Cannabidiol Enhances Mitochondrial Metabolism and Antioxidant Defenses in Human Intestinal Epithelial Caco-2 Cells

• Published in: Nutrients 2024-11, Vol.16 (22), p.3843
• Main Authors: Bravo Iniguez, Alejandro, Sun, Qi, Cui, Qiaorong, Du, Min, Zhu, Mei-Jun
• Format: Article
• Language: English
• Subjects: AMP-Activated Protein Kinases - metabolism; Antibodies; Antioxidants; Antioxidants - metabolism; Antioxidants - pharmacology; Biosynthesis; Caco-2 Cells; Cannabidiol; Cannabidiol - pharmacology; Dehydrogenases; Enzymes; Ethylenediaminetetraacetic acid; Free radicals; Health aspects; Homeostasis; Humans; Inflammatory bowel disease; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Kinases; Metabolism; Metabolites; Mitochondria - drug effects; Mitochondria - metabolism; Oxidative stress; Oxidative Stress - drug effects; Penicillin G; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; Phosphorylation; Phosphorylation - drug effects; Protein kinases; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; Sirtuin 3 - metabolism; Statistical analysis; Transcription factors
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu16223843

The reintroduction of hemp production has resulted in increased consumption of cannabidiol (CBD) products, particularly CBD oil, yet their effects on intestinal health are not fully understood. Proper mitochondrial function and antioxidant defenses are vital for maintaining the intestinal epithelial barrier. AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator (PGC)1α are key mediators of mitochondrial metabolism. Using Caco-2 cells, we found that CBD oil promoted AMPK phosphorylation, upregulated differentiation markers, and enhanced PGC1α/SIRT3 mitochondrial signaling. CBD oil reduced reactive oxygen species production and increased antioxidant enzymes. Moreover, CBD oil also increased levels of citrate, malate, and succinate-key metabolites of the tricarboxylic acid cycle-alongside upregulation of pyruvate dehydrogenase and isocitrate dehydrogenase 1. Similarly, pure CBD induced metabolic and antioxidant signaling. CBD enhances mitochondrial metabolic activity and antioxidant defense in Caco-2 cells, making it a promising candidate for treating intestinal dysfunction.