Background:
Leishmaniasis is an infectious disease with high global prevalence. Each year, numerous cases appear across Asia, Africa, and South America. The disease spreads so widely because controlling infected sandflies and rodents proves extremely difficult. These vectors live constantly around humans and livestock, making transmission nearly inevitable. When an infection occurs, it creates economic losses in animal production while causing psychological stress in humans and small companion animals like dogs. Methods: We used a network pharmacology strategy to investigate protein similarities between Leishmania infection and the compound kaempferol. We started by identifying kaempferol-associated proteins from relevant databases, then retrieved Leishmania-related proteins. The resulting Venn diagram revealed ۱۶ shared target proteins. We built a protein-protein interaction (PPI) network with these findings, creating a structure of ۱۶ nodes and ۳۲ edges. Topological analysis of this data gave us insights into the key protein interactions involved. Results: Our computer-designed
PPI network aimed to identify potential therapeutic targets against Leishmania infection. The proteins PTGS۲, MMP۹, and AKT۱ showed the highest degree centrality values at ۷, ۹, and ۱۱, respectively. AKT۱ functions as a central multitasking molecular switch within cells. PTGS۲ acts as an inducible enzyme that plays an important role in inflammatory responses, while MMP۹ handles tissue remodeling. The AKT۱ protein, with its high betweenness value of ۰.۳۴۰, might significantly impact both disease development and therapeutic regulation. Its closeness centrality of ۰.۸۶۶ suggests it coordinates biological activities in important ways. Conclusion: These findings suggest kaempferol could work as a prodrug candidate because it shares protein targets with Leishmania. This makes it a promising molecular target for potential therapeutic pathways against leishmaniasis.