Cryptolepine，抗疟植物（Lindl.）Schlechter的主要生物碱，可诱导斑马鱼胚胎出现畸形。

Cryptolepine, the Main Alkaloid of the Antimalarial (Lindl.) Schlechter, Induces Malformations in Zebrafish Embryos.

作者信息

Mensah Kwesi Boadu, Benneh Charles, Forkuo Arnold Donkor, Ansah Charles

机构信息

Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

Department of Pharmacology, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana.

出版信息

Biochem Res Int. 2019 Jul 8;2019:7076986. doi: 10.1155/2019/7076986. eCollection 2019.

DOI:10.1155/2019/7076986

PMID:31360547

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6644280/

Abstract

BACKGROUND

Previous studies on cryptolepine, the antimalarial and cytotoxic alkaloid of , showed that it preferentially accumulates in rapidly proliferating cells and melanin-containing tissues. Subsequently, we demonstrated that cryptolepine was toxic to murine embryos but no signs of teratogenicity. developmental studies can be confounded by maternal effects. Here, we hypothesized that cryptolepine-induced embryo toxicity occurs at least partly through direct inhibition of embryogenesis rather than indirectly through the induction of maternal toxicity.

AIM

To determine the effects of cryptolepine on developing zebrafish embryos .

METHODS

Healthy synchronized zebrafish eggs were treated with cryptolepine (10 - 5 × 10 M), benzyl penicillin (6 - 6 × 10 M), or mercury chloride (3.7 × 10 - 3.7 × 10 nM) from 6 to 72 hours postfertilization. Developing embryos were assessed at 24, 48, 72, and 96 hours under microscope for lethality, hatching rate, and malformation.

RESULTS

LC for cryptolepine in the study was found to be 260 ± 0.174 M. Cryptolepine induced dose- and time-dependent mortality from the 24 to 96 hours postfertilization. Lower cryptolepine concentration (<100 M) caused mortality, approximately 15-18%, only after the 48 hours postfertilization. The most sensitive period of embryo lethality corresponded well with the pharyngula (24 to 48 hours) and hatching (48 to 72 hours) stages of embryonic development. Cryptolepine (10 - 5 × 10 M) dose dependently inhibited the hatching rate. At doses above 500 M, hatching was completely inhibited. Mercury chloride (3.7 × 10 - 3.7 × 10 nM), used as positive control, induced a consistent pattern of embryo lethality at all stages of development, whereas benzyl penicillin (6 - 6 × 10 M), used as negative control, did not induce any significant embryo lethality. Morphological examination of (postfertilization day 5) of eleutheroembryos treated during embryonic development with cryptolepine showed decreased body length (growth inhibition), decreased eye diameter and bulginess, enlarged pericardia, and enlarged yolk sac and muscle malformations.

CONCLUSION

Cryptolepine induces malformations, growth retardation, and mortalities in rapidly dividing zebrafish embryos .

摘要

背景

先前对隐丹参酮（一种从[植物名称未给出]中提取的抗疟疾和具有细胞毒性的生物碱）的研究表明，它优先在快速增殖的细胞和含黑色素的组织中积累。随后，我们证明隐丹参酮对小鼠胚胎有毒性，但没有致畸迹象。发育研究可能会受到母体效应的干扰。在这里，我们假设隐丹参酮诱导的胚胎毒性至少部分是通过直接抑制胚胎发育，而不是通过诱导母体毒性间接发生的。

目的

确定隐丹参酮对斑马鱼胚胎发育的影响。

方法

在受精后6至72小时，用隐丹参酮（10⁻⁵×10⁻³M）、苄青霉素（6×10⁻⁶M）或氯化汞（3.7×10⁻⁹至3.7×10⁻⁸nM）处理健康同步化的斑马鱼卵。在显微镜下于24、48、72和96小时评估发育中的胚胎的致死率、孵化率和畸形情况。

结果

本研究中隐丹参酮的半数致死浓度（LC）为260±0.174μM。隐丹参酮在受精后24至96小时诱导剂量和时间依赖性死亡率。较低的隐丹参酮浓度（<100μM）仅在受精后48小时后导致约15 - 18%的死亡率。胚胎致死最敏感的时期与胚胎发育的咽胚期（24至48小时）和孵化期（48至72小时）高度吻合。隐丹参酮（10⁻⁵×10⁻³M）剂量依赖性地抑制孵化率。在剂量高于500μM时，孵化完全被抑制。用作阳性对照的氯化汞（3.7×10⁻⁹至3.7×10⁻⁸nM）在发育的所有阶段均诱导一致的胚胎致死模式，而用作阴性对照的苄青霉素（6×10⁻⁶M）未诱导任何显著的胚胎致死率。对在胚胎发育期间用隐丹参酮处理的孵化后第5天的斑马鱼幼胚进行形态学检查，发现体长减小（生长抑制）、眼直径和突出度减小、心包扩大、卵黄囊增大以及肌肉畸形。