2. Academic Validation
  3. Design, synthesis and evaluation of ursodeoxycholic acid-cinnamic acid hybrids as potential anti-inflammatory agents by inhibiting Akt/NF-κB and MAPK signaling pathways

Design, synthesis and evaluation of ursodeoxycholic acid-cinnamic acid hybrids as potential anti-inflammatory agents by inhibiting Akt/NF-κB and MAPK signaling pathways

  • Eur J Med Chem. 2023 Nov 15;260:115785. doi: 10.1016/j.ejmech.2023.115785.
Xiaoxue Li 1,  Yue Hu 1,  Bingxin He 1,  Lingyu Li 1,  Yu Tian 1,  Yingjie Xiao 1,  Hai Shang 2,  Zhongmei Zou 3
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. Electronic address: [email protected].
  • 3 Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address: [email protected].
PMID: 37678142 DOI: 10.1016/j.ejmech.2023.115785
Abstract

A series of ursodeoxycholic acid (UDCA)-cinnamic acid hybrids were designed and synthesized. The anti-inflammatory activity of these derivatives was screened through evaluating their inhibitory effects of LPS-induced nitric oxide production in RAW264.7 macrophages. The preliminary structure-activity relationship was concluded. Among them, 2m showed the best inhibitory activity against NO (IC50 = 7.70 μM) with no significant toxicity. Further study revealed that 2m significantly decreased the levels of TNF-α, IL-1β, IL-6 and PGE2, down-regulated the expression of iNOS and COX-2. Preliminary mechanism study indicated that the anti-inflammatory activity of 2m was related to the inhibition of the Akt/NF-κB and MAPK signaling pathway. Furthermore, 2m reduced inflammation by a mouse model of LPS-induced inflammatory disease in vivo. In brief, our findings indicated that 2m might serve as a new lead compound for further development of anti-inflammatory agents.

Keywords

Akt/NF-κB and MAPK signaling pathway; Anti-inflammatory; Hybrid; Mechanism; Ursodeoxycholic acid.

Figures
Products