Akazue Pearl Ihuoma, Quashie Neils Ben, Osei-Safo Dorcas, Vaughan Sue, de Koning Harry P, Gwira Theresa Manful
West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Ghana.
Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Ghana.
Phytomed Plus. 2025 May;5(2):None. doi: 10.1016/j.phyplu.2025.100793.
The use of herbal medicines to treat ailments is a common practice in several regions in Africa, relying on knowledge systems that have evolved over several generations. These herbal remedies are often based on anecdotal claims, many of which lack scientific validation. This study investigates the mode of action of two bioactive fractions, F1 (IC: 8.5 µg/mL) and F5 (IC: 7.4 µg/mL), derived from a dichloromethane extract of a herbal mixture, consisting of and , that is commonly used in Ghana to treat parasitic fevers. Both fractions exhibited trypanocidal effects with minimal cytotoxicity to mammalian cells. F5 induced necrotic cell death through mitochondrial oxidative stress, evidenced by a 3.5-fold increase in mitochondrial reactive oxygen species at 2 × IC (< 0.0001) and significant mitochondrial membrane depolarization (< 0.01). In contrast, F1 primarily disrupted kinetoplast segregation, increasing 2K1 N cells by 3.2-fold at 1 × IC (< 0.0001) and instigating an accumulation of dyskinetoplastic cells (0KXN). Both fractions induced morphological distortions, nuclear fragmentation, and loss of flagellar integrity. This study provides the first mechanistic insights into the antitrypanosomal activity of bioactive fractions obtained from a mixture of and . The distinct targeting of mitochondrial ROS production (F5) and kinetoplast replication (F1) highlights their potential as leads for the development of new antitrypanosomal drugs with novel mechanisms of action. These findings reinforce the value of ethnomedicinal plants as sources of novel bioactive compounds.
在非洲的几个地区，使用草药治疗疾病是一种常见的做法，这依赖于历经几代人发展而来的知识体系。这些草药疗法往往基于传闻说法，其中许多缺乏科学验证。本研究调查了从一种草药混合物的二氯甲烷提取物中获得的两种生物活性组分F1（IC：8.5 µg/mL）和F5（IC：7.4 µg/mL）的作用模式，该草药混合物由[具体草药1]和[具体草药2]组成，在加纳常用于治疗寄生虫热。两种组分均表现出杀锥虫作用，对哺乳动物细胞的细胞毒性最小。F5通过线粒体氧化应激诱导坏死性细胞死亡，在2×IC（<0.0001）时线粒体活性氧增加3.5倍以及显著的线粒体膜去极化（<0.01）证明了这一点。相比之下，F1主要破坏动基体分离，在1×IC（<0.0001）时使2K1N细胞增加3.2倍，并促使运动发育不全细胞（0KXN）积累。两种组分均诱导形态畸变、核碎裂和鞭毛完整性丧失。本研究首次对从[具体草药1]和[具体草药2]混合物中获得的生物活性组分的抗锥虫活性提供了机制性见解。线粒体ROS产生（F5）和动基体复制（F1）的不同靶向突出了它们作为具有新作用机制的新型抗锥虫药物开发先导物的潜力。这些发现强化了民族药用植物作为新型生物活性化合物来源的价值。
