Repurposing the Antipsychotic Olanzapine as a Protective Agent in Colitis: Involvement of P65 NF-κB/TLR4 Pathway and Serotonin Signaling
| Author | Tayebeh Noori | en |
| Author | Mohammadreza Esmailzadeh | en |
| Author | Antoni Sureda | en |
| Author | Mozafar Khazaei | en |
| Author | Mohammad Hosein Farzaei | en |
| Author | Sina Korani | en |
| Author | Samira Shirooie | en |
| Orcid | Tayebeh Noori [0000-0002-3894-5179] | en |
| Orcid | Mohammadreza Esmailzadeh [0009-0008-2479-0576] | en |
| Orcid | Antoni Sureda [0000-0001-8656-6838] | en |
| Orcid | Mozafar Khazaei [0000-0003-0536-3217] | en |
| Orcid | Mohammad Hosein Farzaei [0000-0001-7081-6521] | en |
| Orcid | Sina Korani [0009-0007-8537-8799] | en |
| Orcid | Samira Shirooie [0000-0002-5000-3387] | en |
| Issued Date | 2026-12-31 | en |
| Abstract | Background: Serotonin acts as an immune modulator, and altered serotonin signaling has been linked to intestinal inflammation. Olanzapine is an atypical antipsychotic with high affinity for serotonin 5-HT2A receptors, which it antagonizes. Objectives: This study investigated the effects of olanzapine on acetic acid-induced colitis in rats. Methods: Thirty-five rats were randomly assigned to seven groups (n = 5 per group): control, acetic acid, sulfasalazine (500 mg/kg), olanzapine (2.5 or 5 mg/kg), serotonin (1 mg/kg), and olanzapine (5 mg/kg) plus serotonin (1 mg/kg). After three days of pretreatment, colitis was induced in groups 2 - 7 by rectal administration of 1 mL of 4% acetic acid. Drug administration resumed two hours after induction and continued daily for five days. A 7-cm segment of distal colonic tissue was then collected for microscopic examination, hematoxylin and eosin (H&E) staining, and immunohistochemical assessment of nuclear factor κB (NF-κB) p65 and Toll-like receptor 4 (TLR4) protein expression. Results: Macroscopic examination revealed significant differences in inflammation and mucosal integrity between the acetic acid group and the sulfasalazine and olanzapine groups. Protein expression of NF-κB p65 and TLR4 was markedly lower in the olanzapine groups than in the acetic acid group and was significantly lower in the olanzapine plus serotonin group than in the serotonin group. Conclusions: Through its antagonistic effects on serotonin and its reduction of NF-κB/TLR4 pathway activity, olanzapine reduced inflammation and mucosal damage, as assessed macroscopically and histologically. Further investigations are needed to confirm and extend these findings. | en |
| DOI | https://doi.org/10.5812/jrps-170324 | en |
| URI | https://brieflands.com/journals/jrps/articles/170324 | en |
| Keyword | Olanzapine | en |
| Keyword | Colitis | en |
| Keyword | Serotonin | en |
| Keyword | Acetic Acid | en |
| Keyword | Rat | en |
| Publisher | Brieflands | en |
| Title | Repurposing the Antipsychotic Olanzapine as a Protective Agent in Colitis: Involvement of P65 NF-κB/TLR4 Pathway and Serotonin Signaling | en |
| Type | Research Article | en |