Amira S Hendawy, Abdel-Nasser A Sabra, Mina Y George, Eman Rashad, Ebtehal El-Demerdash, Sanaa S Botros
{"title":"维格列汀和二氨基二苯砜对小鼠曼氏血吸虫病的抗纤维化作用。","authors":"Amira S Hendawy, Abdel-Nasser A Sabra, Mina Y George, Eman Rashad, Ebtehal El-Demerdash, Sanaa S Botros","doi":"10.1038/s41598-025-91955-4","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"10084"},"PeriodicalIF":3.9000,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933376/pdf/","citationCount":"0","resultStr":"{\"title\":\"The antifibrotic effect of Vildagliptin and Diaminodiphenyl Sulfone in murine schistosomiasis mansoni.\",\"authors\":\"Amira S Hendawy, Abdel-Nasser A Sabra, Mina Y George, Eman Rashad, Ebtehal El-Demerdash, Sanaa S Botros\",\"doi\":\"10.1038/s41598-025-91955-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":21811,\"journal\":{\"name\":\"Scientific Reports\",\"volume\":\"15 1\",\"pages\":\"10084\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-03-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933376/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Scientific Reports\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41598-025-91955-4\",\"RegionNum\":2,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Scientific Reports","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41598-025-91955-4","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
The antifibrotic effect of Vildagliptin and Diaminodiphenyl Sulfone in murine schistosomiasis mansoni.
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.
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