First-in-class drug Oroxylin A tables for treating hepatic and gastrointestinal disorders: From preclinical development to clinical research

Oroxylin A (OA) is a natural flavonoid mainly derived from the plants Oroxylum indicum\ (L.) Kurz and Scutellaria baicalensis Georgi. At present, OA is available via chemical synthesis and displays polypharmacological properties, including anticancer, anti-inflammatory, anti-microbial, multi-organ protective effects and so on. Currently, the first-in-class drug OA tables are currently undergoing Phase Ib/IIa clinical trials for HCC treatment. Numbers of evidence indicates that OA exhibits therapeutic potential against multiple disorders of hepatic and gastrointestinal (GI) system, including hepatocellular carcinoma (HCC), hepatic fibrosis, fatty liver disease, hepatitis, liver injury, colitis and colorectal cancer. OA exerts its therapeutic effects primarily by modulating several crucial signaling pathways, including those associated with apoptosis, oxidative stress, inflammation, glucolipid metabolism and the activation of fibrosis. The oral pharmacokinetics of OA is distinguished by phase II metabolism, hydrolysis, and enterohepatic recycling. Here, this review provides a thorough overview of the critical stages involved in the development of OA tables, presenting a holistic perspective on the progression of this first-in-class drug from preclinical to clinical phases. It includes the synthesis of active pharmaceutical ingredients, pharmacokinetics, pharmacological efficacy, toxicology, drug delivery, and the latest advancements in clinical trials. Importantly, we investigate the potential mechanisms by which OA may influence the gut-liver axis, and speculate that these interactions may provide health benefits associated with OA that surpass the limitations posed by its poor bioavailability.