Table 4.

Summary of the findings of preclinical studies that investigated the inotropic effects of Berberis vulgaris extracts

Study ID	Active constituent	Study Design/ Animal model	Findings
Zhang et al 2011 (50)	Berbamine	Rats (in vitro)	Berbamine increased myocardial contractility by increasing intracellular Ca+2concentrations. It also enhanced myofilament Ca+2 sensitivity by increasing cytosolic protein kinase C (PKCɛ)
Zeng and Li 2001 (36)	Berberine	Human trials	Berberine reduced the frequency of ventricular premature complexes and increased the left ventricular ejection fraction (EF) in patients with congestive heart failure
Hu et al 1992 (52)	Berbamine compound E6	Rats (in vitro)	Berbamine compound E6 inhibited calmodulin-dependent myosin light chain kinase (MLCK) in a dose-dependent manner, an effect which was antagonized by the addition of more calmodulin. This suggests that berbamine has an inotropic effect by competitive antagonism with calmodulin
Xu 1986 (51)	O-(4-ethoxyl-butyl) berbamine (EBB)	Human trial	EBB had a more potent calmodulin antagonist activity than berbamine. This antagonism is competitive because it can be reversed by adding higher doses of calmodulin