Polyphenol-rich fermented hempseed ethanol extracts improve obesity, oxidative stress, and neural health in high-glucose diet-induced Caenorhabditis elegans

Whole hempseed (WHS), fermented whole hempseed (FWHS), dehulled hempseed (DHS), and fermented dehulled hempseed (FDHS) ethanol extracts were tested for their toxicity and physiological benefits in relation to their phenolic profiles. The safety of all samples was confirmed by the absence of toxic effects on HepG2 cells. FWHS exhibited the highest capacity to inhibit lipase activity (70.80%) and acetylcholinesterase (AChE) (78.94%) in vitro. Similarly, in HepG2 cells, FWHS revealed the greatest ability to reduce the accumulation of reactive oxygen species (ROS). Fermented hempseed demonstrated superior antioxidant, neuroprotective and anti-fat potential, counteracting ageing in high glucose diet-induced C. elegans than unfermented. HPLC and UHPLC-Q-TOF-MS/MS² phenolic identification revealed the presence of diverse flavonoids, phenolic acids, lignanamides, and phenylamides in hempseed extracts. Among these polyphenols, quercetin, gallic acid, and kaempferol exhibited excellent antioxidant potential, whereas N-trans-feruloyl tyramine displayed the highest anti-lipase potential. This study suggests that polyphenol-rich hempseed exhibits potent antioxidant, and anti-obesity effects, and could improve neural health.