# Impact of Melatonin Application in Winemaking on Phenolic Content, Tryptophan Metabolites, and Bioactivity of Red Wine

## TL;DR

Adding melatonin during winemaking boosts antioxidants and health benefits in red wine, including higher phenolic content and cancer cell toxicity.

## Contribution

First study to investigate melatonin's impact on wine quality and bioactivity during vinification.

## Key findings

- Melatonin increased total phenolic and flavonoid content in Moldova red wine.
- Melatonin-enriched wine showed higher antioxidant activity and cytotoxicity against cancer cells.
- Kynurenic acid levels rose, potentially enhancing wine's health benefits.

## Abstract

Global wine consumption drives the interest for high-quality wine with enhanced health benefits. Yeast-produced tryptophan metabolites, including melatonin, a potent antioxidant, emerged as promising agents for enhancing functional properties of food and beverages. This study represents the pioneering work addressing whether melatonin supplementation during vinification affects Moldova red wine quality. Total phenolic/flavonoid contents, DPPH, and FRAP assays were measured via spectrophotometry, anthocyanins, and tryptophan metabolites using UPLC-MS/MS and UPLC-FLD, as well as cytotoxicity with the MTT assay. Results showed that addition of melatonin during the winemaking process increased total phenolic/flavonoid content, as well as the antioxidant capacity evidenced by increased anti-DPPH radical activity. These effects might be due to the stimulation of phenolic compound biosynthesis, particularly anthocyanins malvidin-3-O-glucoside, peonidin-3-O-glucoside, and delphinidin 3-O-glucoside, which were found to be increased in the treated wine. Additionally, the study revealed that melatonin-enriched wine exhibited increased cytotoxicity against two cancer cell lines, HCT116 and PANC-1. Finally, melatonin supplementation enhanced the concentration of kynurenic acid, which, due to its cytoprotective and antioxidant properties, could further increase the health benefits of the resulting wine. These findings offer promising avenue for future research of melatonin-driven functional properties of wine and provide step forward to a natural product with added value.