Exploring Metabolic Disruption and Redox Modulation by Senna Leaf Extracts Induces Mortality in the Zoonotic Parasite <i>Hymenolepis diminuta</i>

Senna leaf extracts exhibit strong anthelmintic effects against the zoonotic cestode <i>Hymenolepis diminuta</i>, inducing profound morphological and biochemical alteration. This study investigated the underlying mechanisms, focusing on glycolytic disruption and reactive nitrogen species (RNS) generation. Live <i>H. diminuta</i> were exposed in vitro to leaf extracts from <i>Senna alata</i>, <i>Senna alexandrina</i>, and <i>Senna occidentalis</i> (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.