Pharmacological advances of honokiol: Mechanisms, targets and therapeutic potential (Review)

Honokiol (HKL), a bioactive biphenolic lignan isolated from the bark of Magnolia officinalis, possesses diverse pharmacological properties, including neuroprotective, antitumor, anti-inflammatory and metabolic regulatory effects. Despite its therapeutic promise, the clinical application of HKL is severely restricted by its hydrophobicity and low oral bioavailability. The present review systematically summarized 99 studies (90 original articles and nine reviews) on the pharmacological profile of HKL. It detailed HKL's molecular interactions with key signaling targets, such as sirtuin 3, NOD-like receptor family pyrin domain containing 3-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes, Yes-associated protein/transcriptional coactivator with PDZ-binding motif, adenosine monophosphate-activated protein kinase and signal transducer and activator of transcription 3, which underly its efficacy against cancer (ovarian, liver, breast, colorectal, and lung), neurodegeneration (Alzheimer's and Parkinson's disease), metabolic disorders (diabetes, nonalcoholic fatty liver disease and obesity) and inflammatory and infectious diseases. Furthermore, the present review critically evaluated recently developed strategies to overcome its pharmacokinetic limitations. The present review offered an updated theoretical basis for understanding the structure-activity relationship of HKL and provided insights into its translation from bench to bedside.