Comparative Anticonvulsant Efficacy of Natural, Artificial and Cultivated Bovis Calculus in PTZ-Induced Acute Seizures

Background: Bovis Calculus (NBC) is widely used for the management of convulsive disorder, but its clinical application is constrained by limited availability and high cost. Bovis Calculus Artifactus (BCA) and Bovis Calculus Sativus (BCS) are commonly employed as substitutes. However, systematic evidence comparing their anticonvulsant efficacy and pharmacological characteristics remains limited. Methods: This study evaluated the substitution potential of BCA and BCS relative to NBC and characterized their distinct pharmacological profiles in a pentylenetetrazol (PTZ)-induced acute seizure mouse model. Seizure latency and duration were evaluated, hippocampal pathology was examined by hematoxylin–eosin and Nissl staining, neurotransmitters and neuroinflammatory factors were quantified. Network pharmacology and molecular docking analyses were used to explore the underlying mechanisms. Results: The results showed that preventive administration of NBC, BCA, and BCS significantly alleviated PTZ-induced acute seizures, although their efficacy patterns differed markedly. NBC exhibited the broadest anticonvulsant spectrum, significantly prolonging seizure latency at multiple seizure stages. BCS showed a more restricted effect, primarily delaying stage IV seizures, whereas BCA predominantly reduced seizure frequency without significantly affecting seizure latency, suggesting that seizure frequency may represent a sensitive endpoint for evaluating certain anticonvulsant agents. Histopathological analyses demonstrated that all three preparations exerted neuroprotective effects in hippocampal subregions. NBC provided the most extensive morphological preservation in H&E staining, while all treatments significantly improved neuronal survival as assessed by Nissl staining. Biochemical analyses revealed distinct regulatory characteristics among the three Bovis Calculus sources. All treatments partially restored PTZ-induced neurotransmitter disturbances and attenuated neuroinflammatory responses. BCA showed prominent regulation of neurotransmitters and IL-1β, NBC exhibited broader modulation of neurotransmitter homeostasis, whereas BCS displayed stronger suppression of IL-6 and TNF-α despite limited effects on 5-HT regulation. These findings indicate that comparable protective effects against PTZ-induced acute seizures may be achieved through different neurochemical and inflammatory regulatory patterns. Network pharmacology and molecular docking analyses further suggested the potential involvement of PI3K-AKT and MAPK-related signaling pathways in the effects of NBC and its substitutes. Conclusions: Collectively, this study provides a comparative evaluation of NBC, BCA, and BCS and indicates that their protective activities against PTZ-induced seizures are associated with distinct neurochemical and anti-inflammatory profiles. These findings offer experimental evidence supporting the rational evaluation and application of alternative Bovis Calculus resources.