Table 2.

Evidences addressing alleviating impact of TXNIP modulation in endothelial dysfunction

Endothelial complication	Model		TXNIP inhibition		Main findings	Reference
	Subject	Stimuli	Pharmacological	Genetic
Diabetic endothelial dysfunction	Human aortic endothelial cells	High glucose	Metformin		Reduced nuclear entry of ChREBP and FOXO1 as well as their recruitment on the TXNIP promoter, partially through AMPK	[147]
	In vitro HUVECs	High glucose	Mangiferin		Attenuate IRE1α phosphorylation Reduce ROS/TXNIP/NLRP3 inflammasome activation	[148]
	In vitro HUVECs In vivo	High glucose HGD rats	Rutin		Reduced Nox4 and ROS Inhibited TXNIP/NLRP3/Caspase-1 Restored phenylephrine-mediated contractions and acetylcholine-induced relaxations in aortic tissue	[149]
	In vitro HUVECs	High glucose	Teneligliptin		Reduced TXNIP And ER stress, apoptosis, and cell cycle inhibitors As well as EC proliferation	[150]
Diabetic retinopathy	In vitro Rat retina ECs Ex vivo Rat retia	High glucose STZ rats	Azaserine (inhibitor of HBP pathway)	siRNAs	Reduced sclerotic fibronectin and COX-II (in vitro) Abolishes diabetes-induced retinal gliosis and ganglion injury (ex vivo)	[126]
	In vivo	STZ rats	Curcumin		Reduced leukocyte-endothelium interaction, and inhibiting ICAM-1 and NOX2 expression.	[151]
	In vitro human retinal microvascular ECs	High glucose	Minocycline	siRNA	Attenuated ROS/TXNIP/NLRP3 inflammasome activation Decrease cell permeability and apoptosis	[100]
	In vitro human retinal microvascular ECs	Moderately high glucose		siRNA	Reduced ROS and uncontrolled angiogenesis By blocking VEGFR2 and the downstream Akt/mTOR	[152]
Endothelial ER stress	In vitro Rat aortic ECs	Palmitate	Salicylate AICAR	siRNA	Activate AMPK Suppressed ROS-associated ER stress Reduced TXNIP/NLRP3 inflammasome activation	[153]
	In vitro HUVECs	Palmitate	Astragaloside IV Cycloastragenol		Ameliorated endothelial dysfunction by inhibiting inflammation and reducing cell apoptosis, through AMPK regulation	[154]
	In vitro Rat aortic EC In vivo	palmitate HFD rats	Ilexgenin A		Enhance AMPK activity Suppressed ROS-associated TXNIP/NLRP3 induction, through AMPK activation Reduced EC inflammation and apoptosis	[155]
	HUVECs	Palmitate	Quercetin Luteolin EGCG		Suppressed ROS-associated TXNIP/NLRP3 induction, partly through AMPK activation Reduced EC inflammation and apoptosis	[73]
	In vitro HUVECs	Thapsigargin	Mangiferin		Prevents TG-induced loss of NO production inhibited TG-induced TXNIP/IL-1β secretion	[148]
	In vivo	HFD rats	Mangiferin		Prevented ER stress-associated TXNIP/NLRP3 inflammasome through AMPK activity Improved endothelium-dependent vasodilation in response to insulin/insulin resistance	[156]
Endothelial aging	In vivo	Natural/diet-induced aged mice	Resveratrol	KO mice	Prevent rise in NADPH oxidase by diet-induced aging Decrease collagen accumulation Decrease nuclear TXNIP	[157]