Thioredoxin interacting protein, a key molecular switch between oxidative stress and sterile inflammation in cellular response

Table 2 Summary of studies on modulation of thioredoxin interacting protein expression using drug repurposing in animal models

Ref.	Treatment		Animal model	Main findings
[84]	Verapamil (0.15 mg/kg), intra venous	1 h	Hyperglycemic mouse model middle cerebral artery occlusion	Reduced infarct area, hemorrhagic transformation and blood brain barrier damage. Improved stroke outcome and neuro inflammation in response to hyperglycemic stroke
[7]	Verapamil po	1 h	NMDA- optic neuropathy	Improved retinal neurodegeneration by altering antioxidant status and disrupting the Trx-ASK-1 inhibitory complex
[67]	Verapamil, 25 mg/kg/d, IP	1 wk	high-fat diet-induced obesity- 10 wk	Improved hepatic inflammation, metabolic homeostasis in NAFLD via TXNIP-NLRP3 inflammasome activation
[104]	Verapamil		High-fat diet-prediabetic neuropathy	improved prediabetic neuropathy, inflammation via inhibition of TXNIP and NLRP3-inflammasome activation
[10], [105]	Verapamil, 100 mg/kg	Po daily	STZ- and HFD-obesity model	Inhibit TXNIP expression and restore beta-cell function, improve glucose level in STZ- and HFD-obesity model
[100]	Metformin		STZ-diabetes mouse	Suppressed TXNIP/NLRP3 inflammasome activation, reduced cell apoptosis in adipose tissue
[99]	Metformin		ApoE-/- + STZ mice	Inhibited TXNIP/NLRP3 inflammasome activation, and suppressed diabetes-accelerated atherosclerosis in apoE-/- mice
[101]	Ezetimibe (250 µg, 500 µg, 1 mg)	1 hIntra-nasal	Rat model middle cerebral artery occlusion	Improved infarct volume, neurological outcome Increased activation of AMPK, modulated oxidative stress, microglial activation and TXNIP/NLRP3 activation
[103]	SRI-37330	Po daily	STZ-mouse model and obesity-induced (db/db) diabetes	Inhibited glucagon secretion and function, reduced hepatic glucose production, and reversed hepatic steatosis
[105]	W2476, 200 mg/kg	Po daily	STZ- and HFD-obesity model	Inhibit TXNIP expression and restore beta-cell function, improve glucose level in STZ- and HFD-obesity model
[34]	GW0742 (25 μg/kg; intranasal)	1 h/ 24 h	Rat pups with hypoxic ischemia	GW0742 significantly reduced the activation of TXNIP/NLRP3 inflammasome, pro-inflammatory microglia

TXNIP: Thioredoxin interacting protein; NLRP3: NOD-like receptor pyrin domain containing 3; HFD: High fat diet; NMDA: N-methyl D-aspartate.