Review Article

Therapeutic Effects and Mechanisms of Action of Garlic (Allium sativum) on Nonalcoholic Fatty Liver Disease: A Comprehensive Systematic Literature Review

Table 1

Characteristics of studies investigating the potential role of garlic in NAFLD.

Author’s nameStudy designNumber and type of subjectsDosage and type of administrationAssayStudy durationRouteMain results

Animal studies
Xiao et al. [42]In vivoRats (n = 7)200 mg/kg SAMCTransmission electron microscopy, RNA isolation and analysis, real-time PCR, ELISA, histopathological examination, protein determination, western blot8 weeksOral(i) Decrease in the concentrations/activities/expressions ofSREBP1c, TNF-α, IL-1b, iNOS, COX-2.MCP-1, MIP-2, IL-6, TGF-b, PC-1, ALT, FFAS, αSMA, MDA, CYP2E1, NTR formation, SOCS3 protein adducts in the live.
(ii) An increase in adiponectin, GPx, and CAT concentrations

Lee et al. [39]In vivoMice (n = 6)500 mg/kgELISA, western blot, real-time PCR, histological analysis, ovarian morphological analysis, measurement of hormones, measurement of the ROS level and mitochondrial membrane potential, plasmid construction and luciferase assays8 weeksOral(i) Reduction of the elevated serum AST, ALT, and GGT activities as well as TG, TC, serum glucose, serum insulin, and HOMA-IR, concentrations also decrease liver steatosis, liver weight
,(ii) Reduction in the elevated ACC, CPT-1 JNK, pJNK, TNF-α, SREBP-1c, SCD-1, MDA, BAX, caspase 3 and enhancement of the liver glutathione content, AMPK, PPAR-α

Fajrani et al. [37]In vivoRats (n = 18)450, 900, and 1350 mg/kgELISA, histological analysis26 daysOral(i) Decrease in serum concentrations of MDA, HOMA-IR, insulin, and FBG and decrease in body weight and visceral fat

Yang et al. [43]In vivoRats (n = 12)10 and 20 mg/kgELISA, gene expression, histological analysis, assay of malondialdehyde and protein carbonyl, oxidative stress measurement8 weeksOral(ii) Decrease in serum concentrations of LDL-C, TG, TC, FBG, PPARγ hepatic malondialdehyde content, and increase in HDL-C;
(iii) The effect of regulation of lipid metabolism via a connection with the regulation of ACC α1, ACC β1, FASN, DGAT, SREBP-1 and 2, HMG-CoAR, SCD 1, and 1 in hepatic tissue

Lai et al. [38]In vivoRats (n = 30)25, 50, and 100 mg/kgELISA, assay of glutathione, malondialdehyde, protein carbonyl, and oxidative stress measurement12 weeksOral(i) A reduction in the expression of genes related to fatty acid (SREBP-1c, FAS, ACC, HMGCR, CPT-1, and CYP2E1) pathways, reducing the composition of plasma fatty acids (LDL-C, TG, TC) and the expression of relevant genes including TNF-α, IL-1β, and IL-6, and inhibition of oxidative stress-related biomarker concentrations
(ii) Decrease in serum concentrations of LDL-C, TG, TC, FBG, PPARγ and increase in HDL-C, antioxidative enzymes, namely, GSH, SOD, CAT, catalase, GPx, GRd, GST, PPAR
Nurmawati et al. [40]In vivoRats (n = 18)450, 900 and 1350 mg/kgELISA4 weeksOral(i) Decrease in serum concentrations of PAI-1 TC, LDL-C TG and increase in HDL-C level

Seif El-Din et al. [41]In vivoRats (n = 10)500 mg/kg/dayELISA, western blot, real-time PCR8 weeksOral(i) Decrease in activities of serum ALT, AST, ALP, leptin, cholesterol, triglycerides, TNF-α, TGF-β, and the concentrations of hepatic MDA.
(ii) Increase in the activities of GR, GST, SOD, and glutathione peroxidase as well as the concentrations of glutathione
(iii) There was no change in body weight and ovaries.

Wu et al. [44]In vivoRats (n = 10)100 mg/kg b.w./d i.p.ELISA, western blot, real-time PCR8 weeksOral(i) A decrease in the levels/activities of ALT, AST, MDA, COX-2
(ii) Elevation in the activities of SOD

Akt: protein kinase B, AMH: anti-mullerian hormone, AMPK: AMP-activated protein kinase, BAX: BCL-2-associated X-protein, BMI: body mass index, CYP11A1: cytochrome P450 family 11 subfamily A member 1, CYP17A1: cytochrome P450 17A1, CYP21: cytochrome P450c21, CAT: catalase, COX: cyclooxygenase, ELISA: enzyme-linked immunosorbent assay, FBG: fasting blood glucose, FSH: follicle-stimulating hormone, GKG: glucokinase, GPX: glutathione peroxidase, HDL-C: high-density lipoprotein cholesterol, HMGCR: hydroxy-3-methylglutaryl-CoA, HOMA-IR: homeostasis model of assessment-insulin resistance, HSD3B1: hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1, ICP-OES: inductively coupled plasma optical emission spectrometry, IGF1: insulin like growth factor 1, IL: interleukin, IR: insulin resistance, LDL-C: low-density lipoprotein cholesterol, LH: luteinizing hormone, MDA: malondialdehyde, NF-ΚB: nuclear factor-κB, PCR: polymerase chain reaction, PI3K: phosphatidylinositol 3-kinase, RNS: reactive nitrogen species, ROS: reactive oxygen species, SIRT: sirtuin, SOD: super oxide dismutase, TAC: total antioxidant capacity, TGF-β: transforming growth factor β, TNF-α: tumor necrosis factor α, TG: triglycerides, TC: total cholesterol, VLDL: very-low-density lipoprotein, VEGF: vascular endothelial growth factor, and VEGF: vascular endothelial growth factor.