Abstract：
Giardiasis is a prevalent parasitic diarrheal disease caused by Giardia lamblia, affecting people worldwide. Recently, the availability of several drugs for its treatment has highlighted issues such as multidrug resistance, limited effectiveness and undesirable side effects. Therefore, it is necessary to develop alternative new drugs and treatment strategies that can enhance therapeutic outcomes and effectively treat giardiasis. Natural compounds show promise in the search for more potent anti-giardial agents. Our investigation focused on the effect of Andrographolide (ADG), an active compound of the Andrographis paniculata plant, on Giardia lamblia, assessing trophozoite growth, morphological changes, cell cycle arrest, DNA damage and inhibition of gene expression associated with pathogenic factors. ADG demonstrated anti-Giardia activity almost equivalent to the reference drug metronidazole, with an IC50 value of 4.99 μM after 24 h of incubation. In cytotoxicity assessments and morphological examinations, it showed significant alterations in trophozoite shape and size and effectively hindered the adhesion of trophozoites. It also caused excessive ROS generation, DNA damage, cell cycle arrest and inhibited the gene expression related to pathogenesis. Our findings have revealed the anti-giardial efficacy of ADG, suggesting its potential as an agent against Giardia infections. This could offer a natural and low-risk treatment option for giardiasis, reducing the risk of side effects and drug resistance.
摘要：
贾第鞭毛虫病是由贾第鞭毛虫引起的一种常见的寄生虫性腹泻病,影响全世界的人。最近,几种治疗药物的可用性突出了诸如多药耐药性等问题，有限的有效性和不良的副作用。因此,有必要开发可提高治疗效果并有效治疗贾第鞭毛虫病的替代新药和治疗策略.天然化合物在寻找更有效的抗贾第虫药物方面显示出希望。我们的调查集中在穿心莲内酯（ADG）的效果，穿心莲植物的活性化合物，在贾第鞭毛虫上，评估滋养体生长，形态变化,细胞周期停滞,与致病因素相关的DNA损伤和基因表达抑制。ADG的抗贾第鞭毛虫活性几乎与参比药物甲硝唑相当，孵育24小时后的IC50值为4.99μM。在细胞毒性评估和形态学检查中，它显示出滋养体形状和大小的显着变化，并有效地阻止了滋养体的粘附。它也导致过量的ROS生成，DNA损伤,细胞周期阻滞并抑制与发病相关的基因表达。我们的研究结果揭示了ADG的抗贾第虫疗效，表明其作为对抗贾第虫感染的药物的潜力。这可以为贾第鞭毛虫病提供自然和低风险的治疗选择，降低副作用和耐药性的风险。
