Preventive agents for neurodegenerative diseases from resin of Dracaena cochinchinensis attenuate LPS-induced microglia over-activation
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Our previous research revealed resin of Dracaena cochinchinensis as a candidate for therapy of neurodegenerative diseases. In the present study, the material basis of Chinese Dragon’s blood and the primary mechanism of the effective components are discussed. Multiple chromatography and spectra analysis were utilized to identify effective constituents. The production of NO was determined using nitrite assay in BV-2 microglial cells stimulated with lipopolysaccharide (LPS). Cell viability was tested using MTT assay. The mRNA level of inducible nitric oxide synthase (iNOS) was investigated by quantitative real-time PCR (qRT-PCR), and the production of IL-6 and TNF-α in the cell supernatants was tested by ELISA. The bioassay-directed separation of the effective extract of D. cochinchinensis afforded two new compounds, a stilbene-flavane dimer (2) and a quinoid flavonoid (11), in addition to 25 known compounds. The evaluation of their anti-neuroinflammatory activities showed that 5, 9, 12, 13, and 14 could exhibit significant anti-neuroinflammatory effects without cytotoxities at the tested concentration, compared to a positive control, minocycline (21.87 ± 2.36 µM). A primary mechanistic study revealed that the effective components could inhibit over-activation of microglial through decreasing the expressions of iNOS, proinflammatory cytokines IL-6 and TNF-α in LPS- induced BV2 microglial cells. Chalcone 9, homoisoflavane 5 and flavone 12–14 are considered to be responsible for the anti-neuroinflammatory effects of Chinese Dragon’s blood. These could inhibit neuroinflammation by reducing the expressions of iNOS, IL-6 and TNF-α in over-activated microglial. Furthermore, the SAR is briefly discussed.
KeywordsResin of Dracaena cochinchinensis Neurodegenerative diseases Neuroinflammation Microglial cells Bioactive chemical compositions Primary mechanism
The work was supported partially by National Natural Science Foundation of China (Grant no. 81473108, 81673323, U1403102, 81473330, U1603125), Natural Science Foundation of Liaoning Province, Liaoning, China (Grant no. 2015020732), Shenyang science and technology research project, Liaoning, China (Grant no. F15-199-1-26), Research Project for Key laboratory of Liaoning Educational Committee, Liaoning, China (Grant no. LZ2015067), The project of the State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (CMEMR2017-B03, CMEMR2018-B01), Program for Liaoning Excellent Talents in University (LR2015022) and the Fundamental Research Funds for the Central Universities (N162004003).
Compliance with ethical standards
Conflict of interest
The Author(s) declare(s) that they have no conflicts of interest.
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