Research Article Details
| Article ID: | A07548 |
| PMID: | 32446270 |
| Source: | Br J Pharmacol |
| Title: | Astaxanthin attenuates hepatic damage and mitochondrial dysfunction in non-alcoholic fatty liver disease by up-regulating the FGF21/PGC-1α pathway. |
| Abstract: | BACKGROUND AND PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. Astaxanthin (Ax) is a carotenoid, and beneficial effects of astaxanthin, including anti-oxidative, anti-inflammatory, and anti-tumour activity, have been identified. The present study aimed to elucidate the protective effect of astaxanthin against NAFLD and its underlying mechanism. EXPERIMENTAL APPROACH: Mice were fed either a high fat or chow diet, with or without astaxanthin, for up to 12 weeks. L02 cells were treated with free fatty acids combined with different doses of astaxanthin for 48 h. Histopathology, expression of lipid metabolism, inflammation, apoptosis, and fibrosis-related gene expression were assessed. And the function of mitochondria was also evaluated. KEY RESULTS: The results indicated that astaxanthin attenuated HFD- and FFA-induced lipid accumulation and its associated oxidative stress, cell apoptosis, inflammation, and fibrosis both in vivo and in vitro. Astaxanthin up-regulated FGF21 and PGC-1α expression in damaged hepatocytes, which suggested an unrecognized mechanism of astaxanthin on ameliorating NAFLD. CONCLUSION AND IMPLICATIONS: Astaxanthin attenuated hepatocyte damage and mitochondrial dysfunction in NAFLD by up-regulating FGF21/PGC-1α pathway. Our results suggest that astaxanthin may become a promising drug to treat or relieve NAFLD. |
| DOI: | 10.1111/bph.15099 |
| 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 |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | 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 |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D019 | Astaxanthin | Chemical drug | DB06543 | -- | -- | Under clinical trials | Details |
| D581 | sobetirome | Chemical drug | -- | Thyroid hormone receptor beta agonists | Enhance lipid metabolism | Under investigation | Details |