Esculetin is a
coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as Sonchus grandifolius, Aesculus turbinata, etc.
Free radicals lead to the development of oxidative stress causing
inflammation,
arthritis,
cancer, diabetes,
fatty liver disease, etc. These further reduce the efficacy of anticancer drugs, activate inflammatory signaling pathways, degrade joints and cartilage, and disrupt the glycemic index and normal function of liver
enzymes. For instance, the current treatment modalities used in
arthritis such as non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatoid drugs, and
lipoxygenase inhibitors present limited efficacy and adverse effects. Thus, there is a constant need to find newer and safer alternatives.
Esculetin has an immense antioxidative potential thereby alleviating
arthritis, diabetes,
malignancies, and hepatic disorders. Structurally,
esculetin contains two
hydroxyl groups, which enhance its ability to function as an
antioxidant by inhibiting oxidative stress in pathological conditions.
Leukotriene B4 synthesis, NF-κB and MPAK pathway activation, and inflammatory
cytokine production are the main causes of bone and joint deterioration in
arthritis, whereas
esculetin treatment reverses these factors and relieves the disease condition. In contrast, lipid peroxidation caused by upregulation of TGF-β-mediated expression and dysfunction of
antioxidant enzymes is inhibited by
esculetin therapy, thus reducing
liver fibrosis by acting on the PI3K/FoxO1 pathway. Therefore, targeting NF-κB, pro-inflammatory
cytokines, TGF-β and oxidative stress may be a therapeutic strategy to alleviate
arthritis and
liver fibrosis.