期刊
METABOLITES
卷 12, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/metabo12111055
关键词
flavone; Notholirion thomsonianum; cholinesterases; oxidative stress; inflammation
资金
- Deputy for Research and InnovationMinistry of Education, Kingdom of Saudi Arabia [NU/IF/INT/01/007]
- HEC [5291/Federal/NRPU/RD/HEC/2016]
In this study, a natural flavone was isolated from Notholirion thomsonianum, which showed effective activity against Alzheimer's, inflammation, and oxidative stress. This discovery could lay a foundation for future research in drug development.
Plants' bioactives are well-known safe drugs for vital diseases. Flavones and Flavonoid-rich dietary supplements are known to exhibit neuroprotective potential. In this study, we isolated a flavone 2-(3,4-dimethoxyphenyl)-3,7-dihydroxy-4H-chromen-4-one from Notholirion thomsonianum and it was evaluated against various targets of the oxidative stress-related neurological disorders. The compound showed excellent acetyl and butyrylcholinesterase inhibitions in its profile, giving IC50 values of 1.37 and 0.95 mu M, respectively. Similarly, in in-vitro MAO-B assay, our flavone exhibited an IC50 value of 0.14 mu M in comparison to the standard safinamide (IC50 0.025 mu M). In in-vitro anti-inflammatory assay, our isolated compound exhibited IC50 values of 7.09, 0.38 and 0.84 mu M against COX-1, COX-2 and 5-LOX, respectively. The COX-2 selectivity (SI) of the compound was 18.70. The compound was found safe in animals and was very effective in carrageenan-induced inflammation. Due to the polar groups in the structure, a very excellent antioxidant profile was observed in both in-vitro and in-vivo models. The compound was docked into the target proteins of the respective activities and the binding energies confirmed the potency of our compound. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) results showed that the isolated flavone has a good GIT absorption ability and comes with no hepatic and cardiotoxicity. In addition, the skin sensitization test, in-vitro human cell line activation test (h-CLAT) and KeratinoSens have revealed that isolated flavone is not skin sensitive with a confidence score of 59.6% and 91.6%. Herein, we have isolated a natural flavone with an effective profile against Alzheimer's, inflammation and oxidative stress. The exploration of this natural flavone will provide a baseline for future research in the field of drug development.
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