Esculetin: A review of its pharmacology and pharmacokinetics

Esculetin is a natural dihydroxy coumarin; it is mainly extracted from twig skin and the trunk bark of the Chinese herbal medicine Fraxinus rhynchophylla Hance. Emerging evidence suggests that esculetin has a wide range of pharmacological activities. Based on its fundamental properties, including antioxidant, antiinflammatory, antiapoptotic, anticancer, antidiabetic, neuroprotective, and cardiovascular protective activities, as well as antibacterial activity, among others, esculetin is expected to be a therapeutic drug for specific disease indications, such as cancer, diabetes, atherosclerosis, Alzheimer's disease (AD), Parkinson's disease (PD), nonalcoholic fatty liver disease (NAFLD), and other diseases. The oral bioavailability of esculetin was shown by studies to be low. The extensive glucuronidation was described to be the main metabolic pathway of esculetin and C-7 phenolic hydroxyl to be its major metabolic site. With the development of scientific research technology, the pharmacological effects of esculetin are identified and its potential for the treatment of diseases is demonstrated. The underlining mechanisms of action and biological activities as well as the pharmacokinetic data of the analyzed compound reported so far are highlighted in this review with the aim of becoming a proven, and applicable insight and reference for further studies on the utilization of esculetin.

Automated summary

Esculetin is a natural compound with diverse pharmacological activities, making it a potential therapeutic drug for conditions like cancer and diabetes. Studies have shown low oral bioavailability and glucuronidation as the main metabolic pathway for esculetin, with the major metabolic site being the C-7 phenolic hydroxyl.