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.

[Advances in cardiovascular protection effects and mechanisms of allicin].

Cardiovascular diseases(CVD) with high morbidity and mortality pose severe threats to human life. Allicin, a main active ingredient of garlic, possesses multiple pharmaceutical activities. It not only exerts cardioprotective effects but also prevents the risk factors for CVD. Allicin exerts cardioprotective effects via a variety of mechanisms, including inhibiting oxidative stress, apoptosis, autophagy, and inflammatory responses, regulating lipid metabolism and gut microbiota, inducing hydrogen sulfide production, and dilating vessels. Despite the valuable cardioprotective effects, the instability of allicin has hindered the basic research and clinical application. This paper reviews the progress in the cardioprotective effects and mechanisms of allicin in the last decade and summarizes the methods to improve the stability of allicin. In addition, this review provides a reference for further research and development of allicin in cardiovascular protection.

Current studies and potential future research directions on biological effects and related mechanisms of allicin.

Allicin, a thiosulfonate extract from freshly minced garlic, has been reported to have various biological effects on different organs and systems of animals and human. It can reduce oxidative stress, inhibit inflammatory response, resist pathogen infection and regulate intestinal flora. In addition, dozens of studies also demonstrated allicin could reduce blood glucose level, protect cardiovascular system and nervous system, and fight against cancers. Allicin was widely used in disease prevention and health care. However, more investigations on human cohort study are needed to verify the biological or clinical effects of allicin in the future. In this review, we summarized the biological effects of allicin from previous outstanding and valuable studies and provided useful information for future studies on the health effects of allicin.

Natural Compound Allicin Containing Thiosulfinate Moieties as Transmembrane Protein 16A (TMEM16A) Ion Channel Inhibitor for Food Adjuvant Therapy of Lung Cancer.

Cancer is one of the most serious malignant diseases, and chemotherapy is cancer's main clinical treatment method. However, chemotherapy inevitably produces drug resistance, and side effects accompany them. Adjuvant therapy is an effective way to enhance chemotherapeutic drug sensitivity and reduce side effects. This study found allicin, garlic's active ingredient, is an inhibitor of transmembrane protein 16A (TMEM16A), a novel drug target of lung adenocarcinoma. Allicin concentration-dependently inhibited TMEM16A currents with an IC50 of 24.35 ± 4.14 µM. Allicin thiosulfinate moieties bound with R535A/E624A/E633A residues of TMEM16A blocked the ion transport function and downregulated TMEM16A protein expression affecting the mitogen-activated protein kinase signal transduction. Then, allicin reduced the viability and migration of LA795 cells, and induced cell apoptosis. Moreover, multitarget combination administration results indicated that the therapeutic effect of 3.56 mg/kg allicin and 3 mg/kg cisplatin combined administration was superior to the superposition of the two drugs alone, demonstrating that the anticancer effects of allicin and cisplatin were synergistic. In addition, low-concentration combined administration also avoided the side effects of cisplatin in mice. Based on the good tumor suppressor effect and high biosafety of allicin and cisplatin combination in vivo, allicin can be used for food adjuvant therapy of cisplatin chemotherapy.

Cellular Mechanisms Underlying the Cardioprotective Role of Allicin on Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are a group of diseases in which the common denominator is the affection of blood vessels, heart tissue, and heart rhythm. The genesis of CVD is complex and multifactorial; therefore, approaches are often based on multidisciplinary management and more than one drug is used to achieve the optimal control of risk factors (dyslipidemia, hypertension, hypertrophy, oxidative stress, endothelial dysfunction, inflammation). In this context, allicin, a sulfur compound naturally derived from garlic, has shown beneficial effects on several cardiovascular risk factors through the modulation of cellular mechanisms and signaling pathways. Effective pharmacological treatments for CVD or its risk factors have not been developed or are unknown in clinical practice. Thus, this work aimed to review the cellular mechanisms through which allicin exerts its therapeutic effects and to show why it could be a therapeutic option for the prevention or treatment of CVD and its risk factors.

Therapeutic Potential of Allicin and Aged Garlic Extract in Alzheimer's Disease.

Garlic, Allium sativum, has long been utilized for a number of medicinal purposes around the world, and its medical benefits have been well documented. The health benefits of garlic likely arise from a wide variety of components, possibly working synergistically. Garlic and garlic extracts, especially aged garlic extracts (AGEs), are rich in bioactive compounds, with potent anti-inflammatory, antioxidant and neuroprotective activities. In light of these effects, garlic and its components have been examined in experimental models of Alzheimer's disease (AD), the most common form of dementia without therapy, and a growing health concern in aging societies. With the aim of offering an updated overview, this paper reviews the chemical composition, metabolism and bioavailability of garlic bioactive compounds. In addition, it provides an overview of signaling mechanisms triggered by garlic derivatives, with a focus on allicin and AGE, to improve learning and memory.

Allicin as a Volatile or Nebulisable Antimycotic for the Treatment of Pulmonary Mycoses: In Vitro Studies Using a Lung Flow Test Rig.

Fungal infections of the lung are an increasing problem worldwide and the search for novel therapeutic agents is a current challenge due to emerging resistance to current antimycotics. The volatile defence substance allicin is formed naturally by freshly injured garlic plants and exhibits broad antimicrobial potency. Chemically synthesised allicin was active against selected fungi upon direct contact and via the gas phase at comparable concentrations to the pharmaceutically used antimycotic amphotericin B. We investigated the suppression of fungal growth by allicin vapour and aerosols in vitro in a test rig at air flow conditions mimicking the human lung. The effect of allicin via the gas phase was enhanced by ethanol. Our results suggest that allicin is a potential candidate for development for use in antifungal therapy for lung and upper respiratory tract infections.

Anticancer potential of allicin: A review.

Phytochemicals have attracted attention in the oncological field because they are biologically friendly and have relevant pharmacological activities. Thanks to the intense and unique spicy aroma, garlic is one of the most used plants for cooking. Its consumption is correlated to health beneficial effects towards several chronic diseases, such as cancer, mainly attributable to allicin, a bioactive sulfur compound stored in different plant parts in a precursor form. The objective of this review is to present and critically discuss the chemistry and biosynthesis of allicin, its pharmacokinetic profile, its anticancer mechanisms and molecular targets, and its selectivity towards tumor cells. The research carried out so far revealed that allicin suppresses the growth of different types of tumors. In particular, it targets many signaling pathways associated with cancer development. Future research directions are also outlined to further characterize this promising natural product.

Pharmacoinformatics and hypothetical studies on allicin, curcumin, and gingerol as potential candidates against COVID-19-associated proteases.

Medicinal plants have been known to provide the essential raw material for the majority of antiviral drugs. This study demonstrated the putative inhibitory potential of curcumin, allicin, and gingerol towards cathepsin K, COVID-19 main protease, and SARS-CoV 3 C-like protease. The pharmacokinetic properties were predicted through the SwissADME server while the corresponding binding affinity of the selected phytocompounds towards the proteins was computed using PyRx-Python Prescription 0.8 and the binding free energy were computed based on conventional molecular dynamics using LARMD server. The ADMET properties revealed all the drugs possess drug-like properties. Curcumin has the highest binding affinities with all the selected proteases while allicin has the lowest binding affinities towards the proteases. Moreover, it was observed that curcumin exhibited the highest binding free energy of -17.90 ± 0.23,  -18.21 ± 0.25, and -9.67 ± 0.08 kcal/mol for Cathepsin K, COVID-19 main protease, and SARS-CoV 3 C-like protease, respectively. Based on the activities of the phytocompounds against coronavirus target proteases involved in the viral entry as evident from the results, the study, therefore, suggests that these phytocompounds could be valuable for the development of drugs useful for the prevention of coronavirus entry and replication.Communicated by Ramaswamy H. Sarma.

Potential Therapeutic Effects of Natural Plant Compounds in Kidney Disease.

BACKGROUND: The blockade of the progression or onset of pathological events is essential for the homeostasis of an organism. Some common pathological mechanisms involving a wide range of diseases are the uncontrolled inflammatory reactions that promote fibrosis, oxidative reactions, and other alterations. Natural plant compounds (NPCs) are bioactive elements obtained from natural sources that can regulate physiological processes. Inflammation is recognized as an important factor in the development and evolution of chronic renal damage. Consequently, any compound able to modulate inflammation or inflammation-related processes can be thought of as a renal protective agent and/or a potential treatment tool for controlling renal damage. The objective of this research was to review the beneficial effects of bioactive natural compounds on kidney damage to reveal their efficacy as demonstrated in clinical studies. METHODS: This systematic review is based on relevant studies focused on the impact of NPCs with therapeutic potential for kidney disease treatment in humans. RESULTS: Clinical studies have evaluated NPCs as a different way to treat or prevent renal damage and appear to show some benefits in improving OS, inflammation, and antioxidant capacity, therefore making them promising therapeutic tools to reduce or prevent the onset and progression of KD pathogenesis. CONCLUSIONS: This review shows the promising clinical properties of NPC in KD therapy. However, more robust clinical trials are needed to establish their safety and therapeutic effects in the area of renal damage.

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.

The Garlic Compound Z-Ajoene, S-Thiolates COX2 and STAT3 and Dampens the Inflammatory Response in RAW264.7 Macrophages.

SCOPE: Garlic (Allium sativum) has been used for centuries as a prophylactic and therapeutic medicinal agent to control inflammation-associated pathologies. To investigate the underlying mechanisms, an in vitro inflammatory model is established using RAW264.7 murine macrophages exposed to low-doses of lipopolysaccharide (LPS) in the presence of garlic compounds allicin and Z-ajoene (ZA), mimicking regular garlic consumption. METHODS AND RESULTS: Both allicin and Z-ajoene dampen both transcript and protein expression of the pro-inflammatory cytokines IL1ß, IL6, and IL12ß, and upregulate the expression of the anti-inflammatory cytokine IL10. Protein arrays of selected secreted inflammatory mediators confirm that Z-ajoene has a pronounced down-regulatory effect on LPS-induced inflammatory cytokines and chemokines. Many of these proteins are known targets of the transcription factor signal transducer and activator of transcription 3 (STAT3); and indeed, Z-ajoene or its analogue dansyl-ajoene is found to decrease phosphorylation and nuclear translocation of STAT3, and to covalently modify the protein by S-thiolation at Cys108, Cys367, and Cys687. Z-Ajoene dose-dependently and non-competitively inhibit the activity of cyclooxygenase 2 (COX2), possibly attributed to S-thiolation at Cys9 and Cys299. CONCLUSION: The characterization of Z-ajoene's activity of targeting and covalently modifying STAT3 and COX2, both important regulators of inflammation, may contribute to the health benefits of regular dietary garlic consumption.

Effects of dietary patterns combined with dietary phytochemicals on breast cancer metastasis.

AIMS: Dietary phytochemicals and diet types (e.g., the Mediterranean diet) have been shown to have anti-cancer properties. However, the effects of combined treatment with dietary phytochemicals and different diet types on primary and metastatic tumor growth have yet to be investigated. The purpose of this study is to investigate the effects of phytochemicals combined with diet types on breast cancer metastasis. MAIN METHODS: The inhibitory effects on breast cancer metastasis of three phytochemicals (allicin, hesperidin, astragalus polysaccharides) and two diet types (Mediterranean diet, restricted diet), separately or in combination, were evaluated based on: (i) detection of circulating tumor cells (CTCs) using an in vivo capture method; and (ii) primary tumor growth. KEY FINDINGS: All dietary factors significantly inhibited the growth of primary tumors and metastases, with combinations showing enhancing the effects. SIGNIFICANCE: Dietary phytochemicals and diet types should be further evaluated as adjunct therapies and lifestyle modifications in cancer patients. Furthermore, the in vivo CTC capture method allows dynamic monitoring of cancer metastasis over time, providing a useful approach to evaluating treatment effects in real-time.

Effect of allicin on antioxidant defense system, and immune response after carbofuran exposure in Nile tilapia, Oreochromis niloticus.

In this work, allicin was evaluated as an immunostimulant and antioxidant agent preventing Nile tilapia; Oreochromis niloticus against carbofuran toxicity. Fish (60 ± 8 g) were allocated to five groups; the first group (control), the second group was fed 1 g/kg allicin-supplemented diets without carbofuran intoxication, the third group exposed to 1/10 LC50 carbofuran (0.246 mg/L). While the fourth, and fifth groups were fed allicin supplemented diet at concentration of 0.5 and 1 g/kg diet, respectively, and exposed to carbofuran at the same concentration similar to the one of the third group. After 30 days, fish exposed to carbofuran showed high ALT, AST, ALP, cholesterol, glucose, cortisol, uric acid, and creatinine levels. However, serum AChE, total proteins, immunoglobulins, and lysozyme activity were markedly (P ≤ 0.05) reduced in carbofuran exposed tilapia fish. Moreover, malondialdehyde (MDA) level was significantly increased in liver, and kidneys tissues of carbofuran exposed fish. Whereas, catalase (CAT) activity, superoxide dismutase (SOD), and total antioxidant capacity (TAC) were decreased (P ≤ 0.05) significantly in both liver, and kidneys tissues after exposure to carbofuran. Interestingly, tilapia fish treated with carbofuran (0.246 mg/L) and fed (0.5 and 1 g/kg diet) allicin in both the 4th & 5th groups, respectively, decreased serum biochemical parameters; and hepatorenal (MDA) levels, as well as increased AChE, immunological profile, and oxidative stress biomarkers. The results suggested that co- administration of allicin at the high dose is more capable of improving the biochemical, and immunological parameters, and tissue antioxidant responses of carbofuran treated fish.

Garlic (Allium sativum L.): a potential unique therapeutic food rich in organosulfur and flavonoid compounds to fight with COVID-19.

Coronavirus disease 2019 (COVID-19) is the current major health crisis in the world. A successful strategy to combat the COVID-19 pandemic is the improvement of nutritional pattern. Garlic is one of the most efficient natural antibiotics against the wide spectrum of viruses and bacteria. Organosulfur (e.g., allicin and alliin) and flavonoid (e.g., quercetin) compounds are responsible for immunomodulatory effects of this healthy spice. The viral replication process is accelerated with the main structural protease of SARS-CoV-2. The formation of hydrogen bonds between this serine-type protease and garlic bioactives in the active site regions inhibits the COVID-19 outbreak. The daily dietary intake of garlic and its derived-products as an adjuvant therapy may improve side effects and toxicity of the main therapeutic drugs with reducing the used dose.

Effects of laying breeder hens dietary ß-carotene, curcumin, allicin, and sodium butyrate supplementation on the jejunal microbiota and immune response of their offspring chicks.

Our long-term goal is to improve chick health and reduce the use of antibiotics in the poultry industry via maternal effects. To link jejunal microbes with chicks' different immune levels and growth performance in our previous research, this study investigated jejunal microbes, jejunal inflammation, and immune responses based on a comparison between different groups. Newly hatched Hy-Line chicks were allotted into 3 groups: a chick control group (cCON), a ciprofloxacin lactate treatment group (Cipro)-the chicks of the cCON and Cipro groups were hatched from laying breeder hens given a basal diet-and a 5-wk ß-carotene, curcumin, allicin, and sodium butyrate supplementation group (cCCAB), wherein chicks hatched from laying breeder hens. All groups were fed the same diet for 4 wk; the Cipro group was given ciprofloxacin lactate in drinking water continuously. At the end of the experiment, the results demonstrated that the jejunal microbes of the Cipro group showed significant changes in alpha and beta diversity, and in taxonomy at phylum and genus levels. Statistically, a total of 67 significantly enriched (P < 0.05) taxa were identified between groups by linear discriminant analysis effect size; Firmicutes was significantly enriched (P < 0.05) in the cCCAB group, 65 taxa were significantly enriched (P < 0.05) in the Cipro group, and 32 of the 65 enriched (P < 0.05) taxa were in the Proteobacteria phylum of the Cipro group. Levels of lipopolysaccharide in jejunal content, and nuclear factor kappa-B, and tumor necrosis factor-α in jejunums of the Cipro and cCCAB groups were increased (all P < 0.05) compared to those in the cCON group. There was obvious neutrophil infiltration and upregulated (all P < 0.05) IL-6 mRNA in the Cipro group jejunums compared to the cCON and cCCAB groups. The expression of PSME3 and PSME4 genes was upregulated (all P < 0.05) in the cCCAB group compared to the cCON and Cipro groups. In conclusion, ciprofloxacin lactate administration led to potential hazards in health and growth in chicks via microbial disturbances-induced jejunal inflammation, and laying breeder hens dietary supplementation with ß-carotene, curcumin, allicin, and sodium butyrate could enhance jejunal immunity of their offspring via the interaction between host innate immunity selected microbial colonization and microbiota educated adaptive immunity.

Allicin reduces inflammation by regulating ROS/NLRP3 and autophagy in the context of A. fumigatus infection in mice.

OBJECTIVES: Inhibitory effect of allicin with broad-spectrum antimicrobial activity on A. fumigatus and the regulation mechanism of inflammation and autophagy in vitro and in vivo. METHODS: The corresponding concentration of allicin was prepared according to the needs of the experiment. In vitro, 2 ml 5 × 104 of fungal spores suspension was added to the 6-well plate per hole, and different final concentrations of allicin (1 µl/ml, 2.5 µl/ml, 5 µl/ml, 10 µl/ml, 20 µl/ml, 30 µl/ml) were added. The fungal spores were stained by fluorescent dye SYTO 9 (green) every day, and the spore germination inhibition was detected by flow cytometry in different PH. RAW264.7 cells were cultured and stimulated by A. fumigatus spores for 3 h, then allicin solution was added. Then some cells were stained with ROS probe (green) and hochest33342 (blue). The effect of allicin on ROS was observed by fluorescence microscope. The other part of cells extracted protein from cell lysate and detected the effect of allicin on inflammatory factors and autophagy by Western-blotting. The green and red spots of RAW264.7 cells stably transfected with GFP-RFP-LC3 were observed by fluorescence microscopy. In vivo, A. fumigatus spore was injected intratracheally into mice, then allicin was injected intravenously at a concentration of 5 mg/kg/day for 7 consecutive days. The survival status, pulmonary fungal load and weight of mice was recorded continuously for 30 days and detected the changes of lung by pathological examination and immunohistochemistry. RESULTS: In vitro, allicin significantly inhibited the spore germination of A. fumigatus within 24 h in a dose-dependent manner and it had a stable inhibition on the spore germination of A. fumigatus in acidic environment. Cell experiments showed that allicin inhibited intracellular spore germination by inhibiting ROS production, inflammation and autophagy. In the animal experiment, the survival rate and body weight of allicin injection group were higher than that of non injection group, while the spore load of lung was lower than that of non injection group (P < 0.05). CONCLUSIONS: These results support that allicin reduces inflammation and autophagy resistance to A. fumigatus infection, It also provides a possible treatment for Aspergillus infectious diseases, i.e. early anti-inflammation, antibiotics or drugs that inhibit excessive autophagy.

Differential effects of alliin and allicin on apoptosis and senescence in luminal A and triple-negative breast cancer: Caspase, ΔΨm, and pro-apoptotic gene involvement.

Breast cancer is the most frequent cancer in women worldwide, and drug resistance is common in all breast cancer types. The combination of natural products with chemotherapies has attracted attention, as it was found that natural compounds enhance the effects of standard cancer chemotherapeutic drugs and protect from side effects. Into the different natural products, garlic has been recognized for its antitumor properties. It is suggested that its anticancer effects are associated with its organo-sulfur compounds, especially alliin and allicin. Here, we evaluated the effects of both molecules on cell death, senescence, and their senolytic potential in luminal A and triple-negative breast cancer cells. MCF-7 (luminal A) and HCC-70 (triple-negative) cells were cultured and treated with different concentrations of alliin or allicin. Then, cell viability was determined using the WST-1 reagent. Apoptosis and caspase activity were evaluated by flow cytometry; ΔΨm was assessed using a JC-10 fluorometric assay kit. Apoptosis-related genes were evaluated by RT-PCR. Proliferation was measured using bromodeoxyuridine incorporation. We also evaluated clonogenicity, senescence (ß-Galactosidase Staining), and the senolytic effect of the compounds. Our results showed that allicin has antiproliferative, anticlonogenic, and senolytic effects. In addition, allicin decreased cell viability and induced apoptosis by loss of ΔΨm, caspase-3, caspase-8, and caspase-9 activation, upregulation of NOXA, P21, and BAK, as well as downregulation of BCL-XL expression. Contrary to allicin, alliin promoted clonogenicity, induced senescence, and did not exhibit pro-apoptotic effects in breast cancer cells.

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.

Review: antimicrobial properties of allicin used alone or in combination with other medications.

Garlic (Allium sativum L.) is a well-known spice widely utilised for its medicinal properties. There is an extensive record of the many beneficial health effects of garlic which can be traced back to as early as the ancient Egyptian era. One of the most studied properties of garlic is its ability to cure certain ailments caused by infections. In the 1940s, the antimicrobial activities exhibited by garlic were first reported to be due to allicin, a volatile compound extracted from raw garlic. Since then, allicin has been widely investigated for its putative inhibitory activities against a wide range of microorganisms. Allicin has demonstrated a preference for targeting the thiol-containing proteins and/or enzymes in microorganisms. It has also demonstrated the ability to regulate several genes essential for the virulence of microorganisms. Recently, it was reported that allicin may function better in combination with other antimicrobials compared to when used alone. When used in combination with antibiotics or antifungals, allicin enhanced the antimicrobial activities of these substances and improved the antimicrobial efficacy. Hence, it is likely that combination therapy of allicin with additional antimicrobial drug(s) could serve as a viable alternative for combating rising antimicrobial resistance. This review focuses on the antimicrobial activities exhibited by allicin alone as well as in combination with other substances. The mechanisms of action of allicin elucidated by some of the studies are also highlighted in the present review in order to provide a comprehensive overview of this versatile bioactive compound and the mechanistic evidence supporting its potential use in antimicrobial therapy.