Department of Pharmacy, Banasthali Vidyapith Banasthali, P.O. Rajasthan 304022, India.
Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali 304022, Rajasthan, India.
Curr Mol Pharmacol. 2022;15(5):763-778. doi: 10.2174/1874467214666210920104352.
Epoxide hydrolase (EH) is a crucial enzyme responsible for catabolism, detoxification, and regulation of signaling molecules in various organisms including human beings. In mammals, EHs are classified according to their DNA sequence, sub-cellular location, and activity into eight major classes: soluble EH (sEH), microsomal EH (mEH), leukotriene A4 hydrolase (LTA4H), cholesterol EH (ChEH), hepoxilin EH, paternally expressed gene 1 (peg1/MEST), EH3, and EH4. The sEH, an α/β-hydrolase fold family enzyme, is an emerging pharmacological target in multiple diseases namely, cardiovascular disease, neurodegenerative disease, chronic pain, fibrosis, diabetes, pulmonary diseases, and immunological disease. It exhibits prominent physiological effects including anti-inflammatory, anti-migratory, and vasodilatory effects. Its efficacy has been documented in various clinical trials and observational studies. This review specifically highlights the development of soluble epoxide hydrolase inhibitors (sEHIs) in the clinical setting for the management of metabolic syndrome and related disorders, such as cardiovascular effects, endothelial dysfunction, arterial disease, hypertension, diabetes, obesity, heart failure, and dyslipidemia. In addition, limitations and future aspects of sEHIs have also been highlighted which will help the investigators to bring the sEHI to the clinics.
环氧化物水解酶（EH）是一种在包括人类在内的各种生物体中负责分解代谢、解毒和调节信号分子的关键酶。在哺乳动物中，EH 根据其 DNA 序列、亚细胞位置和活性分为八大类：可溶性 EH（sEH）、微粒体 EH（mEH）、白三烯 A4 水解酶（LTA4H）、胆固醇 EH（ChEH）、海鞘素 EH、父系表达基因 1（peg1/MEST）、EH3 和 EH4。sEH 是一种 α/β-水解酶折叠家族酶，是多种疾病（如心血管疾病、神经退行性疾病、慢性疼痛、纤维化、糖尿病、肺部疾病和自身免疫性疾病）的新兴药理学靶点。它具有显著的生理作用，包括抗炎、抗迁移和血管舒张作用。其疗效已在各种临床试验和观察性研究中得到证实。本综述特别强调了可溶性环氧化物水解酶抑制剂（sEHIs）在代谢综合征及其相关疾病（如心血管效应、内皮功能障碍、动脉疾病、高血压、糖尿病、肥胖、心力衰竭和血脂异常）管理中的临床应用进展。此外，还强调了 sEHIs 的局限性和未来发展方向，这将有助于研究人员将 sEHI 推向临床。
