Therapeutic Strategy Details
| Strategy ID: | S04 |
| Strategy: | Anti-oxidative stress |
| Other Terms: | oxidative stress |
| Related Targets: | α-tocopherol: antioxidant |
| Related Drugs: | Vitamin E |
| Mechanism: | Disturbances in lipid metabolism lead to hepatic lipid accumulation, which affects different reactive oxygen species (ROS) generators, including mitochondria, endoplasmic reticulum, and NADPH oxidase. Mitochondrial function adapts to NAFLD mainly through the downregulation of the electron transport chain (ETC) and the preserved or enhanced capacity of mitochondrial fatty acid oxidation, which stimulates ROS overproduction within different ETC components upstream of cytochrome c oxidase. |
| Reference (PMIDs): | 10839868; 32156524 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D007 | Alpha-lipoic acid | Chemical drug | DB00166 | LIPT1 | Antioxidant drug | Under clinical trials | Details |
| D020 | Atorvastatin | Chemical drug | DB01076 | DPP4 inhibitor; AHR agonist; HDAC2 inhibitor; NR1I3 ligand | Enhance lipid metabolism | Under clinical trials | Details |
| D133 | Fenofibrate | Chemical drug | DB01039 | PPARA agonist; NR1I2 partial agonist | Anti-inflammatory | Under clinical trials | Details |
| D137 | Fish oil | Biological drug | DB13961 | -- | -- | Under clinical trials | Details |
| D277 | Pitavastatin | Chemical drug | DB08860 | HMGCR inhibitor | Enhance lipid metabolism | Failed in clinical trials | Details |
| D293 | Quercetin | Supplement | DB04216 | AHR; EIF3F; SF3B3; NR1I2 activator | -- | Under clinical trials | Details |
| D312 | Rosuvastatin | Chemical drug | DB01098 | HMGCR inhibitor | Enhance lipid metabolism | Under clinical trials | Details |
| D326 | Selonsertib | Chemical drug | DB14916 | MAP3K5 inhibitor; ASK1 inhibitor | Anti-oxidative stress; Anticancer agent | Failed in clinical trials | Details |
| D367 | Thioctic acid | Chemical drug | DB00166 | -- | Vitamin source drug | Under clinical trials | Details |
| D395 | Zinc | Chemical drug | DB01593 | PSPH; CCS; HDAC1 cofactor; HDAC4 cofactor; INS; UTRN; ASPA cofactor; TP73 cofactor; A2M; AGT; APOBR; APOE; APOL1; C3; C5; CFB; CFH; CFI; CLU; CP; CPN2; DSP; F12; F13B; FGA; GSN; HBB; HPR; JUP; SELENOP; TTR; VTN | -- | Under clinical trials | Details |
| Candidate ID | Source ID | Source Type | Compound Type | Candidate Name | Inclusion Criteria | |
|---|---|---|---|---|---|---|
| R0041 | DB00130 | approved; investigational; nutraceutical | small molecule | L-Glutamine | Therapeutic strategy associated | Details |
| R0044 | DB00134 | approved; nutraceutical | small molecule | Methionine | Therapeutic strategy associated | Details |
| R0045 | DB00137 | approved; investigational; nutraceutical | small molecule | Lutein | Therapeutic strategy associated | Details |
| R0046 | DB00138 | approved; nutraceutical | small molecule | Cystine | Therapeutic strategy associated | Details |
| R0053 | DB00152 | approved; investigational; nutraceutical; vet_approved | small molecule | Thiamine | Therapeutic strategy associated | Details |
| R0065 | DB00178 | approved | small molecule | Ramipril | Therapeutic strategy associated | Details |
| R0088 | DB00227 | approved; investigational | small molecule | Lovastatin | Therapeutic strategy associated | Details |
| R0227 | DB00641 | approved | small molecule | Simvastatin | Therapeutic strategy associated | Details |
| R0243 | DB00694 | approved | small molecule | Daunorubicin | Therapeutic strategy associated | Details |
| R0288 | DB00808 | approved | small molecule | Indapamide | Therapeutic strategy associated | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A00018 | 35252260 | Front Med (Lausanne) | Intermittent Hypoxia Rewires the Liver Transcriptome and Fires up Fatty Acids Usage for Mitochondrial Respiration. | Details |
| A00050 | 35243111 | Transl Gastroenterol Hepatol | Palm tocotrienol rich fraction with palm kernel oil supplementation prevents development of liver steatosis in high fat diet ICR mice. | Details |
| A00054 | 35241921 | J Inflamm Res | Reduction of Hepatic Steatosis, Oxidative Stress, Inflammation, Ballooning and Insulin Resistance After Therapy with Safranal in NAFLD Animal Model: A New Approach. | Details |
| A00072 | 35230646 | Neurochem Res | Non-alcoholic Fatty Liver Disease: Also a Disease of the Brain? A Systematic Review of the Preclinical Evidence. | Details |
| A00082 | 35227772 | Life Sci | sSTEAP4 regulates cellular homeostasis and improves high-fat-diet-caused oxidative stress in hepatocytes. | Details |
| A00092 | 35222799 | Oxid Med Cell Longev | 4-Octyl Itaconate Prevents Free Fatty Acid-Induced Lipid Metabolism Disorder through Activating Nrf2-AMPK Signaling Pathway in Hepatocytes. | Details |
| A00093 | 35222075 | Front Physiol | MicroRNA-122-5p Inhibition Improves Inflammation and Oxidative Stress Damage in Dietary-Induced Non-alcoholic Fatty Liver Disease Through Targeting FOXO3. | Details |
| A00095 | 35221291 | J Pharmacol Exp Ther | Resveratrol attenuates HFD-induced hepatic lipotoxicity by up-regulating Bmi-1 expression. | Details |
| A00100 | 35220131 | Phytomedicine | 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside ameliorates NAFLD via attenuating hepatic steatosis through inhibiting mitochondrial dysfunction dependent on SIRT5. | Details |
| A00116 | 35216100 | Int J Mol Sci | Dysregulation of S-adenosylmethionine Metabolism in Nonalcoholic Steatohepatitis Leads to Polyamine Flux and Oxidative Stress. | Details |
| A00147 | 35208513 | Medicina (Kaunas) | Evaluation of Dose-Dependent Obesity and Diabetes-Related Complications of Water Chestnut (Fruit of Trapa japonica) Extracts in Type II Obese Diabetic Mice Induced by 45% Kcal High-Fat Diet. | Details |
| A00160 | 35204232 | Antioxidants (Basel) | Dietary Selenium Alleviated Mouse Liver Oxidative Stress and NAFLD Induced by Obesity by Regulating the KEAP1/NRF2 Pathway. | Details |
| A00161 | 35204113 | Antioxidants (Basel) | Effects of Colchicine in a Rat Model of Diet-Induced Hyperlipidemia. | Details |
| A00179 | 35196511 | Am J Med Sci | Deciphering the Role of Aquaporins in Metabolic Diseases: A Mini Review. | Details |
| A00183 | 35195377 | Minerva Endocrinol (Torino) | Inflammation is associated with impairment of oxidative status, carbohydrate and lipid metabolism in type 2 diabetes complicated by non-alcoholic fatty liver disease. | Details |
| A00203 | 35187967 | Exp Biol Med (Maywood) | Iron-accumulating splenocytes may exacerbate non-alcoholic steatohepatitis through the production of proinflammatory cytokines and reactive oxygen species. | Details |
| A00206 | 35187020 | Front Nutr | Association of Serum Vitamin C With NAFLD and MAFLD Among Adults in the United States. | Details |
| A00207 | 35186807 | Can J Gastroenterol Hepatol | Therapeutic Effects of Milk Thistle (Silybum marianum L.) and Artichoke (Cynara scolymus L.) on Nonalcoholic Fatty Liver Disease in Type 2 Diabetic Rats. | Details |
| A00240 | 35171164 | Food Funct | Tangeretin improves hepatic steatosis and oxidative stress through the Nrf2 pathway in high fat diet-induced nonalcoholic fatty liver disease mice. | Details |
| A00251 | 35164657 | Bioengineered | Liraglutide inhibits receptor for advanced glycation end products (RAGE)/reduced form of nicotinamide-adenine dinucleotide phosphate (NAPDH) signaling to ameliorate non-alcoholic fatty liver disease (NAFLD) in vivo and vitro. | Details |