从山黄皮中提取的生物碱七叶亭和呋喃香豆素花椒毒素抗恶性疟原虫的抗疟活性：体外滋养体杀伤、裂殖体杀伤和配子体杀伤方法。

Anti-malarial activity of the alkaloid, heptaphylline, and the furanocoumarin, imperatorin, from Clausena anisata against human Plasmodium falciparum malaria parasites: ex vivo trophozoitocidal, schizonticidal and gametocytocidal approach.

机构信息

Department of Phytochemistry, Centre for Plant Medicine Research, P.O. Box 73, Mampong-Akuapem, Ghana.

Department of Quality Management, Centre for Plant Medicine Research, Mampong-Akuapem, Ghana.

出版信息

Malar J. 2023 Sep 9;22(1):264. doi: 10.1186/s12936-023-04678-0.

DOI:10.1186/s12936-023-04678-0

PMID:37689679

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10492307/

Abstract

BACKGROUND

The erythrocytic stage of the life cycle of the malaria parasite, Plasmodium falciparum, consists of trophozoite, schizont and gametocyte stages in humans. Various anti-malarial agents target different stages of the parasite to produce treatment outcomes. This study reports on the stage-specific anti-malarial activity of heptaphylline and imperatorin against human P. falciparum in addition to their cytotoxicity and selectivity indices (SI).

METHODS

The compounds were isolated from Clausena anisata using column chromatography and their structures elucidated using NMR spectroscopy. The anti-malarial activity was determined by measuring the trophozoitocidal, schizonticidal and gametocytocidal activities of the compounds using the SYBR green assay. Cytotoxicity was evaluated using the tetrazolium-based colorimetric assay.

RESULTS

Heptaphylline and imperatorin produced trophozoitocidal, schizonticidal and gametocytocidal activities with ICs of 1.57 (0.2317)-26.92 (0.3144) µM with those of artesunate (the standard drug) being 0.00024 (0.0036)-0.0070 (0.0013) µM. In the cytotoxicity assay, the compounds produced CC greater than 350 µM and SI of 13.76-235.90. Also, the trophozoitocidal and schizonticidal activities of the compounds were more pronounced than their gametocytocidal activity. Imperatorin was 42.04% more trophozoitocidal than hepthaphyline. However, hepthaphyline has more schizonticidal and gametocytocidal properties than imperatorin.

CONCLUSION

Heptaphylline and imperatorin are promising anti-malarial agents, since they possess potent anti-malarial activity with weak cytotoxicity on RBCs. However, imperatorin is a better anti-malarial prophylactic agent whereas heptaphylline is a better malaria treatment agent.

摘要

背景

疟原虫的红细胞生活史阶段包括在人体内的滋养体、裂殖体和配子体阶段。各种抗疟药物针对寄生虫的不同阶段，产生治疗效果。本研究报告了七叶亭和欧前胡素对人类恶性疟原虫的阶段特异性抗疟活性，以及它们的细胞毒性和选择性指数（SI）。

方法

使用柱层析从胡颓子属植物中分离出这两种化合物，并通过 NMR 光谱解析其结构。采用 SYBR 绿色法测定化合物的滋养体杀伤、裂殖体杀伤和配子体杀伤活性，来确定抗疟活性。采用基于四唑的比色法评估细胞毒性。

结果

七叶亭和欧前胡素产生了滋养体杀伤、裂殖体杀伤和配子体杀伤活性，其 ICs 分别为 1.57（0.2317）-26.92（0.3144）µM，而青蒿琥酯（标准药物）的 ICs 分别为 0.00024（0.0036）-0.0070（0.0013）µM。在细胞毒性测定中，这些化合物的 CC 大于 350µM，SI 为 13.76-235.90。此外，这些化合物的滋养体杀伤和裂殖体杀伤活性比配子体杀伤活性更为显著。欧前胡素比七叶亭更能杀伤滋养体，达到 42.04%。然而，七叶亭比欧前胡素有更强的裂殖体杀伤和配子体杀伤作用。