The antifibrotic effect of Vildagliptin and Diaminodiphenyl Sulfone in murine schistosomiasis mansoni

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Hendawy A.S.; Sabra A.-N.A.; George M.Y.; Rashad E.; El-Demerdash E.; Botros S.S.

Journal: Scientific Reports

Publisher: Nature Research

Publication Date: 24 March 2025

Volume / Issue: Volume 15 / Issue 1

Article No.: 10084

ISSN: 20452322

DOI: 10.1038/s41598-025-91955-4

Scopus: View on Scopus

PubMed: 40128243

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Hendawy A.S., Department of Pharmacology, Theodor Bilharz Research Institute, P.O. Box 30, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; Sabra A.-N.A., Department of Pharmacology, Theodor Bilharz Research Institute, P.O. Box 30, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; George M.Y., Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, 11566, Egypt; Rashad E., Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt; El-Demerdash E., Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, 11566, Egypt; Botros S.S., Department of Pharmacology, Theodor Bilharz Research Institute, P.O. Box 30, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt

Abstract

Schistosomiasis drastically affects human health, where S. mansoni-induced hepatic fibrosis remains a serious problem with no available drug yet. The current study aimed to evaluate the hepatoprotective effects of Vildagliptin (Vilda), Diaminodiphenyl Sulfone (DDS), and their combination (Vilda/DDS) against S. mansoni-induced hepatic fibrosis and elucidate their underlying molecular mechanisms. S.mansoni-infected mice were administered praziquantel (PZQ) for two consecutive days, or Vilda, DDS, and Vilda/DDS for 14 consecutive days. Schistosomiasis-induced hepatic fibrosis was assessed parasitologically, biochemically, and pathologically. Results revealed that Vilda, DDS, and Vida/DDS treatments significantly reduced worm count, oogram stages, ova count, and ameliorated the granulomatous inflammatory reactions and hepatotoxicity indices. Moreover, they enhanced hepatic Nrf2/HO-1 pathway with significant increasing SOD and reducing MDA levels. Furthermore, they significantly downregulated the hepatic TLR4/NF-κB and NLRP3 inflammasome pathways leading to a significant reduction in TNF-α and caspase-1 levels which is important in the activation of IL-1β and caspase-3. Notably, significant downregulation in hepatic TGF-β1, α-SMA, and MMP-9 expressions were also recorded. In conclusion, Vilda/DDS showed antioxidant, anti-inflammatory and antifibrotic activities in comparison to either Vilda or DDS alone against S. mansoni-induced hepatic fibrosis. Therefore, Vilda/DDS is a promising approach for managing S. mansoni infection, liver fibrosis, and associated disease morbidity. © The Author(s) 2025.

Keywords

Diaminodiphenyl sulfone; Dipeptidyl Peptidase IV; Fibrosis; Inflammation; Schistosoma mansoni; Vildagliptin; Animals; Disease Models, Animal; Liver; Liver Cirrhosis; Male; Mice; Schistosomiasis mansoni; Sulfones; sulfone; animal; disease model; drug effect; drug therapy; metabolism; mouse; parasitology; pathology

Citation Information

Scopus Citations: 2

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