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EGCG-γ-环糊精包合物的制备及其对 DSS 诱导的小鼠急性溃疡性结肠炎的药物赋形剂联合治疗作用的研究。

Study on the preparation of EGCG-γ-Cyclodextrin inclusion complex and its drug-excipient combined therapeutic effects on the treatment of DSS-induced acute ulcerative colitis in mice.

机构信息

Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 211198 Nanjing, China.

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 210023 Nanjing, China; Jiangsu Province Academy of Traditional Chinese Medicine, 210028 Nanjing, China.

出版信息

Int J Pharm. 2023 Jan 5;630:122419. doi: 10.1016/j.ijpharm.2022.122419. Epub 2022 Nov 21.

Abstract

In this study, γ-cyclodextrins (γ-CD) and epigallocatechin-3-gallate (EGCG) were designed to form an inclusion complex (EGCG-γ-IC) for ulcerative colitis (UC) treatment. The drug-excipient combined therapeutic potential of γ-CD and EGCG was verified, when stability and compliance were also achieved. EGCG-γ-IC effectively inhibited the secretions of NO, TNF-α, and IL-6 and the intracellular ROS in RAW264.7 cells. The effectiveness of EGCG-γ-IC in treating DSS-induced acute UC in mice was observed including improving the histological conditions of the colon, reducing the levels of IL-1β, IL-6, and TNF-α in serum, and restoring MPO, GSH, and sIgA levels in intestinal tissues. Moreover, EGCG-γ-IC had a more prominent effect on regulating bacterial dysbiosis caused by DSS than EGCG and γ-CD alone. Therefore, EGCG-γ-IC designed here displayed UC treating capacity with safety in the long-term application and promised an industrial production potential due to its excellent storage stability.

摘要

在这项研究中,γ-环糊精(γ-CD)和表没食子儿茶素没食子酸酯(EGCG)被设计形成一个包含复合物(EGCG-γ-IC),用于治疗溃疡性结肠炎(UC)。验证了γ-CD 和 EGCG 的药物赋形剂联合治疗潜力,同时还实现了稳定性和顺应性。EGCG-γ-IC 能有效抑制 RAW264.7 细胞中 NO、TNF-α 和 IL-6 的分泌以及细胞内 ROS。观察了 EGCG-γ-IC 对 DSS 诱导的急性 UC 小鼠的治疗效果,包括改善结肠的组织学状况、降低血清中 IL-1β、IL-6 和 TNF-α 的水平,并恢复肠道组织中的 MPO、GSH 和 sIgA 水平。此外,EGCG-γ-IC 对 DSS 引起的细菌失调的调节作用比 EGCG 和 γ-CD 单独作用更为显著。因此,设计的 EGCG-γ-IC 具有长期应用的安全性和治疗 UC 的能力,并因其优异的储存稳定性而具有工业生产潜力。

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