Shenzhen Wanhe Pharmaceutical Co., Ltd., Shenzhen 518107, China.
School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
Cells. 2021 Sep 1;10(9):2271. doi: 10.3390/cells10092271.
General inflammatory diseases include skin inflammation, rheumatoid arthritis, inflammatory bowel diseases, sepsis, arteriosclerosis, and asthma. Although these diseases have been extensively studied, most of them are still difficult to treat. Meanwhile, NF-κB is a transcription factor promoting the expression of many inflammatory mediators. NF-κB is likely to be involved in the mechanism of most inflammatory diseases. We discovered a specific NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), about 20 years ago by molecular design from a natural product. It directly binds to and inactivates NF-κB components. It has been widely used to suppress cellular and animal inflammatory disease models and was shown to be potent in vivo anti-inflammatory activity without any toxicity. We have prepared ointment of DHMEQ for the treatment of severe skin inflammation. It inhibited inflammatory cytokine expressions and lowered the clinical score in mouse models of atopic dermatitis. Intraperitoneal (IP) administration of DHMEQ ameliorated various disease models of inflammation, such as rheumatoid arthritis, sepsis, and also graft rejection. It has been suggested that inflammatory cells in the peritoneal cavity would be important for most peripheral inflammation. In the present review, we describe the synthesis, mechanism of action, and cellular and in vivo anti-inflammatory activities and discuss the clinical use of DHMEQ for inflammatory diseases.
一般炎症性疾病包括皮肤炎症、类风湿性关节炎、炎症性肠病、脓毒症、动脉硬化和哮喘。尽管这些疾病已经得到了广泛的研究，但大多数仍然难以治疗。同时，NF-κB 是一种促进许多炎症介质表达的转录因子。NF-κB 可能参与了大多数炎症性疾病的机制。大约 20 年前，我们通过从天然产物进行分子设计，发现了一种特定的 NF-κB 抑制剂——去羟甲基环氧喹啉（DHMEQ）。它直接与 NF-κB 成分结合并使其失活。它已被广泛用于抑制细胞和动物炎症性疾病模型，并表现出有效的体内抗炎活性，而无任何毒性。我们已经制备了 DHMEQ 软膏用于治疗严重的皮肤炎症。它抑制了炎症细胞因子的表达，并降低了特应性皮炎小鼠模型的临床评分。DHMEQ 的腹腔内（IP）给药改善了类风湿性关节炎、脓毒症和移植物排斥等各种炎症模型。有人认为，腹腔内的炎症细胞对于大多数外周炎症很重要。在本综述中，我们描述了 DHMEQ 的合成、作用机制、细胞和体内抗炎活性，并讨论了其在炎症性疾病中的临床应用。
