2. Academic Validation
  3. Design, synthesis and anti-inflammatory evaluation of aloe-emodin derivatives as potential modulators of Akt, NF-κB and JNK signaling pathways

Design, synthesis and anti-inflammatory evaluation of aloe-emodin derivatives as potential modulators of Akt, NF-κB and JNK signaling pathways

  • Eur J Med Chem. 2022 Aug 5;238:114511. doi: 10.1016/j.ejmech.2022.114511.
Hai Shang 1,  Jing Guo 2,  Pengtao Wang 3,  Lingyu Li 1,  Yu Tian 1,  Xiaoxue Li 4,  Zhongmei Zou 5
Affiliations

Affiliations

  • 1 Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China.
  • 2 Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China; Basic Medical Sciences, Guizhou Medical University, Guizhou, 550025, China.
  • 3 Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China.
  • 4 Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.
  • 5 Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China. Electronic address: zmzou@implad.ac.cn.
PMID: 35689856 DOI: 10.1016/j.ejmech.2022.114511
Abstract

To discover novel anti-inflammatory agents, a series of nitrogen-containing derivatives of aloe-emodin were designed and synthesized. The anti-inflammatory activities of all synthesized derivatives were screened by evaluating their inhibitory effects on LPS-induced nitric oxide production in RAW264.7 macrophages. The preliminary structure-activity relationship was determined. Among them, 2i exhibited the best nitric oxide inhibitory activity (IC50 = 3.15 μM), with no obvious toxicity. Further evaluation of the inhibitory effect of 2i on inflammatory cytokines showed that 2i significantly reduced the levels of TNF-α, IL-1β, IL-6 and PGE2. In addition, 2i markedly downregulated the expression levels of iNOS and COX-2. Preliminary mechanistic studies indicated that the anti-inflammatory effect of 2i might be related to the inhibition of the Akt, NF-κB and JNK signaling pathways. Overall, our findings suggested that 2i might be a promising anti-inflammatory agent, or might serve as a new lead compound for the further development of anti-inflammatory agents.

Keywords

Akt, NF-κB and JNK signaling pathway; Aloe-emodin; Anti-inflammatory; Mechanism; Nitrogen-containing aloe-emodin derivatives.

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