Research Article Details
| Article ID: | A08954 |
| PMID: | 31926984 |
| Source: | J Ethnopharmacol |
| Title: | Sweroside ameliorates NAFLD in high-fat diet induced obese mice through the regulation of lipid metabolism and inflammatory response. |
| Abstract: | ETHNOPHARMACOLOGICAL RELEVANCE: Sweroside, an iridoid derived from Traditional Chinese Medicine, is an active component in Swertia pseudochinensis Hara. Swertia pseudochinensis Hara is first recorded in "Inner Mongolia Chinese Herb Medicine"and is considered as a folk medicine for treating hepatitis in northern China. AIM OF THE STUDY: This study sought to elucidate the role of sweroside in high fat diet induced obesity and fatty liver by using mouse model and investigated the primary molecular mechanism via transcriptomics analysis. MATERIALS AND METHODS: C57BL/6 mice were fed high-fat diet (HFD) for 14 weeks to induce obesity, hyperglycemia, and fatty liver. These mice were subsequently treated with HFD alone or mixed with sweroside (at a daily dosage of 60 mg per kg of BW, 120 mg per kg of BW and 240 mg per kg of BW) for 6 weeks. BW and food intake was monitored weekly. Biochemical and pathological analysis were conducted to investigate the effect of sweroside on NAFLD. RNA-sequence and RT-qPCR analysis were performed to analyze the potential mechanism. RESULTS: The mice treated with sweroside were resistant to HFD-induced body weight gain, insulin resistance and hepatic steatosis. Ingenuity pathway analysis (IPA) demonstrated that hepatic gene networks related to lipid metabolism and inflammatory response were down-regulated in the HFD + sweroside group. PPAR-ɑ was located in the center of the hepatic gene network, and the significantly altered genes were CD36 and FGF21, which are related to hepatic inflammation and lipid metabolism. Consistently, upstream-regulators analysis revealed that the main enriched upstream-regulator was PPAR-ɑ. CONCLUSION: Our results indicate that sweroside may ameliorate obesity with fatty liver via the regulation of lipid metabolism and inflammatory responses. The beneficial effects of sweroside might be closely associated with the regulation of PPAR-α. |
| DOI: | 10.1016/j.jep.2020.112556 |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T03 | Peroxisome proliferator-activated receptor alpha | PPARA | agonist | Nuclear hormone receptor | Q07869 | PPARA_HUMAN | Details |
| T28 | Fibroblast growth factor 21 | FGF21 | analogue | Secreted | Q9NSA1 | FGF21_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 |
| 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 |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |