Abstract：
Parthenium hysterophorus plant has a diverse chemical profile and immense bioactive potential. It exhibits excellent pharmacological properties such as anti-cancer, anti-inflammatory, anti-malarial, microbicidal, and anti-trypanosomal. The present study aims to evaluate the anti-leishmanial potential and toxicological safety of anhydroparthenin isolated from P. hysterophorus. Anydroparthenin was extracted from the leaves of P. hysterophorus and characterized through detailed analysis of 1H, 13C NMR, and HRMS. Dye-based in vitro and ex vivo assays confirmed that anhydroparthenin significantly inhibited both promastigote and amastigote forms of the Leishmania donovani parasites. Both the cytotoxicity experiment and hemolytic assay revealed its non-toxic nature and safety index in the range of 10 to 15. Further, various mechanistic assays suggested that anhydroparthenin led to the generation of oxidative stress, intracellular ATP depletion, alterations in morphology and mitochondrial membrane potential, formation of intracellular lipid bodies, and acidic vesicles, ultimately leading to parasite death. As a dual targeting approach, computational studies and sterol quantification assays confirmed that anhydroparthenin inhibits the Sterol C-24 methyl transferase and Sterol 14-α demethylase proteins involved in the ergosterol biosynthesis in Leishmania parasites. These results suggest that anhydroparthenin could be a promising anti-leishmanial molecule and can be developed as a novel therapeutic stratagem against leishmaniasis.
摘要：
Partheniumhysterophorphus植物具有多样化的化学特征和巨大的生物活性潜力。它表现出优异的药理特性，如抗癌，抗炎,抗疟疾,杀微生物,和抗锥虫。本研究旨在评估从heserophorus中分离出的脱水parthenin的抗利什曼虫潜力和毒理学安全性。Anydroparthenin是从P的叶子中提取的，并通过对1H的详细分析进行表征，13CNMR,和HRMS。基于染料的体外和离体测定证实，脱水parthenin可显着抑制利什曼原虫的前精子和阿马斯蒂根虫形式。细胞毒性实验和溶血实验均显示其无毒性质和安全指数在10至15的范围内。Further,各种机理分析表明，失氢酯导致氧化应激的产生，细胞内ATP耗竭，形态学和线粒体膜电位的改变，细胞内脂体的形成，和酸性囊泡，最终导致寄生虫死亡。作为一种双重目标方法，计算研究和固醇定量测定证实，无氢子酯抑制利什曼原虫寄生虫中参与麦角甾醇生物合成的甾醇C-24甲基转移酶和甾醇14-α脱甲基酶蛋白。这些结果表明，失水parthenin可能是一种有前途的抗利什曼菌分子，可以作为一种新的治疗利什曼病的治疗策略。
