From wild plant to functional ingredient: phytochemical insights and neuroprotective activity of Melissa officinalis subsp. altissima

Melissa officinalis (lemon balm) is a culinary and medicinal herb traditionally used across diverse cultural systems for its cognitive-enhancing and neuroprotective effects. In light of its historical use in herbal teas, dietary supplements, and functional foods, this study investigates the bioactive potential of Melissa officinalis subsp. altissima, a wild subspecies of growing interest in the food and nutraceutical sectors. Wild specimens collected in Corsica (France) were investigated through an integrated metabolomic approach, combining a comprehensive phytochemical characterization of different extractive fractions and essential oils with a targeted biological evaluation performed on a hydroalcoholic extract selected as a representative model of the whole phytocomplex relevant to functional nutrition. Phytochemical profiling using high-resolution NMR spectroscopy identified a range of metabolites, including rosmarinic, chlorogenic, caffeic, and caftaric acids. GC-MS analyses were performed in parallel on the hydrodistilled essential oils and the volatiles obtained via HS-SPME, revealing a rich profile of bioactive volatile compounds such as germacrene-D, α,τ-cadinol, β-caryophyllene, and β-ocimene, which are known for their antioxidant and antimicrobial activities. Biological assays of the hydroalcoholic extracts demonstrated significant antioxidant capacity against hydrogen peroxide-induced oxidative stress in rat hypothalamic cells, as well as anti-inflammatory and neuroprotective effects in ex vivo murine assays. Notably, the extracts modulated the gene expression of key mediators such as TNF-α, NOS-2, IL-6, BDNF, and AChE suggesting a potential role in supporting brain health. These findings reinforce the potential of this lemon balm subspecies as a valuable natural ingredient for the formulation of functional foods and nutraceuticals with antioxidant, neuroprotective, and preservative properties. Moreover, the study underscores the broader significance of native aromatic Plants as sustainable resources for health-oriented food innovation.