Ameliorative Effect of Moringa oleifera Against CUMS-Induced Anxiety in Rats: β-Catenin and 5-HT_{1 A} Crosstalk

Serotonin 1 A receptor (5-HT1 AR) signaling is pivotal for stress response, determining vulnerability or resilience to psychopathology. However, the precise pathological mechanisms underlying its role remain inconsistent. Moringa oleifera (MO), a plant with purported medicinal properties, has demonstrated potential efficacy against psychiatric disorders. However, no available information exists regarding its effects on 5-HT1 A signaling under normal and stressed conditions. This study is aimed at elucidating the effects of MO in conjunction with 5-HT1 A signaling. Rats were randomly assigned to four groups: normal (NRML), normal rats receiving MO orally at 200 mg/kg (MO), rats exposed to chronic unpredictable mild stress (CUMS) for 21 days (CUMS), and stressed rats administered MO from day 15 (CUMS + MO). Behavioral analysis was conducted using forced swimming and open field tests. Serotonergic markers, β-catenin, p-Erk, c-myc, and mTOR were assessed via ELISA, while miRNA clusters and individual miRNAs were analyzed using PCR. No significant differences were observed between the NRML and MO groups, both of which exhibited approximately normal biochemical activity, except for a decreased 5-HIAA/5-HT ratio in the MO group, which was reflected behaviorally. Rats subjected to CUMS displayed defective β-catenin signaling, potentially leading to compensatory activation of 5-HT1 A. Consistently, the CUMS + MO group exhibited normalized 5-HT1 A and 5-HT signaling, accompanied by reduced pThr183-Erk and its downstream targets, c-myc and miR- 203, to mitigate pathological anxiety. Additionally, mTOR and its downstream target, miR- 217, were reduced compared to stressed rats. MO exhibited a promising anxiolytic effect by modulating 5-HT1 A signaling, as evidenced by improved neurobehavioral outcomes and restoring biochemical balance in stressed rats. These findings highlight its potential therapeutic role in anxiety management.