Low-dose Paederia foetida leaf extract as a potential natural antidiarrheal candidate: An in vivo study in enteropathogenic Escherichia coli-induced rat model

Diarrhea remains a major gastrointestinal disorder, and plant-based interventions are increasingly explored for therapeutic potential. This study evaluated the antidiarrheal-associated effects and systemic tolerability of Paederia foetida Linn. leaf extract in Wistar rats with diarrhea induced by enteropathogenic Escherichia coli (EPEC). Rats were divided into six groups: three doses of extract-treated rats (400, 800, and 1,600 mg/kg body weight), Diapet®-treated rats, only EPEC-induced rats, and healthy rats. Body weight, feed intake, fecal consistency, hematological and biochemical parameters, and fecal bacterial profiles were assessed. The 400 mg/kg BW dose (P1) demonstrated the most consistent antidiarrheal effects across evaluated parameters. Rats in this group maintained body weight (mean change 3.3 ± 2.1 g) and consumed a higher proportion of the offered feed (72.33 ± 24.82%) compared with EPEC-induced rats (44.00 ± 8.72%), with values comparable to the Diapet®-treated group. Fecal consistency improved to predominantly solid stools, similar to those observed in healthy and Diapet®-treated rats, whereas higher extract doses were associated with semi-solid stools and reduced feed intake. Hematological analysis indicated that most parameters in the 400 mg/kg BW group remained within physiological reference ranges. Serum alanine aminotransferase (ALT) levels were also within the normal range at this dose (37.1 ± 5.6 U/L), while elevations in ALT and AST were observed at higher extract doses (800 and 1,600 mg/kg BW). Analysis of fecal bacterial profiles revealed no detectable Salmonella or Shigella colonies in the 400 mg/kg BW group, whereas these bacteria were detected in other experimental groups. In contrast, E. coli counts remained relatively stable across groups. Overall, this study provides preclinical evidence that P. foetida leaf extract exhibits dose-dependent antidiarrheal-associated effects in this experimental model, with the 400 mg/kg BW dose demonstrating the most favorable balance between efficacy-related outcomes and systemic tolerability in an EPEC-induced rat model. These findings support further investigation of P. foetida as a potential natural antidiarrheal candidate.