. 2019 Jul 5;8(7):246. doi: 10.3390/foods8070246

Table 1.

The biological activities of garlic and its active components.

Product	Compounds	Study Type	Subjects/ Cell Lines	Main Effects	Possible Mechanisms	Ref.
Antioxidant Activity
Aged garlic extract		In vitro	Human endothelial cells	Protecting cells against oxidative stress	Inducing the expression of several antioxidant enzymes, HO-1 and GCLM subunit, through Nrf2- ARE pathway	[43]
	Saponins	In vitro	Mouse-derived C2C12 myoblasts	Protecting cells against the growth inhibition and DNA damage induced by H₂O₂	Scavenging intracellular reactive oxygen species	[44]
Anti-inflammatory Activity
	Ethyl linoleate	In vitro	Lipopolysaccharide-stimulated RAW 264.7 macrophages	Reducing the production of NO and prostaglandin E-2	Down regulating the expression of iNOS and COX2	[45]
	Garlic 14-kDa protein	In vitro	Lipopolysaccharide-stimulated J774A.1 macrophages	Inhibiting the inflammatory mediators such as NO, TNF-α, and IL-1β	Inhibiting the transcription factor NF-κB signaling pathway	[46]
Aged garlic extract		In vivo	Apolipoprotein E-knockout mice	Inhibiting inflammation	Reducing the level of TNF-α and interleukin IL-1 receptor-associated kinase 4 Increasing the activity of AMPK in the liver	[47]
	Allicin	In vivo	BALB/c mice	Protecting against the inflammatory response induced by schistosome infection		[48]
Garlic tablets (equal to 2.5 g fresh garlic daily)		Clinical trial	40 post-menopausal obese or overweight patients	Alleviating osteoarthritis	Reducing resistin	[49]
Antimicrobial Activity
Garlic “Rosato” and “Caposele”		In vitro	Aspergillus versicolor, Penicillum citrinum and Penicillium expansum	Inhibiting the growth of bacteria		[53]
Aged garlic extract	Allicin	In vitro	Burkholderia cepacian	Inhibiting the growth of bacteria		[54]
	Garlic oil	In vitro	Staphylococcus aureus, Escherichia coli and Bacillus subtilis	Inhibiting the growth of bacteria		[50]
		In vitro	Penicillium funiculosum	Inhibiting the growth of bacteria	Penetrating into cells and organelles Destroying the cell structure Leading to the leakage of cytoplasm and macromolecules	[55]
		In vitro	Candida albicans	Disrupting the normal metabolism of bacteria	Inducing key genes involved in oxidative phosphorylation, the cell cycle, and protein processing in the endoplasmic reticulum	[56]
Raw garlic		Clinical trial	15 patients with H. pylori infection	Inhibiting Helicobacter pylori in the stomach		[57]
Modulating Immune System
Fresh garlic	Polysaccharides/ Fructan	In vitro	RAW 264.7 macrophages	Exerting immunomodulatory effect	Regulating the expressions of IL-6, IL-10, TNF-α, and interferon-γ	[58]
	Garlic oil	In vivo	Wistar rats	Normalizing several immunological parameters of rats, such as the serum total immunoglobulin concentration and T-cell subtype CD4⁺ Combination of garlic oil and levamisole could balance the T-helper 1/ T-helper 2 response		[59,60]
	Selenizing garlic polysaccharides	In vivo	14-day-old chickens	Promoting lymphocyte proliferation Enhancing interferon-γ and IL-2 Increase the serum antibody titer		[61]
Aged garlic extract		Clinical trial	56 healthy human participants	Reducing the occurrence and severity of cold and flu Improving the immune system functions		[8]
Cardiovascular Protection
Aged garlic extract		In vitro	Isolated rat aortic rings	Leading to endothelial-dependent vasodilation	Stimulating the production of NO	[71]
Aged black garlic extract	Polyphenols	In vivo	Isolated hearts of male Sprague–Dawley rats	Relaxing coronary arteries before and after ischemia-reperfusion in rat Preventing the decrease of myocardial contractility		[90]
Aged garlic extract	S-1-propylenecysteine	In vivo	Spontaneous hypertension rats	Improving peripheral blood circulation Reducing the systolic blood pressure		[75]
Fermented garlic extract by Bacillus subtilis		In vivo	Spontaneous hypertension rats	Reducing the systolic blood pressure	Modulating the sGC-cGMP-PKG pathway	[76]
Fermented garlic extract		In vivo	Monocrotaline-induced pulmonary hypertension rats	Alleviating pulmonary hypertension	Decreasing the expression of vascular endothelial cell adhesion molecule-1 and MMP- 9Increasing the expression of PKG and eNOS	[77]
Garlic	Alliin	In vivo	Female Wistar albino rats	Increasing the activity of captopril on inhibiting ACE and hypertension		[72]
1.5% black garlic extract		In vivo	High-fat diet-fed male Sprague–Dawley rats	Modulating the metabolism of lipid and cholesterol Decreasing the levels of blood total lipids, triglyceride, and cholesterol	Reducing the mRNA expression of sterol regulatory element binding protein-1c	[80]
Raw garlic	Allyl methyl sulfide/Allyl methyl sulfoxide	In vivo	Male Sprague–Dawley rats	Reduce cardiac hypertrophy remodeling induced by isoproterenol	Increasing Na⁺/K⁺-ATPase protein level	[83]
Raw garlic		In vivo	Streptomycin-induced diabetic rats	Protecting the heart function Activating sirtuin 3-manganese superoxide dismutase pathway	Deacetylating manganese superoxide dismutase	[84]
Garlic extract		In vivo	Insulin-resistant obese rats	Protecting heart rate variability, cardiac dysfunction, and mitochondrial dysfunction		[86]
Garlic extract		In vivo	Rat model of gentamicin-induced chronic renal failure	Protecting the heart tissue	Reducing oxidative stress Controlling Na⁺/K⁺-ATPase activity and Ca²⁺ levels	[87]
Aged garlic extract	SAC	In vivo	Rats with myocardial dysfunction induced by isoproterenol	Protecting against cardiotoxicity		[88]
Aged garlic extract		In vivo	Apolipoprotein E-knockout mice	Inhibiting inflammatory response to prevent atherosclerosis	Reducing serum level of C-reactive protein and thromboxane B-2, protein level of TNF-α and IL-1 receptor-associated kinase 4 Increasing AMPK activity in the liver	[47]
		In vivo	Apolipoprotein E-knockout mice	Inhibiting the vascular inflammation and lipid deposition in the early stage of atherosclerosis development		[91]
High temperature and high pressure-processed garlic		In vivo	High-cholesterol diet-fed Sprague–Dawley rats	Reducing the levels of total cholesterol, low-density lipoprotein cholesterol and triglyceride		[79]
Garlic		Cohort study	30 patients with diabetic dyslipidemia	Decreasing the level of cholesterol and low-density lipoprotein Increase the level of high-density lipoprotein		[81]
Aged garlic		Clinical trial	41 patients with hypercholesterolemia	Reducing the activity of myeloperoxidase and lipid hydroperoxide in serum Decreasing the concentration of F2-isoprostanes in plasma and urine		[82]
Enzymatic browning processed garlic		Clinical trial	44 patients with hypertension	Reducing systolic blood pressure and diastolic blood pressure		[78]
Anticancer Activity
Garlic extract		In vitro	Bladder cancer EJ cells	Inducing G₂/M-phase cell cycle arrest Inhibiting cell growth Inhibiting cell migration and invasion	Activating the ATM pathway and CHK2; Inhibiting the expression of MMP-9 Reducing the binding activity of transcription factors AP-1, specificity protein-1 and NF-κB motifs Increasing the expression of heat shock protein A6	[113]
Aged garlic extract		In vitro	Colorectal cancer cell lines (SW480 and SW620) ECV304 cells and the transformed rat lung endothelial cells	Decreasing invasive activity Inhibiting cell proliferation Decreasing invasive activity Inhibiting the tube formation of endothelial cells	Inhibiting cell motility	[124]
Aged garlic extract		In vitro	DLD-1 human colon cancer cells (ATCC CCL-221)	Inhibiting cell proliferation	Down regulating the expression of cyclin B1 and CDK1 Inhibiting of activation of NF-κB	[121]
Crude garlic extract	Lipid bioactive compounds	In vitro	Human liver cancer (Hep-G2) Colon cancer (Caco-2) Prostate cancer (PC-3) Breast cancer (MCF-7) Mouse macrophage cell (TIB-71) lines	Inhibiting the growth rate of Hep-G2, PC-3, MCF-7, and TIB-71 cells by 80%–90% at 72 h (P < 0.05).	Inhibiting cell proliferation Inducing cell cycle arrest Inducing apoptosis	[112]
	Allicin	In vitro	Human gastric adenocarcinoma cell line	Inhibiting cell proliferation	Inducing cell cycle arrest at S-phase	[18]
	DATS	In vitro	Human gastric carcinoma cell line (SGC-7901)	Inhibiting cell proliferation Blocking cell cycle Increasing apoptotic cell death	Accumulating Bax, p53, and cytochrome C and decreasing the expression of Bcl-2	[114]
	DATS	In vitro	Human breast cancer cell line (MDA-MB-231)	Inhibiting angiogenesis		[125]
	Z-ajoene	In vitro	Glioblastoma multiforme cells	Inhibiting the growth of the cancer stem cells population		[119]
	Z-ajoene	In vitro	Human breast cancer cells (MDA-MB-231)	Inhibiting cell growth Inducing cell apoptosis	Targeting the folding of proteins in the endoplasmic reticulum of cancer cells	[120]
	SAC	In vitro	Human epithelial ovarian cancer cell line (A2780)	Inhibiting cell proliferation Inducing G₁/S-phase cell cycle arrest Increasing apoptosis Reducing the migration of cells	Decreasing the expression of pro-caspase-3, Parp-1 Bcl-2 and increasing active caspase-3 and Bax Reducing the expression of Wnt5a, phosphorylation protein kinase B and c-Jun proteins	[115]
	SPRC	In vitro	Human pancreatic ductal adenocarcinoma cells (Panc-1)	Inhibiting cell proliferation Inducing apoptosis	Inducing G₂/M-phase cell cycle arrest Regulating the level of JNK protein	[116]
	SAMC	In vitro	Human colorectal carcinoma cell line (SW620)	Inhibiting cell proliferation Inducing cell apoptosis	Regulating JNK and p38 MAPK pathways	[118]
	SAMC	In vitro	Hepatoma cell lines (Hep3B and Huh-7)	Reducing the cell viability Shortening the S phase and increasing the G₀/G₁ phase		[117]
	Alliin	In vitro	Gastric adenocarcinoma cells	Regulating cell apoptosis	Generating reactive oxygen species Decreasing mitochondrial membrane potential by Bax/Bcl-2 Up-regulating cytochrome C	[18]
Aged garlic extract		In vivo	Adult male Wister albino rats treated with cisplatin	Improving the renal histological, ultrastructural and biochemical changes, such as hemorrhage, glomerular atrophy, tubular necrosis and degeneration		[128]
		In vivo	Fibrosarcoma tumors implanted BALB/c mice	Improving the immune responses of mice to fibrosarcoma Inhibiting tumor growth	Increasing the ratio of CD₄⁺/CD₈⁺ Producing interferon-γ in splenocytes	[131]
Garlic and lemon aqueous extract		In vivo	BALB/c mice xenograft model of breast cancer EMT6/P cells	Reducing tumor size Inhibiting angiogenesis Inducing apoptosis Activating the immune system	Inhibiting the expression of vascular endothelial growth factor Increasing interferon-γ, IL-2, and IL-4 levels	[126]
	Allicin	In vivo	Female Swiss albino mice	Alleviating liver injury induced by tamoxifen	Changing the decrease of superoxide dismutase, glutathione and total protein and the increase of aspartate aminotransferase, alkaline phosphatase and alanine aminotransferase levels	[129]
	DADS	In vivo	FVB/N mice	Preventing colorectal tumorigenesis induced by azoxymethane and dextran sulfate	Inhibiting inflammation Inhibiting glycogen-synthase kinase-3β Reducing the nuclear localization of NF-κB	[132]
	DATS	In vivo	Female BALB/c-nude mouse xenograft model of human gastric carcinoma SGC-7901 cells	Inhibiting tumor growth Promoting tumor apoptosis	Regulating the expressions of MMP-9 and E-cadherin protein	[114]
	SPRC	In vivo	Xenograft model of pancreatic ductal adenocarcinoma Panc-1 cells	Inhibiting tumor growth	Regulating the level of JNK protein	[116]
	SAMC	In vivo	Mouse xenograft model of hepatoma Huh-7 cells	Inhibiting tumor growth	Interacting with the Wnt-pathway co-receptor LRP6 on the cell membrane	[117]
Raw, crushed garlic		Cohort study	17 volunteers from Beltsville, Maryland	Up-regulating seven genes including AHR, ARNT, HIF1A, JUN, NFAM1, OSM and REL		[123]
Garlic extract		Cohort study	Patients who received chemotherapy for hematological malignancies	Protective effect on febrile neutropenia in lower-risk subgroup		[130]
Hepatoprotective Activity
Black garlic extract		In vitro	Rat clone-9 hepatocytes	Inhibiting apoptosis, lipid peroxidation, oxidative stress, and inflammation		[136]
Garlic extract		In vivo	Wistar rats	Attenuating the liver damage induced by alloxan Improving plasma biochemical factors of hepatic function, such as urea, creatinine, aspartate transaminase, and alanine transaminase		[137]
Single clove garlic extract		In vivo	Male rabbits	Protecting against CCl₄-induced acute liver injury		[38]
LAFGE		In vivo	C57/BL6 J mice	Reducing the liver lipid level Ameliorating the hepatic steatosis		[142]
LAFGE		In vivo	rats	Inhibiting liver cell apoptosis Protecting liver from acetaminophen-induced liver injury	Suppressing MAPK phosphorylation Down regulating p53	[143]
	Garlic oil	In vivo	1,3-Dichloro-2-propanol-treated rats	Protecting liver	Enhancing the activities of hepatic antioxidant enzymes Blocking metabolic activation of 1, 3-dichloro-2-propanol Reducing the apoptosis in liver	[139]
	DADS	In vivo	Wistar rats	Protecting mice from nonalcoholic fatty liver disease induced by long-term high-fat diet.	Reducing the release of pro-inflammatory cytokines in the liver Increasing antioxidant activity by inhibiting the expression of cytochrome P450 2E1	[141]
	LAFGE	Clinical trial	36 adults with mildly high level of serum gamamyl glutamyl transpeptiase	Improving the levels of gamamyl glutamyl transpeptias and alanine aminotransferase without adverse effects		[144]
Digestive System Protection
Black garlic extract		In vitro	Small intestine	Stimulating gastrointestinal peristalsis Promoting gastrointestinal emptying and facilitates defecation.		[146]
	DADS DAS	In vitro	Interferon-γ-stimulated intestinal cells	Reducing interferon-inducible protein-10, IL-6 Inhibiting NO and the expression of STAT-1		[70]
	DADS DAS	In vivo	Male ICR mice	Improving the colitis induced by dinitrobenzenesulfonic acid		[70]
Garlic and cabbage extract		In vivo	Sprague–Dawley rats	Reducing the length of gastric ulcer, the total gastric acid, gastric juice volume, total bacteria count, and histopathological changes caused by aspirin Improving the pH value of gastric juice		[147]
Aged garlic extract		In vivo	Male albino rats	Healing the gastric mucosal injury induced by indomethacin Reducing the total microbial amount in stomach		[148]
Aged garlic extract		In vivo	Male Wistar rats	Preventing the indomethacin-induced ulcer	Reducing oxidative stress Elevating the level of prostaglandin E-2, glutathione, and NO in gastric tissue	[149]
	Allicin	In vivo	Dextran sulfate sodium-induced colitis mice	Alleviating the ulcerative colitis induced by dextran sulfate sodium	Inhibiting the activation of AP-1/NF-κB/signal transducer and activator of transcription-1 Inhibiting the phosphorylation of p38, JNK, and extracellular signal-regulated kinase 1/2 -regulated PPAR-γ	[150]
Raw garlic		Clinical trial	15 patients with H. pylori infection	Decreasing the bacterial urease activity Reducing the residing of Helicobacter pylori in the stomach		[57]
Anti-Diabetic Activity
Garlic		In vivo	Diabetic rats	Protecting against diabetic retinopathy Improving weight, blood glucose, and morphological changes of retinal tissue		[152]
Garlic		Clinical trial	768 patients with type 2 diabetes mellitus	Reducing fructosamine and glycosylated hemoglobin		[154]
Anti-Obesity Activity
	LAFGE	In vivo	High-fat diet-fed male C57BL/6J mice	Reducing the weight Reducing the epididymal, retroperitoneal, and mesenteric adipose tissue mass	Inhibiting the lipogenesis by down-regulating the mRNA and protein expression of PPAR-γ, C/EBPα, and lipogenic proteins	[9]
Methanolic extract of black garlic		In vivo	High-fat diet-fed male Wistar rats	Reducing the weight Regulating lipid metabolism	Upregulating the expression of AMPK, forkhead box protein O1, perilipin, and adiponectin in the adipose tissue Down-regulating cluster of differentiation 36, plasminogen activator inhibitor 1, resistin, and TNF-α	[156]
	Garlic oil	In vivo	High-fat diet-fed male Sprague–Dawley rats	Counteracting the influence of high-fat diet on the body weight and adipose tissue weight		[155]
Neuroprotection
Aged garlic extract	FruArg	In vitro	Lipopolysaccharide-activated murine BV-2 microglial cells	Alleviating neuroinflammation	Inhibiting the production of NO Regulating the expression of multiple protein targets related to oxidative stress	[157]
Garlic extract		In vivo	Female Wistar rats	Reducing the concentration of Pb in the blood and brain Preventing the Pb-induced apoptosis of neurons		[159]
Aged garlic extract		In vivo	Adult male Wistar rats	Attenuating the damage of working memory	Improving the loss of cholinergic neurons Increasing the level of vesicular glutamate transporter 1 and glutamate decarboxylase in the hippocampal area	[161]
Ethanol extract of garlic		In vivo	Diabetic Wistar rats	Improving memory	Increasing the activity of Na⁺/K⁺ ATPase, Ca²⁺ ATPase, and glutamine synthetase in the hippocampus	[162]
	Z-ajoene	In vivo	Male gerbils	Preventing I/R-induced delayed neuronal death and gliosis region of the hippocampus	Reducing lipid peroxidation in the CA1	[15]
	SAC	In vivo	Male albino Wistar rats	Ameliorating the cognitive impairment	Reducing oxidative stress, neuroinflammation, astrogliosis, and acetylcholinesterase activity	[164]
Renal Protection
Aqueous extract of garlic		In vivo	Type 1 diabetic rats	Reducing the oxidative stress in the kidneys		[165]
Aqueous extract of garlic		In vivo	Wistar rats	Improving the renal plasma biochemical factors induced by alloxan		[137]
	DATS	In vivo	Male albino rats	Protecting the kidney from oxidative stress injury induced by As	Activating the Nrf2-ARE pathway	[166]

Abbreviations: ACE, angiotensin-converting enzyme; AHR, aryl hydrocarbon receptor; allicin, diallyl thiosulfonate; alliin, S-allyl-cysteine sulfoxide; AMPK, adenosine monophosphate-activated protein kinase; AP-1, activator protein 1; ARE, antioxidant response element; ARNT, aryl hydrocarbon receptor nuclear translocator; ATM, ataxia-telangiectasia mutated; Bax, Bcl-2 associated X; Bcl-2, B cell lymphoma-2; CDK1, cyclin-dependent kinase 1; cGMP, cyclic guanosine monophosphate; CHK2, checkpoint kinase 2; COX2, cyclooxygenase-2; DADS, diallyl disulfide; DAS, diallyl sulfide; DATS, diallyl trisulfide; eNOS, endothelial nitric oxide synthase; FruArg, N-α-(1-deoxy-D-fructos-1-yl)-l-arginine; GCLM, glutamate-cysteine ligase modifier; HIF1A, hypoxia-inducible factor 1α; HO-1, heme oxygenase-1; IL, interleukin; iNOS, inducible NO synthase; JNK, Jun N-terminal kinase; JUN, proto-oncogene c-Jun; LAFGE, fermented garlic extract by Lactobacillus plantarum BL2; MMP-9, matrix metalloproteinase-9; NFAM1, nuclear factor of activated T cells (NFAT) activating protein with immunoreceptor tyrosine-based activation motif 1; NF-κB, nuclear factor-kappa B; NO, nitric oxide; Nrf2, nuclear factor erythrobia-2 related factor 2; OSM, oncostatin M; Parp-1, poly (ADP-ribose) polymerase-1; PKG, protein kinases G; PPAR-γ, peroxisome proliferator-activated receptor-γ; p38 MAPK, p38 mitogen activated protein kinase; REL, V-relavian reticuloendotheliosis viral oncogene homolog; SAC, S-allyl-cysteine; sGC, soluble guanylyl cyclase; SAMC, S-allylmercaptocysteine; SPRC, S-propargyl-l-cysteine; STAT-1, signal transducer and activator of transcription-1; TNF-α, tumor necrosis factor-α; Wnt5a, wingless-type MMTV integration site family member 5A.