1. Natural harmaline acts as novel fluorescent probe for hypochlorous acid and promising therapeutic candidate for rheumatoid arthritis.
- Author
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Zheng D, Zuo Y, Li L, McDowell A, Cao Y, Ye X, Zhou H, Peng C, Deng Y, Lu J, and Fang Y
- Subjects
- Animals, Mice, RAW 264.7 Cells, NF-kappa B metabolism, Anti-Inflammatory Agents chemistry, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents therapeutic use, Reactive Oxygen Species metabolism, Signal Transduction drug effects, Synoviocytes drug effects, Synoviocytes metabolism, Cell Proliferation drug effects, Lipopolysaccharides pharmacology, Humans, Peganum chemistry, Hypochlorous Acid metabolism, Fluorescent Dyes chemistry, Arthritis, Rheumatoid drug therapy, Harmaline chemistry, Harmaline pharmacology
- Abstract
Endogenous hypochlorous acid (HOCl) is one of the most important reactive oxygen species (ROS) and acts as a distinct biomarker that is involved in various inflammatory responses including rheumatoid arthritis (RA). Therefore, it's crucial to develop an efficient method for the tracking and analysis of HOCl levels in vivo. Natural products continue to be compounds of interest, because they not only offer diverse and specific molecular scaffolds but also provide invaluable sources for new drug discovery. Herein, we firstly demonstrated harmaline (HML), a natural alkaloid mainly found in Peganum harmala L, could be acted as a novel fluorescent probe for HOCl with exceptional precision and responsiveness. Remarkably, this probe not only specifically tracked HOCl levels in cells and inflammatory RA mouse models, but also exhibited effective anti-inflammatory effects on RAW264.7 cells and anti-proliferative effects on fibroblast-like synoviocytes. Furthermore, HML has the potential to alleviate LPS-induced inflammation by inhibiting the NF-κB signaling pathway. This study represents the first example of a natural product that can simultaneously act as a fluorescent probe for specific ROS and a promising therapeutic candidate for a specific disease, which will undoubtedly extend the application of fluorophore-rich natural products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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