Table 3.

Summary of pharmacological activities of protocatechuic acid.

References	Study Type	Experimental Model	Pharmacological Potential	Study Outcomes
42	in vitro	human omental and murine cell line 3T3-L1 adipocytes	Antiglycemic	↑glucose uptake, ↑GLUT4 translocation, ↑adiponectin, ↑PPARγ activity, ↑adiponectin expressions, ↑GLUT4 expressions
48	in vivo	Male Balb/cA mice	Anti-inflammatory, anti-glycemic, anti-hyperlipidemia	↓plasma glucose, ↑insulin levels, ↓TG, ↓TC, ↓PAI-1, ↓fibrinogen, ↑AT-III, ↑protein C, ↓CRP, ↓vWF, ↓IL-6, ↓TNF-α, ↓MCP-1
49	in vitro	Mouse aortic endothelial cell (MAEC)	Anti-inflammatory and anti-atherosclerosis	↓monocyte adhesion to TNF-α activated MAECs, ↓VCAM-1 expression, ↓ICAM-1 expression, ↓NF-κB binding activity
	in vivo	apolipoprotein E (ApoE)-deficient mouse model		↓VCAM-1 and ICAM-1 expression, ↓NF-κB activity, ↓plasma-soluble VCAM-1 and ICAM-1, ↓aortic sinus plaque area, ↓cholesterol accumulation in aortas
50	in vitro	Isolated peripheral blood monocytes (PBMs) from ApoE-deficient mice	Anti-inflammatory and anti-atherogenic	↓CCR2 protein and mRNA expression, ↓mouse PBMs chemokine migration toward CCL2
	in vivo	ApoE-deficient mice		↓CCR2 protein and mRNA expression, ↓macrophage infiltration into the abdominal cavity
43	in vivo	male Wister albino rats	Anti-hyperglycemic	↓plasma glucose levels, ↑Hb, ↓HbA1c levels, ↑plasma insulin levels, ↑hexokinase activity, ↑glycogen content, ↓glucose 6-phosphatase, ↓fructose 1,6-bisphosphatase, ↓pancreas adipose tissue, normalized pancreatic islets within normal limit.
51	in vivo	Male Wister albino rats	Anti-hyperlipidemia	↓TC, ↓TG, ↓LDL-C, ↑HDL-C level
52	in vitro	RAW 264.7	Anti-inflammatory	↓TNF-α, ↓IL-1β, ↓NO, ↓PGE2, ↓iNOS, ↓COX-2, ↓IkB-𝛼 degradation, ↓NF-kB phosphorylation, inhibit nuclear translocation of p65, inhibit p38, ERK and JNK activation in MAPK pathway.
	in vivo	Male BALB/c mice		↓leukocyte number, ↓TNF-α, ↓IL-1β, ↓PGE2, ↓COX-2 , ↓NF-κB activation

Abbreviation: AT-III, Anticoagulation Factors Antithrombin III; CCR2, CC Chemokine Receptor 2; CCL2, CC Ligand-2; COX-2, Cyclooxygenase-2; CRP, C-Reactive protein; FFA, Free Fatty Acids; GLUT4, Glucose Transporter Type 4; Hb, Haemoglobin; HbAlc, Glycosylated Haemoglobin; HDL-C, High-Density Lipoprotein Cholesterol; ICAM-1, Intercellular Adhesion Molecule 1; IL-1𝛽, Interleukin-1𝛽; IL-6, interleukin- 6; iNOS, Inducible Nitric Oxide Synthase; LDL-C, Low Density Lipoprotein Cholesterol; MCP-1, Monocyte Chemoattractant Protein-1; NF-κB, Nuclear Factor-κB; PAI-1, Plasminogen Activator Inhibitor-1; PGE2, Prostaglandin E2; PPARγ, Peroxisome Proliferator-Activated Receptor-γ; TC, Total Cholesterol; TG, Triglycerides; TNF-α, Tumor Necrosis Factor-α; VCAM-1, Vascular Cell Adhesion Molecule 1; Vwf, von Willebrand factor