针对恶性疟原虫的红细胞内生命周期揭示了来自多蕊麻和轮叶血桐的抗疟药物发现起点。

Targeting the intra-erythrocytic life cycle of Plasmodium falciparum unveils antimalarial drug discovery starting points from Drymaria cordata and Macaranga monandra.

作者信息

Youbi Kamche Aubin, Tali Mariscal Brice Tchatat, Ngouana Vincent, Wendji Monkam Diana Sandra, Souleyman Hassan, Dongmo Yanick Kevin Melogmo, Dongmo Kevine Johane Jumeta, Nana Olga, Woutouoba Ntieche David, Dize Darline, Mbouna Cedric Derick Jiatsa, Tsouh Fokou Patrick Valere, Boyom Fabrice Fekam

机构信息

Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Advanced Research & Health Innovation Hub, P.O. Box 20133, Yaoundé, Cameroon.

Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Department of Pharmaceutical Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Dschang, P.O. Box 96, Dschang, Cameroon.

出版信息

J Ethnopharmacol. 2025 Sep 1:120518. doi: 10.1016/j.jep.2025.120518.

DOI:10.1016/j.jep.2025.120518

PMID:40902808

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Drymaria cordata and Macaranga monandra are two medicinal plants traditionally used in Cameroon to treat malaria, but their scientific validation remains unclear.

AIM OF THE STUDY

To validate the antiplasmodial action of extracts and fractions derived from Drymaria cordata and Macaranga monandra.

MATERIALS AND METHODS

Aqueous, methanolic, ethanolic, and hydroethanolic extracts of D. cordata (whole plant) and M. monandra (bark) were prepared by maceration followed by liquid-liquid partition of actives. Extracts and fractions were screened against chloroquine-sensitive (Pf3D7) and multidrug-resistant (PfDd2) strains of P. falciparum, while selectivity was determined on Vero cells. Stage-specific analysis and killing dynamics of potent fractions were profiled, complemented with UHPLC-MS analysis coupled to in silico prediction of pharmacokinetics of identified metabolites.

RESULTS

D. cordata ethanolic extract showed moderate activity (ICPfDd2: 18.9μg/mL; ICPf3D7: 24.51μg/mL), while all four M. monandra extracts exhibited good activity (IC < 8μg/mL). The methanolic bark extract (MMBME) was highly potent and selective (ICPfDd2: 2.46 μg/mL, SI > 203; ICPf3D7: 1.02 μg/mL, SI > 487). Fractionation yielded two active fractions from MMBME: F2 (ICPfDd2: 0.60 μg/mL, ICPf3D7: 3.42 μg/mL) and F3 (ICPfDd2: 0.92 μg/mL, ICPf3D7: 2.46 μg/mL). Fractions F2 and F3 arrested ring-stage development, lysed trophozoite-infected red blood cells, and blocked merozoite egress. UHPLC-MS analysis identified 17 metabolites in fractions F2 and F3, including fatty acyls, flavonoids, phenols, terpenes, and coumarins. Lecanoric acid was predicted as a promising antimalarial candidate.

CONCLUSIONS

Macaranga monandra bark fractions F2 and F3 are potent sources of antiplasmodial compounds targeting multiple asexual blood stages (ABS).

摘要

民族药理学相关性

心叶球花报春和轮叶血桐是喀麦隆传统上用于治疗疟疾的两种药用植物，但其科学验证仍不明确。

研究目的

验证心叶球花报春和轮叶血桐提取物及馏分的抗疟作用。

材料与方法

通过浸渍法制备心叶球花报春（全株）和轮叶血桐（树皮）的水提取物、甲醇提取物、乙醇提取物和氢乙醇提取物，然后对活性成分进行液-液分配。针对氯喹敏感（Pf3D7）和多药耐药（PfDd2）的恶性疟原虫菌株对提取物和馏分进行筛选，同时在Vero细胞上测定其选择性。对有效馏分进行阶段特异性分析和杀伤动力学分析，并辅以超高效液相色谱-质谱分析以及对已鉴定代谢物的药代动力学进行计算机模拟预测。

结果

心叶球花报春乙醇提取物显示出中等活性（PfDd2的IC：18.9μg/mL；Pf3D7的IC：24.51μg/mL），而轮叶血桐的所有四种提取物均表现出良好活性（IC<8μg/mL）。甲醇树皮提取物（MMBME）具有高效力和选择性（PfDd2的IC：2.46μg/mL，SI>203；Pf3D7的IC：1.02μg/mL，SI>487）。分级分离从MMBME中得到两个活性馏分：F2（PfDd2的IC：0.60μg/mL，Pf3D7的IC：3.42μg/mL）和F3（PfDd2的IC：0.92μg/mL，Pf3D7的IC：2.46μg/mL）。馏分F2和F3阻止环状体阶段发育，裂解被滋养体感染的红细胞，并阻断裂殖子逸出。超高效液相色谱-质谱分析在馏分F2和F3中鉴定出17种代谢物，包括脂肪酰基、黄酮类、酚类、萜类和香豆素类。地衣缩酚酸被预测为一种有前景的抗疟候选物。