The role and mechanism of tetramethylpyrazine for atherosclerosis in animal models: A systematic review and meta-analysis

PLoS One. 2022 May 2;17(5):e0267968. doi: 10.1371/journal.pone.0267968. eCollection 2022.


Background: Atherosclerosis(AS) is widely recognized as a risk factor for incident cardiovascular and cerebrovascular diseases. Tetramethylpyrazine (TMP) is the active ingredient of Ligusticum wallichii that possesses a variety of biological activities against atherosclerosis.

Objective: This systematic review and meta-analysis sought to study the impact of and mechanism of tetramethylpyrazine for atherosclerosis in animal models.

Methods: A systematic search was conducted of PubMed, Embase, Cochrane Library, Web of Science database, Chinese Biomedical (CBM) database, China National Knowledge Infrastructure (CNKI), WanFang data, and Vip Journal Integration Platform, covering the period from the respective start date of each database to December 2021. We used SYRCLE's 10-item checklist and Rev-Man 5.3 software to analyze the data and the risk of bias.

Results: Twelve studies, including 258 animals, met the inclusion criteria. Compared with the control group, TMP significantly reduced aortic atherosclerotic lesion area, and induced significant decreases in levels of TC (SMD = -2.67, 95% CI -3.68 to -1.67, P < 0.00001), TG (SMD = -2.43, 95% CI -3.39 to -1.47, P < 0.00001), and LDL-C (SMD = -2.87, 95% CI -4.16 to -1.58, P < 0.00001), as well as increasing HDL-C (SMD = 2.04, 95% CI 1.05 to 3.03, P = 0.001). TMP also significantly modulated plasma inflammatory responses and biological signals associated with atherosclerosis. In subgroup analysis, the groups of high-dose TMP (≥50 mg/kg) showed better results than those of the control group. No difference between various durations of treatment groups or various assessing location groups.

Conclusion: TMP exerts anti-atherosclerosis functions in an animal model of AS mediated by anti-inflammatory action, antioxidant action, ameliorating lipid metabolism disorder, protection of endothelial function, antiplatelet activity, reducing the proliferation and migration of smooth muscle cells, inhibition of angiogenesis, antiplatelet aggregation. Due to the limitations of the quantity and quality of current studies, the above conclusions need to be verified by more high-quality studies.

Trial registration number: PROSPERO registration no.CRD42021288874.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aortic Diseases*
  • Atherosclerosis* / pathology
  • Disease Models, Animal
  • Humans
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use


  • Pyrazines
  • tetramethylpyrazine

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (NSFC. 82074200, 81873117). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.