Enhanced Lignanamide Absorption and Antioxidative Effect of Extruded Hempseed (Cannabis sativa L.) Hull in Caco-2 Intestinal Cell Culture.

Despite the latest pursuit to discover novel phenolic compounds in hempseed and its biological properties, it remains a mystery whether they can be absorbed in the human body. Extrusion treatment and extraction of the free phenolic fraction significantly (p < 0.05) improved human Caco-2 intestinal cell absorption for hempseed hull lignanamides including cannabisin B (Papp value of 1.35 × 10-5 ± 1.0 × 10-6) as compared to the bound fraction of raw hull (Papp value of 2.82 × 10-6 ± 5.2 × 10-7). Co-supplementation of the flavonoid naringenin (20 μM) further improved these absorption rates. Higher cellular antioxidant activity was observed in the free extraction fractions. Treatment with the free phenolic fraction of extruded hempseed hull (100 mg/mL) alleviated tert-butyl hydroperoxide's (25 μM) negative effects on cell viability, intracellular malondialdehyde levels, apoptosis induction, glutathione S-transferase, and glutathione levels. RNA-sequencing with the limma method unveiled a total of 2795 differentially expressed genes in 21 day-old Caco-2 intestinal cells, suggesting the changes in cell metabolism after exposure to extruded hempseed hull extract. This study could promote the utilization of extrusion technology to improve the absorption and antioxidant capacities of bioactive phenolics in plant food processing byproducts.