# Plasma and Brain Metabolomics Uncover Modulation of Bile Acid and Pentose Phosphate Pathways by Melissa officinalis in Obese Rat Model

## TL;DR

This study explores how Melissa officinalis extract affects brain and blood metabolism in obese rats, revealing changes in bile acid and pentose phosphate pathways.

## Contribution

The study identifies novel metabolic pathways in the brain and plasma modulated by Melissa officinalis in an obese rat model.

## Key findings

- MOE reduced blood glucose levels in obese rats, as shown by the oral glucose tolerance test.
- Metabolomic analysis revealed modulation of bile acid biosynthesis in plasma and pentose phosphate metabolism in the brain.
- These findings suggest central and peripheral mechanisms influenced by MOE that may relate to behavioral effects observed in dogs.

## Abstract

While our group previously demonstrated the calming effects of Melissa officinalis extract (MOE) in dogs, the underlying brain-level mechanisms remain unclear. To address this, we investigated these mechanisms in rats using an untargeted metabolomics approach. Twenty-four male Wistar rats were divided into three groups (eight rats per group): control (standard diet, SD), a group fed a high-fat high-sucrose diet (HFHSD), and HFHSD administrated with a hydro-alcoholic standardized MOE (HFHSD MOE) at a dose of 200 mg/kg. Body weight, behavior through elevated plus maze (EPM), and glucose tolerance using the oral glucose tolerance test (OGTT) were monitored. After 12 weeks of supplementation, plasma and brain metabolomes were explored using non-targeted metabolomics. Although the EPM revealed no significant behavioral improvement, the OGTT showed a significant reduction in blood glucose area under the curve (AUC, p < 0.05), suggesting a metabolic effect of MOE. Metabolomic analysis highlighted two key pathways: (1) bile acid biosynthesis in plasma, as previously observed in our dog study, and (2) pentose phosphate metabolism in the brain. These results provide insight into central and peripheral mechanisms influenced by MOE and generate hypotheses on pathways potentially linked to previously reported behavioral effects in dogs, offering targets for nutritional interventions.