidants, chelating agents, reducing agents and cosolvents, on the stability and the activity of alliinase extracted from garlic. The effects of the storage temperature and relative humidity on the stability of lyophilized alliinase was demonstrated. A combination of the short half-life, high reactivity and non-specificity to particular proteins are reasons most bacteria cannot deal with allicin's mode of action and develop effective defence mechanism, which could be the key to sustainable drug design addressing serious problems with escalating emergence of multidrug-resistant (MDR) bacterial strains.

A Chromosome-Level Genome Assembly of Garlic (Allium sativum) Provides Insights into Genome Evolution and Allicin Biosynthesis.

Garlic, an economically important vegetable, spice, and medicinal crop, produces highly enlarged bulbs and unique organosulfur compounds. Here, we report a chromosome-level genome assembly for garlic, with a total size of approximately 16.24 Gb, as well as the annotation of 57 561 predicted protein-coding genes, making garlic the first Allium species with a sequenced genome. Analysis of this garlic genome assembly reveals a recent burst of transposable elements, explaining the substantial expansion of the garlic genome. We examined the evolution of certain genes associated with the biosynthesis of allicin and inulin neoseries-type fructans, and provided new insights into the biosynthesis of these two compounds. Furthermore, a large-scale transcriptome was produced to characterize the expression patterns of garlic genes in different tissues and at various growth stages of enlarged bulbs. The reference genome and large-scale transcriptome data generated in this study provide valuable new resources for research on garlic biology and breeding.

Structure and function of a flavin-dependent S-monooxygenase from garlic (Allium sativum).

Allicin is a component of the characteristic smell and flavor of garlic (Allium sativum). A flavin-containing monooxygenase (FMO) produced by A. sativum (AsFMO) was previously proposed to oxidize S-allyl-l-cysteine (SAC) to alliin, an allicin precursor. Here, we present a kinetic and structural characterization of AsFMO that suggests a possible contradiction to this proposal. Results of steady-state kinetic analyses revealed that AsFMO exhibited negligible activity with SAC; however, the enzyme was highly active with l-cysteine, N-acetyl-l-cysteine, and allyl mercaptan. We found that allyl mercaptan with NADPH was the preferred substrate-cofactor combination. Rapid-reaction kinetic analyses showed that NADPH binds tightly (KD of ∼2 µm) to AsFMO and that the hydride transfer occurs with pro-R stereospecificity. We detected the formation of a long-wavelength band when AsFMO was reduced by NADPH, probably representing the formation of a charge-transfer complex. In the absence of substrate, the reduced enzyme, in complex with NADP+, reacted with oxygen and formed an intermediate with a spectrum characteristic of C4a-hydroperoxyflavin, which decays several orders of magnitude more slowly than the kcat The presence of substrate enhanced C4a-hydroperoxyflavin formation and, upon hydroxylation, oxidation occurred with a rate constant similar to the kcat The structure of AsFMO complexed with FAD at 2.08-Å resolution features two domains for binding of FAD and NADPH, representative of class B flavin monooxygenases. These biochemical and structural results are consistent with AsFMO being an S-monooxygenase involved in allicin biosynthesis through direct formation of sulfenic acid and not SAC oxidation.

Effects of laying breeder hens dietary ß-carotene, curcumin, allicin, and sodium butyrate supplementation on the growth performance, immunity, and jejunum morphology of their offspring chicks.

This study evaluated the growth performance, immunity, and jejunum morphology of chicks hatched from laying breeder hens given dietary additive supplementation, as well as chicks receiving direct antibiotic supplementation in early life. Hy-line breeder hens were allotted to 2 groups with 3 replicates. A control group (CON) was fed a basal diet, and the treatment group (CCAB) received ß-carotene, curcumin, allicin, and sodium butyrate in addition to basal diet for 5 wk. Breeder-hen eggs were collected and hatched. The chicks hatched from the CON group were assigned to 2 treatments: a chick control group (cCON) and a chick treatment group (Cipro) given ciprofloxacin lactate into drinking water; the cCON group, Cipro group, and the chicks hatched from the CCAB group (cCCAB) were fed the same diet for 4 wk. The results demonstrated that there were significant differences between the CON and CCAB groups in the serum levels of IgA, IgG, IgM (triple P < 0.01), lysozyme (P < 0.05), and ß-defensin (P < 0.05). The body weights of the cCCAB group's chicks increased at 1, 7, and 28 D of age (P < 0.05, P < 0.05, P < 0.01, respectively), and those of the Cipro group's chicks increased at 7 and 21 D of age (P < 0.01, P < 0.05). The tibial lengths of the cCCAB group's chicks increased at 1, 7, 14, 21, and 28 D of age (P < 0.01, P < 0.05, triple P < 0.01), and the lengths in the Cipro group increased at 7 and 14 D of age (P < 0.01, P < 0.01). Intestinal development, including intestinal length, jejunum morphology, and IgA positive cells, helps to explain these results. The breeder eggs from the CCAB group had higher IgG (P < 0.05) and IgM (P < 0.05) levels in the egg whites and higher IgA, IgG, and IgM levels (triple P < 0.01) in the egg yolks. In conclusion, ß-carotene, curcumin, allicin, and sodium butyrate supplementation of laying breeder hen diets produced more advantages in growth performance and intestinal development in offspring than in chicks directly supplemented with antibiotics.

Genetic and molecular characterization of multicomponent resistance of Pseudomonas against allicin.

The common foodstuff garlic produces the potent antibiotic defense substance allicin after tissue damage. Allicin is a redox toxin that oxidizes glutathione and cellular proteins and makes garlic a highly hostile environment for non-adapted microbes. Genomic clones from a highly allicin-resistant Pseudomonas fluorescens (PfAR-1), which was isolated from garlic, conferred allicin resistance to Pseudomonas syringae and even to Escherichia coli Resistance-conferring genes had redox-related functions and were on core fragments from three similar genomic islands identified by sequencing and in silico analysis. Transposon mutagenesis and overexpression analyses revealed the contribution of individual candidate genes to allicin resistance. Taken together, our data define a multicomponent resistance mechanism against allicin in PfAR-1, achieved through horizontal gene transfer.

Downregulating PI3K/Akt/NF-κB signaling with allicin for ameliorating the progression of osteoarthritis: in vitro and vivo studies.

Osteoarthritis (OA) is characterized by the degeneration and destruction of articular cartilage. Allicin, a dietary garlic active constituent, exerts anti-inflammatory effects on several diseases. However, its effects on OA have not been clearly elucidated. In this study, we explored the effects of allicin on OA in both in vitro and in vivo models. Allicin inhibited interleukin-1ß (IL-1ß) induced overproduction of nitric oxide, inducible nitric oxide synthase, prostaglandin E2, and cyclooxygenase-2, as well as pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-6 in chondrocytes in a dose-dependent manner. Meanwhile, allicin reversed the overproduction of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 and the decrease of aggrecan and type II collagen. Furthermore, allicin dramatically suppressed IL-1ß-stimulated PI3K/Akt/NF-κB activation in chondrocytes. In vivo, treatment with allicin prevented the destruction of cartilage and inhibited PI3K/Akt/NF-κB activation in the cartilage of mice OA models. Taken together, these results indicate that allicin may be a potential therapeutic agent for OA.

Effect of dietary α-ketoglutarate and allicin supplementation on the composition and diversity of the cecal microbial community in growing pigs.

BACKGROUND: The search for substitutes for antibiotics has recently become urgent. In our previous work, dietary α-ketoglutarate (AKG) combined with allicin improved growth performance and enhanced immunity in growing pigs, whereas the effects on them of intestinal microbiota were unclear. Here, we further investigate the effects of dietary AKG and allicin supplementation on the composition and diversity of intestinal microbiota in growing pigs. RESULTS: Treatment with a combination of AKG and allicin enhanced cecal bacteria richness and diversity, as evidenced by changes in Chao 1, ACE, Shannon, and Simpson values when compared to the control group and antibiotics group. At the phylum level, Bacteroidetes and Firmicutes were the two most abundant phyla. Treatment with a combination of AKG and allicin increased the numbers of Firmicutes and reduced the numbers of Bacteroidetes. Prevotella was the most abundant genus; it was increased by treatment with a combination of AKG and allicin. Furthermore, compared with the antibiotic group, the level of acetate was increased in the AKG group with or without allicin. Treatment with a combination of AKG and allicin increased the levels of cecal butyrate and total volatile fatty acids (VFA) when compared with the control group in growing pigs. CONCLUSION: Dietary 1.0% AKG combined with 0.5% allicin improved cecal microbial composition and diversity, which might further promote VFA metabolism in growing pigs. © 2018 Society of Chemical Industry.

Yap1p, the central regulator of the S. cerevisiae oxidative stress response, is activated by allicin, a natural oxidant and defence substance of garlic.

Allicin is a thiol-reactive sulfur-containing natural product from garlic with a broad range of antimicrobial effects against prokaryotes and eukaryotes. Previous work showed that the S. cerevisiae OSI1 gene is highly induced by allicin and other thiol-reactive compounds, and in silico analysis revealed multiple Yap1p binding motifs in the OSI1 promoter sequence. An OSI1-promoter::luciferase reporter construct expressed in Wt and Δyap1 cells showed absolute Yap1p-dependence for allicin-induced OSI1-expression. A GFP: Yap1p fusion protein accumulated in the nucleus within 10min of allicin treatment and a Δyap1 mutant was highly sensitive to allicin. Yap1p regulates glutathione (GSH) metabolism genes, and Δgsh1, Δgsh2 and Δglr1 mutants showed increased sensitivity to allicin. Allicin activated the OSI1-promoter::luciferase reporter construct in Δgpx3 and Δybp1 cells, indicating that allicin activates Yap1p directly rather than via H2O2 production. A systematic series of C-to-A Yap1p exchange mutants showed that the C-term C598 and C620 residues were necessary for allicin activation. These data suggest that Yap1p is an important transcriptional regulator for the resistance of yeast cells to allicin, and that activation occurs by direct modification of C-term cysteines as shown for other electrophiles.

Molecular characterization of ongoing enzymatic reactions in raw garlic cloves using extractive electrospray ionization mass spectrometry.

Characterization of enzymatic reactions occurring in untreated biological samples is of increasing interest. Herein, the chemical conversion of alliin to allicin, catalyzed by allinase, in raw garlic cloves has been followed in vivo by internal extractive electrospray ionization mass spectrometry (iEESI-MS). Both precursors and products of the enzymatic reaction were instantaneously extracted by infused solution running throughout the tissue and directly electrospray ionized on the edge of the bulk sample for online MS analysis. Compared to the room-temperature (+25 °C) scenario, the alliin conversion in garlic cloves decreased by (7.2 ± 1.4) times upon heating to +80 °C and by (5.9 ± 0.8) times upon cooling to -16 °C. Exposure of garlic to gentle ultrasound irradiation for 3 h accelerated the reaction by (1.2 ± 0.1) times. A 10 s microwave irradiation promoted alliin conversion by (1.6 ± 0.4) times, but longer exposure to microwave irradiation (90 s) slowed the reaction by (28.5 ± 7.5) times compared to the reference analysis. This method has been further employed to monitor the germination process of garlic. These data revealed that over a 2 day garlic sprouting, the allicin/alliin ratio increased by (2.2 ± 0.5) times, and the averaged degree of polymerization for the detected oligosaccharides/polysaccharides decreased from 11.6 to 9.4. Overall, these findings suggest the potential use of iEESI-MS for in vivo studies of enzymatic reactions in native biological matrices.

Allium sativum: facts and myths regarding human health.

Garlic (Allium sativum L. fam. Alliaceae) is one of the most researched and best-selling herbal products on the market. For centuries it was used as a traditional remedy for most health-related disorders. Also, it is widely used as a food ingredient--spice and aphrodisiac. Garlic's properties result from a combination of variety biologically active substances which all together are responsible for its curative effect. The compounds contained in garlic synergistically influence each other so that they can have different effects. The active ingredients of garlic include enzymes (e.g. alliinase), sulfur-containing compounds such as alliin and compounds produced enzymatically from alliin (e.g. allicin). There is a lot of variation among garlic products sold for medicinal purposes. The concentration of Allicin (main active ingredient) and the source of garlic's distinctive odor depend on processing method. Allicin is unstable, and changes into a different chemicals rather quickly. It's documented that products obtained even without allicin such as aged garlic extract (AGE), have a clear and significant biological effect in immune system improvement, treatment of cardiovascular diseases, cancer, liver and other areas. Some products have a coating (enteric coating) to protect them against attack by stomach acids. Clinically, garlic has been evaluated for a number of purposes, including treatment of hypertension, hypercholesterolemia, diabetes, rheumatoid arthritis, cold or the prevention of atherosclerosis and the development of tumors. Many available publications indicates possible antibacterial, anti-hypertensive and anti-thrombotic properties of garlic. Due to the chemical complexity of garlic and the use of different processing methods we obtain formulations with varying degrees of efficacy and safety.

Short-term heating reduces the anti-inflammatory effects of fresh raw garlic extracts on the LPS-induced production of NO and pro-inflammatory cytokines by downregulating allicin activity in RAW 264.7 macrophages.

Garlic has a variety of biologic activities, including anti-inflammatory properties. Although garlic has several biologic activities, some people dislike eating fresh raw garlic because of its strong taste and smell. Therefore, garlic formulations involving heating procedures have been developed. In this study, we investigated whether short-term heating affects the anti-inflammatory properties of garlic. Fresh and heated raw garlic extracts (FRGE and HRGE) were prepared with incubation at 25 °C and 95 °C, respectively, for 2 h. Treatment with FRGE and HRGE significantly reduced the LPS-induced increase in the pro-inflammatory cytokine concentration (TNF-α, IL-1ß, and IL-6) and NO through HO-1 upregulation in RAW 264.7 macrophages. The anti-inflammatory effect was greater in FRGE than in HRGE. The allicin concentration was higher in FRGE than in HRGE. Allicin treatment showed reduced production of pro-inflammatory cytokines and NO and increased HO-1 activity. The results show that the decrease in LPS-induced NO and pro-inflammatory cytokines in RAW 264.7 macrophages through HO-1 induction was greater for FRGE compared with HRGE. Additionally, the results indicate that allicin is responsible for the anti-inflammatory effect of FRGE. Our results suggest a potential therapeutic use of allicin in the treatment of chronic inflammatory disease.

Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites.

The effects of a compound including the secondary metabolites of garlic, propyl thiosulphinate (PTS) and propyl thiosulphinate oxide (PTSO), on the in vitro and in vivo parameters of chicken gut immunity during experimental Eimeria acervulina infection were evaluated. In in vitro assays, the compound comprised of PTSO (67 %) and PTS (33 %) dose-dependently killed invasive E. acervulina sporozoites and stimulated higher spleen cell proliferation. Broiler chickens continuously fed from hatch with PTSO/PTS compound-supplemented diet and orally challenged with live E. acervulina oocysts had increased body weight gain, decreased faecal oocyst excretion and greater E. acervulina profilin antibody responses, compared with chickens fed a non-supplemented diet. Differential gene expression by microarray hybridisation identified 1227 transcripts whose levels were significantly altered in the intestinal lymphocytes of PTSO/PTS-fed birds compared with non-supplemented controls (552 up-regulated, 675 down-regulated). Biological pathway analysis identified the altered transcripts as belonging to the categories 'Disease and Disorder' and 'Physiological System Development and Function'. In the former category, the most significant function identified was 'Inflammatory Response', while the most significant function in the latter category was 'Cardiovascular System Development and Function'. This new information documents the immunologic and genomic changes that occur in chickens following PTSO/PTS dietary supplementation, which are relevant to protective immunity during avian coccidiosis.

Low-frequency and low-intensity ultrasound accelerates alliinase-catalysed synthesis of allicin in freshly crushed garlic.

BACKGROUND: The well-known chemically and therapeutically active compound allicin is formed in crushed garlic by the interaction of alliin with alliinase. In this study, low-frequency and low-intensity ultrasound was employed to accelerate the alliinase-catalysed synthesis of allicin in freshly crushed garlic. RESULTS: The optimal conditions for improvement of the alliinase-catalysed synthesis of allicin in freshly crushed garlic were found to be as follows: ultrasound intensity 0.4 W cm⁻², ultrasound frequency 50 kHz, enzymatic reaction temperature 35 °C and reaction time 30 min. Under these conditions the yield of allicin was increased by about 25.2% compared with the control without ultrasound. Alliinase in the freshly crushed garlic was purified by ammonium sulfate precipitation and gel filtration on a Sephacryl S-200 column. The employed ultrasound increased the activity of the purified alliinase by about 42.8%, did not affect the enzyme's temperature optimum and improved its thermal stability. CONCLUSION: The results of this study indicated that the activity of alliinase in freshly crushed garlic might be enhanced by low-frequency and low-intensity ultrasound, thereby accelerating the alliinase-catalysed conversion of alliin in garlic to allicin.

[HPLC tandem-mass spectrometric analysis of the chemical components and decomposition products of allicin extract of garlic].

To analyze the chemical components and decomposition products in allicin extract of garlic, the chemical components screening and identification were made with HPLC-MS/MS method by full scan TIC MS, HPLC retention time, product MS spectra and chemical reference standards. The stability of the extract in water and alcoholic solutions was also investigated. There were five major components in allicin extract which were all identified as thiosulfinates. The extract was stable for at least 3 months when stored at -20 degrees C as water solution, but obvious decomposition was observed with the increase of alcoholic concentration. The decomposition products were also identified by HPLC-MS/MS.

Thermostability of allicin determined by chemical and biological assays.

The garlic-derived antibacterial principle, alk(en)yl sulfinate compounds, has long been considered as very short-lived substance. However, there are some data showing a rather more stable nature of allicin. We determined here the thermostability of allicin by a systematic analyses employing chemical quantification and an antibacterial activity assay. Allicin in an aqueous extract of garlic was degraded stoichiometrically in proportion to the temperature; we estimated the half-life of allicin to be about a year at 4 degrees C (from 1.8 mg/ml to 0.9 mg/ml) and 32 d at 15 degrees C, but only 1 d at 37 degrees C (from 2.0 mg/ml to 1.0 mg/ml). The half-life values for antibacterial activity showed a similar trend in results: 63 d or more at 4 degrees C for both antibacterial activities, 14 d for anti-staphylococcal activity, and 26 d for anti-escherichia activity at 15 degrees C, but only 1.2 d and 1.9 d for the respective activities at 37 degrees C. Such antibacterial activities were attributable to the major allicin, allyl 2-propenylthiosulfinate. Surprisingly, the decline in the quantity of allicin was not accompanied by its degradation; instead, allicin became a larger molecule, ajoene, which was 3-times larger than allicin.

2-(1H-pyrrolyl)carboxylic acids as pigment precursors in garlic greening.

Six model compounds having a 2-(1 H-pyrrolyl)carboxylic acid moiety and a hydrophobic R group were synthesized to study their effects on garlic greening, the structures of which are similar to that of 2-(3,4-dimethyl-1 H-pyrrolyl)-3-methylbutanoic acid (PP-Val) (a possible pigment precursor for garlic greening). The puree of freshly harvested garlic bulbs turned green after being soaked in solutions of all these compounds, and with both increasing concentrations and incubation time the green color of the puree became deeper. In contrast, neither pyrrole alone nor pyrrole combined with free amino acids had the ability to discolor the puree. The compounds exhibited a good relationship between structure and activity of garlic greening, namely, the smaller the size of the R group, the larger the contribution. Also, it was found that the unidentified yellow species can be produced by reacting the model compounds with pyruvic acid at room temperature (23-25 degrees C). Moreover, blue species were formed by incubation of the model compounds with di(2-propenyl) thiosulfinate at room temperature. On the basis of these observations, a pathway for garlic greening was proposed.

Improving knowledge of garlic paste greening through the design of an experimental strategy.

The furthering of scientific knowledge depends in part upon the reproducibility of experimental results. When experimental conditions are not set with sufficient precision, the resulting background noise often leads to poorly reproduced and even faulty experiments. An example of the catastrophic consequences of this background noise can be found in the design of strategies for the development of solutions aimed at preventing garlic paste greening, where reported results are contradictory. To avoid such consequences, this paper presents a two-step strategy based on the concept of experimental design. In the first step, the critical factors inherent to the problem are identified, using a 2(III)(7-4) Plackett-Burman experimental design, from a list of seven apparent critical factors (ACF); subsequently, the critical factors thus identified are considered as the factors to be optimized (FO), and optimization is performed using a Box and Wilson experimental design to identify the stationary point of the system. Optimal conditions for preventing garlic greening are examined after analysis of the complex process of green-pigment development, which involves both chemical and enzymatic reactions and is strongly influenced by pH, with an overall pH optimum of 4.5. The critical step in the greening process is the synthesis of thiosulfinates (allicin) from cysteine sulfoxides (alliin). Cysteine inhibits the greening process at this critical stage; no greening precursors are formed in the presence of around 1% cysteine. However, the optimal conditions for greening prevention are very sensitive both to the type of garlic and to manufacturing conditions. This suggests that optimal solutions for garlic greening prevention should be sought on a case-by-case basis, using the strategy presented here.

Amplification of vacuole-targeting fungicidal activity of antibacterial antibiotic polymyxin B by allicin, an allyl sulfur compound from garlic.

A cationic antibacterial peptide, polymyxin B (PMB), was evaluated as an antifungal antibiotic against various yeasts and filamentous fungi when used in combination with allicin, an allyl sulfur compound from garlic. Allicin was not lethal but could markedly amplify the fungicidal activity of PMB, which was weakly detected with the increase in the plasma membrane permeability in Saccharomyces cerevisiae. Their combined actions caused a dynamic structural damage to the yeast vacuole as judged by the disappearance of its swollen spherical architecture. The vacuole-targeting activity of PMB was similarly amplified in medium with t-butyl hydroperoxide as a substitute for the action of allicin. These findings suggest that the allicin-mediated lipoperoxide production in fungal plasma membrane is the cause of the enhancement in the cellular uptake of PMB as well as its action against the vacuole.