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

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.

Effects of clopidogrel on inflammatory cytokines and adhesion molecules in human endothelial cells: Role of nitric oxide mediating pleiotropic effects

“…In this context, no modification of sICAM‐1 concentration has been reported recently for patients with vascular disease . Clopidogrel was also associated with reduced serum sICAM‐1 in a model of rats with coronary microembolization . For the first time, we found that clopidogrel reduces ICAM‐1 expression in the surface of endothelial cells induced by TNF‐α and that this reduction is dependent on NO bioavailability.…”

“…25 Clopidogrel was also associated with reduced serum sICAM-1 in a model of rats with coronary microembolization. 28 For the first time, we found that clopidogrel reduces ICAM-1 expression in the surface of endothelial cells induced by TNFα and that this reduction is dependent on NO bioavailability. A recent work also using an in vitro model of endothelial cells, particularly human aortic endothelial cells (HAECs), showed that clopidogrel also reduced the surface expression of the vascular cellular adhesion molecule (VCAM-1).…”

Ligustrazine Exerts Cardioprotection in Animal Models of Myocardial Ischemia/Reperfusion Injury: Preclinical Evidence and Possible Mechanisms

“…Then, we removed 9 studies in which data of result is not available. Finally, 25 eligible studies (Xu et al, 1997 ; Wan et al, 1998 ; Liang et al, 1999 , 2000 ; Duan et al, 2000 ; Zhang et al, 2003 , 2007 , 2015 , 2016 ; Wang et al, 2005 ; Li et al, 2006 ; Xu and Zhang, 2006 ; Chen et al, 2007 ; Tang et al, 2007 ; Yang and Rui, 2007 ; Hu et al, 2008 ; Shang et al, 2008 ; Yang et al, 2008 ; Gu et al, 2009 ; Li and Li, 2010 ; Liu and Niu, 2011 ; Zhai et al, 2011 ; Lv et al, 2012 , 2016 ; Zhao et al, 2012 ) were included in qualitative analysis (Figure 2 ).…”

“…Twenty-two studies (Xu et al, 1997 ; Wan et al, 1998 ; Liang et al, 1999 , 2000 ; Duan et al, 2000 ; Zhang et al, 2003 , 2007 ; Wang et al, 2005 ; Li et al, 2006 ; Xu and Zhang, 2006 ; Chen et al, 2007 ; Tang et al, 2007 ; Yang and Rui, 2007 ; Hu et al, 2008 ; Shang et al, 2008 ; Yang et al, 2008 ; Gu et al, 2009 ; Li and Li, 2010 ; Liu and Niu, 2011 ; Zhai et al, 2011 ; Zhao et al, 2012 ; Lv et al, 2016 ) were published in Chinese, and 3 studies (Lv et al, 2012 ; Zhang et al, 2015 , 2016 ) were published in English between 1997 and 2016. Male/female Sprague Dawley rats were used in 11 studies (Duan et al, 2000 ; Li et al, 2006 ; Chen et al, 2007 ; Yang et al, 2008 ; Gu et al, 2009 ; Li and Li, 2010 ; Liu and Niu, 2011 ; Lv et al, 2012 , 2016 ; Zhao et al, 2012 ; Zhang et al, 2015 , 2016 ), male/female Wistar rats in 7 studies (Wan et al, 1998 ; Liang et al, 1999 ; Xu and Zhang, 2006 ; Zhang et al, 2007 ; Hu et al, 2008 ; Shang et al, 2008 ; Zhai et al, 2011 ), male/female Kunming mice in 1 study (Li et al, 2006 ), and male/female rabbits in 6 studies (Xu et al, 1997 ; Liang et al, 2000 ; Zhang et al, 2003 ; Wang et al, 2005 ; Tang et al, 2007 ; Yang and Rui, 2007 ). To induce anesthesia, 2 studies (Zhang et al, 2007 ; Zhai et al, 2011 ) used chloral hydrate; 1 study (Zhang et al, 2015 ) used sevoflurane; 8 studies (Li...…”

Comparative effectiveness of different antiplatelet agents at reducing TNF‐driven inflammatory responses in a mouse model

“…Many studies have demonstrated that sarpogrelate and clopidogrel decrease the LPS‐induced increase in TNF in rat serum and lymphocyte infiltration through histological analysis . Clopidogrel reduced serum TNF and IL‐1β release in rats with coronary microembolization and experimental LPS‐induced mouse model . Sarpogrelate decreased immune cell infiltration and NOS2 and TNF expression in diabetic mice.…”