Xanthohumol (XN)

Xanthohumol is a bioactive prenylated chalcone-type flavonoid primarily derived from the female inflorescences of the hop plant (Humulus lupulus) and is the most abundant prenylflavonoid found in beer [15]. It is widely recognized for its broad spectrum of biological activities, including potent antioxidant, anti-inflammatory, and anticancer properties [6, 10]. At the molecular level, xanthohumol functions as a multi-targeted agent that modulates key signaling pathways such as NF-κB, Nrf2/ARE, and Akt/mTOR [3, 16]. It also interacts directly with specific proteins such as Myeloid Differentiation Protein 2 (MD-2) and kinases like FLT3 and SRPK1 to exert its pharmacological effects [4, 14]. These interactions enable xanthohumol to regulate oxidative stress, suppress chronic inflammation, and induce apoptosis in various cancer cell lines [16, 18]. Beyond oncology, research has demonstrated its potential in treating metabolic syndrome, chronic liver disease, and neurodegenerative disorders such as Alzheimer's and Parkinson's disease [6, 11]. Despite its promising therapeutic profile, the clinical advancement of xanthohumol is currently hindered by its poor aqueous solubility and low systemic bioavailability [9, 10]. Ongoing clinical research, such as the Phase I XMaS trial, continues to investigate its safety, tolerability, and metabolic signature in humans [5, 13].

Other names

(E)-1-[2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-enyl)phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one2',4',4-trihydroxy-6'-methoxy-3'-prenylchalcone3'-prenyl-2',4',4-trihydroxy-6'-methoxychalcone

Xanthohumol acts through a multi-targeted mechanism that includes inhibiting the NF-κB inflammatory signaling pathway [3, 10], activating the Nrf2/ARE antioxidant response [10, 16], and directly binding to the hydrophobic cavity of Myeloid Differentiation Protein 2 (MD-2) to block TLR4-mediated immune activation [14]. It also functions as a kinase inhibitor, targeting the ATP-binding domains of FLT3 and SRPK1 [4], and modulates the Akt/mTOR and MAPK/ERK axes to suppress cell proliferation [6, 16].