Tanshinone IIA inhibits foam cell formation and alleviates atherosclerosis by regulating the Hedgehog signaling pathway through TRPM2 suppression

  • Sci Rep. 2026 May 18;16(1):22440. doi: 10.1038/s41598-026-51659-9.
Yajuan Yin  #  1 ,  Xiaocui Shi  #  2 ,  Wenyun Tan  #  3 ,  Xiao Zhang  2 ,  Xiufang Jiang  4  5 ,  Mei Liu  2 ,  Jianan Xu  2 ,  Da Liu  2 ,  Le Wang  2 ,  Mei Wei  2 ,  Gang Liu  2  5  6  7  8 ,  Fangfang Ma  9 ,  Mingqi Zheng  10  11  12  13  14
Affiliations
  • 1. Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
  • 2. Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
  • 3. Department of Emergency, The First Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
  • 4. Department of Medical Affairs, The First Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
  • 5. Hebei Key Laboratory of Cardiac Injury Repair Mechanism Study, Shijiazhuang, 050000, Hebei, China.
  • 6. Hebei Key Laboratory of Heart and Metabolism, Shijiazhuang, 050000, Hebei, China.
  • 7. Hebei Engineering Research Center of Intelligent Medical Clinical Application, Shijiazhuang, 050000, Hebei, China.
  • 8. Hebei International Joint Research Center for Structural Heart Disease, Shijiazhuang, 050000, Hebei, China.
  • 9. Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China. [email protected].
  • 10. Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China. [email protected].
  • 11. Hebei Key Laboratory of Cardiac Injury Repair Mechanism Study, Shijiazhuang, 050000, Hebei, China. [email protected].
  • 12. Hebei Key Laboratory of Heart and Metabolism, Shijiazhuang, 050000, Hebei, China. [email protected].
  • 13. Hebei Engineering Research Center of Intelligent Medical Clinical Application, Shijiazhuang, 050000, Hebei, China. [email protected].
  • 14. Hebei International Joint Research Center for Structural Heart Disease, Shijiazhuang, 050000, Hebei, China. [email protected].
  • # Contributed equally.
PMID: 42151241 DOI: 10.1038/s41598-026-51659-9
Abstract

The development of foam cells is crucial in the advancement of atherosclerosis (AS). Tanshinone IIA (Tan IIA), the primary lipophilic component of Salvia miltiorrhiza, has various pharmacological effects. Despite this, the precise role of Tan IIA in AS has not been fully elucidated. In this research, we employed apoE-/- mice to establish an AS model. Oil Red O and HE staining indicated that Tan IIA obviously reduced plaque areas in both the aorta and aortic arch. Additionally, serum analysis revealed that Tan IIA notably decreased lipid and inflammatory factor levels in AS mice. In vitro studies showed that Tan IIA primarily prevented foam cell formation by enhancing Cholesterol efflux rather than increasing lipid uptake. Mechanistic investigations reveal that Tan IIA suppresses the Hedgehog (Hh) signaling pathway by downregulating the expression of transient receptor potential melastatin 2 (TRPM2) and subsequently inhibiting Ca²⁺ influx. This cascade ultimately attenuates foam cell formation and impedes the progression of AS. Overall, this research provides a solid theoretical foundation for the potential application of Tan IIA in the treatment of AS.

Keywords
Atherosclerosis; Foam cell formation; Hedgehog signaling pathway; TRPM2; Tanshinone IIA.
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