Novel treatment from a botanical formulation Si-Miao-Yong-an decoction inhibits vasa vasorum angiogenesis and stabilizes atherosclerosis plaques via the Wnt1/β-catenin signalling pathway

Pharm Biol. 2023 Dec;61(1):1364-1373. doi: 10.1080/13880209.2023.2249061.


Context: Si-Miao-Yong-An (SMYA) has been widely used for the clinical treatment of atherosclerosis (AS). Yet, its complete mechanism of action is not fully understood.

Objective: To investigate the mechanism by which SMYA stabilizes AS plaques from the perspective of inhibiting vasa vasorum (VV) angiogenesis.

Materials and methods: We used male ApoE-/- mice to establish an AS model. The mice were divided into model, SMYA (11.7 mg/kg/d), and simvastatin (SVTT) (2.6 mg/kg/d) groups. Mice were given SMYA or SVTT by daily gavage for 8 weeks. HE staining, immunofluorescence double-labelling staining, and immunohistochemical staining were used to observe the pathological changes in the plaques. Finally, the protein and mRNA expression levels of the Wnt1/β-catenin signalling pathway were detected by Western blot and qRT-PCR, respectively.

Results: SMYA significantly attenuated cholesterol crystallization, and lipid accumulation in AS plaques, resulting in smaller plaque size (0.25 mm2 vs. 0.46 mm2), and lowering ratio of plaque to lumen area (20.04% vs. 38.33%) and VV density (50.64/mm2 vs. 98.02/mm2). Meanwhile, SMYA suppressed both the positive area percentage of Wnt1 (2.53 vs. 3.56), β-catenin (3.33 vs. 5.65) and Cyclin D1 (2.10 vs. 3.27) proteins in the aortic root plaques, and mRNA expression of Wnt1 (1.38 vs. 2.09), β-catenin (2.05 vs. 3.25) and Cyclin D1 (1.39 vs. 2.57).

Discussion and conclusions: SMYA has a protective effect against AS, which may be related to its anti-VV angiogenesis in plaques, suggesting that SMYA has the potential as a novel botanical formulation in the treatment of AS.

Keywords: Chinese medicine preparation; endothelial cell proliferation; intraplaque neovascularization; vulnerable plaque.

MeSH terms

  • Animals
  • Atherosclerosis* / drug therapy
  • Cyclin D1
  • Male
  • Mice
  • RNA, Messenger
  • Vasa Vasorum
  • Wnt Signaling Pathway*
  • beta Catenin


  • beta Catenin
  • Cyclin D1
  • RNA, Messenger
  • si-miao-yong-an decoction

Grants and funding

This research was funded by QI HUANG Scholars (Junping Zhang) Special Funding (National Traditional Chinese Medicine People’s Education Letter [2022] No.6), Tianjin Famous Traditional Chinese Medicine (Junping Zhang) Inheritance Studio Special Funding (Jin Wei Zhong [2020] No.732) and National Natural Science Foundation of China (grant number 81774232).