Research Article Details
| Article ID: | A02751 |
| PMID: | 34260003 |
| Source: | Neurochem Res |
| Title: | Resveratrol Protects SH-SY5Y Cells Against Oleic Acid-Induced Glucolipid Metabolic Dysfunction and Cell Injuries Via the Wnt/β-Catenin Signalling Pathway. |
| Abstract: | Resveratrol (RES) is a polyphenol with diverse beneficial biological and pharmacological activities, and our previous results have demonstrated its neuroprotective effects in several metabolic diseases, including non-alcoholic fatty liver disease. The aim of the present study is to investigate the potential effect of RES against oleic acid (OA)-induced cell injuries in SH-SY5Y cells and explore the possible mechanism. Based on the dose- and time-dependent effects of OA on cell proliferation and LDH release, SH-SY5Y cells were challenged with OA and incubated with or without RES (10-5-10-9 mM) or sitagliptin (STG, 10-7 mM). Lipid accumulation, SREBP1 and PPARα protein expression, glucose consumption and IRS1, AKT, ERK phosphorylation under insulin stimulation, and ROS production were detected. The protein expression of brain-derived neurotrophic factor (BDNF), Copine 6, and key molecules in the Wnt/β-catenin signalling pathway were measured via western blot. The expression of Wnt 1 was also measured via immunofluorescence staining. The results showed that RES treatment could alleviate the neurotoxicity induced by OA, as indicated by the increased cell proliferation and the decreased concentration of LDH in the supernatant. The increased lipid deposition and protein expression of SREBP1 and PPARα induced by OA was also reversed by treatment with RES. Moreover, RES could upregulate glucose consumption and the protein expression of phosphorylated IRS1, AKT, ERK and reduced ROS production in OA-induced SH-SY5Y cells. Furthermore, RES treatment reversed the imbalanced protein expression of BDNF, Copine 6, p-β-catenin, and Wnt 1 in SH-SY5Y cells induced by OA and decreased the hyperexpression of p-GSK3β. However, these effects were suppressed by DKK1, which is a specific antagonist of the Wnt signalling pathway. These results suggested that RES has a neuroprotective effect against OA-induced cell injury and dysfunctional glucolipid metabolism, and the mechanism might involve its ability to regulate oxidative stress and insulin resistance via the Wnt/β-catenin signalling pathway. |
| DOI: | 10.1007/s11064-021-03398-8 |
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | 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 | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D301 | Resveratrol | Chemical drug | DB02709 | ALOX15; ALOX5; AHR; NR1I2; NR1I3 | Anticancer agent | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D338 | Sitagliptin | Chemical drug | DB01261 | DPP4 inhibitor | Antidiabetic drug | 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 |