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Synthesis and Evaluation of Bakuchiol Derivatives as Potent Anti-inflammatory Agents in Vitro and in Vivo .
- Source :
-
Journal of natural products [J Nat Prod] 2022 Jan 28; Vol. 85 (1), pp. 15-24. Date of Electronic Publication: 2022 Jan 08. - Publication Year :
- 2022
-
Abstract
- Bakuchiol, a prenylated phenolic monoterpene derived from the fruit of Psoralen corylifolia L. (Buguzhi), is widely used to treat tumors, viruses, inflammation, and bacterial infections. In this study, we designed and synthesized 30 bakuchiol derivatives to identify new anti-inflammatory drugs. The anti-inflammatory activities of the derivatives were screened using lipopolysaccharide-induced RAW264.7 cells. To evaluate the anti-inflammatory activity of the compounds, we measured nitric oxide (NO), interleukin-6, and tumor necrosis factor-α production. Based on the screening results, compound 7a displayed more pronounced activity than bakuchiol and celecoxib. Furthermore, the mechanistic studies indicated that 7a inhibited pro-inflammatory cytokine release, which was correlated with activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway and blockade of the nuclear factor-κB/mitogen-activated protein kinase signaling pathway. The in vivo anti-inflammatory activity in zebrafish indicated that 7a inhibited NO and reactive oxygen species production in a dose-dependent manner. These results indicate that 7a is a potential candidate for development as an anti-inflammatory agent.
- Subjects :
- Animals
Cytokines metabolism
Heme Oxygenase-1 metabolism
In Vitro Techniques
Inflammation Mediators metabolism
Mice
Molecular Structure
NF-E2-Related Factor 2 metabolism
NF-kappa B metabolism
Phenols chemistry
RAW 264.7 Cells
Signal Transduction drug effects
Anti-Inflammatory Agents pharmacology
Phenols chemical synthesis
Phenols pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6025
- Volume :
- 85
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of natural products
- Publication Type :
- Academic Journal
- Accession number :
- 35000392
- Full Text :
- https://doi.org/10.1021/acs.jnatprod.1c00377