Coffee cascara is an underutilized byproduct of coffee processing that has the potential for value-added applications due to its rich phytochemical content and antioxidant properties. The aim of this study was to characterize the phytochemical composition and antioxidant activity of coffee cascara sourced from seven geographic regions, and where possible, a variety of farms in different regions. We compared two different extraction methods: hot water/sonication-assisted extraction and methanol–water extraction to generate phytochemical content. The antioxidant capacity of extracts was assessed through different assays. Correlations between phytochemical compounds and different antioxidant activities were analyzed first using Pearson’s correlations and then substantiated further using principal component analysis (PCA). The dominant phytochemicals identified in the extracted coffee cascara included gallic acid, chlorogenic acid isomers, mangiferin, protocatechuic acid and rutin. Among the water-extracted samples, the Brazil sample exhibited the highest oxygen radical absorbance capacity (ORAC) value, whereas the Zambia sample had the highest 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) value and the Laos sample showed the greatest inhibition of 2′,7′-Dichlorofluorescein diacetate (DCFH-DA) fluorescence. For methanol extracts, the highest ORAC and ABTS values were from the Indonesia sample, and the Laos sample showed the strongest inhibition of DCFH-DA fluorescence. The results show the distinct phytochemical composition and antioxidant activity of coffee cascara according to geographical clustering using PCA. Specifically, gallic acid, p-hydroxybenzoic acid and to a lesser extent rutin correlated (p < 0.05) with ABTS and DCFH-DA assays. This study revealed significant variation in the chemical composition and antioxidant properties of coffee cascara across different geographic regions; less so with different farms associated with the location. The findings offer evidence for potential upscaling of coffee cascara waste for use in value-added functional food or nutraceutical applications.

Curcumin is a major bioactive component present in turmeric, attributed with a bright yellow color; however, with low solubility and susceptibility to photooxidation, many of the purported health benefits are actually limited. We developed an encapsulation delivery system to produce curcumin nanoparticles using α-cyclodextrin as a carrier and Tween 80 as a surfactant for the purpose of increasing photostability and bioavailability. We used RSM to determine an optimal curcumin nanoparticle (NP) size of 386.4 ± 21.3 nm and entrapment efficiency of 97.4 ± 2.9% for use in functional tests conducted in differentiated Caco-2 cells. Curcumin-NP showed greater (p = 0.001) (74.32 ± 4.20%) stability compared to free curcumin (36.74 ± 3.03%), after treatment with pulsed light, at the highest 20 J/cm² energy input. The release behavior of curcumin-NPs was pH-dependent and showed a 5 times higher intestinal epithelial cellular uptake and 21.3% decrease of TEER-value, compared to free curcumin (p = 0.017). Compared with free curcumin, the curcumin-NPs had higher antioxidant capacity in all tests while exhibited lower antioxidant capacity loss after pulsed light treatment. Moreover, pre-exposure of curcumin-NPs to pulsed light treatment showed no apparent cytotoxicity effects in Caco-2 cells. In conclusion, using α-cyclodextrin for curcumin-NP encapsulation enhanced both bioavailability and photostability, leading to greater intestinal intracellular antioxidant capacity and no loss in cell viability.

Hydrogen peroxide (H₂O₂) is a key extracellular redox signaling molecule that regulates diverse physiological processes, including immune cell activation and proliferation. However, its role in maintaining extracellular redox balance and mediating intercellular signaling remains underexplored. In this study, we investigated how extracellular depletion of H₂O₂ by catalase modulates intracellular signaling pathways in macrophages. Catalase treatment effectively depleted extracellular H₂O₂ in a concentration- and time-dependent manner, leading to activation of mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, as well as nuclear translocation of the nuclear factor κB (NF-κB) p65 subunit. Perturbation of extracellular redox status resulted in robust upregulation of inflammatory and oxidative stress–related genes, including cyclooxygenase-2 (COX-2), C-C motif chemokine ligand 5 (CCL5), inducible nitric oxide synthase (iNOS), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This transcriptional response was accompanied by increased nitric oxide (NO) production and enhanced nuclear translocation and DNA-binding activity of nuclear factor erythroid 2–related factor 2 (Nrf2). Mechanistically, our data suggest that NO-mediated S-nitrosylation contributes to activation of the cellular antioxidant response. In addition, catalase-mediated depletion of extracellular H₂O₂ significantly (p < 0.05) suppressed 5-bromo-2′-deoxyuridine (BrdU) incorporation, indicating inhibition of macrophage proliferation. Together, these findings demonstrate that extracellular H₂O₂ functions as a physiological redox signal that maintains cellular homeostasis, and that its removal triggers a coordinated intracellular response involving both inflammatory activation and antioxidant defense. This study highlights the critical role of extracellular redox balance in shaping macrophage function and provides mechanistic insight into how changes in the oxidative environment regulate downstream immune signaling pathways.