Research Article Details
| Article ID: | A10027 |
| PMID: | 31520549 |
| Source: | Fundam Clin Pharmacol |
| Title: | Tanshinone IIA reduces palmitate-induced apoptosis via inhibition of endoplasmic reticulum stress in HepG2 liver cells. |
| Abstract: | Research has indicated that stress on the endoplasmic reticulum (ER) of a cell affects the pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). Palmitate, a saturated fatty acid, is known to induce toxicity and cell death in various types of cells. Tanshinone IIA (Tan IIA), one of the effective components of the traditional Chinese medicine Danshen, was reported to exhibit a variety of biochemical activities, including amelioration of ER stress-mediated apoptosis in renal preservation. To address the hypothesis that tan IIA attenuates apoptosis and triglycerides (TG) accumulation via reducing ER stress, we studied the effect of tan IIA on experimentally induced ER stress using palmitate in HepG2 cells. Palmitate led to cytotoxicity, TG accumulation, and apoptosis in HepG2 cells and also strongly induced ER stress indicated by increased GRP78, phosphorylation of eIF2α, ATF6, and CHOP. Pretreatment with tan IIA (10 μm) significantly increased cell viability, decreased apoptotic cell death, and reduced the activity of caspase-3. Meanwhile, tan IIA significantly decreased palmitate-induced TG accumulation. Moreover, tan IIA significantly suppressed the phosphorylation of eIF2α, and inhibited GRP78, ATF6, and CHOP expression. In conclusion, tan IIA protects the HepG2 cells exposed to palmitate partially by inhibiting excessive ER stress, ER stress-induced apoptosis, and hepatic steatosis. Therefore, tan IIA has therapeutic potential in the treatment of NAFLD. |
| DOI: | 10.1111/fcp.12510 |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | 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 |