State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences , University of Macau , Taipa , Macau 999078 , China.
School of Life Sciences , The Chinese University of Hong Kong , Shatin, New Territories , Hong Kong China.
J Agric Food Chem. 2019 Jul 17;67(28):7783-7792. doi: 10.1021/acs.jafc.9b00764. Epub 2019 Jul 3.
The increasing use of pesticides in agriculture and gardening has caused severe deterioration to both the ecosystem and the health of users (human beings), so there is an urgent need for eco- and user-friendly pesticides. Among a variety of herbicides, paraquat (PQ), frequently used as an effective herbicidal agent worldwide, is well-known for its serious toxicity that has killed, and harmed, thousands of people and countless wildlife such as fish. Herein, we present a facile supramolecular formulation of PQ@cucurbit[7]uril (PQ@CB[7]), prepared by simply mixing PQ with equivalent (molar) CB[7] in water. With addition of CB[7], PQ's cellular uptake was dramatically inhibited. The reactive oxygen species (ROS) generation and the associated apoptosis otherwise induced by PQ in cellular models were both reduced, resulting in increased cellular viability. In a wildtype zebrafish model that is a typical fragile wildlife species in the ecosystem, the supramolecular formulation exhibited significantly reduced hepatotoxicity and increased survival rate, in comparison with those of the fish exposed to free PQ. In a mouse model that is clinically relevant to human being, the administration of PQ@CB[7] significantly alleviated major organ injuries and unusual hematological parameters that were otherwise induced by free PQ, resulting in a significantly increased survival rate. Meanwhile, this formulation maintained effective herbicidal activity that was equivalent to that of free PQ. Taken together, this facile supramolecular PQ formulation is providing not only an extremely rare example of an eco- and user-friendly herbicide that has been desired for decades but also a practical solution for green agriculture.
农业和园艺中农药使用的增加导致生态系统和使用者（人类）的健康受到严重恶化，因此急需环保和对用户友好的农药。在各种除草剂中，百草枯（PQ）作为一种在全球范围内广泛使用的有效除草剂，以其严重毒性而闻名，已导致数千人以及无数野生动物（如鱼类）死亡和受伤。在此，我们提出了一种简便的 PQ@葫芦[7]脲（PQ@CB[7]）超分子制剂，通过简单地将 PQ 与等摩尔的 CB[7]在水中混合制备而成。加入 CB[7]后，PQ 的细胞摄取量明显受到抑制。在细胞模型中，否则由 PQ 诱导的活性氧（ROS）生成和相关凋亡均减少，导致细胞活力增加。在野生型斑马鱼模型中，该模型是生态系统中典型的脆弱野生动物物种，与暴露于游离 PQ 的鱼类相比，该超分子制剂表现出明显降低的肝毒性和提高的存活率。在与人类临床相关的小鼠模型中，PQ@CB[7]的给药显著缓解了游离 PQ 否则引起的主要器官损伤和异常血液学参数，导致存活率显著提高。同时，该制剂保持了与游离 PQ 相当的有效除草活性。综上所述，这种简便的 PQ 超分子制剂不仅为人们渴望了数十年的环保和对用户友好的除草剂提供了一个极其罕见的例子，而且为绿色农业提供了一个实用的解决方案。
