Kaempferol activity on Cryptosporidium parvum infection in an experimentally infected immunocompromised mouse model: In silico and in vivo investigations.

CONTEXT: No vaccine or effective therapy for cryptosporidiosis currently exists, except for nitazoxanide (NTZ), which has limited effectiveness in immunocompromised hosts. Kaempferol (KPF), a naturally occurring flavonoid, has various pharmacological effects and promising antiparasitic properties.

OBJECTIVE

The current work aimed to examine the impact of KPF compared with NTZ on Cryptosporidium parvum (C. parvum) using both in silico molecular docking and in vivo studies with an experimentally infected immunocompromised mouse model.

MATERIALS AND

METHODS

The present study utilized KPF and NTZ as multi-target ligands to predict, determine, and evaluate their in silico target-interacted forms, thereby demonstrating their therapeutic properties against C. parvum. Mice were immunosuppressed and divided into six groups: DEXA, Model, KPF as prophylaxis, treatment with KPF, NTZ, and a combination of KPF and NTZ. Treatment efficacy was assessed through parasitological, histopathological examination, and immunohistochemical analysis of intestinal tissues using NLRP3 protein.

RESULTS

The in silico findings supported the use of KPF and NTZ as inhibitors of C. parvum growth by blocking the action of C. parvum choline and pyruvate kinases. The in vivo study demonstrated that KPF exhibits anti-cryptosporidial efficacy, particularly when combined with NTZ. The KPF+NTZ had the best results, as evidenced by a significant decrease (p < 0.001) in oocyst shedding of 83%, improved intestinal histological damage, and inhibition of the NLRP3 inflammasome pathway.

DISCUSSION AND

CONCLUSION

KPF demonstrated the potential to mitigate the consequences of cryptosporidiosis and serve as an adjuvant agent to NTZ by reducing the oocyst burden, alleviating intestinal inflammation, and facilitating mucosal repair.