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.

Antineoplastic drug cisplatin remains the drug of choice for various solid tumours including breast cancer. But dose dependent nephrotoxicity is the major drawback in majority of platinum based chemotherapy regimens. Recent reports have shown that inflammatory pathways are the main offender for cisplatin induced nephrotoxicity. The present study was undertaken to assess the effect of rosiglitazone, a PPARγ agonist and an anti-inflammatory agent, on cisplatin induced nephrotoxicity, and its anticancer activity in DMBA induced breast cancer rats.

Little is known regarding the role of hyperglycaemia on histone H3 modifications and, in turn, altering the expression of genes during the development of diabetes-associated complications. In the present study, we have investigated the hyperinsulinaemia/hyperglycaemia-induced epigenetic changes and alteration of Fbn1 (fibrillin 1) and Col3A1 (collagen type III α1) gene expression. Insulin resistance and Type 2 diabetes in male Sprague–Dawley rats was developed by feeding rats an HFD (high-fat diet) and administering a low dose of STZ (streptozotocin). Hyperglycaemia induced deacetylation and dephosphorylation of histone H3 in the heart and kidneys of diabetic rats. Furthermore, mRNA expression of Fbn1 and Col3A1 increased in the kidneys and decreased in the heart under hyperglycaemic/hyperinsulinaemic conditions. Similar to mRNA expression, chromatin immunoprecipitation also showed an increase in the level of histone H3 acetylation of the Fbn1 gene, but not of the Col3A1 gene. Our present findings suggests that the change in expression of the Fbn1 gene is epigenetically regulated, but the expression of the Col3A1 gene may either be independent of epigenetic regulation or may involve other histone modifications. We provide the first evidence regarding the role of hyperglycaemia/hyperinsulinaemia in altering histone H3 modifications, which may result in the alteration of extracellular matrix gene expression.