Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Apr;37(4):463-72.
doi: 10.1038/aps.2015.147. Epub 2016 Feb 29.

Pretreatment with a combination of ligustrazine and berberine improves cardiac function in rats with coronary microembolization

Ying Zhang  1   2   3 , Xiao-juan Ma  2   3 , Chun-yu Guo  4 , Ming-ming Wang  2   3 , Na Kou  1   2   3 , Hua Qu  1   2   3 , Hui-min Mao  1   2   3 , Da-zhuo Shi  2   3
Affiliations

Pretreatment with a combination of ligustrazine and berberine improves cardiac function in rats with coronary microembolization

Ying Zhang et al. Acta Pharmacol Sin. 2016 Apr.

Abstract

Aim: We have shown that a combination of ligustrazine and berberine produces more effective inhibition on platelet activation and inflammatory reactions in rat acute myocardial infarction compared with either agent alone. In this study we evaluated the beneficial effects of a combination of ligustrazine and berberine in a rat model of coronary microembolization (CME).

Methods: SD rats were treated with ligustrazine, berberine, ligustrazine+berberine, or clopidogrel for 2 weeks. When the treatment completed, CME was induced by injection of sodium laurate into the left ventricular, while obstructing the ascending aorta. All rats were intubated for hemodynamic measurements. Blood samples were collected for biochemical analyses, flow cytometry, and ELISAs. Heart tissues were isolated for histopathology and subsequent protein analyses.

Results: Pretreatment with the combination of ligustrazine (27 mg·kg(-1)·d(-1)) and berberine (90 mg·kg(-1)·d(-1)) significantly improved cardiac function, and decreased myocardial necrosis, inflammatory cell infiltration, microthrombosis and serum CK-MB levels in CME rats. In addition, this combination significantly decreased plasma ET-1 levels and von Willebrand factor, inhibited ADP-induced platelet activation, and reduced TNFα, IL-1β, ICAM-1 and RANTES levels in serum and heart tissues. The protective effects of this combination were more prominent than those of ligustrazine or berberine alone, but comparable to those of a positive control clopidogrel (6.75 mg·kg(-1)·d(-1)).

Conclusion: The combination of ligustrazine and berberine significantly improved cardiac function in rat CME model via a mechanism involving antiplatelet and anti-inflammatory effects.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Visualization of inflammatory cellular infiltrates (red arrows) by hematoxylin and eosin staining (×200; bar=100 μm). Rat heart tissue sections are shown from the sham (A), coronary microembolization (CME) model (B), ligustrazine (C), berberine (D), L+B (E), clopidogrel treatment groups (F). L, Ligustrazine; B, Berberine.
Figure 2
Figure 2
In situ coronary microthrombi were visualized by Carstairs staining. Rat heart tissue sections are shown from the: coronary microembolization (CME) model (A) and sham treatment (B) groups. Multiple arteriolar thrombi (arrow heads) were detected in the CME model group, but not in the sham group. (×200; bar=100 μm).
Figure 3
Figure 3
Myocardial necrosis (red arrows) was visualized by Heidenhain staining. Rat heart tissue sections are shown from the the sham (A), coronary microembolization (CME) model (B), ligustrazine (C), berberine (D), L+B (E), clopidogrel treatment groups (F). L, Ligustrazine; B, Berberine. Necrotic myocardium was stained brown to black. (×200; bar=100 μm).
Figure 4
Figure 4
Plasma levels of von Willebrand factor (vWF) and endothelin-1 (ET-1) after ligustrazine and berberine treatment. Data are expressed as mean±SEM. n=6. bP<0.05 vs sham. eP<0.05 vs coronary micro-embolization (CME) model.
Figure 5
Figure 5
Effect of treatment with ligustrazine and berberine (L+B) on platelet activation. Data are expressed as mean±SEM. n=6. bP<0.05 vs sham. eP<0.05 vs coronary microembolization (CME) model.
Figure 6
Figure 6
Effect of treatment with ligustrazine and berberine (L+B) on serum inflammatory mediators. Data are expressed as mean±SEM. n=6. bP<0.05 vs sham. eP<0.05 vs coronary microembolization (CME) model. hP<0.05 vs ligustrazine or berberine alone.
Figure 7
Figure 7
Western blot images of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, intracellular adhesion molecule-1 (ICAM-1), and regulated on activation, normal T cell-expressed and secreted (RANTES) protein levels in myocardial cells. Densitometric data are expressed as mean±SEM. n=6. bP<0.05 vs sham. eP<0.05 vs coronary microembolization (CME) model. hP<0.05 vs ligustrazine or berberine alone.
See this image and copyright information in PMC

References

    1. Erbel R, Heusch G. Coronary microembolization. J Am Coll Cardiol 2000; 36: 22–4. - PubMed
    1. Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med 2007; 356: 830–40. - PubMed
    1. Gulati M, Cooper-DeHoff RM, McClure C, Johnson BD, Shaw LJ, Handberg EM, et al. Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women's Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project. Arch Intern Med 2009; 169: 843–50. - PMC - PubMed
    1. Davì G, Patrono C. Platelet activation and atherothrombosis. New Engl J Med 2007; 357: 2482–94. - PubMed
    1. Wang H, Zhong WJ, Huang MW, Wu XY Chen H. Efficacy of dual antiplatelet therapy combined with Naoxintong capsules following coronary microembolization induced by homologous microthrombi in rats. Chin J Integr Med 2011; 17: 917–24. - PubMed

Publication types