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抗疟草药 Prabchompoothaweep 疗法成分的抗疟疗效和毒理学评估,有望成为抗疟药物研发的候选药物。

Antimalarial efficacy and toxicological assessment of medicinal plant ingredients of Prabchompoothaweep remedy as a candidate for antimalarial drug development.

机构信息

Department of Medical Science, School of Medicine, Walailak University, Nakhon Si Thammarat, Thailand.

Research Center in Tropical Pathobiology, Walailak University, Nakhon Si Thammarat, 80160, Thailand.

出版信息

BMC Complement Med Ther. 2023 Jan 18;23(1):12. doi: 10.1186/s12906-023-03835-x.

Abstract

BACKGROUND

Drug resistance exists in almost all antimalarial drugs currently in use, leading to an urgent need to identify new antimalarial drugs. Medicinal plant use is an alternative approach to antimalarial chemotherapy. This study aimed to explore potent medicinal plants from Prabchompoothaweep remedy for antimalarial drug development.

METHODS

Forty-eight crude extracts from Prabchompoothaweep remedy and its 23 plants ingredients were investigated in vitro for antimalarial properties using Plasmodium lactate dehydrogenase (pLDH) enzyme against Plasmodium falciparum K1 strain and toxicity effects were evaluated in Vero cells. The plant with promising antimalarial activity was further investigated using gas chromatography-mass spectrometry (GC-MS) to identify phytochemicals. Antimalarial activity in mice was evaluated using a four-day suppressive test against Plasmodium berghei ANKA at dose of 200, 400, and 600 mg/kg body weight, and acute toxicity was analyzed.

RESULTS

Of the 48 crude extracts, 13 (27.08%) showed high antimalarial activity against the K1 strain of P. falciparum (IC <  10 μg/ml) and 9 extracts (18.75%) were moderately active (IC = 11-50 μg/ml). Additionally, the ethanolic extract of Prabchompoothaweep remedy showed moderate antimalarial activity against the K1 strain of P. falciparum (IC = 14.13 μg/ml). Based on in vitro antimalarial and toxicity results, antimalarial activity of the aqueous fruit extract of Terminalia arjuna (IC = 4.05 μg/ml and CC = 219.6 μg/ml) was further studied in mice. GC-MS analysis of T. arjuna extract identified 22 compounds. The most abundant compounds were pyrogallol, gallic acid, shikimic acid, oleamide, 5-hydroxymethylfurfural, 1,1-diethoxy-ethane, quinic acid, and furfural. Analysis of the four-day suppressive test indicated that T. arjuna extract at dose of 200, 400, and 600 mg/kg body weight significantly suppressed the Plasmodium parasites by 28.33, 45.77, and 67.95%, respectively. In the acute toxicity study, T. arjuna extract was non-toxic at 2000 mg/kg body weight.

CONCLUSIONS

The aqueous fruit extract of T. arjuna exerts antimalarial activity against Plasmodium parasites found in humans (P. falciparum K1) and mice (P. berghei ANKA). Acute toxicity studies showed that T. arjuna extract did not show any lethality or adverse effects up to a dose of 2000 mg/kg.

摘要

背景

目前使用的几乎所有抗疟药物都存在耐药性,因此迫切需要寻找新的抗疟药物。药用植物的使用是抗疟化疗的一种替代方法。本研究旨在探索 Prabchompoothaweep 疗法中的潜在药用植物,以开发抗疟药物。

方法

用乳酸脱氢酶(pLDH)法检测 Prabchompoothaweep 疗法及其 23 种植物成分的 48 种粗提取物对恶性疟原虫 K1 株的抗疟活性,并在非洲绿猴肾细胞(Vero 细胞)中评估其毒性作用。对具有潜在抗疟活性的植物进行气相色谱-质谱联用(GC-MS)分析,以鉴定其植物化学成分。采用 4 天抑制试验,以 200、400 和 600mg/kg 体重的剂量,在感染伯氏疟原虫 ANKA 的小鼠体内评估抗疟活性,并进行急性毒性分析。

结果

在 48 种粗提取物中,有 13 种(27.08%)对恶性疟原虫 K1 株表现出高抗疟活性(IC < 10μg/ml),9 种(18.75%)提取物表现出中度抗疟活性(IC = 11-50μg/ml)。此外,Prabchompoothaweep 疗法的乙醇提取物对恶性疟原虫 K1 株也表现出中度抗疟活性(IC = 14.13μg/ml)。根据体外抗疟和毒性结果,进一步研究了桃金娘科植物 Arjuna 的水提果提取物对小鼠的抗疟活性。GC-MS 分析表明,Arjuna 提取物中鉴定出 22 种化合物。最丰富的化合物是焦没食子酸、没食子酸、莽草酸、油酰胺、5-羟甲基糠醛、1,1-二乙氧基乙烷、奎尼酸和糠醛。4 天抑制试验分析表明,Arjuna 提取物在 200、400 和 600mg/kg 体重剂量下,分别显著抑制 28.33%、45.77%和 67.95%的疟原虫。在急性毒性研究中,Arjuna 提取物在 2000mg/kg 体重时无毒性。

结论

桃金娘科植物 Arjuna 的水提果提取物对人类(恶性疟原虫 K1)和小鼠(伯氏疟原虫 ANKA)疟原虫具有抗疟活性。急性毒性研究表明,Arjuna 提取物在高达 2000mg/kg 体重的剂量下无致死性或不良反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39a9/9847039/a03d835f6420/12906_2023_3835_Fig1_HTML.jpg

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