ReferenceID 6306
Dihydroquercetin protects against renal fibrosis by activating the Nrf2 pathway
Phytomedicine
BACKGROUND: Dihydroquercetin (DHQ) is an antifibrotic agent. However, whether DHQ can prevent renal fibrosis remains unknown. PURPOSE: This study aimed to investigate the effects of DHQ on tubulointerstitial fibrosis and
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
- 6306
- Evidence Id
- 22896
- Core Evidence Id
- 22896
- Source Reference Id
- 5883
- Herb2 Reference Id
- HBREF006680
- Subject Paper Key
- HBIN045672_32120244
- Pubmed Id
- 32120244
- Doi
- 10.1016/j.phymed.2020.153185
- Paper Title
- Dihydroquercetin protects against renal fibrosis by activating the Nrf2 pathway
- Paper Abstract
- BACKGROUND: Dihydroquercetin (DHQ) is an antifibrotic agent. However, whether DHQ can prevent renal fibrosis remains unknown. PURPOSE: This study aimed to investigate the effects of DHQ on tubulointerstitial fibrosis and its underlying mechanisms in unilateral ureteral obstruction (UUO) mice in vivo and NRK-49F cells in vitro. METHODS: In vivo, UUO mice received vehicle or DHQ treatment. In vitro, NRK-49F cells were pretreated with DHQ and exposed to transforming growth factor-beta1 (TGF-beta1). Changes in fibroblast activation, collagen synthesis, oxidative stress, and related signaling pathways were assessed by immunohistochemical staining, Western blot analysis, real-time reverse transcription-PCR, and fluorescence microscopy. RESULTS: UUO induced tubular atrophy, inflammation, fibroblast differentiation into myofibroblast, and collagen deposition, whereas DHQ ameliorated these effects. UUO also resulted in decreased levels of nuclear factor-erythroid-2-related factor 2 (Nrf2), catalase, and heme oxygenase-1, but increased H2O2 and malondialdehyde levels. DHQ treatment corrected these changes. In vitro, the intracellular Nrf2 level of NRK-49F exposed to TGF-beta1 decreased. However, DHQ rescued intracellular Nrf2 level and promoted nuclear translocation of Nrf2. DHQ scavenged TGF-beta1-induced accumulation of reactive oxygen species, inhibited TGF-beta1-induced Smad3 phosphorylation, and prevented TGF-beta1-induced fibroblast activation and collagen synthesis in NRK-49F. Nrf2 knockdown could suppress the DHQ-mediated inhibitory effects on oxidative stress, Smad3 phosphorylation, fibroblast activation, and collagen deposition. Furthermore, DHQ ameliorated established renal fibrosis in UUO mice. CONCLUSIONS: DHQ posed remarkable preventive and therapeutic effects on UUO-induced renal fibrosis and suppressed fibroblast activation by reducing oxidative stress and Smad3 phosphorylation via Nrf2 signaling. This study provided a mechanistic basis for the clinical application of DHQ in renal fibrosis treatment.
- Journal
- Phytomedicine
- Publish Year
- 2020
- Experiment Subject
- mouse; nrk-49f cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Tubular Atrophy; Inflammation; Renal Fibrosis; Tubulointerstitial Fibrosis; Unilateral Ureteral Obstruction
- Paper Title Cn
- Paper Title En
- Dihydroquercetin protects against renal fibrosis by activating the Nrf2 pathway
- Bilingual Status
- semi_complete