Pharmacy Discipline, Life Science School, Khulna University, Khulna, Bangladesh.
Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh.
J Ethnopharmacol. 2024 Jun 28;328:118132. doi: 10.1016/j.jep.2024.118132. Epub 2024 Mar 31.
Infections caused by parasitic worms or helminth continue to pose a great burden on human and animal health, particularly in underdeveloped tropical and subtropical countries where they are endemic. Current anthelmintic drugs present serious limitations and the emergence of drug resistance has made it increasingly challenging to combat such infections (helminthiases). In Bangladesh, medicinal plants are often used by indigenous communities for the treatment of helminthiases. Knowledge on such plants along with screening for their anthelmintic activity has the potential to lead to the discovery of phytochemicals that could serve as novel molecular scaffolds for the development of new anthelminthic drugs.
The purpose of this study was i) to conduct an ethnobotanical survey to gather data on Bangladeshi medicinal plants used in the treatment of helminthiases, ii) to test plants with the highest use values for their in vitro anthelmintic activity, and iii) to carry out in silico screening on phytochemicals present in the most active plant extract to investigate their ability to disrupt β-tubulin function in helminths.
The ethnobotanical survey was conducted across three sub-districts of Bangladesh, namely Mathbaria, Phultala and Khan Jahan Ali. The in vitro screening for anthelmintic activity was performed in a motility test using adult Haemonchus contortus worms. Virtual screening using PyRx was performed on the phytochemicals reported from the most active plant, exploring their interactions with the colchicine binding site of the β-tubulin protein target (PDB ID: 1SA0).
The survey respondents reported a total of 32 plants for treating helminthiases. Based on their use values, the most popular choices were Ananas comosus (L.) Merr., Azadirachta indica A.Juss., Carica papaya L., Citrus maxima (Burm.) Merr., Curcuma longa L., Momordica charantia L., Nigella sativa L. and Syzygium cumini (L.) Skeels. In vitro anthelmintic testing revealed that A. indica leaves and bark had the highest activity with LC values of 16 mg/mL in both cases. Other plant extracts also exhibited good anthelmintic activity with LC values ranging from 16 to 52 mg/mL, while the value for albendazole (positive control) was 8.39 mg/mL. The limonoids nimbolide and 28-deoxonimbolide showed a binding affinity of -8.9 kcal/mol, and satisfied all drug-likeness parameters. The control ligand N-deacetyl-N-(2-mercaptoacetyl)colchicine had a binding affinity of -6.9 kcal/mol.
Further in silico and in vitro studies are warranted on the identified limonoids to confirm the potential of these derivatives as novel drug templates for helminthiases. The current study supports the need for an ethnobotanical survey-based approach to discover novel drug templates for helminthiases.
寄生虫或蠕虫引起的感染继续对人类和动物健康造成巨大负担，尤其是在寄生虫病流行的欠发达热带和亚热带国家。目前的驱虫药存在严重的局限性，耐药性的出现使得对抗此类感染（蠕虫病）变得越来越具有挑战性。在孟加拉国，土著社区经常使用药用植物来治疗蠕虫病。对这些植物的了解以及对其驱虫活性的筛选有可能发现可作为新型驱虫药物开发的新型分子支架的植物化学物质。
本研究的目的是：i）进行民族植物学调查，收集用于治疗蠕虫病的孟加拉药用植物数据，ii）测试具有最高使用价值的植物的体外驱虫活性，以及 iii）对最活跃植物提取物中的植物化学物质进行计算机筛选，以研究它们破坏蠕虫β-微管蛋白功能的能力。
民族植物学调查在孟加拉国的三个分区（即马塔巴里、法尔塔拉和汗贾汉阿里）进行。使用成年捻转血矛线虫进行体外驱虫活性筛选的运动试验。使用 PyRx 进行虚拟筛选，对最活跃植物中报道的植物化学物质进行筛选，探索它们与β-微管蛋白蛋白靶标（PDB ID：1SA0）的秋水仙素结合位点的相互作用。
调查受访者共报告了 32 种用于治疗蠕虫病的植物。根据它们的使用价值，最受欢迎的选择是菠萝（Ananas comosus (L.) Merr.）、印度楝（Azadirachta indica A.Juss.）、番木瓜（Carica papaya L.）、甜橙（Citrus maxima (Burm.) Merr.）、姜黄（Curcuma longa L.）、苦瓜（Momordica charantia L.）、黑种草（Nigella sativa L.）和锡兰肉桂（Syzygium cumini (L.) Skeels）。体外驱虫试验表明，印度楝叶和树皮的活性最高，LC 值均为 16 mg/mL。其他植物提取物也表现出良好的驱虫活性，LC 值范围为 16 至 52 mg/mL，而阿苯达唑（阳性对照）的值为 8.39 mg/mL。柠檬苦素 nimbolide 和 28-去氧 nimbolide 表现出 -8.9 kcal/mol 的结合亲和力，并满足所有药物相似性参数。对照配体 N-去乙酰基-N-（2-巯基乙酰基）秋水仙碱的结合亲和力为-6.9 kcal/mol。
需要对鉴定出的柠檬苦素进行进一步的计算机模拟和体外研究，以确认这些衍生物作为新型驱虫药物模板治疗蠕虫病的潜力。本研究支持基于民族植物学调查的方法来发现治疗蠕虫病的新型药物模板。
