Table 2.

A brief review of reports on the effect of garlic on diabetes, diabetic retinopathy, BDNF, and VEGF

Garlic (and its compounds)	The subject under study	Outcome	Refs.
Garlic effect on diabetes
Aged garlic extract	STZ-induced diabetic rat	BMI (−), GLU (−), insulin (+), CL (−), TG (−), UP (−)	[32]
Garlic + met	T2D patients	Garlic: FBS (−), insulin (+), TC (−), risk of cardiovascular disease (−) Garlic + Met: more glycemic control and antihyperlipidemic activity	[15]
Garlic oil	STZ-induced diabetic rat	UP (−), GTT (+), insulin (+)	[36]
Chewing vs swallowed garlic	T2D patient (uncontrolled dyslipidemia	CL (−), TG (−), SBP (−), DBP (−), even with increasing fat intake; *Swallowed garlic had no significant effect on serum lipids	[22]
Raw crushed garlic	Metabolic syndrome patient	FBS and other metabolic syndrome elements (−)	[24]
Garlic extract	STZ-induced diabetic rat	GLU (−), insulin (+)
Raw garlic extract	STZ-induced diabetic rat	GLU (−), CL (−), TG (−), UP (−)	[38]
VO (3mpa)2 complex	3T3-L1 preadipocytes STZ-induced diabetic mice	PI3K/Akt pathway (−), GLUT4 translocation to the plasma membrane (+), GLU (−)	[39]
Garlic oil /DATS	Diabetic rat	Insulin (+), GTT (+)	[16]
VO (alx)2 (Allixin isolated from dried garlic)	rat adipocytes T1D model mice	serum glucose (−), insulin resistance (+), GTT (+), *The plasma adiponectin level was not changed	[43]
Aqueous extract of raw garlic	alloxan-induced diabetic male rabbit	GLU (−), CL (−)	[45]
Aged garlic extract	STZ-induced diabetic rat	GLU (−), GHb (−), Renoprotective effect (+)	[38, 46]
Alliin (S-allyl cysteine sulfoxide)	DIO mice	Insulin sensitivity (+), CL (−), TG (−)	[47]
Garlic extract	T2D patient	GLU (−), CL (−)	[49]
Aged garlic extract	Immobilization stress in mice	renal cell hypertrophy (−), corticosterone (−), GLU (−)	[57]
Garlic	Metabolic syndromes in fructose fed rat	insulin sensitivity (+)	[64]
s-allyl cysteine-enriched black garlic juice	STZ-induced insulin-deficient mice	BMI (−), GLU (−), insulin (+)	[129]
Aged black garlic	db/db mice	insulin resistance (−), TC (−), TG (−), HDL (+)	[130]
Garlic Effect on VEGF
Aged garlic extract	T2D patients at high cardiovascular risk	No significant change in endothelial cell function, vascular inflammation, oxidative stress or resistance to insulin	[23]
Aged garlic extract	Rat	Coronary arteries relaxation (+), myocardial contractility (−)	[77]
Alliin	Chick chorioallantoic membrane (CAM) model	Human endothelial cell proliferation (−), VEGF-induced angiogenesis (−) *The effect was boosted by the antioxidant vitamins C and E	[84]
Aged garlic solution	Chicken dorsum skin excisional lesion	Wound closure (+), re-epithelialization (+), dermal matrix regeneration (+), angiogenesis (+)	[88]
DAS	B16F-10 melanoma cell induced capillary formation in C57BL/6 mice	Tumor-directed capillary formation (−), IL-1 (−), IL-6 (−), TNF-α (−), GM-CSF (−)	[89]
Aged garlic extract	Colorectal carcinoma cells	Tumor growth (−), neovascularization (−), endothelial cell motility (−), endothelial cell proliferation (−), tube formation (−)	[91]
Garlic + lemon aqueous extraction	Mice with breast cancer	Angiogenesis (−), apoptosis (+)	[94]
DADS	Human prostate cancer cell line	PI3K/Akt (−), Ras/Raf (−), MMPs (−), pro-inflammatory/pro-angiogenic molecules (−), VEGF (−)	[96]
Garlic-derived extracellular vesicles	A549 human lung carcinoma cells	VEGF (−), programmed cell death (+), *Normal cells were unaffected by treatment	[98]
Garlic oil	Avian embryo chorioallantoic membranes	Microvessel (−)	[131]
Garlic powder	ductal breast carcinoma cells	VEGF (−), Angiogenesis (−)	[90]
Garlic stem extract	melanoma cells	Cell growth (−) cell migration (−)	[99]
Garlic effect on BDNF
Aged garlic extract	Cerebral ischemia rat	8-OHdG (+), TNFα (+), COX-2 (+), The damage caused by neuronal injury (−)	[115]
DADS, DATS	Chronic constriction injury rat	Strong improvement in discomfort, H2S (+), BDNF (+), Nrf2 (+)	[116]
Allixin	Cultured neurons from fetal rat brain	Neurotrophic activity (+), nerve cells viability (+), division site per axon in hippocampal neurons (+)	[117]
Garlic essential oil	Mouse dentate gyrus	BDNF (+), AChE (−)	[118]
S-allyl-L-cysteine	Mouse dentate gyrus	Neuroblast proliferation (+), neuroblast differentiation (+)	[118]
Garlic essential oil	Rats utilizing the forced swimming test and unexpected chronic mild stress	The immobilization period (−), The sucrose preference index (+), 5-HT (+), DA (+), hippocampal BDNF (+), CREB (+), and protein kinase B (AKT) (+)	[119]
DADS	Hippocampal neural cell proliferation in the adult brain	Hippocampal neurogenesis (−), neurocognitive functions (−), BDNF (−), CREB (−), ERK (−)	[120]
DAS/DADS	Human malignant Neuroblastoma SH-SY5Y cells	Anti-apoptotic factors (−), calpain and intrinsic caspase cascade (+), hippocampal neurogenesis (−), neurocognitive functions (−), BDNF (−), CREB (−), ERK (−)	[121]
Garlic extract	Hippocampus cell in diabetic rat	hippocampus Na + /K + ATPase (+), Ca2 + ATPase (+)	[107]
DATS	diabetic rats heart tissue	NO2−(−), O2−(−), Bax, caspase-3 and -9 (−)	[113]
Garlic effect on DR
Garlic	Pre-diabetes induced retinal abnormalities in high fructose fed rat model	Functional, structural, and molecular abnormalities of the retina (−)	[125]
Aqueous garlic extract	Diabetic Wistar rat	Retinal oxidative stress serum glucose (−), TGF-β2 (−), IL-1β (−)	[124, 126]
Garlic	Patients with diabetic macular edema	Visual acuity (+), CMT (−), IOP (−)	[128]

AChE Acetylcholinesterase, BMI body mass index, CL Cholesterol, CREB c-AMP response element-binding protein, DADS Diallyl disulfide, DAS diallyl sulfide, DATS Diallyl trisulfide, DBP diastolic blood pressure, db/db mice diabetic mice, DIO diet induced obese, FBS fasting blood sugar, GHb Glycosylated hemoglobin, GLU glucose, GTT glucose tolerance test, HDL high density lipoprotein cholesterol, Met metformin, Nrf2 nuclear factor erythroid 2-related factor 2, SBP systolic blood pressure, TC total cholesterol, TG triglyceride, T1D type 1 diabetes, T2D type 2 diabetes, UP urinary protein