Honokiol as a next-generation phytotherapeutic: Anticancer, neuroprotective, and nanomedicine perspectives

Honokiol ( 厚朴酚, Hou Po Fen ), a biphenolic compound derived from the bark of Magnolia officinalis ( 厚朴, Hou Po ), has emerged as a promising phytochemical with multi-target pharmacological activities. Traditionally used in East Asian medicine, it is now being investigated for applications in cancer, neurodegenerative disorders, inflammation, and infectious diseases. Its therapeutic promise is attributed to its ability to modulate critical signaling pathways including NF-κB, STAT3, PI3K/Akt/mTOR, and Nrf2. This review synthesizes and critically analyzes published evidence on honokiol’s chemical properties, mechanisms of action, pharmacological activities, and nanotechnology-based delivery systems. Literature was sourced from PubMed, Scopus, and Web of Science databases, focusing on preclinical, clinical, and formulation studies of honokiol between 2000–2025. Key molecular targets, in vitro and in vivo efficacy, and translational challenges were evaluated and summarized. Honokiol demonstrates potent antioxidant, anti-inflammatory, anticancer, antimicrobial, and neuroprotective activities. It effectively induces apoptosis, inhibits angiogenesis, and modulates tumor microenvironmental factors. Neuroprotective actions include attenuation of neuroinflammation, preservation of mitochondrial function, and improvement of cognitive performance. Nanocarrier-based systems—such as liposomes, polymeric nanoparticles, micelles, and nanoemulsions—significantly improve honokiol’s solubility, stability, and bioavailability. Preclinical data confirm efficacy across cancer, neurological, and inflammatory models, though clinical evidence remains limited. Honokiol represents a promising next-generation phytotherapeutic candidate bridging traditional Chinese medicine and modern molecular pharmacology. Despite strong preclinical support, translational progress is hindered by low water solubility, poor bioavailability, limited clinical trials, and regulatory challenges. Advances in nanotechnology, epigenetic modulation, and personalized medicine approaches may accelerate clinical adoption. Future research should focus on standardized formulations, biomarker-driven trials, and integration with emerging therapeutic technologies.