Antioxidative Property and Molecular Mechanisms Underlying Geniposide-Mediated Therapeutic Effects in Diabetes Mellitus and Cardiovascular Disease

Table 3

Preclinical evidence of therapeutic potential from geniposide.

System	Disorder	Model	Dose	Administration route	Pharmacological action	Reference
Endocrine system	Type 2 DM	Spontaneously obese; Type 2 diabetic TSOD mice	0.1% and 0.3%	Intragastric administration	Reducing the body weight and visceral fat accumulation and alleviating abnormal lipid metabolism and intrahepatic lipid accumulation	[16]
	Type 2 DM	Free fatty acid-treated HepG2 cells	10, 50, 100 μM	Incubation	Blocking the accumulation of intracellular lipid resulted from the free fatty acid treatment and enhanced the PPARα expression	[16]
	Type 2 DM	HepG2 cell model of insulin resistance	15.63-125 mg/L	Incubation	Promoting autophagy and inhibiting insulin resistance in the HepG2 cells, which may be associated with the dynamic regulation of the P62/NF-κB/GLUT-4 pathway	[123]
	Type 2 DM	Palmitate-treated INS-1 cells	1, 10, 100 μM	Incubation	Relieving β-cell apoptosis via activation of the GLP-1 receptor	[132]
	Type 2 DM	Cultured mouse islets after challenge with diabetic stimuli	20 μM	Incubation	Promoting β regeneration and survival via regulating β-catenin/TCF7L2 pathway	[132]
	Type 2 DM	HepG2 cells	1, 10, 100 μM	Incubation	Suppressing hepatic glucose production via AMPK signaling pathway	[137]
	Type 1or 2 DM	High glucose-induced glucotoxic insulinoma cells	10 μM	Incubation	Improving β-cell function and increasing the proliferation of β-cells exposed to prolonged hyperglycemia	[128]
	Type 1 DM	Rat pancreatic islets	10 μM	Incubation	Stimulating insulin secretion in pancreatic β-cells by regulating GLP-1 receptor/cAMP signaling and Ca^2+ channels	[133]
	Type 1 DM	Rat pancreatic INS-1 cells	10 μM	Incubation	Enhancing glucose uptake via activating AMPK in pancreatic β cells	[138]
	Diabetic nephropathy	Diabetic rats induced by streptozotocin	50, 100 mg/kg/d	Intragastric administration	Suppressing NF-κB mediated inflammation response	[135]
Cardiovascular system	Myocardium I/R	Hypoxia/reoxygenation-induced H9c2 Cells	10, 20, 40, 80 μM	Incubation	Enhancing mitochondrial function via the GLP-1 receptor mediated the PI3K/Akt signaling pathway	[10]
	Atherosclerosis	ApoE^−/− mice fed a high-cholesterol diet	100 mg/kg/d	Oral administration	Increasing proliferation of smooth muscle cells and suppressing inflammation	[94]
	Atherosclerosis	ApoE^−/− mice fed a high-cholesterol diet	100 mg/kg/d	Oral administration	Decreasing the dendritic cells numbers and inhibiting dendritic cell maturation in bone marrow and infiltration into lesions	[99]
	Atherosclerosis	ApoE^−/− mice fed a high-cholesterol diet	100 mg/kg/d	Oral administration	Regulating lipid and promoting the number and function of Treg cells	[103]
	Cardiac hypertrophy	Mice with transverse aortic constriction	50 mg/kg/d	Oral administration	Activating the GLP-1 receptor/AMPKα pathway, inhibiting ERS and oxidative stress	[17]
	Cardiac fibrosis	Mice induced by isoprenaline	50 mg/kg/d	Oral administration	Suppressing oxidative stress, ERS, and acetylated Smad3 in a SIRT1-dependent manner and inhibiting the phosphorylated-Samd3 pathway independent of SIRT1 activation	[78]
	Obesity-related cardiac injury	Mice induced by high-fat food	50 mg/kg/d	Oral administration	Alleviating inflammation in a SIRT1-dependent manner and inhibiting cardiomyocyte apoptosis in a AMPKα-dependent manner	[92]
	Cerebral I/R injury	OGD/R-induced SH-SY5Y cells	10 μM	Incubation	Inhibition of endoplasmic reticulum stress and autophagy	[108]
	Ischemic stroke.	tMCAO rats	75 mg/kg/d	Intraperitoneal injections	Protecting neurons against post-ischemic neurovascular injury through the activation of GluN2A/AKT/ERK pathways	[115]