Unravelling the effects of specific ingredients of kamishoyosan in reducing aggressive biting behavior in chronically isolated mice to inanimate objects

Kamishoyosan (KSS) is a well-known traditional Japanese herbal medicine used to treat psychiatric symptoms, such as irritation. We previously reported that KSS decreases mouse aggressive biting behavior (ABB) to inanimate objects using the Aggression Response Meter, however, it was not revealed which ingredient of KSS is effective. In this study, we used real-time reverse transcriptase (RT) PCR to investigate the mRNA expression of 5-HT-related genes in SH-SY5Y cells cultured in a medium containing the ten individual herbal medicines in KSS. The cells treated with shakuyaku showed increase of tryptophan hydroxylase mRNA expression, whereas those cultured in a medium containing botanpi showed decreased monoamine oxidase A and B mRNA levels. We investigated the ABB of mice administered with Paeonia lactiflora (shakuyaku) or Paeonia suffruticosa (botanpi). We also examined the gene expression in cells treated with paeoniflorin (PF), a main active component in shakuyaku, and the ABB of PF-treated mice. We found that shakuyaku or PF administration reduced ABB in male and female mice, whereas botanpi treatment mitigated ABB only in males. WAY-100635, a 5-HT1A receptor antagonist, abolished ABB-reducing effect of shakuyaku and botanpi. These results suggest that shakuyaku and botanpi are activate ingredient to reduce ABB through activation on serotoninergic neurotransmission.