Zhang Yibing, Li Min, Li Xiangjun, Zhang Tong, Qin Meng, Ren Liqun
Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, Changchun, China.
Department of Ophthalmology, First Hospital of Jilin University, Changchun, China.
Front Pharmacol. 2018 Jun 5;9:602. doi: 10.3389/fphar.2018.00602. eCollection 2018.
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.
多项研究试图在动物模型中探究生物活性生物碱与动脉粥样硬化性心血管疾病预防之间的关系，但其结果并不一致。此外，生物碱对动脉粥样硬化的直接影响在患者中几乎未得到研究。因此，本系统评价的目的是评估生物碱对载脂蛋白E（ApoE）小鼠模型主动脉粥样硬化的影响。通过检索PubMed和Embase来识别评估分离生物碱对载脂蛋白E缺陷小鼠动脉粥样硬化影响的研究。使用SYRCLE偏倚风险工具评估研究质量。我们采用随机效应模型对14项研究进行荟萃分析，以确定生物碱的总体效应，并进行亚组分析以比较异喹啉生物碱和吲哚生物碱的效应。纳入的大多数研究质量较低。我们明确指出，给予生物碱与主动脉粥样硬化病变面积减小显著相关（标准化均数差-3.19，95%可信区间-3.88，-2.51）。需要指出的是，各研究的实验特征差异较大，方法学的变异性也可能导致异质性。亚组分析表明，异喹啉生物碱（标准化均数差-4.19，95%可信区间-5.18，-3.20）和吲哚生物碱（标准化均数差-2.73，95%可信区间-3.56，-1.90）明显减轻了动脉粥样硬化负担。异喹啉生物碱和吲哚生物碱似乎对ApoE小鼠具有直接的抗动脉粥样硬化作用。除了动物模型研究的局限性外，本系统评价可为未来高质量的临床前动物试验和临床开发提供重要参考。
