Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama 930-0194, Japan.
Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama 930-0194, Japan; Sekolah Tinggi Ilmu Farmasi Makassar, Perintis Kemerdekaan Street KM13.7, Makassar 90242, Indonesia.
Bioorg Med Chem Lett. 2020 Jan 15;30(2):126841. doi: 10.1016/j.bmcl.2019.126841. Epub 2019 Dec 3.
Inflammation is an extensively recognized link to many pathological diseases. It is a host response for protection from infections and tissue damage. Infections trigger acute inflammation; however, persistent infection will contribute to chronic inflammation and higher disease susceptibility. Deregulated inflammatory responses can cause excessive or long-lasting tissue damage, manifested as cancer, immune disorders, diabetes, etc. NF-κB is a central mediator of pro-inflammatory gene induction and functions in both innate and adaptive immune cells; therefore, the anti-inflammatory regulation of NF-κB is needed. Natural products reportedly play an important role in controlling the inflammatory response pathways. However, the anti-inflammatory activities of isopimara-8-(14),15-diene diterpenoids have not yet been fully elucidated. To elucidate the anti-inflammatory activities of the isopimara-8(14),15-diene diterpenoids, we investigated 21 isopimara-8(14),15-diene diterpenoids previously isolated from Kaempferia pulchra rhizomes. Eleven compounds exhibited NO inhibitory activity against lipopolysaccharide (LPS)-induced RAW264.7 cells, with IC values ranging from 30 to 100 μM. Furthermore, the most potent kaempulchraols P and Q, with IC values of 39.88 and 36.05 μM, respectively, inhibited the NF-κB-mediated transactivation of a luciferase reporter gene, IL-6 production, and COX-2 expression, with an effective dose of 25 μM. These findings provide new insights into the anti-inflammatory activities of the isopimara-8(14),15-diene diterpenoids.
炎症是许多病理疾病的广泛公认的联系。它是宿主对感染和组织损伤的保护反应。感染引发急性炎症；然而，持续的感染将导致慢性炎症和更高的疾病易感性。失调的炎症反应会导致过度或持久的组织损伤，表现为癌症、免疫紊乱、糖尿病等。NF-κB 是促炎基因诱导的核心介质，在先天和适应性免疫细胞中都有功能；因此，需要对 NF-κB 进行抗炎调节。据报道，天然产物在控制炎症反应途径方面发挥着重要作用。然而，异帕马拉-8-(14),15-二烯二萜的抗炎活性尚未得到充分阐明。为了阐明异帕马拉-8(14),15-二烯二萜的抗炎活性，我们研究了先前从 Kaempferia pulchra 根茎中分离得到的 21 种异帕马拉-8(14),15-二烯二萜。有 11 种化合物对脂多糖 (LPS) 诱导的 RAW264.7 细胞具有 NO 抑制活性，IC 值范围为 30 至 100 μM。此外，最有效的 kaempulchraols P 和 Q，IC 值分别为 39.88 和 36.05 μM，分别抑制 NF-κB 介导的荧光素酶报告基因的转录激活、IL-6 产生和 COX-2 表达，有效剂量为 25 μM。这些发现为异帕马拉-8(14),15-二烯二萜的抗炎活性提供了新的见解。
