Abstract
Background: 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.Methods: 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.Results: 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.Conclusion: 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.
Highlights
Atherosclerosis is one of the major causes for cardiovascular diseases including coronary heart disease (CHD), the leading cause of morbidity and mortality worldwide could be generally the cardiovascular disorders and CHD alone (Mozaffarian et al, 2016)
The alkaloids treatment performed on ApoE−/− mice reported consistent findings that were confirmed by the present metaanalysis
Based on the coherent results, isoquinoline alkaloids, and indole alkaloids could potentially have a therapeutic effect on atherosclerosis
Summary
Atherosclerosis is one of the major causes for cardiovascular diseases including coronary heart disease (CHD), the leading cause of morbidity and mortality worldwide could be generally the cardiovascular disorders and CHD alone (Mozaffarian et al, 2016). Identifying novel therapeutic strategies for more effective prevention and treatment in atherosclerosis, remains a topic of interest (Ford et al, 2018). Alkaloid has received emerging interest from pharmacologists and health practitioners with its multi therapeutic effects, including hypocholesteremic capacity, antiinflammatory, anti-oxidative, and anti-atherosclerotic properties (Jun et al, 2016). Extensive studies in animal models of hyperlipidaemia have supported the beneficial effects of natural alkaloid to delay atherosclerotic progression. The relatively therapeutic effects of natural alkaloids have not been confirmed in patients. Several studies have attempted to relate the bioactive alkaloid with atherosclerotic cardiovascular diseases prevention in animal models, providing inconsistent results. The direct anti-atherosclerotic effects of alkaloid have hardly been studied in patients. The aim of this systematic review was to assess the reported effects of alkaloids on aortic atherosclerosis in ApoE−/− mouse models
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