Abstract
Cannabis sativa L. (C. sativa), commonly known as hemp, is widely recognized for its diverse range of bioactive compounds with therapeutic potential in medicinal, industrial, and nutritional applications. This study investigates the use of adventitious roots (ARs) derived from C. sativa as a scalable platform for producing bioactive metabolites with immunomodulatory and anti-inflammatory properties. We first isolated extracts from C. sativa ARs (CS-AR) using various solvents: methanol (MeOH-E), chloroform (CHCl(3)-E), and hexane (Hexane-E), and explored their effects on dendritic cell (DC) maturation, a key process involved in immune responses. Notably, MeOH-E demonstrated strong anti-inflammatory effects without inducing cytotoxicity in DCs, distinguishing it from the other extracts. Metabolomic analysis of these extracts annotated the presence of cannabinoid derivatives and metabolites, including cannabinoid glycoside derivatives, cannabigerolic acid-O-acetate (CBGA-O-acetate), cannabidiol diacetate derivatives, and cannabidiol mono-acetate mono-benzoate. Among these, cannabinoid glycoside derivatives and CBGA-O-acetate were found to be present at higher levels in MeOH-E. Further investigation into the functional properties of MeOH-E revealed that it could suppress the expression of key surface molecules and antigen-presenting ability in mature DCs, alongside attenuating mitogen-activated protein kinase (MAPK) signaling pathways as well as nuclear factor kappa-B (NF-κB) signaling. Additionally, MeOH-E inhibited T cell proliferation and activation. These findings underscore the CS-AR system as a promising, reproducible biotechnological platform for producing therapeutic bioactive compounds for inflammatory diseases, with significant potential for application in the pharmaceutical and nutraceutical industries.