ReferenceID 4501
Effects of andrographolide on renal tubulointersticial injury and fibrosis. Evidence of its mechanism of action
Phytomedicine
BACKGROUND: Diabetic nephropathy (DN) is associated with renal interstitial injury and fibrosis. Our previous study showed that andrographolide protected against the progression of DN and high glucose (HG)-induced mesang
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- Reference Id
- 4501
- Evidence Id
- 21091
- Core Evidence Id
- 21091
- Source Reference Id
- 2280
- Herb2 Reference Id
- HBREF003077
- Subject Paper Key
- HBIN016019_34332282
- Pubmed Id
- 34332282
- Doi
- 10.1016/j.phymed.2021.153650
- Paper Title
- Effects of andrographolide on renal tubulointersticial injury and fibrosis. Evidence of its mechanism of action
- Paper Abstract
- BACKGROUND: Diabetic nephropathy (DN) is associated with renal interstitial injury and fibrosis. Our previous study showed that andrographolide protected against the progression of DN and high glucose (HG)-induced mesangial dysfunction. However, the protective effects of andrographolide on renal tubular epithelial cells have not been fully elucidated. PURPOSE: To determine the protective effects of andrographolide on renal tubular damage and explore the underlying mechanism. STUDY DESIGN: Human tubular epithelial cells (HK-2 cells) were treated with andrographolide (5 and 10 muM) under HG conditions. Diabetic mice were treated with andrographolide (i.p. 2 and 4 mg/kg, twice per week). METHODS: Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence and flow cytometry were used to analyze the effects of andrographolide on renal tubular injury and fibrotic mechanisms in HK-2 cells. The protective effects of andrographolide against renal tubulointerstitial injury and fibrosis were investigated in diabetic mice fed a high-fat diet (HFD). Renal interstitial tissue was collected at sacrifice for immunohistochemistry, immunofluorescence analysis, RT-PCR and Western blotting to analyze the effects of andrographolide on renal tubular injury and fibrosis. RESULTS: In vitro assay results indicated that andrographolide (5 and 10 muM) effectively inhibited HG-induced apoptosis, epithelial-mesenchymal transition (EMT) and collagen deposition in HK-2 cells. Mechanistically, HG stimulated mitochondrial reactive oxygen species (mtROS)-mediated NOD-like receptor family and pyrin domain-containing protein 3 (NLRP3) inflammasome activation and EMT in tubular epithelial cells, and andrographolide (5 and 10 muM) inhibited these effects by ameliorating mitochondrial dysfunction. In vivo, treatment with andrographolide (2 and 4 mg/kg) inhibited renal tubular cell apoptosis, EMT and tubulointerstitial fibrosis, mitochondrial dysfunction and NLRP3 inflammasome activation in diabetic mice. CONCLUSION: Andrographolide (5 and 10 muM) prevents HG-induced renal tubular cell damage, and andrographolide (2 and 4 mg/kg) protects against the progression of diabetic tubular injury and fibrosis in mice by suppressing mitochondrial dysfunction and NLRP3 inflammasome activation.
- Journal
- Phytomedicine
- Publish Year
- 2021
- Experiment Subject
- mouse; human; hk-2 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Renal Tubular Injury; Diabetic; Diabetic Tubular Injury; Mesangial Dysfunction; Tubulointerstitial Fibrosis; Fibrosis; Mitochondrial Dysfunction; Diabetic Nephropathy; Renal Interstitial Injury; Renal Tubulointerstitial Injury
- Paper Title Cn
- Paper Title En
- Effects of andrographolide on renal tubulointersticial injury and fibrosis. Evidence of its mechanism of action
- Bilingual Status
- semi_complete