Xanthohumol

Prenylated flavonoid xanthohumol (XN) from hops was comprehensively investigated for its anti-osteoarthritic potential in vitro and in vivo. XN dose-dependently inhibited IL-1β-induced iNOS, COX-2, TNF-α, IL-6, NO and PGE₂ expressions, and reversed downregulation of type II collagen and aggrecan expressions in IL-1β-stimulated murine chondrocytes. XN inhibited IL-1β-induced degradation of IκBα and nuclear translocation of p65 subunit, preventing activation of NF-κB signaling pathway, while activating Nrf2/HO-1 pathway. Depletion of Nrf2 significantly compromises the protective effects of XN. In the surgical destabilization of the medial meniscus mouse model of OA, daily oral administration of XN reduced cartilage erosion, osteophyte formation and joint space narrowing, while upregulating the articular expression of Nrf2.

Fig. 1 Model proposing the role of Xanthohumol (XN) in osteoarthritis therapy. (Chen X.; et al. 2021)

Xanthohumol (Xn) is active against various diseases with its anti-inflammatory, anticancer, antiviral, antibacterial, antidiabetic, antiplatelet and antimalarial properties. However, its clinical application is restricted due to its poor aqueous solubility, high photosensitivity, short half-life and low oral bioavailability.
Biodegradable polymers and natural-based delivery carriers have been extensively reviewed. Nanoparticles, nanomicelles, nanoliposomes, solid lipid nanoparticles (SLN), self-nanoemulsifying drug delivery systems (SNEDDS) and liquisolid-based colon-targeted powders derived from poly(lactic-co-glycolic acid) (PLGA), poly(caprolactone) (PCL), chitosan, lipids, cyclodextrins, protein Z, electrospun fibres and microemulsions were developed and demonstrated 1.4-145-fold improved solubility, 4-47-fold increase in bioavailability, sustained release behaviour, and greater in vitro cytoprotective or antimicrobial efficacy than Xn alone. Hybrid scaffolds comprising electrospun nanofibres with hydroxyapatite-g-PLLA were also fabricated to provide enhanced mechanical properties with gradient Xn release for tissue engineering applications.

Fig. 2 Different formulations for Xanthohumol (Xn) delivery. (Oledzka E.; et al. 2024)