Andrographolide induced cytotoxicity and cell cycle arrest in Giardia trophozoites

• Published in: Experimental parasitology 2024-07, Vol.262, p.108773, Article 108773
• Main Authors: Haldar, Tapas, Sardar, Sanjib K., Ghosal, Ajanta, Prasad, Akash, Nakano, Yumiko Saito, Dutta, Shanta, Nozaki, Tomoyoshi, Ganguly, Sandipan
• Format: Article
• Language: English
• Subjects: active ingredients; ADG; adhesion; Andrographis paniculata; andrographolide; Cell cycle; cell cycle checkpoints; cytotoxicity; diarrhea; Diarrhoea; DNA damage; DNA degradation; gene expression; gene expression regulation; Giardia lamblia; Giardiasis; metronidazole; multiple drug resistance; parasitology; pathogenesis; risk; therapeutics; trophozoites
• ISSN: 0014-4894; 1090-2449; 1090-2449
• DOI: 10.1016/j.exppara.2024.108773

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. [Display omitted] •The in vitro inhibitory effects of ADG on the proliferation and cell death of Giardia trophozoites.•ADG led to trophozoite shrinkage, membrane rupture and remarkable changes in morphology.•The administration of ADG led to a reduction of cells in the S/G2M phase.•ADG led to the production of excessive intracellular ROS in Giardia trophozoites.