PUBLICATION
Evaluation of Phenazine Derivatives from the Lichen-Associated Streptomyces flavidovirens as Potent Antineuroinflammatory Agents In Vitro and In Vivo
- Authors
- Gao, L.L., Gao, Y.Q., Liu, W.Y., Stadler, M., Zhu, Y.T., Qi, J.Z., Han, W.B., Gao, J.M.
- ID
- ZDB-PUB-240815-1
- Date
- 2024
- Source
- Journal of natural products 87(8): 1930-1940 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Lipopolysaccharides/pharmacology
- Mice
- Zebrafish*
- Microglia/drug effects
- Signal Transduction/drug effects
- Molecular Structure
- Tumor Necrosis Factor-alpha/metabolism
- Lichens*/chemistry
- Anti-Inflammatory Agents*/chemistry
- Anti-Inflammatory Agents*/pharmacology
- NF-E2-Related Factor 2/metabolism
- NF-kappa B*/metabolism
- Phenazines*/chemistry
- Phenazines*/pharmacology
- Oxidative Stress/drug effects
- Streptomyces*/chemistry
- PubMed
- 39140432 Full text @ J. Nat. Prod.
Citation
Gao, L.L., Gao, Y.Q., Liu, W.Y., Stadler, M., Zhu, Y.T., Qi, J.Z., Han, W.B., Gao, J.M. (2024) Evaluation of Phenazine Derivatives from the Lichen-Associated Streptomyces flavidovirens as Potent Antineuroinflammatory Agents In Vitro and In Vivo. Journal of natural products. 87(8):1930-1940.
Abstract
Eighteen nitrogen-containing compounds (1-18) were isolated from cultures of the lichen-associated Streptomyces flavidovirens collected from the Qinghai-Tibet Plateau, including seven phenazine derivatives with three new ones, named subphenazines A-C (2-4), two new furan pyrrolidones (8-9), and nine known alkaloids. The structures were elucidated by spectroscopic data analysis, and absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. The phenazine-type derivatives, in particular compound 3, exhibited significantly better antineuroinflammatory activity than other isolated compounds (8-18). Compound 3 inhibited the release of proinflammatory cytokines including IL-6, TNF-α, and PGE2, and the nuclear translocation of NF-κB; it also reduced the oxidative stress and activated the Nrf2 signaling pathway in LPS-induced BV2 microglia cells. In vivo anti-inflammatory activity in zebrafish indicated that 3 inhibited LPS-stimulated ROS generation. These findings suggested that compound 3 might be a potent antineuroinflammatory agent through the regulation of the NF-κB/Nrf2 signaling pathways.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping