# Exploring Metabolic Disruption and Redox Modulation by Senna Leaf Extracts Induces Mortality in the Zoonotic Parasite Hymenolepis diminuta

## TL;DR

Senna leaf extracts kill the zoonotic tapeworm Hymenolepis diminuta by disrupting its energy metabolism and causing oxidative stress.

## Contribution

This study reveals the novel mechanism by which senna leaf extracts induce mortality in Hymenolepis diminuta through glycolytic disruption and reactive nitrogen species generation.

## Key findings

- Senna leaf extracts significantly alter energy metabolism in Hymenolepis diminuta, increasing glycogen phosphorylase activity and decreasing glycogen synthase activity.
- Parasites exposed to senna leaf extracts show elevated nitric oxide levels and NOS activity, indicating oxidative stress and mitochondrial dysfunction.
- Inhibition of key glycolytic enzymes and elevation of lactate dehydrogenase activity suggest a shift to anaerobic metabolism in treated parasites.

## Abstract

Senna leaf extracts exhibit strong anthelmintic effects against the zoonotic cestode Hymenolepis diminuta, inducing profound morphological and biochemical alteration. This study investigated the underlying mechanisms, focusing on glycolytic disruption and reactive nitrogen species (RNS) generation. Live H. diminuta were exposed in vitro to leaf extracts from Senna alata, Senna alexandrina, and Senna occidentalis (40 mg/mL), with praziquantel as a positive control. Biochemical assays demonstrated that there is a significant alteration in energy metabolism. Glycogen phosphorylase (GPase) activity increased, whereas glycogen synthase (GSase) activity declined, indicating enhanced glycogen catabolism. Parasites accumulated glucose and lactate but exhibited reduced pyruvate and malate, suggesting a shift towards anaerobic metabolism. Key glycolytic enzymes, including pyruvate kinase, phosphofructokinase, phosphoenolpyruvate carboxykinase, and malate dehydrogenase were inhibited, whereas lactate dehydrogenase and glutamate dehydrogenase activities were elevated. Histochemical analysis corroborated these enzymatic changes, demonstrating mitochondrial stress and redox imbalance. Notably, nitric oxide synthase (NOS) activity and nitric oxide (NO) levels were significantly elevated, indicating activation of the NO/cGMP signaling pathway. The resulting oxidative stress disrupted calcium homeostasis and induced flaccid paralysis. Collectively, our results indicate that senna leaf extracts compromise parasite viability by interfering with glycolytic metabolism and promoting RNS generation, underscoring their potential as effective plant‐derived anthelmintic agents.