Therefore, ultimately block the viral replication and reduced cellular viral load. Whereas, Fig. Targeting the entry or adsorption of virus to host cells by an effective entry-blocking or entry-inhibiting agent would be a potential strategy for therapeutic intervention because of easy access to the site of action, low cellular toxicity and damage, inhibition of the spread of the virus within the infected individual or lower risk to develop viral resistance to a therapy Teissier et al.
Entry into the host cell via crossing the cellular membrane is the first essential step of a viral life cycle for both enveloped surrounded by lipid bilayer or non-enveloped virus bounded by proteinaceous capsid. During close contact of viruses with host cell membranes specific interactions between membrane receptors and viral envelope or capsid proteins occurre to allow virus entry into the host cell followed by a cascade of signaling steps initiating replication of the virus in the cytosol or nucleus Thorley et al.
Medicinal plants and their isolated constituents have already shown their antiviral potential by inhibiting viral entry into the host cell as a part of their mechanism of action Lin et al. Research shows that crude GE and its OSCs exert their antiviral activity through interaction with the viral cell surface charge molecule and subsequently block or inhibit viral entry into host cells Table 3 , Table 4.
Influenza virus is an enveloped virus surrounded by hemagglutinin protein that interact with sialic acid receptors on cell membrane to enter host cells Byrd-Leotis et al. Active phytoconstituents present in the aqueous GE might be involved in the interference of viral membrane fusion by inhibiting this penetration phase in host cells Mehrbod et al.
Recently, another in-vivo investigation was carried out by Harazem et al. Harazem et al. The results demonstrated that thiosulfinate constituents were more active allicin; EC 50 0.
Both the crude extract and thiosulfinate compounds were more active against enveloped viruses herpes simplex virus-1 and 2, parainfluenza-3, vaccinia virus, vesicular stomatitis virus than non-enveloped virus human rhinovirus-2 and their direct viricidal properties were due to the disruption of viral envelope and cell membrane rather than any intracellular antiviral mechanism Fig.
It is well stablished that OSCs, and allicin and its derivatives contribute significantly to garlics antiviral properties Bayan et al. During exposure to allicin or its derivatives many enzymes that contain catalytically important thiol-groups are oxidized and inhibited Leontiev et al.
Sulfur containing compounds in garlic have also been reported to inhibit viral integrin signaling pathways to block the entry of virus into host cells Tatarintsev et al. Ajoene is the sulfur containing compound isolated from garlic that possesses potent EC 50 0. Walder et al. Another study demonstrated that a non-organosulfur proteinous compound, a lectin, derived from garlic, showed antiviral activity against severe acute respiratory syndrome-coronavirus SARS-CoV via inhibition of early viral attachment and inhibitory activity at the end of the infectious virus cycle Keyaerts et al.
Inhibition of viral replication is another potential target for chemotherapeutic intervention. The effectiveness of viral replication inhibitors is dependent on their impact on viral protein synthesis, reverse transcription, viral DNA polymerization, enzymatic reactions involved in viral DNA or RNA synthesis and viral integration into host cells Clercq, An advantage of inhibiting the viral replication is the specificity to infected cells rather than normal cells Desselberger, Natural products have been reported to inhibit viral replication for a wide range of viruses Oliveira et al.
Garlic and its constituents have been reported to exert antiviral effects by inhibiting viral replication against a number of pathogenic viruses. Mehrbood et al. Virus load in the infected cells was also reduced Mehrbod et al. Researchers believe that the infection prevention was due to the inhibition of viral fusion to VERO cells due to the blockage of cell surface receptors important for virus integration into host cells Mehmood et al.
These cell surface receptors are glycoproteins or glycolipids that facilitate the viral fusion through interaction with hemagglutinin protein of the viral cell surface Chang et al. Another study conducted by Chavan et al.
Post-exposure treatment revealed that the anti-influenza activity of the GE extracts might be due to the inhibition of virus replication or blocking virus budding from the infected MDCK cells Fig. A similar study was conducted by Mohajer Shoji et al. The results of both co-treatment and post exposure of aqueous GE on corona infected embryonic eggs showed significant increase of the embryonic index which suggests that GE could have an inhibitory effect on virus replication, however, no mechanism of action was specified Mohajer Shojai et al.
The RT enzyme has become a very significant therapeutic target with a number of specific inhibitors designed to suppress viral growth and infection. The discovery of more RT inhibitors is of great importance, because of increased viral resistance to current treatment Miceli et al.
Although a number of natural products and traditional medicines have shown activity against a variety of viral infections including retrovirus such as HIV , only a very few of them are active against the RT Kun Silprasit et al. The OSCs in garlic have been described as possessing anti-HIV activity through the inhibition of viral replication in a number of studies.
For example, it has been shown that synthetic ajoene can significantly protect acutely HIV-1 infected Molt-4 cells EC 50 0. There was no report found on allicin ability to inhibit HIV, but a recent study reported that allicin can inhibit replication of reticuloendotheliosis virus REV and alleviates the infection in chicken Wang et al.
REV is a retrovirus in the Retroviridae family and causes an immunosuppressive syndrome in different avian hosts. The study conducted by Wang et al. Allitridin is another active OSC of garlic. A number of in-vitro and in-vivo studies have reporting on its potent inhibitory activity towards human cytomegalovirus HCMV.
It is well known that immediate-early genes IEGs upregulation in HCMV plays a significant role in the regulation of its transcription as well as replication Fig. Another study evaluating the pre- and post-treatment 2 days efficacy of allitridin in MCMV-induced hepatitis of immunosuppressed mice ref showed, that viral load in liver, level of plasma alanine aminotransferase ALT or histological lesion in mice liver was significantly reduced pre- and post-treatment indicatinga possible therapeutic efficacy of allitribin in MCMV hepatitis Liu et al.
Following an acute viral infection, the host immune system tries to clear the virus quickly through killing the infected cells or the release of cellular proinflammatory cytokines Oldstone, These immune responses comprise of an initial innate immune response killing or eliminating infected cells via macrophages, NK cells or dendritic cells and then elevation of adaptive immunity via T and B cells antigen-specific response to kill infected cells and release inflammatory cytokines to inhibit viral replication Fig.
Several reports have highlighted immunomodulatory properties of natural products or plant extracts. These activities play a crucial role in the alleviation of viral infection, the regulation of viral replication, decrease of viral spreading and viral load Ganjhu et al.
Garlic has been reported to possesses immunomodulating properties in a number of in-vitro and in-vivo studies. The organosulfur compounds seem to be the main garlic constituents responsible for these effects. Venkatesh, Other constituents such as lectins and water-soluble fructans polysaccharide have also shown immunomodulating potential Li et al. Research shows that GE and its OSCs have immune enhancing activities to prevent different viral infections both in-vitro and in-vivo Guo et al.
Liu et al. The immunomodulatory effect of GE was also shown against HCMV infection in-vitro with its prophylactic use suggested in immunocompromised patients Guo et al. Another preclinical study in mice confirmed that CMV might modulate cellular Treg functions to escape the host immune surveillance for causing acute or chronic infection Li et al.
Proposed mechanism of immunomodulatory effect of garlic and its OSCs in viral infected host. In the figure, the mechanism of immunomodulatory activity of garlic and its OSCs shown to involve in the elevation of innate immune response via macrophage and natural killer NK cells as well as enhancing adaptive immunity through T cells and B cells.
OSCs have also shown anti-inflammatory activities including in viral infections. Dengue virus DENV infection-initiated inflammation is an important host immune response. It causes pathogenicity via the induction of proinflammatory cytokines and chemokines leading to vascular leakage and endothelial permeability Hall et al.
It is reported that oxidative stress has a crucial role in triggering inflammation Olagnier et al. In case of DENV infection induced oxidative stress has also been reported to link to the development of inflammation and the induction of pro-inflammatory cytokines Seet et al.
As such the alleviation of oxidative stress, as well as inflammation, are possible strategies for the treatment of Dengue Fever. Other reports also show that allicin is able to alleviate oxidative damage and inflammation caused by REV infection in an in-vivo model Wang et al. An immune enhancing effect of garlic was also confirmed in a randomized clinical trial with 17 volunteers who had a garlic-free or garlic-containing meal for 10 days. The trial showed that garlic can upregulate immune response genes and activate apoptosis and the xenobiotic metabolism in people who regularly consume garlic containing meals Charron et al.
Pre-clinical studies of garlic and its OSCs show to have antiviral activity against a number of viral infections. The increasing number of pre-clinical studies on this topic indicates the necessity to optimize garlic's clinical evaluation. A number of clinical trials have shown antiviral effects of garlic against viral cold and flu infections Hiltunen et al. Josling et al. Table 5. At the end of the trial, including an extra week of follow up, the active group showed significantly fewer and shorter incidences of the cold than the placebo group.
Viral re-infection was also higher in the placebo group than active group Josling, The results of this study suggest that the reduction of viral infection and reinfection can be decreased through daily garlic supplementation.
Another randomized double-blinded controlled trial tested powdered garlic extract PGE as a cellulose formulation to see whether it prevented airborne infection in 52 frequent travelers 26 in each group, garlic formulation vs. Health and infection episodes were recorded in a daily diary. There were significantly fewer and shorter periods of infections observed in the group treated with PGE, and PGE group participants were less likely to be infected with an airborne pathogen when PGE was taken Hiltunen et al.
The mechanism of airborne infection prevention was not explained, but it might be due to garlic's antiviral and immunomodulatory effects as noted in preclinical studies. Around the same time of the first clinical trial with garlic, a Russian group Andrianova et al. The trial investigated whether this formulation can prevent acute respiratory viral infection ARVI compared to benzimidazole Andrianova et al. In the second stage of the trial, at a lower dose ARVI morbidity was reduced by about 1.
The highlights that garlic products can play a role in the prevention of non-specific ARVI in children Andrianova et al. Garlic are immune modulators and reports suggest dietary meal containing garlic raw or crushed can influence the expression of immunity in humans Abdullah, ; Charron et al. A recent clinical trial has shown that diet supplemented with aged garlic extract AGE can modulate the inflammation and immunity of adults with obesity Xu et al.
With the question in mind whether GE supplementation can modify the immunity in humans and protect from colds and flu, Nantz et al. This study was adapted well as an explanation of molecular mechanism of protective effect of GE against common cold and flu Andrianova et al.
Garlic and its OSCs have shown to prevent viral induced hepatitis in a number of preclinical studies Table 3 , Table 4.
These results confirm previous research that indicated that pretreatment of GO and DDB can protect chemical-induced liver injury by elevating GSH level as well as lowering serum lipid levels Park et al. To date no simple and easy treatment that eradicates RMCW exists, although it seems that treatment of warts by intralesional immunotherapy is effective, Horn et al. Kenawy et al. The active group applied LGE to the largest one of RMCW twice per day for 28 days, whereas, placebo group participants applied saline twice a day for 28 days.
Garlic extract proved to be effective in the complete eradication of cutaneous warts Lipke, and recently Mousavi et al. The molecular mechanism of the effect of garlic against genital warts is not clear, but a number of mechanisms have been proposed including garlic induced enhancement of immunity and cellular function, antiviral effect of garlic and a garlic induced increase in serum GSH Mousavi et al.
Viral infections are a leading global challenge due to the increase in viral drug resistance and rapid mutations. Plants, as a natural medicine, have a long history of use against infectious diseases and as a potential source of novel drug discovery.
Garlic has been used widely for thousands of years as a functional food and a spice as well as a traditional medicine against a number of diseases including infections. Allicin and its derivatives, ajoene, allitridin and garlicin, were found to be the most promising OSCs of garlic and are responsible for several of garlic's therapeutic activities including the prevention of viral infections. Consumption of fresh, cooked and supplemented garlic are well tolerated at a reasonable level in or with a meal and regarded as safe by the FDA.
Studies conducted in in-vivo and in-vitro test models clearly demonstrate antiviral potential of garlic and its OSCs against a wide range of viruses; for example from the Adenoviridae, Arteriviridae, Coronaviridae, Flaviviridae, Flaviviridae, Herpesviridae, Orthomyxoviridae, Picornaviridae, Paramyxoviridae, Poxvirus , Rhabdoviridae and Retroviridae family.
The present review gives insight into the antiviral effects of garlic and its OSCs in pre-clinical and clinical studies, and highlights the variety of mechanisms through which these effects are achieved.
Blocking viral entry and fusion into host cells, inhibiting viral RNA polymerase, reverse transcriptase, and viral replication, as well as enhancing host immune response were the major pathways for antiviral activity of garlic and its OSCs. Immunomodulatory activity was shown to elevate the innate immune response via macrophage and NK cells, as well as enhance adaptive immunity through T cells, B cells and anti-inflammatory cytokines.
Randomized clinical trials utilizing a variety of commercial garlic preparations revealed a prophylactic effect of garlic in the prevention and treatment of a number of viral infections in human including the common cold and flu, viral induced hepatitis and warts. Improved immune response was claimed to be responsible for these effects. Thus the literature review highlights the antiviral potential of garlic and its various OSC's, their possible therapeutic use in the prevention of viral infections, as well as in antiviral drug development.
However, more high quality, clinical research, including long-term cohort studies and pharmacokinetic investigations need to be conducted to further elucidate garlic's and its OSCs role in antiviral therapy. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The author would like to thank Prof. Hossain for his valuable comments and feedback on the primary version of the manuscript.
National Center for Biotechnology Information , U. Trends Food Sci Technol. Published online Aug Ali , e Jamil A. Sarker f. Eunus S. Jamil A. Satyajit D. Author information Article notes Copyright and License information Disclaimer.
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This article has been cited by other articles in PMC. Abstract Background Garlic Allium sativum L. Scope and approach The aim of this review is to systematically summarize pre-clinical and clinical investigations on antiviral effects of garlic and its OSCs as well as to further analyse recent findings on the mechanisms that underpin these antiviral actions. Table 1 List of viruses with their family and common infection syndrome on which garlic extract and its organosulfur compounds reported to have antiviral activity.
Open in a separate window. Table 2 List of different commercial garlic preparations, method of preparation and their principle OSCs.
Table 3 Pre-clinical investigations in-vitro and in-vivo of antiviral activity of garlic extract. Mehrbod et al.
Wang et al. Table 5 Randomized controlled clinical investigations of garlic A. Andrianova et al. First stage tolerance study with two parallel group treated children and placebo control ; 2nd stage: 42 children in efficacy group, 41 control group and 73 benzimidazole group with mean age 10—12 yrs. Safety and tolerability were assessed based on adverse events and laboratory test results. Lee et al. Mousavi et al. Literature search strategy and data extraction A number of databases including PubMed, Cochrane library, Google Scholar and Science Direct were used to search literature on garlic and its OSCs for this review.
Results and discussion 3. Clinical studies of garlic and its organosulfur compounds against viral infection Pre-clinical studies of garlic and its OSCs show to have antiviral activity against a number of viral infections.
Conclusion and perspectives Viral infections are a leading global challenge due to the increase in viral drug resistance and rapid mutations. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Acknowledgement The author would like to thank Prof. References Abad J. Tomato spotted wilt virus on potato in eastern North Carolina. American Journal of Potato Research.
A strategic call to utilize Echinacea-garlic in flu-cold seasons. Journal of the National Medical Association. Anti-bacterial effect of garlic Allium sativum against clinical isolates of Staphylococcus aureus and Escherichia coli from patients attending Hawassa Referral Hospital, Ethiopia.
Journal of Infectious Diseases and Treatment. In-vitro studies of some medicinal plants extracts for antiviral activity against rotavirus. Dengue haemorrhagic fever or dengue shock syndrome in children. BMJ Clinical Evidence. Biological, molecular, and serological studies of a novel strain of grapevine leafroll-associated virus 2. Virus Genes. Clarifying the real bioactive constituents of garlic. Journal of Nutrition. Effect of long-acting garlic tablets "allicor" on the incidence of acute respiratory viral infections in children.
Terapevticheskii Arkhiv. Antimicrobial properties of allicin from garlic. Microbes and Infection. Immunomodulation and anti-inflammatory effects of garlic compounds. Journal of Immunology Research. Garlic Allium sativum and traditional medicine. Turkiye Parazitoloji Dergisi. Garlic: A review of potential therapeutic effects. Avicenna Journal of Phytomedicine.
Allicin: Chemistry and biological properties. The interplay between the host receptor and influenza virus hemagglutinin and neuraminidase. International Journal of Molecular Sciences. Drug design for hemagglutinin: Screening and molecular dynamics from traditional Chinese medicine database. Journal of the Taiwan Institute of Chemical Engineers. A single meal containing raw, crushed garlic influences expression of immunity and cancer related genes in whole blood of humans.
Journal Of Nutrition. Assessment of anti-influenza activity and hemagglutination inhibition of Plumbago indica and Allium sativum extracts. Pharmacognosy Research. In-vitro anti-adenoviral activity of five Allium plants. Osong Public Health and Research Perspectives. Molecular targets for antiviral agents. Journal of Pharmacology and Experimental Therapeutics. Rotavirus infection. Nature Reviews.
Disease Primers. Garlic oil is also an effective supplement, and is typically prepared using steam distillation. Garlic oil is distinct from garlic-flavored oil used for cooking, which is made by infusing raw garlic into cooking oils. Common types of garlic supplements include powdered garlic, aged garlic extract, and garlic oil.
Aged garlic extract may offer the greatest health benefits. While there is no established effective dosage of garlic, some studies on raw garlic use mg crushed raw garlic per kilogram of body weight twice per day.
This equals about three to four cloves per day You may also take an aged garlic extract supplement. Studies investigating the health benefits of aged garlic use varying dosages ranging from mg to 2, mg 6 , There is no established effective dosage of raw garlic or garlic supplements. Eating a balanced diet and maintaining a healthy lifestyle are essential for keeping your immune system in good shape.
Studies suggest that garlic may help fight colds and the flu. It may reduce your risk of developing an illness, and help you recover faster. At the end of the day, garlic is both tasty and super nutritious. There are many excellent reasons to include it in your diet.
This article is based on scientific evidence, written by experts and fact checked by experts. Our team of licensed nutritionists and dietitians strive to be objective, unbiased, honest and to present both sides of the argument.
This article contains scientific references. The numbers in the parentheses 1, 2, 3 are clickable links to peer-reviewed scientific papers. Garlic is a popular ingredient enjoyed for both its unique flavor and powerful health benefits.
This article takes a closer look at whether you should…. This is a detailed article about garlic and its health benefits. Here are 11 ways that garlic can improve your health, supported by science. Garlic is a delicious and common ingredient that adds flavor and depth to many dishes. This article reviews the best ways to store garlic. Garlic is a nutrient-rich addition to any diet.
PubMed, Cochrane library, Google Scholar and Science Direct databases were searched and articles up to June were included in this review. The alleviation of viral infection was also shown to link with immunomodulatory effects of garlic and its OSCs. Clinical studies further demonstrated a prophylactic effect of garlic in the prevention of widespread viral infections in humans through enhancing the immune response.
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