Role of magnolol in gastrointestinal cancers: Recent trends and future perspectives

Gastrointestinal cancers represent a major global health burden and are associated with high morbidity and mortality worldwide. Despite advances in conventional therapies, treatment outcomes remain limited due to therapy resistance, toxicity, and poor long-term efficacy, highlighting the need for novel and complementary therapeutic strategies. Magnolol, a biphenolic lignan isolated from Magnolia officinalis, has attracted considerable attention due to its reported anticancer activity in multiple gastrointestinal malignancies. This review systematically summarizes current preclinical evidence on the anticancer effects of magnolol in oral, esophageal, gastric, colorectal, pancreatic, and liver cancers. Available studies demonstrate that magnolol inhibits cancer cell proliferation, migration, invasion, angiogenesis, and epithelial-mesenchymal transition, while inducing cell cycle arrest and apoptosis. These effects are mediated through modulation of key cancer-associated signaling pathways, including PI3K/Akt/NF-κB, MAPK/JNK, ERK, TGF-β/Smad, and caspase-dependent apoptotic pathways. The review further highlights recent insights into the structure-activity relationship of magnolol and its semi-synthetic derivatives, emphasizing how targeted chemical modifications influence anticancer potency and mechanistic specificity. In addition, challenges related to magnolol's poor aqueous solubility, rapid metabolism, and limited bioavailability are discussed, with particular focus on nanotechnology-based delivery systems developed to improve its pharmacokinetic profile and therapeutic performance. This current review provides an integrated overview of magnolol's molecular mechanisms, chemical optimization strategies, and translational limitations in gastrointestinal cancer therapy, and outlines future research directions necessary to support its progression toward clinical application.