Esculetin: A review of its pharmacology and pharmacokinetics

Abstract

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.

Discovery of natural products to block SARS-CoV-2 S-protein interaction with Neuropilin-1 receptor: A molecular dynamics simulation approach

“…Esculetin has demonstrated anti-proliferative and anti-oxidative effects [ 60 ] and displayed an inhibitory activity on aldose reductase to deter galactose-induced cataractogenesis [ 61 ]. Esculetin was shown to alleviate H 2 O 2 -induced oxidative damage of lung fibroblasts in animals, and 0.1–10 μg/ml of esculetin displayed a protective effect against lipid peroxidation and DNA damage [ 62 ]. The compound demonstrated anti-inflammatory activity in human nasal epithelial cells, whereby using esculetin (10–40 μM) inhibited the production of inflammatory cytokines (IL-6 and IL-8) through the suppression of the NF- K B signaling pathway [ 63 ].…”

“…The compound demonstrated anti-inflammatory activity in human nasal epithelial cells, whereby using esculetin (10–40 μM) inhibited the production of inflammatory cytokines (IL-6 and IL-8) through the suppression of the NF- K B signaling pathway [ 63 ]. In another report, esculetin attenuated the histopathological change of lung, pulmonary wet-to-dy weight ratio, the infiltration of inflammatory cells and the generation of inflammatory cytokines in lung epithelial cells and mouse model studies [ 62 ]. In addition, computational studies using coumarin derivatives have blocked the interaction between the SARS-CoV-2 S-protein receptor-binding domain (RBD) and ACE2, revealing their inhibitory role against various SARS-CoV-2 targets [ [64] , [65] , [66] ].…”

Metabolites and chemometric study of Perilla (Perilla frutescens) from different varieties and geographical origins

“…And the average relative content of those seven compounds in red PF was significantly higher than that in green PF. 6,7‐Dihydroxycoumarin is a coumarin with antibacterial, antioxidant, antitumor, and anti‐inflammatory activities (Chu et al., 2017; Gong et al., 2017; Zhang et al., 2022). Flavonoids mainly exist in the form of aglycones or glycosides, and have a wide range of pharmacological activities, such as antioxidant and free radical scavenging, antitumor, anti‐inflammatory, antibacterial, and so on (Nakajima et al., 2015; Shen et al., 2014; Woo et al., 2014).…”

Towards Bioprospection of Commercial Materials of Mentha spicata L. Using a Combined Strategy of Metabolomics and Biological Activity Analyses

“…This is in agreement with the studies where salvigenin and esculetin present low antioxidant activity. Indeed, salvigening is reported with lipid-lowering and mitochondrial-stimulating activity, while esculentin shows anti-inflammatory, anti-apoptotic, anticancer, antidiabetic, and neuroprotective activities [ 37 , 38 ]. The antimicrobial causality analysis shows that the compounds with the most significant influence on the MRSA and E. faecalis inhibition are chlorogenic acid and esculentin, which are metabolites that are reported as compounds with an antibiotic capacity on gram-positive bacteria [ 38 , 39 ].…”