Table 1.

In-vivo and in-vitro protective actions associated with chlorogenic acid.

No	Conditions	Details of Assay	Biological Sex	Application	Analytical Findings	Refs
1	Metabolic syndrome	High carbohydrate, high fat diet induced model	Male wistar mice	In-vivo	Alleviates high-fat-diet, high carbohydrates triggered liver, cardiovascular and metabolic alterations.	[66]
		-	Male tsumura suzuki obese diabetes rats (TSOD)	In-vivo	Ameliorates the disrupted plasma short-chain fatty acids (SCFA) and gut microbiome.	[67]
		High fat/high fructose fed model	Male sprague-dawley mouse	In-vivo	Diminishes food intake, weight gain, circulating triglycerides and their accumulation in the liver (liver steatosis).	[68]
2	Obesity	High-fat-diet (HFD) induced model	ICR male mice	In-vivo	Stimulates body loss and altered mRNA expressions of lipolysis and lipogenesis associated genes in the adipose tissue. Reverses the HFD triggered gut microbiota dysbiosis, and also suppressing plasma lipid levels, growth of Desulfovibrionaceae, Ruminococcaceae, Lachnospiraceae, Erysipelotrichaceae, and elevating the growth of Bacteroidaceae, Lactobacillaceae.	[69]
		HFD induced model	Male sprague-dawley rats	In-vivo	Decreases serum insulin level, abnormal islet hyperplasia, and blood glucose.	[70]
		HFD induced model	C57BL/6 J rats	In-vivo	Modulates body weight, food intake, energy balance shift and enhanced body temperature, thermal dissipation, and brown adipose tissue activity.	[71]
		HFD induced model	Female ICR rats	In-vivo	Suppresses intraperitoneal adipose tissue weight, body weight gain, hepatic TC and TG level, IL −6 concentrations, Leptin, serum LDL-c, FFA, expressions of transcriptional regulators (SREBP-1c and LXRα), HMGR, FAS and improved the phosphorylation of AMPKα.	[72]
		Monosodium glutamate induced model and oleic acid induced model	Mouse and human fatty liver in HepG2 cells	In-vivo and in-vitro	Down-regulates fats deposition in the liver, blood lipid levels, mRNA and protein expressions of uncoupling protein-1 (UCP1) and peroxisome proliferator activated receptor gamma, coactivator 1α (PGC-1α).	[73]
		Perfluorooctanoic acid exposure induced model	ICR mice	In-vivo	Attenuates obesity, disruption of gut barrier integrity, lipid metabolism disorders, and hepatic inflammation.	[74]
		HFD induced obesity and insulin resistance model	Male C57BL/6 J mice	In-vivo	Alters body weight gain, insulin resistance, evaluated via hyperglycemia, glucose and insulin intolerance.	[75]
3	Hyperlipidemia	High fat diet induced model	Male Sprague-dawley rats	In-vivo	Represses triglycerides, acetyl-CoA carboxylase (ACC), plasma free fatty acids (FFA) and increased carnitine palmitoyltransferase-1 (CPT-1) via activation of AMPK mechanism.	[76]
4	NAFLD and atherosclerosis	High fat diet induced model	C57BL/6 rats	In-vivo	Diminishes RAS component expression, triglycerides, cholesterol, LDL and enhanced HDL plasma levels.	[77]
5	Diabetic nephropathy	High fat diet induced model	Male sprague-dawley mice	In-vivo	Potentiates heme oxygenase-1 expression (HO-1), and nuclear translocation of nuclear factor erythroid-derived-2-related factor 2 (Nrf2); repressed nuclear translocation of nuclear factor kappa beta (NF-kB) and IKB phosphorylation.	[78]
		Streptozotocin induced model	Male sprague-dawley rats	In-vivo	Decreases levels of lipid peroxidation malondialdehyde, cyclooxygenase-2 protein, serum creatinine, blood urea nitrogen, and blood glucose; enhances the effects of catalase (CAT), glutathione peroxidase (GSH-px) and superoxide dismutase (SOD); obstructs the expression of activating transcription factor-6, C/EBP homology protein and the phosphorylation of eukaryotic initiation factor 2α and double stranded RNA-activated protein kinase-like endoplasmic reticulum kinase.	[79]
6	Diabetes	HFD and streptozotocin (STZ) induced model	Female sprague-dawley rats	In-vivo	Hampers insulin concentration, serum glucose, diabetes onset, mRNA levels of hepatic G-6-Pase, and ameliorated mRNA levels of skeletal muscle GLUT4, serum triglyceride, low density lipoprotein levels, total cholesterol, visceral fat weight, body weight and glucose tolerance.	[80]
		HFD and induced model	Female db/db mice	In-vivo	Attenuates level of fasting blood glucose (FBG), body fat, glycosylated hemoglobin (HbA1c), TGF-β1 protein expression, aldose reductase (AR), and up-regulated the protein expression of adiponectin receptors (ADPNRs), AMPK phosphorylation, and the mRNA and protein levels of peroxisome proliferator activated receptor alpha (PPAR-α).	[81]
		Streptozotocin induced model	Male wistar rats and L6 cell line	In-vivo and In-vitro	Promotes glucose tolerance and impaired basal hyperglycemia.	[82]
		Streptozotocin induced model	Adult male wistar rats	In-vivo	Alleviates platelet aggregation and increased adenosine monophosphate (AMP) hydrolysis in the cerebral cortex	[83]
		HFD and STZ mice	Male ICR mice	In-vivo	Down-regulates fasting blood glucose (FBG), fasting serum insulin, glycosylated serum protein levels, and also improved antioxidative effects.	[84]
7	Hypertension	-	Male SHR and wistar-Kyoto rats	In-vivo	Suppresses oxidative stress (ROS), vascular hypertrophy, endothelial dysfunction, and hypertension; improved bioavailability of nitric oxide (NO).	[85]
		Cyclosporine induced model	Male wistar rats	In-vivo	Study 1: Impairs systolic blood pressure, heart rates, angiotensin-1 converting enzyme (ACE), arginase, butrylcholinesterase (BChE), acetylcholinesterase (AChE), GSH content, and MDA level; promotes bioavailability of NO and CAT activity. Study 2: Alters the activities of ACE, e-nucleotide triphosphate dephosphorylase (e-NTPDase), adenosine deaminase (ADA), 5ʹ nucleotidase and MDA level.	[86, 87]
8	Neuropathic pain	Chronic constrictive nerve injury (CCI) induced model	Male sprague-dawley mice	In-vivo	Study 1: Prevents the occurrence of mechanical hyperalgesia. Study 2: Alleviates cold and mechanical hyperalgesia partly via triggering GABAergic transmission in the spinal cord.	[88, 89]