Isoquinoline Alkaloids and Indole Alkaloids Attenuate Aortic Atherosclerosis in Apolipoprotein E Deficient Mice: A Systematic Review and Meta-Analysis.

Several studies have attempted to relate the bioactive alkaloid with atherosclerotic cardiovascular diseases prevention in animal models, providing inconsistent results. Moreover, the direct anti-atherosclerotic effects of alkaloid have hardly been studied in patients. Therefore, the aim of this systematic review was to assess the reported effects of alkaloids on aortic atherosclerosis in ApoE mouse models. : Pubmed and Embase were searched to identify studies which estimated the effect of isolated alkaloids on atherosclerosis in apolipoprotein E deficient mice. Study quality was assessed using SYRCLE's risk of bias tool. We conducted a meta-analysis across 14 studies using a random-effect model to determine the overall effect of the alkaloids, and performed subgroup analyses to compare the effects of the isoquinolone alkaloids and indole alkaloids. The quality of the included studies was low in the majority of included studies. We clarified that alkaloid administration was significantly associated with reduced aortic atherosclerotic lesion area (SMD -3.19, 95% CI -3.88, -2.51). It is important to remark that the experimental characteristics of studies were quite diverse, and the methodological variability could also contribute to heterogeneity. Subgroup analyses suggested that the isoquinoline alkaloids (SMD -4.19, 95% CI -5.18, -3.20), and the indole alkaloids (SMD -2.73, 95% CI -3.56, -1.90) obviously decreased atherosclerotic burden. Isoquinoline alkaloids and indole alkaloids appear to have a direct anti-atherosclerotic effect in ApoE mice. Besides the limitations of animal modal studies, this systematic review could provide an important reference for future preclinical animal trials of good quality and clinical development.