Advances in Pharmacological Activities and Drug Delivery Systems of Licochalcone A.

Licochalcone A (Lic A) is a natural chalcone compound extracted from Glycyrrhiza inflata Batal, which exhibits a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anti-tumor, analgesic, hepatoprotective and antibacterial properties. Regarding its pharmacological effects, Lic A demonstrates inhibitory effects on various tumors, such as hepatocellular carcinoma, colorectal carcinoma, and leukemia. These effects are achieved by modulating key signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen- activated protein kinase (MAPK), and phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (Akt). However, the therapeutic potential of Lic A is remarkably hampered by its poor aqueous solubility and low permeation efficiency, which lead to inadequate absorption and poor bioavailability, posing formidable challenges for both oral and transdermal delivery. To address these limitations, advanced technologies such as micelles, mesoporous silica nanoparticles, cell-penetrating peptides, self-microemulsifying drug delivery systems, and eutectogels have been employed to enhance the solubility, permeability, and bioavailability of Lic A, thereby expanding its potential applications. This review aims to summarize the pharmacological effects, signal pathways, and mechanisms of action of Lic A. Moreover, it discusses recent research progress in improving its oral and transdermal delivery efficiency, further summarizing its clinical application and development prospects. Collectively, the work provides a comprehensive reference and methodological guidance for in-depth investigations of Lic A, as well as the exploration and formulation optimization of other flavonoid ingredients.