Pharmacological and Therapeutic Applications of Esculetin

Abstract

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.

Protective effects of esculetin against ovary ischemia–reperfusion injury model in rats

“…Esculetin has been shown to have therapeutic effects in a variety of conditions, including free radical scavenging, suppression of various dysregulated transcription factors in cancer, and effects on inflammatory pathways involved in diseases such as arthritis, glycaemic index, and fatty liver syndrome. [ 17 ]…”

“…Esculetin has been shown to have therapeutic effects in a variety of conditions, including free radical scavenging, suppression of various dysregulated transcription factors in cancer, and effects on inflammatory pathways involved in diseases such as arthritis, glycaemic index, and fatty liver syndrome. [17] Due to the effects of esculetin on various systems, this study looked at the effects of esculetin on a rat ovarian I/R injury model. To our knowledge, there are no studies investigating the effects of esculetin on ovarian I/R injury.…”

Design, Synthesis, and Biological Evaluation of Esculetin–Furoxan–DEAC Ternary Hybrids for Anti-Triple Negative Breast Cancer

“…Natural products with novel structures are an important source of anti-cancer candidates. Esculetin (Esc) is a natural simple coumarin, which has a variety of pharmacological activities, such as anti-inflammatory, anti-tumor, , anti-oxidant, and so on . Esc can increase the expression of cyclophilin D (CypD) within cancer cells, leading to the opening of the mitochondrial permeability transition pore (PTP) .…”

“…Esculetin (Esc) is a natural simple coumarin, which has a variety of pharmacological activities, such as anti-inflammatory, 4 anti-tumor, 5,6 antioxidant, 7 and so on. 8 Esc can increase the expression of cyclophilin D (CypD) within cancer cells, leading to the opening of the mitochondrial permeability transition pore (PTP). 9 This process results in the release of pro-apoptotic proteins from the mitochondria and triggers cancer cell apoptosis.…”

Network pharmacology and molecular docking reveal potential mechanism of esculetin in the treatment of ulcerative colitis

“…Esculetin has been shown to have many pharmacological activities in vitro and in vivo, including antioxidant, anticancer, anti-inflammatory, antidiabetic, anti-atherosclerotic, and so on. [6][7][8] A recent study demonstrated that administration of esculetin ameliorated intestinal inflammation and reduced serum levels of the pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 in a mouse model of dextrose sodium sulfate (DSS)-induced UC. [9] However, the mechanism by which it protects against UC remains to be discovered.…”