Table 1.

Mechanisms of ferulic acid improving metabolic syndrome components.

Effects of FA	Experimental Models	Dose/Concentration of FA	Course of Treatment	Results	Mechanisms	References
Anti-hyperglycemia	HFD-induced obese mice	25 and 50 mg/kg	8 weeks	↓ blood glucose level ↓ insulin resistance ↑ the serum adiponectin level	↓ gluconeogenic genes	[36]
	Isolated psoas muscle tissues of rat/α-glucosidase, α-amylase (in vitro)	15, 30, 60, 120 and 240 μg/mL	2 h	↓ blood glucose level	↑ muscle glucose uptake ↓ carbohydrate enzyme activities	[41]
	High fat and fructose-induced T2D rat	50 mg/kg	30 days	↓ blood glucose and serum insulin levels ↑ glucose tolerance and insulin tolerance	↓ gluconeogenesis ↓ negative regulators of insulin signaling ↑ hepatic glycogenesis	[59]
	HFD-induced obese male C57BL/6N mice	High-fat diet supplemented with 0.5% FA	7 weeks	↓ blood glucose level	↓ gluconeogenesis ↑ glucokinase activity ↑ insulin secretion	[60]
	HFD-induced obese C57BL/6 mice	10 mg/kg	12 weeks	↓ blood glucose level	Phosphorylation and inactivation of FoxO1	[62]
	HFD and high fructose water-induced diabetic Wistar rats (in vitro)	50 mg/kg	30 days	↓ hepatic GLUT2 expression	Impairing the interaction between these transcription factors (SREBP1c, HNF1α and HNF3β) and GLUT2 gene promoter.	[63]
	STZ-induced diabetic Wistar rats (in vitro and vivo)	50 mg/kg	8 weeks	↓ blood glucose level ↑ plasma insulin level	↑ phosphorylation of PI3K, Akt, AMPK	[66]
	Differentiated L6 myotubes (in vitro)	25 μM	3 h	↑ uptake of 2-deoxyglucose	Regulation of P13K-dependent pathway	[68]
	3T3-L1 adipocytes (in vitro)	25 μM	24 h	↑ uptake of 2-deoxyglucose	↑ PI3K expression	[69]
	Alloxan-induced diabetic mice	10 mg/kg	15 days	↓ basic biochemical marker (glucose, urea and uric acid, etc.)	↓ the proinflammatory factor, NF-κB	[72]
	HFD-gestational diabetic rats	20 mg/kg	12 weeks	↓ β-cells apoptosis Improvement of insulin signaling	↑ the expression of p-IRS1, p-IRS2, p-PI3K, GLUT1, GLUT3 and GLUT4 ↑ protein expression of visfatin	[76]
	Human amylin peptide (in vitro)	10 μM and 40 μM	6 h	↓ β-cells apoptosis ↑ β-cells mass	↓ islet amyloid cytotoxicity to β-cells	[77]
Anti-hypertension and anti-hyperlipidemia	Thoracic aortic rings from male WKY rats and SHR (in vitro)	10−5 to 10−3 mol/L	30 min	↑ endothelial function	↑ bioavailability of basal and stimulated NO	[84]
	2K1C hypertensive rats	10−5 to 10−3 mol/L	30 min	↑ endothelial function	↑ bioavailability of NO	[87]
	Stroke-prone spontaneously hypertensive rats	9.5 mg/kg	6 h	↓ blood pressure	↓ ACE activity in the plasma	[98]
	Diet-induced hypercholesterolemia rats	high-cholesterol diet supplemented with 0.013% FA	5 weeks	↓ the plasma TG and TC concentrations	↓ HMG-Co A reductase	[117]
	Diet-induced hypercholesterolemia weaned piglets	diet supplemented with 0.05% and 0.45% FA	5 weeks	↑ lipid metabolism	↑ lipolysis and fatty acid oxidation	[118]
	Oleic-acid-treated HepG2 cells (in vitro)	0, 12.5, 25 and 50 μg/ml	24 h	↓ cellular lipid accumulation	↓ ERK1/2, JNK1/2/3 and HGMB1 expression	[119]
	Diet-induced hypercholesterolemia mice	0.5%FA diet	7 weeks	↓ plasma and hepatic TC and TG concentrations ↓ lipid peroxidation rate ↓ high-density lipoprotein cholesterol level	↑ fecal lipid excretion Regulation of lipogenic enzymes activities	[120]
	Eight-week-old male db/db diabetic mice	25, 50 and 100 mg/kg	7 days	↑ lipid metabolism	Trigger of the mitochondrial membrane distribution of ACSL 1	[121]
	HFD-induced ApoE−/− mice	40 mg/kg	12 weeks	↑ lipid metabolism	↑ AMPK α phosphorylation ↓ SREBP 1 and ACC 1 expression	[122]
Anti-obesity	3T3-L1 adipocytes (in vitro)	10 μM	24 h	↑ release of glycerol content ↓ lipogenic activities	↓ PPAR γ, C/EBP α and FAS expression ↑ lipolysis-related factors	[123]
	3T3-L1 adipocytes (in vitro)/HFD-induced obese mice	0.2–2 mM/25 and 50 mg/kg	10 days/90 days	↓ cellular lipid accumulation ↓ adipogenesis and lipid accumulation ↓ body weight gain	↓ key transcriptional factors expression ↑ p38MAPK and ERK1/2 signaling pathways Activation of pAMP-α to upregulate HSL	[143]
	Embryo stem cells (ESCs) and adipose-derived mesenchymal stem cells (ADMSCs) (in vitro)	Diet with ferulic acid (5 g/kg diet)	8 weeks	↑ body weight loss ↑ glucose homeostasis, lipid profiling and hepatic steatosis	↑ ADMSCs self-renewal	[149]
	3T3-L1 adipocytes (in vitro)	25, 50 and 100 μM	8 days	↓ adipogenesis	↑ HO-1 expression	[150]

Note: ↑: stimulate, increase, enhance; ↓: inhibit, decrease, reduce; NI: no information; HFD: high fat diet; T2D: type 2 diabetes; STZ: streptozotocin; PI3K: phosphatidylinositol 3-kinase; Akt: phosphorylated-protein kinase B; AMPK: AMP-activated protein kinase; NF-κB: nuclear factor kappa-B; WKY: Wistar Kyoto; SHR: spontaneously hypertensive rats; NO: nitric oxide; 2K1C: two-kidney, one-clip; ACE: Angiotensin-1-converting enzyme; HMG-Co A: Hydroxymethylglutaryl coenzyme A reductase; ERK: extracellular signal-regulated kinase; JNK: c-Jun amino-terminal kinase; ACSL1: long-chain acyl-CoA synthase 1; SREBP1: sterol regulatory element-binding protein 1; ACC 1: acetyl-CoA carboxylase 1; PPAR γ: peroxisome proliferator-activated receptor γ; C/EBP α: CCAAT/enhancer-binding protein α; FAS: fatty acid synthase; MAPK: Mitogen activated protein kinase; HSL: hormonal sensitive lipase.