Research Article Details

Article ID: A34076
PMID: 24471744
Source: J Pharm Pharmacol
Title: Bupropion effects on high-fat diet-induced steatohepatitis and endothelial dysfunction in rats: role of tumour necrosis factor-alpha.
Abstract: OBJECTIVES: This study aimed to elucidate the effect of bupropion (BUP) on high-fat diet (HFD)-treated rats that is to say the action of BUP on diabetes and hyperlipidemia with its consequences on liver and endothelial function. METHODS: Male Wistar rats were fed HFD or normal chow for 15 weeks then given either BUP (50 mg/kg) or distilled water by gavage for 4 weeks. The effect of BUP on diabetes, hyperlipidemia, hepatic and vascular functions as well as tumour necrosis factor-alpha (TNF)-α were assessed. The intima-media thickness of the aorta was evaluated. KEY FINDINGS: BUP significantly decreased serum lipid, liver enzyme, homeostasis model assessment for insulin resistance (HOMA-IR), serum TNF-α and the impaired glucose tolerance. Liver from rats with non-alcoholic steatohepatitis (NASH) demonstrated significant higher TNF-α level, inflammatory cell infiltration, ballooning and steatosis which significantly ameliorated by BUP treatment. Neither intima/media ratio nor vascular reactivity to acetylcholine is improved by BUP treatment. CONCLUSIONS: NASH induced by a HFD was associated with hyperlipidemia, insulin resistance, endothelial dysfunction and increase in liver TNF-α. All of these may contribute to the pathogenesis of NASH. BUP has potential role in improving metabolic and hepatic function with negative vascular effect. Since BUP is a well-known antidepressant, it will be a candidate drug in treatment of depression in hepatic diseased or metabolic disturbed patients.
DOI: 10.1111/jphp.12213

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
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

Diseases ID DO ID Disease Name Definition Class
I17 1596 Mental depression Mental depression disease of mental health/ cognitive disorder/ mood disorder Details
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
I07 1936 Arteriosclerosis Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C35768 disease of anatomical entity/cardiovascular system disease/ vascular disease/ artery disease 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
D075 Choline Supplement DB00122 PLD2 product of; PLD1 product of -- Under clinical trials Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details