Exploring the Potential of Hop (Humulus lupulus) Cone Residue: Chemical Characterization and Evaluation of Bioactivities

Humulus lupulus L. (hops), belonging to the Cannabaceae family, is grown mainly for brewing, with 98% of global production directed to this sector. Moreover, large volumes of female cone residues are generated as by-products, representing a valuable source of bioactive compounds that can be valorized under green chemistry principles. This study aimed to extract bioactive compounds from hop cone residues sourced from craft breweries using ultrasound-assisted (EH-UA) and microwave-assisted (EH-MA) extraction methods. Hydroalcoholic extracts (70%) were analyzed for chemical composition, antioxidant, antimicrobial, antiproliferative, nitric oxide (NO)-production inhibition, and photoprotective activities. GC-MS identified 32 compounds in EH-MA and 30 in EH-UA, including terpenes, sesquiterpenes, oxygenated sesquiterpenes, and fatty acids. Both extracts demonstrated strong antioxidant activity in cell-based (TBARS, OxHLIA) and chemical (DPPH, ABTS, FRAP) assays, particularly EH-MA. Significant antibacterial activity was observed, especially against Enterobacter cloacae, Pseudomonas aeruginosa, and Staphylococcus aureus (MIC 1–10 mg/mL), as well as antifungal activity against Aspergillus brasiliensis (MIC 2–2.5 mg/mL). Selective antiproliferative activity was observed against tumor cell lines Caco-2 and MCF-7 (GI50 25 μg/mL), without cytotoxicity toward nontumor cell lines Vero and PLP2 (GI50 > 400 μg/mL). All extracts inhibited the production of the inflammation mediator NO, with EH-MA showing the most potent effect (IC50 of 35 μg/mL), followed by EH-UA (IC50 of 55 μg/mL). Photoprotective potential was also demonstrated, with SPF values of 19 (EH-MA) and 18 (EH-UA). In conclusion, hop cone residues can yield multifunctional extracts with antioxidant, antimicrobial, antiproliferative, anti-inflammatory, and photoprotective activities, which support their sustainable upcycling for pharmacological, nutraceutical, and cosmetic applications.