Background: Aggression is a multidimensional behaviour influenced by stress, arousal, social isolation and central inhibitory control. This study evaluated the acute oral safety of methanolic leaf extracts of Piper methysticum G. Forst. and Buchanania lanzan Spreng., selected experimental doses and compared their anti-aggressive effects in food shock-induced and isolation-induced aggression models. Methods: In an OECD Test Guideline 425 limit study, female Swiss albino mice received a single oral dose of 2000 mg/kg of either extract and were observed for 14 days. For each aggression model, male Swiss albino mice were allocated to vehicle control, diazepam 2 mg/kg, Piper methysticum 100, 200 or 400 mg/kg, or Buchanania lanzan 100, 200 or 400 mg/kg groups (n=6). Treatments were administered orally. Food shock consisted of 0.5 mA stimulation for 0.5 s at 10-s intervals over a 5-min observation period. In the isolation model, mice were housed individually for 7 days and challenged with a similar-weight male intruder for 5 min. Results: Neither extract produced mortality or major toxicity at 2000 mg/kg; body weight remained stable, indicating an approximate oral LD50 greater than 2000 mg/kg. Doses of 100, 200 and 400 mg/kg were therefore selected. Both extracts reduced aggressive behaviour dose-dependently. In the food shock model, Piper methysticum and Buchanania lanzan at 400 mg/kg reduced fights by 64.60% and 56.64%, respectively. In isolation-induced aggression, the corresponding reductions in attack frequency were 64.18% and 55.22%. Both high-dose effects were highly significant versus control (p<0.001), although diazepam remained more active. Conclusion: The extracts showed preliminary acute tolerability and anti-aggressive-like effects in stress- and isolation-related models, with Piper methysticum consistently more active. The findings are preclinical and require repeated-dose toxicity, locomotor controls and mechanistic validation before therapeutic translation.
Poonam Yadav, Sushila Kaura, "Acute Oral Safety and Comparative Anti-Aggressive Effects of Methanolic Leaf Extracts of Piper methysticum G. Forst and Buchanania lanzan Spreng. in Mouse Models", Vol. 4, Issue 2, 23-05-2026, pp. 50-60. DOI: 10.5281/zenodo.21428088