The Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, People's Republic of China; The Key Laboratory of Anti-inflammatory of Immune medicines, Ministry of Education, People's Republic of China; Institute for Liver Diseases of Anhui Medical University, People's Republic of China.
The Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, People's Republic of China; The Key Laboratory of Anti-inflammatory of Immune medicines, Ministry of Education, People's Republic of China; Institute for Liver Diseases of Anhui Medical University, People's Republic of China.
Int Immunopharmacol. 2018 Aug;61:82-91. doi: 10.1016/j.intimp.2018.05.009. Epub 2018 May 28.
Hesperetin has been known to exert several activities such as anti-oxidant, antitumor and anti-inflammatory. To find hesperetin derivatives showing better activity, sixteen novel hesperetin derivatives were designed and synthesized. The new obtained compounds were investigated for their anti-inflammatory activity by inhibiting interleukin-1β (IL-1β), interleukin-6 (IL-6) and production of nitric oxide (NO) in mouse RAW264.7 macrophages, and the structure-activity relationship of them was discussed. Among them, the compound 1l, 2c demonstrated more effective inhibitory activity of IL-1β and IL-6, meanwhile, the compound 1l showed the best inhibition of NO production. The results of NO inhibition study were basically accord with the molecular docking results of inducible nitric oxide synthase (iNOS). Furthermore, the expression of LPS-induced iNOS and components of NF-κB signaling pathway were reduced by compound 1l. Our results suggest that the inhibitory effect of compound 1l on LPS-stimulated inflammatory mediator production in RAW 264.7 cells is associated with the suppression of NF-κB signaling pathway and inhibition of iNOS protein and iNOS activity. From in vivo study, it was also observed that compound 1l had hepato-protective and anti-inflammatory effects in CCl-induced acute liver injury mouse models.
橙皮素具有抗氧化、抗肿瘤和抗炎等多种活性。为了寻找活性更好的橙皮素衍生物，设计并合成了 16 种新型橙皮素衍生物。通过抑制小鼠 RAW264.7 巨噬细胞中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和一氧化氮（NO）的产生，研究了新获得的化合物的抗炎活性，并讨论了它们的构效关系。其中，化合物 1l、2c 对 IL-1β 和 IL-6 的抑制活性更强，同时，化合物 1l 对 NO 生成的抑制作用最好。NO 抑制研究的结果与诱导型一氧化氮合酶（iNOS）的分子对接结果基本一致。此外，化合物 1l 还降低了 LPS 诱导的 iNOS 表达和 NF-κB 信号通路的组成。我们的研究结果表明，化合物 1l 抑制 LPS 刺激的 RAW 264.7 细胞中炎症介质产生的作用与抑制 NF-κB 信号通路以及抑制 iNOS 蛋白和 iNOS 活性有关。在体内研究中，还观察到化合物 1l 在 CCl 诱导的急性肝损伤小鼠模型中具有肝保护和抗炎作用。
