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抗疟证据、宿主线粒体生物学以及青蒿和常山复合提取物对感染疟原虫小鼠的可能作用机制

Antiplasmodial evidence, host mitochondrial biology and possible mechanisms of action of a composite extract of and in -infected mice.

作者信息

Olanlokun John Oludele, Odedeyi Aminat, Oderinde Solomon Obaloluwa, Owolabi Bunmi Adesola, Koorbanally Neil Anthony, Olorunsogo Olufunso Olabode

机构信息

Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.

School of Chemistry and Physics, University of KwaZulu-Natal, Durban, 4000 South Africa.

出版信息

J Parasit Dis. 2024 Dec;48(4):872-890. doi: 10.1007/s12639-024-01714-x. Epub 2024 Aug 9.

Abstract

A. Juss (Meliaceae) (AI) and L. (Zingiberaceae) (CL) are used for malaria treatment but their anti-glycolytic and host mitochondrial effects have not been studied. The AI stem-bark and CL rhizomes were extracted with methanol. Methanol extract of CL (Turmeric) was partitioned to yield methanol fraction (MF). Swiss mice infected with (NK 65 strain) were treated with 200 and 400 mg/kg of AI and turmeric for seven days. Turmeric and MF (200 and 400 mg/kg) were combined with 400 mg/kg AI to treat mice infected with i (ANKA strain) for four days. Drug and infected controls mice were treated with artemether lumefantrine (10 mg/kg) and distilled water (10 mL/kg), respectively. Serum lactate dehydrogenase (LDH) and aldolase activities were determined. Liver mitochondria were obtained for mitochondrial permeability transition (mPT) pore opening and FF ATPase assays. The curcumin content of turmeric was determined using HPLC while LD of Turmeric and AI was also determined. The AI, and its combination with turmeric decreased parasite load and increased chemosuppression in both sensitive and resistant studies while MF and its combinations with AI induced mPT pore opening. In the resistant experiment, AI + Turmeric 400 mg/kg decreased FF ATPase, LDH and aldolase activities against the infected control. The LD values of both extracts were above 2000 mg/kg while the MF had the highest curcumin content. Antiplasmodial mechanisms of action of AI, CL and their combinations involve anti-glycolytic effects. Their composite formulations are more potent in malaria treatment.

摘要

A. Juss(楝科)(AI)和L.(姜科)(CL)被用于疟疾治疗,但其抗糖酵解和对宿主线粒体的影响尚未得到研究。AI的茎皮和CL的根茎用甲醇提取。CL(姜黄)的甲醇提取物经分离得到甲醇馏分(MF)。用200和400mg/kg的AI和姜黄对感染疟原虫(NK 65株)的瑞士小鼠进行为期7天的治疗。将姜黄和MF(200和400mg/kg)与400mg/kg的AI联合用于治疗感染疟原虫(ANKA株)的小鼠4天。药物对照组和感染对照组小鼠分别用蒿甲醚-本芴醇(10mg/kg)和蒸馏水(10mL/kg)进行治疗。测定血清乳酸脱氢酶(LDH)和醛缩酶活性。获取肝脏线粒体用于线粒体通透性转换(mPT)孔开放和F0F1 ATP酶分析。用高效液相色谱法测定姜黄中的姜黄素含量,同时也测定姜黄和AI的半数致死量(LD)。在敏感和抗性研究中,AI及其与姜黄的组合均降低了寄生虫载量并增强了化学抑制作用,而MF及其与AI的组合诱导了mPT孔开放。在抗性实验中,400mg/kg的AI + 姜黄降低了感染对照组的F0F1 ATP酶、LDH和醛缩酶活性。两种提取物的LD值均高于2000mg/kg,而MF的姜黄素含量最高。AI、CL及其组合的抗疟作用机制涉及抗糖酵解作用。它们的复合制剂在疟疾治疗中更有效。

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