Research Article Details
| Article ID: | A00926 |
| PMID: | 34927282 |
| Source: | Drug Dev Res |
| Title: | Schisandrin B ameliorates non-alcoholic liver disease through anti-inflammation activation in diabetic mice. |
| Abstract: | Type 2 diabetes mellitus (T2DM) is a metabolic risk factor associated with non-alcoholic liver disease (NAFLD). Schisandrin B (Sch B) is a promising agent for NAFLD. However, the actions of Sch B on diabetes-associated NAFLD and the underlying mechanisms are not characterized. This study aimed to assess whether Sch B has beneficial effects on T2DM-associated NAFLD. Sch B (50 mg/kg, gavage) was administrated to C57BL/KSJ db/db mice for 2 weeks. Body weight, liver weight, blood glucose, and insulin resistance were measured. Serum lipid level and liver function were detected using the biochemistry analyzer. Quantitative Real-Time PCR assay was used to evaluate mRNA levers of lipid metabolism genes. Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining was performed to measure apoptosis in the liver. Pathological analysis and immunohistochemistry assessment were used to analyze hepatic steatosis and inflammatory infiltration. Sch B supplementation significantly decrease body weight, related liver weight, blood glucose, and serum insulin, and improved insulin resistance in db/db mice. Sch B obviously corrected NAFLD phenotypes including lipid deposition, steatohepatitis, and high levels of hepatic enzymes and serum lipid. In addition, mRNA levels of Sterol response element-bind protein 1c (SREBP-1c), fatty acid synthetase (Fasn), and acetyl-CoA carboxylase (ACC) were markedly downregulated by Sch B treatment. TUNEL-positive cells were also decreased by Sch B. Furthermore, Sch B inhibited the Kupffer cells, IL-1β, and TNF-α infiltration to the liver. Sch B ameliorated insulin resistance and lipid accumulation under high glucose conditions, which was partly associated with its inhibition of apoptosis and anti-inflammatory actions. |
| DOI: | 10.1002/ddr.21905 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T08 | Tumor necrosis factor | TNF | inhibitor | Cytokine | P01375 | TNFA_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |