Amino acid metabolites profiling in unpredictable chronic mild stress-induced depressive rats and the protective effects of Gastrodia elata Blume and Gastrodin

J Ethnopharmacol. 2024 Oct 10:118906. doi: 10.1016/j.jep.2024.118906. Online ahead of print.

Abstract

Ethnopharmacological relevance: Major depressive disorder (MDD) is a prevalent condition that affects approximately 350 million people worldwide. Several studies have identified changes in amino acids in the blood of MDD patients, suggesting their potential as biomarkers to better understand their role in depression. Gastrodia elata Blume (GEB) and its active compound gastrodin (GAS) are recognized for their antidepressant properties. However, their effects on amino acid profiles and their potential role in alleviating depression remain poorly understood. Understanding how GEB and GAS influence amino acid metabolism may offer novel insights into their mechanisms in alleviating depression, potentially leading to more targeted therapeutic strategies.

Aim of the study: This study aimed to investigate the potential role of supplementing GEB and its active compound GAS to reverse altered amino acid profiles in depressed rats.

Materials and methods: To achieve this, six-week-old SD rats were induced depressive-like behaviors by the UCMS rat model for 5 weeks. Groups receiving GEB or GAS were administered orally via gavage daily within the UCMS model. Serum samples were collected and analyzed using a targeted metabolomics approach employing LC-MS for amino acid profiling.

Results: A total of 38 amino acid metabolites were identified, 17 of which were significantly altered following UCMS. UCMS rats exhibited perturbed arginine biosynthesis, arginine and proline metabolism pathways. Changes in key amino acids in these metabolic pathways were reversed following supplementation with GEB and GAS, which also alleviated depressive symptoms.

Conclusions: In conclusion, UCMS-induced depression in rats causes changes in some amino acid metabolites similar to those found in human depression, validating its relevance as a model for studying depression. Additionally, the research suggests that GEB and GAS may exert antidepressant effects by regulating amino acid metabolism.

Keywords: Gastrodia elata Blume; Metabolomics; amino acid profiling; depression; gastrodin.