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Tanshinone IIA Alleviates Pyroptosis through SIRT1/NLRP3 Pathway to Improve Diabetic Nephropathy

Wencong Tian1, Peng Song1, Junhao Zang2

  • 1Department of General Surgery, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Nankai University Tianjin 300122, P. R. China.

The American Journal of Chinese Medicine
|January 25, 2026
PubMed

Insights

Tanshinone IIA (Tan IIA) effectively treats diabetic nephropathy (DN) by inhibiting pyroptosis, a cell death pathway. This protection involves the SIRT1/NLRP3 pathway, offering a new therapeutic strategy for DN.

Area of Science:

  • Nephrology
  • Pharmacology
  • Molecular Biology

Background:

  • Diabetic nephropathy (DN) is a severe diabetes complication with limited treatment options.
  • Pyroptosis, a pro-inflammatory cell death, contributes to DN progression.
  • Tanshinone IIA (Tan IIA), from *S. miltiorrhiza*, has anti-inflammatory and antioxidant effects, but its role in DN pyroptosis is unknown.

Purpose of the Study:

  • To investigate the effect of Tan IIA on pyroptosis in diabetic nephropathy.
  • To elucidate the molecular mechanisms underlying Tan IIA's action in DN.

Main Methods:

  • A diabetic nephropathy (DN) mouse model was induced using streptozotocin (STZ).
  • Mice received Tan IIA treatment via gavage for 10 weeks.
  • Key protein expressions (caspase-1, GSDMD, SIRT1, NLRP3) were analyzed in renal tissues and HK-2 cells.

Main Results:

  • Tan IIA significantly inhibited caspase-1 and gasdermin D (GSDMD)-mediated pyroptosis, alleviating renal injury in DN mice.
  • Tan IIA treatment increased silent information regulator 1 (SIRT1) expression and decreased NLR family pyrin domain containing 3 (NLRP3) expression.
  • SIRT1 suppression abolished the protective effects of Tan IIA against DN and its inhibition of pyroptosis.

Conclusions:

  • Tan IIA demonstrates protective effects against diabetic nephropathy.
  • Tan IIA inhibits pyroptosis via the SIRT1/NLRP3 pathway, suggesting a novel therapeutic mechanism for DN.
Keywords:
Diabetic NephropathyPyroptosisS. miltiorrhiza BungeSIRT1Tanshinone IIA

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