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来源于普那菊 Roxburghii Wall. 的奎那醇(普那菊科)具有强大的抗疟作用:临床前疗效及其与 PfLDH 的相互作用。

Quebrachitol from Putranjiva roxburghii Wall. (Putranjivaceae) a potent antimalarial: Pre-clinical efficacy and its interaction with PfLDH.

机构信息

Phytochemistry, Analytical Chemistry Laboratory, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.

Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.

出版信息

Parasitol Int. 2023 Feb;92:102675. doi: 10.1016/j.parint.2022.102675. Epub 2022 Sep 8.

DOI:10.1016/j.parint.2022.102675
PMID:36089201
Abstract

Researchers are exploring natural resources in search of a new and effective anti-malarial compound to address the challenges in malarial treatment due to emerging incidences of drug-resistant strains. Following background knowledge of traditional medicine, we evaluated the in-vitro and in-vivo anti-malarial efficacy of Putranjiva P. roxburghii (Putranjivaceae) twigs ethanol extracts and fraction (PRT). In-vitro parasite-specific lactate dehydrogenase (pLDH) assay was performed using a chloroquine-sensitive Plasmodium falciparum strain. The results of the in-vitro study were further validated by in-vivo anti-malarial studies on P. berghei Keyberg 173 (K173) infected mice. The crude ethanol extract of the PRT showed the most moderate antiparasitic activity (IC = 15.51 μg/mL). In contrast, its butanol fraction extract showed potent activity (IC = 5.14 μg/mL) with a selectivity index (SI) of 28.87. Two phytochemicals, viz. 2, 4 dihydroxy-5-(hydroxymethyl) benzoic acid (DHMBA), and quebrachitol (QBC), were identified with anti-parasitic activity (IC = 5.01 μg/mL and 0.87 μg/mL) and selectivity index (SI) of 45 and 158. The in-vivo studies confirmed the significant anti-malarial activity of QBC at the dose of 30 and 60 mg/kg body weight with chemo-suppression values of 73.26% and 61.88%, respectively. The present study demonstrates the bioactive marker-based standardization of P. roxburghii twig, the antiplasmodial potential of PRT, and the role of QBC in suppressing parasitemia. The findings of the study support QBC as a prospective lead for a natural product-based adjunct remedy to conventional antiparasitic agents for malarial infectious.

摘要

研究人员正在探索自然资源,以寻找一种新的、有效的抗疟化合物,以应对由于抗药性疟原虫株的出现而给疟疾治疗带来的挑战。在了解传统医学背景知识的基础上,我们评估了 Putranjiva P. roxburghii(Putranjivaceae)嫩枝乙醇提取物和馏分(PRT)的体外和体内抗疟疗效。使用氯喹敏感的恶性疟原虫(Plasmodium falciparum)株进行了寄生虫特异性乳酸脱氢酶(pLDH)的体外寄生虫特异性乳酸脱氢酶(pLDH)检测。体外研究的结果通过对感染 P. berghei Keyberg 173(K173)的小鼠进行体内抗疟研究进一步验证。PRT 的粗乙醇提取物显示出中等程度的抗寄生虫活性(IC = 15.51μg/mL)。相比之下,其正丁醇馏分提取物表现出较强的活性(IC = 5.14μg/mL),选择性指数(SI)为 28.87。两种植物化学物质,即 2,4-二羟基-5-(羟甲基)苯甲酸(DHMBA)和奎巴醇(QBC),被鉴定具有抗寄生虫活性(IC = 5.01μg/mL 和 0.87μg/mL)和选择性指数(SI)分别为 45 和 158。体内研究证实,QBC 在 30 和 60mg/kg 体重剂量下具有显著的抗疟活性,化学抑制率分别为 73.26%和 61.88%。本研究证明了基于生物活性标志物的 P. roxburghii 嫩枝的标准化、PRT 的抗疟潜力以及 QBC 在抑制寄生虫血症中的作用。该研究结果支持 QBC 作为一种有前景的天然产物佐剂的先导化合物,用于治疗疟疾感染的传统抗寄生虫药物。

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