Abstract
The sustainable utilization of biomass-derived bioactives addresses the growing demand for natural health products and supports sustainable development goals by reducing reliance on synthetic chemicals in healthcare. Cannabis sativa biomass, in particular, has emerged as a valuable resource within this context. This study focuses on the hydroethanolic extract of C. sativa leaves (CSE), which exhibited significant levels of phenolic compounds contributing to robust antioxidant activity. Evaluation using potassium ferricyanide, ABTS, and DPPH methods revealed potent radical scavenging activity comparable to the Trolox standard. UPLC-MS/MS profiling identified cannabinoids as the predominant secondary metabolites in CSE, with flavonoids also present in substantial quantities. This study investigated the anti-inflammatory potential of CSE on RAW 264.7 macrophages and IL-1β-stimulated C-20/A4 immortalized human chondrocytes, demonstrating protective effects without cytotoxic or mutagenic effects. Mechanistically, CSE reduced inflammation by inhibiting the MAPK and NF-κB signaling pathways. In silico approaches showed the ability of CSE's main metabolites to bind and influence MAPK and NF-κB activity, confirming in vitro evidence. Incorporating C. sativa leaf extract into a hyaluronic acid-based formulation showed biotechnological promise for treating joint inflammation. Future research should aim to elucidate the molecular mechanisms underlying these effects and explore the potential of CSE-derived compounds in mitigating osteoarthritis progression. This approach highlights the significance of utilizing annually increasing biomass waste for sustainable bioactivity and environmental impact reduction.