Zim, M. M. R. | bioRxiv Science

bioRxiv2025

Modulation of serotonergic, dopaminergic and tubulin-associated pathways by tannin-free natural products in Caenorhabditis elegans reveals effective anthelmintic drug targets

Despite of the Southeast Asias rich medicinal flora, Bangladesh behinds in utilizing the Caenorhabditis elegans model for lead anthelmintic compound discovery. Moreover, target-specific resistance (TSR) and non-target-specific resistance (NTSR) surge have influenced the lead compounds bio-discovery over the past decades. To date, prior researches are limited to basic efficacy tests and conventional extraction protocol. Therefore, the study was designed to assess the anthelmintic potency of 19 tannin-free natural products (NPs) induced alterations of neurotransmission in C. elegans. The anthelmintic activity was assessed by examining the motility (head thrashes and body bends), mortality, egg hatch inhibition (EHI) and expression of cat-1, ser-1, dat-1, and tba-1 genes. Eleven (11) plant extracts, Azadirachta indica A. Juss., Cassia alata L., Portulaca oleracea L., Saraca asoca (Roxb.) W.J.de Wilde, Eleusine indica L. Gaertn., Persicaria hydropiper L. Delarbre, Foeniculum vulgare Mill., Clerodendrum infortunatum L., Linum usitatissimum L., Hibiscus rosa-sinensis L., and Vitex negundo L. revealed a significant neurobehavioral and developmental impairments in C. elegans. Persicaria hydropiper L. Delarbre @ 1{square}mg/mL, caused the lowest body bending (31{square}{+/-}{square}1.7, p{square}<{square}0.01), while Eleusine indica L. Gaertn. reduced head thrashing (66.3{square}{+/-}{square}3.0, p{square}<{square}0.01). L. usitatissimum L. exhibited the highest lethality (87.3{square}{+/-}{square}1.8%, p{square}<{square}0.01) and the LD{square}{square} values of Eleusine indica L. Gaertn. (0.40{square}mg/mL) and Linum usitatissimum L. (0.411{square}mg/mL) were the lowest. Interestingly, C. infortunatum L. exhibited the strongest EHI (97.5{square}{+/-}{square}3.0%, p{square}<{square}0.01). Gene expression analysis revealed a significant down-regulation of the dopaminergic and serotonergic pathway indicating the metabolic and reproductive disruptions. This pioneering study underscores the anthelmintic potency of native plant extracts, highlighting their neuromodulatory and developmental impact on C. elegans. Altogether, these findings suggest that the selected genes may serve as potential drug targets, paving the way for lead compounds identification and development to the advance anthelmintic drug discovery from the NPs.

biochemistry↗

bioRxiv2025

Insights into the genetic diversity and population structure of prevalent Theileria orientalis in Bangladesh

Theileria orientalis, an obligatory intracellular blood protozoon, which causes the substantial economic losses to the cattle industry and is widely prevalent throughout Bangladesh. The study was aimed to assess the nationwide prevalence, genetic diversity and evolutionary divergence of T. orientalis parasites in Bangladesh analyzing bovine blood samples. The genetic characterization, haplotype network analysis and Codon-based evolutionary divergence was conducted by targeting the major piroplasm surface protein (MPSP) gene. The overall prevalence of T. orientalis was 63.75% (n = 800), as determined by MPSP-PCR across the eight divisions of Bangladesh with significant regional variation. Subsequent phylogenetic analysis showed that the query MPSP sequences were clustered into two genotypes namely 5 and 7. Genetic diversity indicated high haplotype and moderate nucleotide diversity but consistent with contrasting demographic and selective pressures across regions. The evolutionary divergence analysis revealed the complex genetic landscape of T. orientalis population which shaped by historical expansion, ongoing gene flow and localized diversification. The haplotype network analysis identified total 29 distinct haplotypes, highlighting substantial diversity within the two genotypes. These findings demonstrate the occurrence and genetic richness of T. orientalis in cattle of Bangladesh. Although the pathogenic impact could not be assessed in this study, the presence of diverse genotypes suggests a need for continued surveillance and future research to determine the clinical and economic relevance of this parasite.

molecular biology↗