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自身免疫性疾病的候选药物。

Drug Candidates for Autoimmune Diseases.

作者信息

Saurin Sabrina, Meineck Myriam, Erkel Gerhard, Opatz Till, Weinmann-Menke Julia, Pautz Andrea

机构信息

1st Department of Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany.

Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany.

出版信息

Pharmaceuticals (Basel). 2022 Apr 20;15(5):503. doi: 10.3390/ph15050503.

Abstract

Most of the immunosuppressive drugs used in the clinic to prevent organ rejection or to treat autoimmune disorders were originally isolated from fungi or bacteria. Therefore, in addition to plants, these are valuable sources for identification of new potent drugs. Many side effects of established drugs limit their usage and make the identification of new immunosuppressants necessary. In this review, we present a comprehensive overview of natural products with potent anti-inflammatory activities that have been tested successfully in different models of chronic inflammatory autoimmune diseases. Some of these candidates already have passed first clinical trials. The anti-inflammatory potency of these natural products was often comparable to those of established drugs, and they could be used at least in addition to standard therapy to reduce their dose to minimize unwanted side effects. A frequent mode of action is the inhibition of classical inflammatory signaling pathways, such as NF-κB, in combination with downregulation of oxidative stress. A drawback for the therapeutic use of those natural products is their moderate bioavailability, which can be optimized by chemical modifications and, in addition, further safety studies are necessary. Altogether, very interesting candidate compounds exist which have the potential to serve as starting points for the development of new immunosuppressive drugs.

摘要

临床上用于预防器官排斥或治疗自身免疫性疾病的大多数免疫抑制药物最初都是从真菌或细菌中分离出来的。因此,除了植物之外,这些也是鉴定新型强效药物的宝贵来源。现有药物的许多副作用限制了它们的使用,因此有必要鉴定新的免疫抑制剂。在这篇综述中,我们全面概述了具有强效抗炎活性的天然产物,这些天然产物已在不同的慢性炎症性自身免疫疾病模型中得到成功测试。其中一些候选药物已经通过了一期临床试验。这些天然产物的抗炎效力通常与现有药物相当,并且至少可以与标准疗法联合使用,以降低其剂量,从而将不良副作用降至最低。常见的作用方式是抑制经典的炎症信号通路,如核因子κB(NF-κB),同时下调氧化应激。这些天然产物用于治疗的一个缺点是它们的生物利用度适中,这可以通过化学修饰来优化,此外,还需要进一步的安全性研究。总之,存在非常有趣的候选化合物,它们有可能作为开发新型免疫抑制药物的起点。

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