Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathway.

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  • Additional Information
    • Source:
      Publisher: Taylor & Francis Country of Publication: England NLM ID: 9812552 Publication Model: Print Cited Medium: Internet ISSN: 1744-5116 (Electronic) Linking ISSN: 13880209 NLM ISO Abbreviation: Pharm Biol Subsets: MEDLINE
    • Publication Information:
      Publication: [London] : Taylor & Francis
      Original Publication: Lisse, the Netherlands : Swets & Zeitlinger, c1998-
    • Subject Terms:
    • Abstract:
      Context: Kirenol possesses anti-inflammatory, antifibrotic and anti-arthritic effects. However, its reno-protective effects against diabetic nephropathy (DN) have not been evaluated.
      Objective: This study explores the reno-protective effects of kirenol against DN and clarifies the potential mechanisms.
      Materials and Methods: The mesangial cells were treated with 20 µM kirenol and 10 ng/mL human recombinant TGF-β1 or 30 mM glucose for 24 h. Then the cells were harvested to assay the expression of the target genes or proteins. Thirty C57BL/6J male mice were given high-fat diet with streptozotocin injection to induce diabetes and then were randomized into three groups ( n  = 10): vehicle administration (DM group), 2 mg/kg kirenol (DM + kirenol group) and 200 mg/kg metformin (Met group) for 3 months, orally. A healthy group (Con, n  = 10) was included as the control.
      Results: Compared to the DM group, kirenol treatment decreased the phosphorylation of Smad2/3 and NF-κB (0.64- and 0.43-fold) as well as the accumulation of FN and Col IV (0.58- and 0.35-fold); moreover, the expression of IκBα was restored to normal level by kirenol treatment both in vivo and in vitro . After kirenol treatment, IL-6 expression was decreased 0.35- and 0.57-fold, and TNF-α expression was decreased 0.34- and 0.46-fold, in vitro and in vivo , respectively. Furthermore, kirenol alleviated the glomerular basement membrane thickness and foot process fusion.
      Discussion and Conclusions: Kirenol could alleviate DN by downregulating the TGF-β/Smads and the NF-κB signal pathway. Our study provides a potential mechanism for the treatment of DN with kirenol.
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    • Contributed Indexing:
      Keywords: IL-6; TNF-α; collagen IV; fibronectin; mesangial cells
    • Accession Number:
      0 (Diterpenes)
      0 (NF-kappa B)
      0 (Transforming Growth Factor beta)
      0 (Transforming Growth Factor beta1)
      0 (kirenol)
    • Publication Date:
      Date Created: 20220908 Date Completed: 20220912 Latest Revision: 20220914
    • Publication Date:
      20231215
    • Accession Number:
      PMC9467559
    • Accession Number:
      10.1080/13880209.2022.2112239
    • Accession Number:
      36073930