施氏鳞果草提取物及其各馏分对恶性疟原虫敏感及耐药血液期寄生虫的体外抗疟活性

In vitro antiplasmodial activities of extract and fractions from Lepidobotrys staudtii against sensitive and resistant blood-stage parasites of Plasmodium falciparum.

作者信息

Magoudjou Pekam Jeannette Nina, Efange Noella Molisa, Mishro Lakshminarayana, Keumoe Rodrigue, Ndjakou Bruno Lenta, Ayong Lawrence, Njayou Frédéric Nico, Moundipa Paul Fewou, Rajendran Vinoth

机构信息

Laboratory of Pharmacology and Toxicology, Department of Biochemistry, Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon; Malaria Research Unit, Centre Pasteur du Cameroun, P.O. Box 1274, Yaoundé, Cameroon; Department of Microbiology, School of Life Sciences, Pondicherry University, Puducherry, 605014, India.

Malaria Research Unit, Centre Pasteur du Cameroun, P.O. Box 1274, Yaoundé, Cameroon; Department of Biochemistry and Molecular Biology, University of Buea, Cameroon.

出版信息

Int J Parasitol Drugs Drug Resist. 2025 Aug 25;29:100610. doi: 10.1016/j.ijpddr.2025.100610.

DOI:10.1016/j.ijpddr.2025.100610

PMID:40925110

Abstract

Antimalarial resistance is a primary challenge in the treatment of malaria. The ongoing search for novel drug sources remains a critical strategy for addressing this issue. This study evaluated the blood stage antiplasmodial and cytotoxic activities of the crude extract and fractions obtained from Lepidobotrys staudtii. The crude extract and all fractions exhibited promising antiplasmodial activity (IC < 10 μg/mL) against all the tested Plasmodium falciparum strains (Pf3D7 drug-sensitive and PfINDO chloroquine-resistant). Notably, the hexane and ethyl acetate fractions exhibited the highest potency, with IC values of 3.73 and 3.4 μg/mL (Pf3D7), respectively. No cytotoxic effects were observed at concentrations of up to 500 μg/mL. The ethyl acetate fraction displayed rapid action (12 h of exposure) against the Pf3D7 and PfINDO strains. The ring stage parasites were particularly susceptible to the fractions, with IC values ranging from 2.17 to 4.87 μg/mL (Pf3D7) and 2.27-6.27 μg/mL (PfINDO). Additionally, combining the fraction with standard antimalarials at fixed sub-inhibitory concentrations significantly reduced IC values. Only the hexane and crude extracts stimulated reactive oxygen species (ROS) production, whereas the other fractions neutralized the ROS. The most potent ethyl acetate fraction arrested parasite developmental progression and merozoite egress. Phytochemical analyses revealed the presence of phenols, flavonoids, tannins, alkaloids, saponins, carbohydrates, glycosides, and proteins. Reverse Phase High Performance Liquid Chromatography (RP-HPLC) analysis revealed that the fractions comprised a diverse array of compounds, resulting in varying levels of parasite-killing. This study emphasizes the blood-stage antiplasmodial properties of the stem bark extract and fractions of L. staudtii, underscoring their potential as a promising source of antimalarial agents.

摘要

抗疟耐药性是疟疾治疗中的主要挑战。持续寻找新型药物来源仍然是解决这一问题的关键策略。本研究评估了从施氏鳞果木中获得的粗提物及其馏分的血液期抗疟原虫和细胞毒性活性。粗提物及其所有馏分对所有测试的恶性疟原虫菌株（Pf3D7药物敏感株和PfINDO氯喹耐药株）均表现出有前景的抗疟原虫活性（IC<10μg/mL）。值得注意的是，己烷和乙酸乙酯馏分的活性最强，Pf3D7的IC值分别为3.73和3.4μg/mL。在浓度高达500μg/mL时未观察到细胞毒性作用。乙酸乙酯馏分对Pf3D7和PfINDO菌株显示出快速作用（暴露12小时）。环状体期寄生虫对这些馏分特别敏感，Pf3D7的IC值范围为2.17至4.87μg/mL，PfINDO为2.27 - 6.27μg/mL。此外，将该馏分与标准抗疟药以固定的亚抑制浓度联合使用可显著降低IC值。只有己烷和粗提物刺激活性氧（ROS）的产生，而其他馏分则中和了ROS。活性最强的乙酸乙酯馏分阻止了寄生虫的发育进程和裂殖子逸出。植物化学分析表明存在酚类、黄酮类、单宁、生物碱、皂苷、碳水化合物、糖苷和蛋白质。反相高效液相色谱（RP - HPLC）分析表明，这些馏分包含多种化合物，导致杀寄生虫水平各不相同。本研究强调了施氏鳞果木茎皮提取物及其馏分的血液期抗疟原虫特性，突出了它们作为有前景的抗疟药物来源潜力。