ReferenceID 2840
Scutellarin ameliorates hepatic lipid accumulation by enhancing autophagy and suppressing IRE1α/XBP1 pathway
Phytother Res
Nonalcoholic fatty liver disease is the most prevalent liver disease characterized by excessive lipid accumulation in hepatocytes. Endoplasmic reticulum (ER) stress and autophagy play an important role in lipid accumulat
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 2840
- Evidence Id
- 19430
- Core Evidence Id
- 19430
- Source Reference Id
- 5672
- Herb2 Reference Id
- HBREF006469
- Subject Paper Key
- HBIN043533_34859513
- Pubmed Id
- 34859513
- Doi
- 10.1002/ptr.7344
- Paper Title
- Scutellarin ameliorates hepatic lipid accumulation by enhancing autophagy and suppressing IRE1α/XBP1 pathway
- Paper Abstract
- Nonalcoholic fatty liver disease is the most prevalent liver disease characterized by excessive lipid accumulation in hepatocytes. Endoplasmic reticulum (ER) stress and autophagy play an important role in lipid accumulation. In this study, scutellarin (Scu) was examined in palmitic acid-treated HepG2 cells and C57/BL6 mice fed a high-fat diet (HFD). Scu reduced intracellular lipid content and inhibited sterol regulatory element binding protein-1c (SREBP-1c)-mediated lipid synthesis and fatty acid translocase-mediated lipid uptake in HepG2 cells. Additionally, Scu restored impaired autophagy and inhibited excessive activation of ER stress in vivo and in vitro. Moreover, Scu upregulated forkhead box O transcription factor 1-mediated autophagy by inhibiting inositol-requiring enzyme 1alpha (IRE1alpha)/X-box-binding protein 1 (XBP1) branch activation, while XBP1s overexpression exacerbated the lipid accumulation and impaired autophagy in HepG2 cells and also weakened the positive effects of Scu. Furthermore, Scu attenuated ER stress by activating autophagy, ultimately downregulating SREBP-1c-mediated lipid synthesis, and autophagy inhibitors offset these beneficial effects. Scu inhibited the crosstalk between autophagy and ER stress and downregulated saturated fatty acid-induced lipid accumulation in hepatocytes. These findings demonstrate that Scu ameliorates hepatic lipid accumulation by enhancing autophagy and suppressing ER stress via the IRE1alpha/XBP1 pathway.
- Journal
- Phytother Res
- Publish Year
- 2022
- Experiment Subject
- mouse; hepg2 cells; palmitic acid-treated hepg2 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Nonalcoholic Fatty Liver Disease; Liver Disease
- Paper Title Cn
- Paper Title En
- Scutellarin ameliorates hepatic lipid accumulation by enhancing autophagy and suppressing IRE1α/XBP1 pathway
- Bilingual Status
- semi_complete