Design, Synthesis, and In Vitro and In Vivo Biological Evaluation of Limonin Derivatives for Anti-Inflammation Therapy

  • J Agric Food Chem. 2021 Nov 17;69(45):13487-13499. doi: 10.1021/acs.jafc.1c04989.
Ming Bian  1  2  3 ,  Guohua Gong  1  3  4 ,  Pang Lei  5 ,  Huanhuan Du  1  3 ,  Chunmei Bai  1  3 ,  Chengxi Wei  1  3 ,  Zheshan Quan  2 ,  Qianqian Ma  1  3
Affiliations
  • 1. Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Inner Mongolia, Tongliao 028000, P. R. China.
  • 2. College of Pharmacy, Yanbian University, Yanji City, Jilin 133002, China.
  • 3. Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Inner Mongolia Autonomous Region, Tongliao 028000, China.
  • 4. First Clinical Medical of Inner Mongolia Minzu University, Inner Mongolia, Tongliao 028000, P. R. China.
  • 5. Nanchong Key Laboratory of Individualized Drug Therapy, Department of Pharmacy, the Second Clinical Medical College of North Sichuan Medical College, Nanchong Central Hospital, Nanchong, Sichuan 637000, China.
PMID: 34713702 DOI: 10.1021/acs.jafc.1c04989
Abstract

In this study, limonin derivatives were used to design new anti-inflammatory compounds with high pharmacological activity and low toxicity. A total of 23 new limonin derivatives were discovered, synthesized, and screened for their anti-inflammatory activity against lipopolysaccharide (LPS)-treated RAW 264.7 cells. Of them, compound f4 was found to be the most active, with a higher efficiency compared with limonin and celecoxib. Subsequently, we studied the mechanism underlying the activity of f4 and found that it inhibited proinflammatory cytokines by blocking the NF-κB/MAPK signaling pathway in LPS-treated RAW 264.7 cells as well as mice. In conclusion, f4 may be a promising anti-inflammatory lead compound.

Keywords
RAW 264.7 cells; acute lung injury; anti-inflammatory; limonin; structural modification.
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