Trans-resveratrol (RSV) is a non-flavonoid polyphenol (stilbene) with numerous biological activities, such as anti-tumor activities. However, RSV is rapidly metabolized, which limits its therapeutic use. The availability of RSV analogues with similar activities for use in vivo is therefore a major challenge. For this purpose, several isomeric analogues of RSV, aza-stilbenes (AZA-ST 1a–g), were synthesized, and their toxicities were characterized and compared to those of RSV on murine N2a neuronal cells using especially flow cytometric methods. All AZA-ST 1a–g have an inhibitory concentration 50 (IC50) between 11.3 and 25 µM when determined by the crystal violet assay, while that of RSV is 14.5 µM. This led to the characterization of AZA-ST 1a–g—induced cell death, compared to RSV, using three concentrations encompassing the IC50s (6.25, 12.5 and 25 µM). For AZA-ST 1a–g and RSV, an increase in plasma membrane permeability to propidium iodide was observed, and the proportion of cells with depolarized mitochondria measured with DiOC₆(3) was increased. An overproduction of reactive oxygen species (ROS) was also observed on whole cells and at the mitochondrial level using dihydroethidium and MitoSox Red, respectively. However, only RSV induced a mode of cell death by apoptosis associated with a marked increase in the proportion of cells with condensed and/or fragmented nuclei (12.5 µM: 22 ± 9%; 25 µM: 80 ± 10%) identified after staining with Hoechst 33342 and which are characteristic of apoptotic cells. With AZA-ST, a slight but significant increase in the percentage of apoptotic cells was only detected with AZA-ST 1b (25 µM: 17 ± 1%) and AZA-ST 1d (25 µM: 26 ± 4%). Furthermore, only RSV induced significant cell cycle modifications associated with an increase in the percentage of cells in the S phase. Thus, AZA-ST 1a–g—induced cell death is characterized by an alteration of the plasma membrane, an induction of mitochondrial depolarization (loss of ΔΨm), and an overproduction of ROS, which may or may not result in a weak induction of apoptosis without modification of the distribution of the cells in the different phases of the cell cycle.

Oxidative stress plays a key role in tissue damage during inflammation, highlighting the need for effective antioxidant interventions. This study investigates the antioxidant potential of argan oil (AO)—obtained from Argania spinosa (L.) Skeels almonds—in comparison with olive oil (OO), cactus seed oil (CSO), and colza oil (CO). Quantitative analyses of total polyphenols and pigments—including chlorophylls, carotenoids, and xanthophylls—were conducted alongside antioxidant capacity assessments via DPPH, ABTS, and FRAP assays. The methanolic fraction consistently demonstrated the highest phenolic concentration and antioxidant efficacy across all oils. To establish in vivo relevance, a male C57BL/6J mouse model of acute oxidative stress was induced by lipopolysaccharide (LPS) administration. Pretreatment with oils significantly modulated key oxidative stress biomarkers—SOD, CAT, GPx activities, GSH levels, and lipid peroxidation (MDA)—in both heart and kidney. LPS challenge induced marked oxidative imbalance, notably increasing enzymatic activity and MDA levels, while depleting GSH in the heart and elevating it in the kidney. However, pretreatment with oils effectively restored redox homeostasis, with AO showing particularly potent effects and a stronger regulatory effect observed in the kidney. Hierarchical clustering of z-score-normalized heatmaps revealed distinct oxidative stress signatures, clearly separating LPS-treated heart and kidney tissues from other groups due to heightened oxidative markers. In contrast, oil-treated and oil-combined-with-LPS groups clustered closer to the control, underscoring the protective effect of oils against LPS-induced oxidative stress, with efficiency varying by oil type. Pearson correlation analysis, complemented by multivariate principal component analysis (PCA), further emphasized strong positive associations between antioxidant enzymes (SOD, CAT, GPx) and MDA levels, while GSH exhibited tissue-specific behavior—negatively correlated in the heart but positively in the kidney—highlighting divergent redox regulation between organs. Collectively, AO demonstrated robust cardioprotective and nephroprotective properties, supporting its potential as a natural dietary strategy against inflammation-induced oxidative stress.