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Background <p>Diabetic nephropathy (DN), a major diabetic microvascular complication, is the primary cause of end-stage renal disease worldwide. It is characterized by mesangial cell fibrosis and chronic inflammation, which current treatments cannot completely reverse. Baicalein, a major flavonoid from Scutellaria baicalensis Georgi, has anti-inflammatory and antifibrotic activities, but its role and mechanism in high glucose (HG)-induced mesangial cell injury (a key DN feature) remain unclear.</p> Objective <p>This study investigated baicalein’s effects on rat glomerular mesangial cells (HBZY-1) and validated key findings in human primary glomerular mesangial cells.</p> Methods <p>CCK-8 assay identified 10–20&#xa0;μM as baicalein’s non-cytotoxic range (cell viability ≥ 90%).</p> Results <p>Further experiments demonstrated that baicalein dose-dependently inhibited HG-induced increases in fibrotic markers (α-SMA, FN, COL1A1) at both mRNA (qRT-PCR) and protein levels (Western blot, immunofluorescence), and reduced proinflammatory cytokines (IL-6, TNF-α, MCP-1) at transcriptional (qRT-PCR) and secretory levels (ELISA). Western blot analysis demonstrated that baicalein dose-dependently activated the AMPK pathway by increasing p-AMPK/AMPK at Thr172 and inhibited the TGF-β/Smad pathway by reducing TGF-β1 and p-Smad2/3/Smad2/3. Using the AMPK inhibitor Compound C, we confirmed baicalein’s anti-fibrotic, anti-inflammatory, and TGF-β/Smad-inhibitory effects were closely associated with AMPK activity. Molecular docking showed baicalein stably bound the AMPK β-subunit’s C-terminal domain (PDB ID: 4EAK), suggesting a potential interaction that may contribute to AMPK activation.</p> Conclusion <p>Baicalein protects against HG-induced mesangial cell injury via an AMPK-associated mechanism linked to the suppression of fibrosis and inflammation, highlighting it as a promising DN therapeutic candidate for further preclinical and clinical study.</p>

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Baicalein alleviates high glucose-induced mesangial cell fibrosis and inflammation in diabetic nephropathy: roles of AMPK activation and TGF-β1 inhibition

  • 期刊论文

  • 发表日期：

    2026年7月1日

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  • Hongtao Tan,
  • Yingshan Li,
  • Yicong Li,
  • Junxian Chen,
  • Weiwei Yuan

摘要

Background

Diabetic nephropathy (DN), a major diabetic microvascular complication, is the primary cause of end-stage renal disease worldwide. It is characterized by mesangial cell fibrosis and chronic inflammation, which current treatments cannot completely reverse. Baicalein, a major flavonoid from Scutellaria baicalensis Georgi, has anti-inflammatory and antifibrotic activities, but its role and mechanism in high glucose (HG)-induced mesangial cell injury (a key DN feature) remain unclear.

Objective

This study investigated baicalein’s effects on rat glomerular mesangial cells (HBZY-1) and validated key findings in human primary glomerular mesangial cells.

Methods

CCK-8 assay identified 10–20 μM as baicalein’s non-cytotoxic range (cell viability ≥ 90%).

Results

Further experiments demonstrated that baicalein dose-dependently inhibited HG-induced increases in fibrotic markers (α-SMA, FN, COL1A1) at both mRNA (qRT-PCR) and protein levels (Western blot, immunofluorescence), and reduced proinflammatory cytokines (IL-6, TNF-α, MCP-1) at transcriptional (qRT-PCR) and secretory levels (ELISA). Western blot analysis demonstrated that baicalein dose-dependently activated the AMPK pathway by increasing p-AMPK/AMPK at Thr172 and inhibited the TGF-β/Smad pathway by reducing TGF-β1 and p-Smad2/3/Smad2/3. Using the AMPK inhibitor Compound C, we confirmed baicalein’s anti-fibrotic, anti-inflammatory, and TGF-β/Smad-inhibitory effects were closely associated with AMPK activity. Molecular docking showed baicalein stably bound the AMPK β-subunit’s C-terminal domain (PDB ID: 4EAK), suggesting a potential interaction that may contribute to AMPK activation.

Conclusion

Baicalein protects against HG-induced mesangial cell injury via an AMPK-associated mechanism linked to the suppression of fibrosis and inflammation, highlighting it as a promising DN therapeutic candidate for further preclinical and clinical study.