The Green Treasure from Appennine Flora for Colon and Liver Health: Characterization and Evaluation of the Protective Effects from Aerial Parts of Helichrysum italicum

Helichrysum italicum Mill. (Asteraceae), a perennial evergreen species native to the Mediterranean basin, has been traditionally employed to treat various inflammatory and infectious diseases, as well as respiratory, digestive, gallbladder, and bladder disorders. The plant is valued for its essential oil. It contains phenols and flavonoids, which play a fundamental role in the protective effects associated with the traditional use of extracts of its aerial parts. The goal of the study was to investigate the phytochemical and biological properties of polar extracts, specifically water and hydroalcoholic (50% ethanol) extracts, obtained from the aerial parts of H. italicum. The extracts were evaluated for phenolic composition and concurrently assessed for antioxidant and enzyme-inhibitory activities. Additionally, the biocompatibility of the extracts was investigated using eco-toxicological models, including Artemia salina lethality and Daphnia magna cardiotoxicity assays, as well as allelopathic studies. CCD841CoN colon epithelial cell viability was also assessed in the presence of the extracts. The extracts’ protective effects were examined in an ex vivo inflammatory model using isolated mouse colon and liver tissues exposed to Escherichia coli lipopolysaccharide (LPS). Their influence on cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) gene expression was investigated, as well. Docking studies were also performed to uncover on the potential mechanisms underpinning the biological effects observed in the study. The phytochemical analysis showed that hydroxycinnamic acids and quercetin derivatives were the primary components in both extracts. In particular, the hydroalcoholic extract showed higher phenol levels and more potent scavenging/reducing and enzyme inhibitory activities against tyrosinase, cholinesterases, glucosidase, and amylase. Using the aforementioned eco-toxicological and in vitro cell models, the extracts’ biocompatibility was determined to be in the range of 200–1000 µg/mL. Within this concentration interval, the extracts effectively mitigated LPS-induced stimulation of COX-2 and IL-6 gene expression. Docking studies suggest that hydroxycinnamic acids (notably chlorogenic acid) and flavonoids (including quercetin, rutin, hyperoside, and isoquercitrin) play a pivotal role in the extracts’ anti-inflammatory activity. In conclusion, this study provides scientific evidence supporting the ethnopharmacological use of H. italicum in managing oxidative stress and inflammatory disorders, especially in the digestive system. Phenolics in the extracts likely enhance their therapeutic potential. These findings warrant further research, including in vivo studies, to assess the extracts’ efficacy and safety profile comprehensively.