Department of Biochemistry, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144001, Punjab, India.
Department of Orthopedic Surgery, New York University Grossman School of Medicine, New York, NY 10010, USA.
Int J Mol Sci. 2022 Oct 20;23(20):12643. doi: 10.3390/ijms232012643.
Esculetin is a coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as , , 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.
七叶灵是一种香豆素化合物，属于苯并吡喃酮类，在、等各种植物中含量丰富。自由基导致氧化应激的发展，引起炎症、关节炎、癌症、糖尿病、脂肪肝疾病等。这些进一步降低了抗癌药物的疗效，激活炎症信号通路，降解关节和软骨，并破坏血糖指数和肝脏酶的正常功能。例如，关节炎目前使用的治疗方式如非甾体抗炎药、改善病情抗风湿药和脂氧合酶抑制剂，疗效有限且有不良反应。因此，不断需要寻找更新、更安全的替代品。七叶灵具有巨大的抗氧化潜力，从而缓解关节炎、糖尿病、恶性肿瘤和肝脏疾病。从结构上看，七叶灵含有两个羟基，通过抑制病理条件下的氧化应激，增强其作为抗氧化剂的功能。白三烯 B4 合成、NF-κB 和 MPAK 途径激活以及炎症细胞因子的产生是关节炎中骨和关节恶化的主要原因，而七叶灵治疗可逆转这些因素并缓解疾病状况。相比之下，七叶灵治疗抑制了 TGF-β 介导的表达上调和抗氧化酶功能障碍引起的脂质过氧化，从而通过作用于 PI3K/FoxO1 途径减少肝纤维化。因此，针对 NF-κB、促炎细胞因子、TGF-β 和氧化应激可能是缓解关节炎和肝纤维化的一种治疗策略。
