Anticoccidial and Protective Effects of Carica papaya Leaf Extract: Insights into NF-κB/Nrf2 Signaling

Avian coccidiosis is caused by Eimeria parasites and is considered as one of the most economically most important diseases affecting the poultry industry.There is need of developing safe and sustainable alternatives to conventional anticoccidial drugs for its control.In the present study, the anticoccidial and protective effects of Carica papaya leaf extract (CPLE) were investigated in broiler chickens experimentally infected with Eimeria, with particular emphasis on its association with NF-κB/Nrf2 signaling.To this end, an in vivo trial was conducted using 300 broiler chicks, which were randomly divided into five groups.Group-I served as uninfected control group in which PBS was administered, whereas Group-II kept as positive control group (the infected medicated control) and received Amprolium (125mg/L) in the drinking water.The group III, IV and V were treated with CPLE at the dose of 100, 200 and 300mg/kg body weight, respectively.Growth performance, hematological and serum biochemical parameters, lesion score, fecal score, oocyst shedding, oxidative stress biomarkers, inflammatory mediators, intestinal histopathology and NF-κB/Nrf2 signaling pathways were assessed.The efficacy of CPLE supplementation was observed to significantly increase body weight gain, feed efficiency, erythrocyte indices, liver function biomarkers compared with infected control.In addition, CPLE reduced intestinal lesion scores, fecal scores, mortality, oocyst scores and fecal oocyst shedding (OPG).Histopathological analysis revealed that the villi architecture was restored in terms of improved intestinal villus height, villus height to crypt depth ratio (P<0.05).Furthermore, CPLE significantly elevated the activity of the enzyme systems of serum superoxide dismutase, catalase and glutathione peroxidase (P<0.05),indicating an improvement in antioxidant capacity, while significantly lowered malondialdehyde concentration (P<0.05).Western blot analysis revealed that CPLE inhibited NF-κB p65 phosphorylation and promoted the Nrf2/HO-1 mediated antioxidant signaling pathway (P<0.05),leading to anti-inflammatory and anti-oxidative effects.In general, CPLE showed an effective protective effect against intestinal damage caused by the infection of Eimeria by combining its antiparasitic, antioxidant, anti-inflammatory and intestinal defense mechanisms.Based on these results, CPLE could be considered as a potential alternative to traditional anticoccidial drugs in sustainable poultry production.