Design, Synthesis, and In Vitro and In Vivo Biological Evaluation of Limonin Derivatives for Anti-Inflammation Therapy.
Ming BianGuohua GongPang LeiHuan-Huan DuChunmei BaiChengxi WeiZhe-Shan QuanQianqian MaPublished in: Journal of agricultural and food chemistry (2021)
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.
Keyphrases
- anti inflammatory
- signaling pathway
- induced apoptosis
- oxidative stress
- pi k akt
- cell cycle arrest
- inflammatory response
- lps induced
- epithelial mesenchymal transition
- stem cells
- cell death
- type diabetes
- structure activity relationship
- toll like receptor
- adipose tissue
- metabolic syndrome
- mesenchymal stem cells
- insulin resistance