Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria.
J Basic Clin Physiol Pharmacol. 2020 Nov 9;32(3):255-266. doi: 10.1515/jbcpp-2020-0046.
Broad spectrum antimalarial drugs without deleterious effects on mitochondria are scarce. It is in this regard that we investigated the potency of methanol extract and solvent fractions of on chloroquine-susceptible and resistant strains of , toxicity and its consequential effects on mitochondrial permeability transition (mPT) pore opening.
Malaria was induced in male Swiss mice with susceptible (NK 65) strain, divided into groups (n=5) and treated with 100, 200 and 400 mg/kg of methanol extract, -hexane, dichloromethane, ethylacetate and methanol fractions daily for seven days. Percentage parasitemia and parasite clearance were determined microscopically. The two most potent fractions were tested on resistant (ANKA) strains. Heme and hemozoin contents were determined spectrophotometrically. The mPT, mitochondrial ATPase (mATPase) and lipid peroxidation (mLPO) were determined spectrophotometrically. Similar groups of animals were used for toxicity studies.
Dichloromethane fraction (400 mg/kg) had the highest antimalarial curative effect via least parasitemia (0.49) and high clearance (96.63) compared with the negative control (10.08, 0.00, respectively), had the highest heme and least hemozoin contents (16.23; 0.03) compared with the negative control (8.2, 0.126, respectively). Malaria infection opened the mPT, caused significant increase in mLPO and enhanced mATPase; while dichloromethane fraction reversed these conditions. Serum ALT, AST, ALP, GGT, urea and creatinine of dichloromethane fraction-treated mice decreased relative to control. No significant lesion was noticed in liver and kidney tissue sections.
Dichloromethane fraction of had the highest antimalarial activity with the highest mito-protective effect and it was well tolerated without toxic effects.
广谱抗疟药物而不损害线粒体的药物却很少见。正是在这方面，我们研究了甲醇提取物和溶剂馏分对氯喹敏感和耐药株的效力、毒性及其对线粒体通透性转换（mPT）孔开放的影响。
用敏感（NK 65）株雄性瑞士小鼠诱导疟疾，分为（n=5）组，每天用 100、200 和 400mg/kg 的甲醇提取物、-己烷、二氯甲烷、乙酸乙酯和甲醇馏分处理 7 天。用显微镜测定疟原虫百分比和寄生虫清除率。对最有效的两种馏分进行了抗药性（ANKA）株的测试。用分光光度法测定血红素和血晶素含量。用分光光度法测定线粒体通透性转换（mPT）、线粒体三磷酸腺苷酶（mATPase）和脂质过氧化（mLPO）。用相似的动物组进行毒性研究。
二氯甲烷馏分（400mg/kg）的抗疟疗效最高，通过最低的疟原虫血症（0.49）和高清除率（96.63）与阴性对照（分别为 10.08，0.00）相比，具有最高的血红素和最低的血晶素含量（16.23；0.03）与阴性对照（分别为 8.2，0.126）相比。疟原虫感染打开了 mPT，导致 mLPO 显著增加，并增强了 mATPase；而二氯甲烷馏分则逆转了这些情况。与对照组相比，二氯甲烷馏分处理的小鼠血清 ALT、AST、ALP、GGT、尿素和肌酐均有所降低。肝和肾组织切片未见明显病变。
甲醇提取物中二氯甲烷馏分的抗疟活性最高，具有最高的线粒体保护作用，且耐受性良好，无毒性作用。
