Nrf2 Pathway and Oxidative Stress as a Common Target for Treatment of Diabetes and Its Comorbidities
Abstract
:1. Introduction
2. How Diabetes Induces Oxidative Stress
3. Diabetes and Cardiovascular Disease
3.1. Diabetes and Atherosclerosis
3.2. Nrf2-Targeting Treatment in Diabetic Atherosclerosis
3.3. Diabetes and Cardiomyopathy
3.4. Nrf2-Targeting Treatment in Diabetic Cardiomyopathy
4. Diabetes and Kidney Disease
5. Diabetes and Liver Diseases
5.1. Diabetes and Progression of Non-Alcoholic Liver Disease
5.2. Diabetes and Alcoholic Liver Disease
5.3. Effects of Diabetes Drugs on Liver Responsse to Toxins
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Disease | Drug/Substance | Action in Nrf2 and Other Antioxidative Pathways | References |
---|---|---|---|
Atherosclerosis | Metformin | SOD1 upregulation | [49,51] |
ROS inhibition | |||
Nrf2 upregulation | [52] | ||
Keap1 downregulation | |||
HO-1 upregulation | |||
Upregulation of Nrf2 translocation | |||
Liraglutide | Inhibition of oxLDL uptake | [53] | |
CD36 downregulation | [54] | ||
Nrf2/HO-1 pathway activation | [55] | ||
Promotion of SOD and MPO activities | |||
Promotion of Nrf2 activities | [56] | ||
C. verum/C. cassia | CD36 downregulation | [57] | |
SRA downregulation | |||
Upregulation of Nrf2 translocation | [58] | ||
Nrf2 upregulation | [59] | ||
Keap1 regulation | [60] | ||
Cardiac fibrosis | Empagliflozin | Nrf2 upregulation | [61] |
SOD2 upregulation | |||
Upregulation of Nrf2 translocation | |||
Sitagliptin | Downregulation of inflammatory cytokines | [62] | |
Upregulation of Nrf2 translocation | [63] | ||
Nrf2 upregulation | [64] | ||
HO-1 upregulation |
Disease | Drug/Substance | Action in Nrf2 and Other Antioxidative Pathways | References |
---|---|---|---|
Diabetic nephropathy | A. vera | Reduction of oxidative stress | [102] |
GBE | Nrf2 upregulation | [103,104] | |
HO-1 upregulation | |||
Metformin with L-egt | Nrf2 upregulation | [105] | |
Upregulation of cytoprotective genes and antioxidative enzymes | |||
Downregulation of TGF-β1 gene | |||
Inhibition of the NF-kB inflammatory gene |
Disease | Drug/Substance | Action in Nrf2 and Other Antioxidative Pathways | References |
---|---|---|---|
Nonalcoholic fatty liver disease | Naltrexone | Nrf2 upregulation | [115] |
THBS-1 downregulation | |||
NOX-1 downregulation | |||
Metformin | Nrf2 upregulation | [118] | |
HO-1 upregulation | |||
Liraglutide | Nrf2 upregulation | [119] | |
HO-1 upregulation | |||
Sestrin2 upregulation | |||
Keap1 degradation | |||
Empagliflozin | Nrf2 upregulation | [120] | |
Normalization of cytochrome p450 expression | |||
Alcoholic liver disease | D. tanguticum | Nrf2 upregulation | [121] |
Keap1 downregulation | |||
Dihydromyricetin | Nrf2 upregulation | [122] | |
Keap1 downregulation | |||
HO-1 downregulation | |||
Alleviation of disordered NF-κB and Nrf2 localization | |||
Toxin-induced liver damage | Diallyl disulfide | Nrf2 upregulation and Keap1 downregulation | [123] |
Ellagic acid | [124] | ||
Ursolic acid | [125] | ||
Monoammonium glycyrrhizinate | [126] | ||
Cysteine hydrochloride | |||
Metformin with luteolin | Nrf2 upregulation | [118,127] | |
HO-1 upregulation | |||
Liraglutide | pCREB upregulation | [128] |
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Yi, M.; Cruz Cisneros, L.; Cho, E.J.; Alexander, M.; Kimelman, F.A.; Swentek, L.; Ferrey, A.; Tantisattamo, E.; Ichii, H. Nrf2 Pathway and Oxidative Stress as a Common Target for Treatment of Diabetes and Its Comorbidities. Int. J. Mol. Sci. 2024, 25, 821. https://doi.org/10.3390/ijms25020821
Yi M, Cruz Cisneros L, Cho EJ, Alexander M, Kimelman FA, Swentek L, Ferrey A, Tantisattamo E, Ichii H. Nrf2 Pathway and Oxidative Stress as a Common Target for Treatment of Diabetes and Its Comorbidities. International Journal of Molecular Sciences. 2024; 25(2):821. https://doi.org/10.3390/ijms25020821
Chicago/Turabian StyleYi, Michelle, Leslie Cruz Cisneros, Eric J. Cho, Michael Alexander, Francesca A. Kimelman, Lourdes Swentek, Antoney Ferrey, Ekamol Tantisattamo, and Hirohito Ichii. 2024. "Nrf2 Pathway and Oxidative Stress as a Common Target for Treatment of Diabetes and Its Comorbidities" International Journal of Molecular Sciences 25, no. 2: 821. https://doi.org/10.3390/ijms25020821