Research Article Details
| Article ID: | A18113 |
| PMID: | 27345365 |
| Source: | Sci Rep |
| Title: | New insights into salvianolic acid A action: Regulation of the TXNIP/NLRP3 and TXNIP/ChREBP pathways ameliorates HFD-induced NAFLD in rats. |
| Abstract: | Salvianolic acid A (SalA), one of the most efficacious polyphenol compounds extracted from Radix Salvia miltiorrhiza (Danshen), has been shown to possess many potential pharmacological activities. This study aimed to investigate whether SalA has hepatoprotective effects against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and to further explore the mechanism underlying this process. SalA treatment significantly attenuated HFD-induced obesity and liver injury, and markedly decreased lipid accumulation in HFD-fed rat livers. Moreover, SalA treatment ameliorated HFD-induced hepatic inflammation and oxidative stress by decreasing hepatotoxic levels of cytokines, suppressing the overproduction of reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA) and preventing the decreased expression of superoxide dismutase (SOD). Importantly, SalA reversed the HFD- or palmitic acid (PA)-induced activation of the NLRP3 inflammasome, the nuclear translocation of ChREBP and the up-regulation of FAS, and these effects were accompanied by TXNIP down-regulation. However, TXNIP siRNA treatment partially abrogated the above-mentioned effects of SalA in PA-treated HepG2 cells. Together, our results demonstrated, for the first time, that SalA protects against HFD-induced NAFLD by ameliorating hepatic lipid accumulation and inflammation, and these protective effects may partially due to regulation of the TXNIP/NLRP3 and TXNIP/ChREBP pathways. |
| DOI: | 10.1038/srep28734 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D589 | Minor allele-specific small interfering RNA | Miscellany | -- | PNPLA3-rs738409 (I148M) variant inhibitor | -- | Under investigation | Details |