Unveiling the therapeutic potential of Fisetin: Bridging traditional knowledge with modern medicine

Fisetin (FIS), a pharmacologically active flavonoid present in various fruits and vegetables including strawberries, apples, and persimmons, has attracted considerable attention owing to its broad-spectrum pharmacological activities. Having been traditionally utilized as an antioxidant and anti-inflammatory agent in herbal medicine, FIS is now being developed as a novel therapeutic agent in modern pharmacology. Its wide biological activities involve neuroprotection, antidiabetic, antiobesity, antiatherosclerotic, and significant anticancer activity against lung cancer, colon cancer, prostate cancer, pancreatic cancer, and skin cancer. These activities are mediated through various pathways involving mTOR, Wnt/β-catenin, NF-κB, and TRAIL-induced apoptosis, making FIS a multitargeted pharmacological agent. However, poor solubility and poor bioavailability remain major hurdles in its clinical application. Several novel delivery vehicles including self-nano emulsifying drug delivery systems (SNEDDS), liposomes, ethanol-based delivery vesicles (ethosomes), glycerosomal delivery systems (glycerosomes), and polymeric nanocarriers have been evaluated as vehicles to overcome these limitations. These vehicles significantly increase the solubilizing capacity, stability, and pharmacological efficacy of FIS. Clinical trials have now started evaluating its safety and efficacy in treating osteoarthritis, COVID-19, and chronic kidney disease. This review discusses comprehensively the traditional origin, pharmacodynamic activity, therapeutic applications of FIS, and recent advances in technology involving its formulation vehicles as strong evidence enough to warrant further research as a multipurpose pharmaceutical agent.