|
In vivo studies
|
Empagliflozin Protects against Diet-Induced NLRP-3 Inflammasome Activation and Lipid Accumulation
Benetti et al.
|
2016 |
Experimental
Murine model of diet-induced obesity
(Male C57BL/6J mice) |
Evaluate the ability of Empagliflozin to affect body weight and NLRP3 inflammasome activation |
Empagliflozin
Mixed in diet
(1 mg/kg,
3 mg/kg or
10 mg/kg) |
Decrease in Caspase-1 activation and IL-1β production in mice treated with Empagliflozin
(3 mg/kg and
10 mg/kg) |
The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE-/-
Mice
Leng et al.
|
2016 |
Experimental
Diabetic atherosclerosis in diabetic mice
(Male ApoE−/− mice and C57BL/6J) |
Explore the efficacy of Dapagliflozin on atherosclerosis and the influence on the ROS-NLPR3-Caspase pathway |
Dapagliflozin
Oral gavage
(1 mg/kg) |
Serum levels of NLRP3, IL-1β and IL-18 were reduced after 12 weeks of treatment with Dapagliflozin |
SGLT-2 Inhibition with Dapagliflozin Reduces the Activation of the Nlrp3/ASC Inflammasome and Attenuates the Development of Diabetic Cardiomyopathy in Mice with Type 2 Diabetes. Further Augmentation of the Effects with Saxagliptin, a DPP4 Inhibitor
Ye et al.
|
2017 |
Experimental
Diabetic cardiomyopathy in mice
(Type 2 diabetic (BTBR ob/ob) and wild-type (WT) mice) |
To assess if Dapagliflozin could attenuate the myocardial dysfunction and NLRP3 activation in diabetic mice |
Dapagliflozin
Mixed in diet
(1 mg/kg) |
Dapagliflozin attenuated the activation of the NLRP3 inflammasome (lower mRNA levels of ASC, NALP3, IL-1β and Caspase-1) |
Combined SGLT2 and DPP4 Inhibition Reduces the Activation of the Nlrp3/ASC Inflammasome and Attenuates the Development of Diabetic Nephropathy in Mice with Type 2 Diabetes
Birnbaum et al.
|
2018 |
Experimental
Diabetic Nephropathy in mice
(Male BTBR ob/ob and WT mice) |
Assessed whether Dapagliflozin attenuates the NLRP3 activation and progression of DN in mice |
Dapagliflozin
Mixed in diet
(1 mg/kg) |
Dapagliflozin attenuated the activation of the NLRP3 inflammasome after 8 weeks |
The SGLT2 inhibitor dapagliflozin attenuates the activity of ROS-NLRP3 inflammasome axis in steatohepatitis with diabetes mellitus
Leng et al.
|
2019 |
Experimental
Steatohepatitis in diabetic mice
(ApoE–/– mice) |
Evaluate the effects of Dapagliflozin on liver injury and the influence in oxidative stress and NLRP3 activity |
Dapagliflozin
Oral gavage
(1 mg/kg) |
Dapagliflozin reduced the activity of NLRP3 inflammasome in the liver (NLRP3, Caspase-1, IL-1β and IL-18) |
Empagliflozin Blunts Worsening Cardiac Dysfunction Associated with Reduced
NLRP3 (Nucleotide-Binding Domain-Like Receptor Protein 3)
Inflammasome Activation in Heart Failure
Byrne et al.
|
2020 |
Experimental
Mouse model of heart failure
(Male C57BL/6J mice and male Dahl salt-sensitive rats) |
Evaluate the effects of Empagliflozin on the NLRP3 inflammasome in a mice model of heart failure |
Empagliflozin
Oral gavage
(10 mg/kg) |
Empagliflozin reduced the levels of IL-1B and IL-18, the infiltration of macrophages and transcript levels of NLRP3, NF-kB and Caspae-1 |
Dapagliflozin and Ticagrelor Have Additive Effects on the Attenuation of the Activation of the NLRP3 Inflammasome and the Progression of Diabetic Cardiomyopathy: an AMPK-mTOR Interplay
Chen et al.
|
2020 |
Experimental
Diabetic cardiomyopathy in diabetic mice
(BTBR and WT mice) |
To evaluate whether Dapagliflozin (and Ticagrelor) would attenuate the progression of diabetic cardiomyopathy in T2DM in mice |
Dapagliflozin
Mixed in drinking water (1.5 mg/kg) |
Dapagliflozin reduced mRNA levels of ASC, Caspase-1 and NLRP3 after
12 weeks |
SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease
Kim et al. |
2020 |
Randomized Control Trial
Adults (20–79 years) with T2DM
(Humans) |
Investigate the effects of Empagliflozin over the NLRP3 inflammasome in patients with T2DM and high-risk of cardiovascular disease |
Empagliflozin
Oral – 10 mg or 25mg |
Empagliflozin reduced levels of IL-1B in macrophages and mRNA levels of IL-1β , TNF-A and NLPR3 after
30-days |
Dapagliflozin, an SGLT2 inhibitor, ameliorates acetic acid-induced colitis in rats by targeting NFκB/AMPK/NLRP3 axis
El Rous et al.
|
2021 |
Experimental
Ulcerative Colitis in rats
(Male Sprague–Dawley rats) |
Investigate the effects of Dapagliflozin in a rat model of Ulcerative Colitis, and the possible modulation of the NLRP3 complex/NF-kB |
Dapagliflozin
Oral gavage
(5 mg/kg or
10 mg/kg) |
Seven days of treatment with Dapagliflozin
(10 mg/kg) was able to suppress the signaling of NF-kB as well NLRP3/Caspase-1 activity |
Ticagrelor and Dapagliflozin Have Additive Effects in Ameliorating Diabetic Nephropathy in Mice with Type-2 Diabetes Mellitus
Birnbaum et al.
|
2021 |
Experimental
Diabetic Nephropathy in mice
(Male BTBR ob/ob mice) |
Assessed whether Dapagliflozin (or its association with Ticagrelor) attenuates the NLRP3 activation and progression of DN in mice |
Dapagliflozin
Mixed in drinking water (1.5 mg/kg) |
Dapagliflozin attenuated the activation of the NLRP3 inflammasome after 12 weeks |
The SGLT-2 inhibitor empagliflozin improves myocardial strain, reduces cardiac fibrosis and pro-inflammatory cytokines in non-diabetic mice treated with doxorubicin
Quagliariello et al.
|
2021 |
Experimental
In vitro (cardiomyocyte) and In vivo (mouse)
(Female C57BL/6 mice) |
To evaluate the effects of Empagliflozin (and its association with Doxorubicin) over the NLRP3 inflammasome in cell cultures of cardiomyocytes and in a in vivo model |
Empagliflozin
Concentrations of 50, 100 and 500 nM (In vitro) and oral gavage (10 mg/kg – In vivo) |
Empagliflozin decreased the NF-kB activity (dose-dependent way) and also the activity of the NLRP3 complex |
Crosstalk Among NLRP3 Inflammasome, ETBR Signaling, and miRNAs in Stress-Induced Depression-Like Behavior: a Modulatory Role
for SGLT2 Inhibitors
Muhammad et al.
|
2021 |
Experimental
Depression model in rats
(Male Wistar rats) |
To evaluate the effects of Dapagliflozin as a therapeutic modality in an animal model of depression, and the possible relationship with the NLRP3 Inflammasome |
Dapagliflozin
P.O (1 mg/kg) |
Dapagliflozin was able to suppress the levels of IL-1β and IL-18 as well the activity of the NLRP3 complex after 4 weeks |
SGLT2 inhibitor counteracts NLRP3 inflammasome via tubular metabolite itaconate in fibrosis kidney
Ke et al.
|
2022 |
Experimental
Kidney fibrosis in an ischemia/reperfusion model in mice
(Male C57BL/6J mice) |
To evaluate whether Dapagliflozin would reduce kidney fibrosis through inhibition of the NLRP3 complex in an ischemia/reperfusion model |
Dapagliflozin
Oral gavage
(1 mg/kg) |
Dapagliflozin reversed energy metabolism and inflammation alterations and prevented the NLRP3 activation |
The dynamic interplay between AMPK/NFκB signaling and NLRP3 is a new therapeutic target in inflammation: Emerging role of dapagliflozin in overcoming lipopolysaccharide-mediated lung injury
El-Fattah et al.
|
2022 |
Experimental
Acute lung injury in rats
(Male Sprague-Dawley rats) |
Assessed the role of Dapagliflozin in a model of lipopolysaccharide-induced lung injury in rats |
Dapagliflozin
Oral gavage
(5 mg/kg or
10 mg/kg) |
Dapagliflozin mitigated the lung injury, reduced oxidative stress and inhibited NLRP3 inflammasome and caspase-1 activity through AMPK/NFkB regulation |
Dapagliflozin Alleviates Renal Fibrosis by Inhibiting RIP1-RIP3-MLKL-Mediated Necroinflammation in Unilateral Ureteral Obstruction
Xuan et al.
|
2022 |
Experimental
Renal fibrosis in a unilateral ureter obstruction model
(Male Sprague-Dawley rats) |
Investigate whether Dapagliflozin could provide renal protection against renal fibrosis through anti-inflammatory effects in a rat model of ureter obstruction |
Dapagliflozin
Oral gavage
(10 mg/kg) |
Dapagliflozin alleviated renal fibrosis, expression of pro-inflammatory parameters (IL-1β, IL-18 and NLRP3) and oxidative stress |
Sodium-Glucose Co-transporter-2 Inhibitor of Dapagliflozin Attenuates Myocardial Ischemia/Reperfusion Injury by Limiting NLRP3 Inflammasome Activation and Modulating Autophagy
Yu et al.
|
2022 |
Experimental
Mouse model of myocardial ischemia/reperfusion injury
(Male C57BL/6J mice) |
To assess if Dapagliflozin could protect against myocardial ischemia/reperfusion injury and reduce cardiac inflammation |
Dapagliflozin
Oral gavage
(40 mg/kg) |
Treatment with Dapagliflozin attenuated infarct size, inhibited inflammation and provided cardioprotection through inhibition of inflammasome assembly |
Dapagliflozin, sildenafil and their combination in monocrotaline-induced pulmonary arterial hypertension
Tang et al.
|
2022 |
Experimental
Pulmonary arterial hypertension in rats
(Male Sprague-Dawley rats) |
To investigate if Dapagliflozin could improve pulmonary vascular remodeling by inhibiting NLRP3 inflammasome activation |
Dapagliflozin
Oral gavage
(1 mg/kg) |
Dapagliflozin attenuated right ventricular systolic pressure, pulmonary vascular remodeling and the decreased the NLRP3 activation |
Canagliflozin Ameliorates NLRP3 Inflammasome-Mediated Inflammation Through Inhibiting NF-κB Signaling and Upregulating Bif-1
Niu et al.
|
2022 |
Experimental
Mouse model of autophagy
(Swiss male mice) |
To evaluate the effects of Canagliflozin on inflammasomes and autophagy |
Canagliflozin
Oral gavage
(20 mg/kg) |
Canagliflozin downregulated protein levels of the NLRP3 inflammasome-associated proteins in vivo and in vitro |
Empagliflozin Attenuates Obesity-Related Kidney Dysfunction and NLRP3 Inflammasome Activity Through the HO-1-Adiponectin Axis
Ye et al.
|
2022 |
Experimental
Obesity-related kidney disease in obese mice
(Male C57BL/6J mice) |
Investigate the effects of Empagliflozin on obesity-related kidney disease in obese mice |
Empagliflozin
Oral gavage
(10 mg/kg) |
Treatment with Empagliflozin reduced renal injury and NLRP3 inflammasome activation |
SGLT2 inhibitor, canagliflozin, ameliorates cardiac inflammation in experimental autoimmune myocarditis
Long et al.
|
2022 |
Experimental
Autoimmune myocarditis in mice
(Male BALB/c mice) |
Investigate the effects of Canagliflozin over the inflammatory response in an experimental autoimmune myocarditis mouse model |
Canagliflozin
Oral gavage
(30 mg/kg) |
Canagliflozin alleviated cardiac inflammation, improved cardiac function and downregulated the expressions of the NLRP3 inflammasome complex components |
|
In vitro studies
|
The SGLT2 inhibitor Empagliflozin attenuates interleukin-17A-induced human aortic smooth muscle cell proliferation and migration by targeting TRAF3IP2/ROS/NLRP3/Caspase-1-dependent IL-1β and IL-18 secretion
Sukhanov et al.
|
2021 |
Experimental
In vitro – Cell culture
(Human aortic SMC and HK-2 the human kidney-2 cells) |
Investigate whether Empagliflozin could reduce Oxidative Stress and NLRP3 activity in an in vitro model of aortic smooth muscle cell proliferation |
Empagliflozin Concentrations of 0.1 – 5 uM for 15 minutes |
Treatment with Empagliflozin attenuated oxidative stress, NLRP3 expression, Caspase-1 activation and IL-1β and IL-18 secretion |
Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies
Liu et al.
|
2021 |
Experimental
In vitro (pancreatic B cells) and In vivo (mouse)
(Male BKS-Leprem2Cd479/Gpt mice and male C57BL/6 mice) |
Investigate the effects of Empagliflozin over the NLRP3 inflammasome in pancreatic tissues of diabetic mice and in pancreatic B cells |
Empagliflozin
Concentrations of 50, 100, 200 and 500 nmol/L (in vitro) and oral gavage
(10 mg/kg – in vivo) |
Empagliflozin reduced the expression levels of NLRP3/Caspase-1/GSDMD in vitro and in vivo, and reduced pathological changes and inflammatory infiltration in pancreatic tissues |
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