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<p>Renal fibrosis, a mutual pathological manifestation of chronic kidney disease (CKD), currently has limited therapeutic options. Honokiol (HKL), a polyphenolic compound isolated from <i>Magnolia officinalis</i>, has demonstrated anti-fibrotic effects; however, its molecular mechanisms remain incompletely characterized. The anti-fibrotic effect of HKL was investigated using the unilateral ureteral obstruction (UUO) mouse framework <i>in vivo</i> and transforming growth factor-β1 (TGF-β1)-stimulated HK2 cells <i>in vitro</i>, followed by HKL treatment and assessed by fibrosis markers and signalling axis. Conditional Sirtuin 3 (SIRT3) knockout (cKO) mice and SIRT3 siRNA-transfected HK2 cells were utilised to investigate the function of SIRT3 in mediating HKL’s anti-fibrotic impacts. HKL significantly attenuated renal fibrosis, reducing the deposition of extracellular matrix (ECM) and reversing epithelial-mesenchymal transition. Mechanistically, HKL-activated SIRT3 downregulated Wnt/β-catenin signaling axis, evidenced by decreased nuclear β-catenin accumulation and a subsequent reduction in transcriptional activity, which refers to the activation of fibrosis-related genetic factors like Collagen I, Fibronectin, and α-SMA upon β-catenin binding to TCF/LEF transcription factors. SIRT3 deficiency restored Wnt/β-catenin signaling axis activation and eliminated anti-fibrotic impacts of HKL. HKL mitigates renal fibrosis via SIRT3-mediated suppression of Wnt/β-catenin signaling, proposing a novel targeted therapeutic strategy for CKD-associated fibrosis.</p>

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Honokiol attenuates renal fibrosis via SIRT3-Mediated regulation of Wnt/β-Catenin signaling

  • 期刊论文

  • 发表日期：

    2026年2月10日

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  • Zihao Guo,
  • Jing Wang,
  • Xing Li,
  • Xiang Ren,
  • Yisheng Yin,
  • Yiqun Tian,
  • Zhenliang Qin,
  • Kun Yuan,
  • Xiaoyong Zeng

摘要

Renal fibrosis, a mutual pathological manifestation of chronic kidney disease (CKD), currently has limited therapeutic options. Honokiol (HKL), a polyphenolic compound isolated from Magnolia officinalis, has demonstrated anti-fibrotic effects; however, its molecular mechanisms remain incompletely characterized. The anti-fibrotic effect of HKL was investigated using the unilateral ureteral obstruction (UUO) mouse framework in vivo and transforming growth factor-β1 (TGF-β1)-stimulated HK2 cells in vitro, followed by HKL treatment and assessed by fibrosis markers and signalling axis. Conditional Sirtuin 3 (SIRT3) knockout (cKO) mice and SIRT3 siRNA-transfected HK2 cells were utilised to investigate the function of SIRT3 in mediating HKL’s anti-fibrotic impacts. HKL significantly attenuated renal fibrosis, reducing the deposition of extracellular matrix (ECM) and reversing epithelial-mesenchymal transition. Mechanistically, HKL-activated SIRT3 downregulated Wnt/β-catenin signaling axis, evidenced by decreased nuclear β-catenin accumulation and a subsequent reduction in transcriptional activity, which refers to the activation of fibrosis-related genetic factors like Collagen I, Fibronectin, and α-SMA upon β-catenin binding to TCF/LEF transcription factors. SIRT3 deficiency restored Wnt/β-catenin signaling axis activation and eliminated anti-fibrotic impacts of HKL. HKL mitigates renal fibrosis via SIRT3-mediated suppression of Wnt/β-catenin signaling, proposing a novel targeted therapeutic strategy for CKD-associated fibrosis.