Atomic force microscopy reveals morphological and mechanical properties of schistosoma mansoni tegument.

Schistosoma mansoni, an intravascular parasitic worm and the causative agent of schistosomiasis, relies on its tegument (outer layer) for survival and host interaction. This study explored the morphology and mechanical properties of S. mansoni tegument using Atomic Force Microscopy (AFM). Notably, we employed the PeakForce Quantitative Nanomechanical Mapping (PF-QNM) mode in air, enabling simultaneous acquisition of 3D topography and mechanical property contrasts (adhesion, elastic modulus). Additionally, nanoindentation (AFM contact mode) was performed on female worm tegument for elastic modulus measurement. Both techniques revealed an elastic modulus range of fractions or units of GPa for the tegument. Interestingly, mechanical property maps, particularly adhesion contrast, displayed a recurring pattern of light and dark bands. We also measured the depth of annular furrows on the female tegument, finding an average of 128 ± 10 nm. These findings establish AFM, particularly PF-QNM, as a valuable tool to characterize S. mansoni tegument properties, offering insights for future investigations into parasite biology and its response to immunological or pharmacological challenges.

EDBD-3,6-Epidioxy-1,10-Bisaboladiene-An Endoperoxide Sesquiterpene Obtained from Drimys brasiliensis (Winteraceae) Exhibited Potent Preclinical Efficacy against Schistosoma mansoni Infection.

Schistosomiasis, a neglected tropical disease impacting over 250 million individuals globally, remains a major public health challenge due to its prevalence and significant impact on affected communities. Praziquantel, the sole available treatment, highlights the urgency of the need for novel anthelmintic agents to achieve the World Health Organization (WHO) goal of schistosomiasis elimination. Previous studies reported the promising antiparasitic activity of different terpenoids against Schistosoma mansoni Sambon (Diplostomida: Schistosomatidae). In the present work, the hexane extract from branches of Drimys brasiliensis afforded a diastereomeric mixture of endoperoxide sesquiterpenes, including 3,6-epidioxy-bisabola-1,10-diene (EDBD). This compound was evaluated in vitro and in vivo against S. mansoni. EDBD exhibited a significant reduction in S. mansoni viability in vitro, with an effective concentration (EC50) value of 4.1 µM. Additionally, EDBD demonstrated no toxicity to mammalian cells. In silico analysis predicted good drug-likeness properties, adhering to pharmaceutical industry standards, including favorable ADME profiles. Furthermore, oral treatment of S. mansoni-infected mice with EDBD (400 mg/kg) resulted in a remarkable egg burden reduction (98% and 99% in tissues and feces, respectively) surpassing praziquantel's efficacy. These findings suggest the promising potential of EDBD as a lead molecule for developing a novel schistosomiasis treatment.

Antihistamines H1 as Potential Anthelmintic Agents against the Zoonotic Parasite Angiostrongylus cantonensis.

Infections caused by parasitic helminths pose significant health concerns for both humans and animals. The limited efficacy of existing drugs underscores the urgent need for novel anthelmintic agents. Given the reported potential of antihistamines against various parasites, including worms, this study conducted a screening of clinically available antihistamines against Angiostrongylus cantonensis-a nematode with widespread implications for vertebrate hosts, including humans. Twenty-one anti-H1 antihistamines were screened against first-stage larvae (L1) of A. cantonensis obtained from the feces of infected rats. Standard anthelmintic drugs ivermectin and albendazole were employed for comparative analysis. The findings revealed four active compounds (promethazine, cinnarizine, desloratadine, and rupatadine), with promethazine demonstrating the highest potency (EC50 = 31.6 µM). Additionally, morphological analysis showed that antihistamines induced significant changes in larvae. To understand the mechanism of action, antimuscarinic activities were reported based on average pK i values for human muscarinic receptor (mAChR) subtypes of the evaluated compounds. Furthermore, an analysis of the physicochemical and pharmacodynamic properties of antihistamines revealed that their anthelmintic activity does not correlate with their activity at H1 receptors. This study marks the first documentation of antihistamines' activity against A. cantonensis, offering a valuable contribution to the quest for novel agents effective against zoonotic helminths.