Garcinol In Preclinical Cancer Models: A Systematic Review of Mechanisms, Safety, And Nanodelivery Strategies

Background: Garcinol, a polyisoprenylated benzophenone predominantly derived from Garcinia indica, has gained significant attention due to its wide-ranging pharmacological activities. Traditionally used in Ayurvedic medicine, garcinol exhibits potent antioxidant, anti-inflammatory, antimicrobial, and anticancer properties. Its multitarget potential makes it an emerging candidate for preclinical drug development. Methods: A systematic survey of the literature was performed across PubMed, Scopus, Web of Science, and Google Scholar up to August 2025. Studies were selected based on predefined inclusion criteria encompassing in vitro and in vivo preclinical evaluations of garcinol. Data were extracted regarding disease model, dose, route of administration, pharmacological outcomes, toxicity, and underlying molecular mechanisms. Results: Garcinol demonstrated consistent anti-cancer effects across multiple malignancies including breast, colon, prostate, pancreatic, and lung cancers. Mechanistically, it inhibits NF-κB, STAT3, and histone acetyltransferases, while promoting apoptosis, cell cycle arrest, and mesenchymal-to-epithelial transition in tumor cells. Its antioxidant and anti-inflammatory activities are mediated through suppression of reactive oxygen species, COX-2, and pro-inflammatory cytokines. Beyond oncology, garcinol shows promise in neuroprotection, cardiovascular modulation, antimicrobial defense, and anti-ulcer activity. Preclinical pharmacokinetic studies reveal moderate oral bioavailability, high tissue distribution, and minimal hepatic first-pass metabolism, though limited aqueous solubility remains a barrier. Toxicity profiles in rodents indicate high tolerability with no significant adverse effects. Emerging nanotechnology-based formulations including PLGA, gold nanoconjugates, and protein nanocarriers substantially improve solubility, stability, and therapeutic efficacy. Conclusion: Preclinical evidence positions garcinol as a multitargeted natural compound with broad therapeutic potential and favorable safety. However, translation to clinical application requires addressing formulation challenges, establishing human pharmacokinetics, and conducting well-designed clinical trials.