ReferenceID 6174
Therapeutic Targeting of GSK3β-Regulated Nrf2 and NFκB Signaling Pathways by Salvianolic Acid A Ameliorates Peritoneal Fibrosis
Front Med (Lausanne)
Peritoneal fibrosis is a devastating complication in patients undergoing peritoneal dialysis, with no definite therapy yet available. Salvia miltiorrhiza and its major active component Salvianolic acid A (Sal A) have dem
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Record Fields
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- Reference Id
- 6174
- Evidence Id
- 22764
- Core Evidence Id
- 22764
- Source Reference Id
- 5613
- Herb2 Reference Id
- HBREF006410
- Subject Paper Key
- HBIN042900_35321474
- Pubmed Id
- 35321474
- Doi
- 10.3389/fmed.2022.804899
- Paper Title
- Therapeutic Targeting of GSK3β-Regulated Nrf2 and NFκB Signaling Pathways by Salvianolic Acid A Ameliorates Peritoneal Fibrosis
- Paper Abstract
- Peritoneal fibrosis is a devastating complication in patients undergoing peritoneal dialysis, with no definite therapy yet available. Salvia miltiorrhiza and its major active component Salvianolic acid A (Sal A) have demonstrated a beneficial effect in myriad diseases. However, their effect on peritoneal fibrosis is unknown. In murine models of peritoneal dialysis, daily Sal A treatment substantially improved the peritoneal dialysis fluid (PDF) elicited peritoneal fibrosis, marked by thickening of the submesothelial compact zone, accumulation of extracellular matrix and increased expression of vimentin and PAI-1, concomitant with attenuation of GSK3β hyperactivity. This coincided with diminished nitrotyrosine in peritoneal tissues and increased Nrf2 nuclear translocation, entailing a lessened oxidative injury and reinforced Nrf2 antioxidant response. Meanwhile, inflammatory infiltration and maladaptive angiogenesis in peritoneal tissues provoked by PDF injury were also mitigated by Sal A, associated with a suppressed NFκB activation. Mechanistically, ectopic expression of the constitutively active GSK3β blunted the NFκB-suppressing and Nrf2-activating efficacy of Sal A in peritoneal mesothelial cells exposed to hypertonic dextrose, suggesting that GSK3β inhibition mediates the protective effect of Sal A. Collectively, our findings may open the avenue for developing a novel therapy based on Sal A for preventing peritoneal fibrosis in peritoneal dialysis.
- Journal
- Front Med (Lausanne)
- Publish Year
- 2022
- Experiment Subject
- mouse; patient
- Experiment Type
- Animal Experiment
- Phenotype Related
- GSK3β hyperactivity; Peritoneal Fibrosis
- Paper Title Cn
- Paper Title En
- Therapeutic Targeting of GSK3β-Regulated Nrf2 and NFκB Signaling Pathways by Salvianolic Acid A Ameliorates Peritoneal Fibrosis
- Bilingual Status
- semi_complete