Background/Objectives: Corema album berries are edible fruits from the Iberian Atlantic coast, characterized by a rich polyphenolic composition, which endows their juice with potential protective effects against neurodegeneration. This study aimed to evaluate the potential of the relatively lesser-known C. album berries as a novel neuroprotective agent against neurodegenerative diseases. Methods: The phenolic compounds of the juice were characterized using UHPLC-HRMS (Orbitrap). The SH-SY5Y neuroblastoma line was used to determine the preventive effect of the juice against H₂O₂-induced oxidative stress. Furthermore, neuronal cells were differentiated into dopaminergic and cholinergic lines and exposed to 6-hydroxydopamine and okadaic acid, respectively, to simulate in vitro models of Parkinson’s disease and Alzheimer’s disease. The ability of the juice to enhance neuronal viability under toxic conditions was examined. Additionally, its inhibitory effects on neuroprotective-related enzymes, including MAO-A and MAO-B, were assessed in vitro. Results: Phytochemical characterization reveals that 5-O-caffeoylquinic acid constitutes 80% of the total phenolic compounds. Higher concentrations of the juice effectively protected both differentiated and undifferentiated SH-SY5Y cells from H₂O₂-induced oxidative damage, reducing oxidative stress by approximately 20% and suggesting a dose-dependent mechanism. Moreover, the presence of the juice significantly enhanced the viability of dopaminergic and cholinergic cells exposed to neurotoxic agents. In vitro, the juice inhibited the activity of MAO-A (IC₅₀ = 87.21 µg/mL) and MAO-B (IC₅₀ = 56.50 µg/mL). Conclusions: While these findings highlight C. album berries as a promising neuroprotective agent, further research is required to elucidate its neuroprotective mechanisms in cell and animal models and, ultimately, in human trials.

In a preliminary screening of phytochemical compounds from Andalusian vascular plants, the ethyl acetate extract obtained from the leaves of Corema album (L.) D. Don (Ericaceae) was selected due to its cytotoxic activity. Eight phenolic compounds were isolated from this extract: four chalcones (2′,4′-dihydroxydihydrochalcone, 2′,4′-dihydroxychalcone, 2′,4′-dihydroxy-6′-methoxydihydrochalcone, 2′-methoxy-4′-hydroxydihydrochalcone) and four flavanones (pinocembrin, 6-methylpinocembrin, 6,8-dimethylpinocembrin and 7-O-prenylpinocembrin). Their structures were elucidated using ¹H NMR and ¹³C NMR data, including 2D NMR, as well as mass spectrometry. These compounds were evaluated using the MTT cytotoxicity assay against human colorectal adenocarcinoma (HT-29) and renal adenocarcinoma (ACHN) cell lines. The chalcone 2′,4′-dihydroxychalcone exhibited greater cytotoxicity than the corresponding 2′,4′-dihydroxydihydrochalcone in both cell lines. The IC₅₀ values (µM ± SEM) were 13.31 ± 0.48 and 9.43 ± 0.34 for the chalcone, and 62.23 ± 1.06 and 54.68 ± 1.62 for the dihydrochalcone, respectively. The introduction of methyl groups at positions 6 and 8 of pinocembrin increased cytotoxicity in the ACHN cell line. The IC₅₀ values (µM ± SEM) were 91.28 ± 3.03 for pinocembrin, 64.36 ± 0.53 for 6-methylpinocembrin, and 28.74 ± 0.35 for 6,8-dimethylpinocembrin. These results highlight the leaves of C. album as a promising source of chalcones and flavanones with pharmacological interest.

Corema album, an Atlantic endemic berry traditionally consumed in the Iberian Peninsula, is gaining increasing attention due to its rich phenolic profile. Here, we report for the first time the isolation, structural characterization, and quantification of three chalcones from their fruits: 2',4'-dihydroxydihydrochalcone, 2',4'-dihydroxychalcone, and 2'-methoxy-4'-hydroxydihydrochalcone. Structural elucidation was achieved by NMR and mass spectrometry, and quantification was performed by UHPLC-HRMS. Their antioxidant and anti-inflammatory activities were evaluated in human (THP-1) and murine (RAW 264.7) macrophage models. All compounds significantly reduced intracellular ROS levels under oxidative stress conditions and suppressed LPS-induced production of IL-6 and TNF-α. In RAW 264.7 cells, 2',4'-dihydroxychalcone and 2'-methoxy-4'-hydroxydihydrochalcone decreased nitric oxide production through iNOS downregulation. Moreover, chalcones inhibited COX-2 activity in vitro (IC₅₀ ≈ 45 µM) and modulated NF-κB-related signaling markers, including NF-κB p65, IκBα and IL-1β expression. Notably, 2',4'-dihydroxychalcone increased HO-1 protein levels in both macrophage models. These results highlight the multi-target anti-inflammatory potential of C. album chalcones, mediated through coordinated regulation of oxidative stress and key inflammatory pathways. The findings provide mechanistic support for the traditional use of these berries and underscore their promise as natural anti-inflammatory agents. Further in vivo studies are warranted to evaluate their therapeutic efficacy.