Abstract：
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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).
RESULTS: 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 LC50 values of 16 mg/mL in both cases. Other plant extracts also exhibited good anthelmintic activity with LC50 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.
CONCLUSIONS: 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.
OBJECTIVE: 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.
METHODS: 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).
RESULTS: 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 LC50 values of 16 mg/mL in both cases. Other plant extracts also exhibited good anthelmintic activity with LC50 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.
CONCLUSIONS: 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.
摘要：
背景：由寄生虫或蠕虫引起的感染继续对人类和动物健康构成巨大负担，特别是在不发达的热带和亚热带国家，它们是地方性的。目前的驱虫药存在严重的局限性，耐药性的出现使对抗此类感染（蠕虫酶）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酶。对此类植物的了解以及对其驱虫活性的筛选，有可能导致发现植物化学物质，这些化学物质可以用作开发新的驱虫药物的新型分子支架。
目的：这项研究的目的是i）进行民族植物学调查，以收集用于治疗蠕虫酶的孟加拉国药用植物的数据，ii）以测试具有最高使用值的植物的体外驱虫活性，和iii）对最活跃的植物提取物中存在的植物化学物质进行计算机筛选，以研究它们破坏蠕虫中β-微管蛋白功能的能力。
方法：在孟加拉国的三个分区进行了民族植物学调查，即Mathbaria,Phultala和KhanJahanAli.体外驱虫活性的筛选是在运动试验中使用成虫科蠕虫进行的。使用PyRx对来自最活跃植物的植物化学物质进行虚拟筛选，探索它们与β-微管蛋白靶标(PDBID:1SA0)的秋水仙碱结合位点的相互作用。
结果：调查对象报告了总共32种用于治疗蠕虫酶的植物。根据他们的使用价值，最受欢迎的选择是Ananascomosus（L.）合并。,AzadirachtaindicaA.Jus.,番木瓜L.,最大柑橘（Burm。）合并。,姜黄，苦瓜，NigellasativaL.和Cumini（L.）龙骨。体外驱虫测试表明，in叶和树皮的活性最高，LC50值为16mg/mL。其他植物提取物也表现出良好的驱虫活性，LC50值为16至52mg/mL，而阿苯达唑（阳性对照）的值为8.39mg/mL。柠檬苦素类nimbolide和28-deoxonimbolide的结合亲和力为-8.9kcal/mol，并满足所有药物相似度参数。对照配体N-脱乙酰基-N-(2-巯基乙酰基)秋水仙碱具有〜6.9kcal/mol的结合亲和力。
结论：有必要对已鉴定的柠檬苦素类化合物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蠕虫酶的新型药物模板的潜力。目前的研究支持需要一种基于民族植物学调查的方法来发现蠕虫酶的新药模板。
目的：这项研究的目的是i）进行民族植物学调查，以收集用于治疗蠕虫酶的孟加拉国药用植物的数据，ii）以测试具有最高使用值的植物的体外驱虫活性，和iii）对最活跃的植物提取物中存在的植物化学物质进行计算机筛选，以研究它们破坏蠕虫中β-微管蛋白功能的能力。
方法：在孟加拉国的三个分区进行了民族植物学调查，即Mathbaria,Phultala和KhanJahanAli.体外驱虫活性的筛选是在运动试验中使用成虫科蠕虫进行的。使用PyRx对来自最活跃植物的植物化学物质进行虚拟筛选，探索它们与β-微管蛋白靶标(PDBID:1SA0)的秋水仙碱结合位点的相互作用。
结果：调查对象报告了总共32种用于治疗蠕虫酶的植物。根据他们的使用价值，最受欢迎的选择是Ananascomosus（L.）合并。,AzadirachtaindicaA.Jus.,番木瓜L.,最大柑橘（Burm。）合并。,姜黄，苦瓜，NigellasativaL.和Cumini（L.）龙骨。体外驱虫测试表明，in叶和树皮的活性最高，LC50值为16mg/mL。其他植物提取物也表现出良好的驱虫活性，LC50值为16至52mg/mL，而阿苯达唑（阳性对照）的值为8.39mg/mL。柠檬苦素类nimbolide和28-deoxonimbolide的结合亲和力为-8.9kcal/mol，并满足所有药物相似度参数。对照配体N-脱乙酰基-N-(2-巯基乙酰基)秋水仙碱具有〜6.9kcal/mol的结合亲和力。
结论：有必要对已鉴定的柠檬苦素类化合物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蠕虫酶的新型药物模板的潜力。目前的研究支持需要一种基于民族植物学调查的方法来发现蠕虫酶的新药模板。
