Aporocactus flagelliformis Aqueous Extract Preserves Mitochondrial Integrity Under Glucose‐Induced Oxidative Stress in 3T3‐L1 Adipocytes

Hyperglycemia-induced oxidative stress disrupts mitochondrial homeostasis in adipocytes. This study investigated the biochemical mechanisms by which Aporocactus flagelliformis aqueous extract (AFAE) preserves mitochondrial integrity under glucose overload, moving beyond its role as a simple antioxidant. GC-MS profiling identified an oxygen-rich phytochemical matrix, predominantly comprising malic acid (11.41%), citric acid (10.92%), and myo-inositol (8.74%). Molecular docking against aldose reductase (AKR1B1), a key enzyme in the polyol pathway, revealed a top-ranked binding affinity of -8.234 kcal/mol, forming hydrogen bonds with catalytic residues (TYR48, HIS110). Through methodologically rigorous, independent biological replicates (n ≥ 3) in 3T3-L1 adipocytes exposed to 50 mM glucose, AFAE (0.008-0.8 µg/mL) significantly reduced intracellular and mitochondrial reactive oxygen species, restored mitochondrial membrane potential (ΔΨₘ), and preserved organelle mass. These concurrent stabilizations indicate that AFAE mitigates upstream metabolic triggers potentially alleviating the "NADPH steal" phenomenon associated with excessive AKR1B1 flux rather than merely scavenging downstream ROS. Ultimately, this study provides a coherent preclinical foundation linking the phytochemical composition of AFAE to the modulation of the polyol-pathway-mitochondrial axis, underscoring its potential as a biochemical modulator of cellular redox homeostasis.