4.6 Article

Rapid identification, isolation, and evaluation on anti-neuroinflammatory activity of limonoids derivatives from the root bark of Dictamnus dasycarpus

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ELSEVIER
DOI: 10.1016/j.jpba.2021.114079

关键词

Dictamnus dasycarpus Turcz; Limonoids; UPLC/Q-TOF-MS; UNIFI; Anti-inflammation

资金

  1. National Key Technology R&D Programs New Drug Innovation of China [2018ZX09711001-008-003]
  2. National Traditional Chinese Medicine Standardization Project [2017-110108-83-03-001423]
  3. National Key Research and Development Project [2018YFC1707300]

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A total of 49 limonoids derivatives, including three new ones, were isolated from the root bark of Dictamnus dasycarpus and tested for anti-inflammatory activities. The newly identified compound, DAS, showed strong anti-inflammatory effects by suppressing NF-κB signaling pathways and inhibiting the release of inflammatory cytokines. Our results suggest that obacunone derivatives play an important role in the anti-inflammatory effects of Baixianpi.
A total of 49 limonoids derivatives were rapidly identified by UNIFI software and three new limonoids derivatives, named dasycarinone (1, DAS), isodictamdiol C (2) and dasycarinone A (3), along with nineteen known compounds, were isolated from the root bark of Dictamnus dasycarpus, named as Baixianpi in Chinese. Their structures were elucidated on the basis of spectroscopic data (UV, IR, HR-ESI-MS, NMR, CD spectra and OR). All the compounds were tested for anti-inflammatory activities by suppressing the nitric oxide (NO) production in lipopolysaccharide (LPS) induced BV-2 cells. DAS exhibited a strong anti-inflammatory activity with IC50 value of 1.8 mu M. Nuclear Factor kappa B (NF-kappa B) luciferase assay and enzyme-linked immune sorbent assay indicated that DAS can suppress the release of inflammatory cytokines such as Tumor Necrosis Factor alpha (TNF-alpha), interleukin 6 (IL-6) via inactivating NF-kappa B signaling pathways. Moreover, we found that anti-inflammatory activities of obacunone-class are better than those of limonin-class by analyzing structure-activity relationship. Our results suggested that obacunone derivatives play an important role on anti-inflammation of Baixianpi. As a representative among them, DAS showed a strong anti-inflammatory activity via suppressing NF-kappa B signaling pathways. (C) 2021 Published by Elsevier B.V.

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