2. Academic Validation
  3. The role and mechanism of asiaticoside in regulating smooth muscle cell mitochondrial Drp1 during neointimal hyperplasia and atherosclerosis

The role and mechanism of asiaticoside in regulating smooth muscle cell mitochondrial Drp1 during neointimal hyperplasia and atherosclerosis

  • Biochem Biophys Res Commun. 2026 Jan 8:795:153102. doi: 10.1016/j.bbrc.2025.153102.
Mingyu Liu 1,  Lu Wang 2,  Lina Wang 3,  Tao Yang 4,  Fei Xiang 4,  Junyao Lu 2,  Sixuan Chen 2,  Hui Li 2,  Yaxin He 2,  Wei Wang 5,  Shuyuan Guo 6,  Yuanyuan Guo 7
Affiliations

Affiliations

  • 1 Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China; The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, the First Affiliated Hospital, Harbin Medical University, Harbin 150088, China.
  • 2 The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, the First Affiliated Hospital, Harbin Medical University, Harbin 150088, China.
  • 3 Department of Geriatrics, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
  • 4 Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China.
  • 5 Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China; The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, the First Affiliated Hospital, Harbin Medical University, Harbin 150088, China. Electronic address: [email protected].
  • 6 Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China; The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, the First Affiliated Hospital, Harbin Medical University, Harbin 150088, China. Electronic address: [email protected].
  • 7 Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China; Department of Geriatrics, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China. Electronic address: [email protected].
PMID: 41371186 DOI: 10.1016/j.bbrc.2025.153102
Abstract

Early atherosclerosis is characterized by aberrant proliferation and migration of vascular smooth muscle cells (VSMCs). Asiaticoside (ASI), the primary bioactive constituent of Centella asiatica, has been demonstrated to possess anti-inflammatory and antioxidant properties. However, its mechanisms of action regarding VSMC proliferation and migration remain incompletely understood. Here, we demonstrate that asiaticoside inhibits platelet-derived growth factor-BB (PDGF-BB)-induced proliferation, migration, and phenotypic switching of VSMCs by regulating dynamin-related protein 1 (Drp1). In vivo, oral administration of asiaticoside (50 mg/kg) reduced lipid plaque deposition in atherosclerotic mice and attenuated neointimal hyperplasia in Sprague-Dawley (SD) rats. In vitro, treatment with asiaticoside (100 μM) significantly suppressed PDGF-BB-induced VSMC proliferation and migration. Western blot and quantitative polymerase chain reaction (qPCR) analyses showed that the expression of proliferation markers (Cyclin D1 and proliferating cell nuclear antigen [PCNA]) and migration markers (matrix metalloproteinase-9 [MMP9] and matrix metalloproteinase-2 [MMP2]) was markedly downregulated. Mechanistically, PDGF-BB stimulation upregulated mitochondrial Drp1 expression and promoted its translocation to mitochondria, resulting in mitochondrial fragmentation and dysfunction. Asiaticoside treatment effectively reversed these effects and preserved mitochondrial integrity. Furthermore, we preliminarily found that asiaticoside activates the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Thus, we propose that asiaticoside may inhibit VSMC proliferation, migration, and phenotypic switching via the AMPK/Drp1 axis. Our study highlights the potential therapeutic value of asiaticoside in the prevention and treatment of atherosclerosis and vascular restenosis.

Keywords

Asiaticoside; Atherosclerosis; Drp1; Neointimal hyperplasia; VSMCs.

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