1. Natural flavonoid pectolinarigenin alleviated kidney fibrosis via inhibiting the activation of TGFβ/SMAD3 and JAK2/STAT3 signaling.
- Author
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Li, Yanfen, Guo, Fan, Huang, Rongshuang, Ma, Liang, and Fu, Ping
- Subjects
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RENAL fibrosis , *URETERIC obstruction , *PROTEIN expression , *KIDNEY physiology , *NATURAL products , *FLAVONOIDS , *LUCIFERASES - Abstract
• Pectolinarigenin exhibited antifibrotic activity in TGFβ1-induced fibroblasts. • Pectolinarigenin alleviated kidney fibrosis in mice after UUO surgery. • Pectolinarigenin suppressed SMAD3 phosphorylation in kidneys of UUO mice. • Pectolinarigenin inhibited STAT3 activation in kidneys of UUO mice. Renal fibrosis is a final common manifestation of CKD resulting in progressive loss of kidney function. The activation of SMAD3 and STAT3 played central roles in the pathogenesis of renal fibrosis, which has been recognized as potential targets for antifibrotic therapy. As we known, the potential of natural products as the candidates for drug discovery has been well recognized. Here, we identified that pectolinarigenin (PEC), as a natural flavonoid and a reported STAT3 inhibitor, dose-dependently suppressed TGFβ/SMADs activity in HEK293 cells by luciferase reporter assay. In TGFβ1-stimulated NRK-49F fibroblast, PEC blocked the phosphorylation of SMAD3 and STAT3, and downregulated the major fibrotic gene and protein expression of TGFβ, α-SMA, COL-1, and FN. Notably, oral administration of PEC at a dose of 25 mg/kg/d for 7 days or 14 days effectively ameliorated kidney injury and tubulointerstitial fibrosis after unilateral ureteral obstruction (UUO) surgery in mice. Mechanically, PEC treatment inhibited the phosphorylated activation of SMAD3 and STAT3, which further reduced the protein expression of TGFβ, α-SMA, COL-1, and FN in the obstructed kidneys of UUO mice. In summary, our results suggested that pectolinarigenin alleviated tubulointerstitial fibrosis by inhibiting the activation of SMAD3 and STAT3 signaling. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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