Anti-inflammatory effect of Ailanthus altissima (Mill.) Swingle leaves in lipopolysaccharide-stimulated astrocytes.

Publisher: Elsevier Sequoia Country of Publication: Ireland NLM ID: 7903310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7573 (Electronic) Linking ISSN: 03788741 NLM ISO Abbreviation: J Ethnopharmacol Subsets: MEDLINE

Publication: Limerick : Elsevier Sequoia
Original Publication: Lausanne, Elsevier Sequoia.

Ailanthus/*chemistry ; Anti-Inflammatory Agents/*pharmacology ; Inflammation/*drug therapy ; Plant Extracts/*pharmacology; Animals ; Anti-Inflammatory Agents/isolation & purification ; Astrocytes/drug effects ; Astrocytes/pathology ; Cytokines/metabolism ; Inflammation/pathology ; Lipopolysaccharides ; Male ; Mice ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/drug therapy ; Nitric Oxide/metabolism ; Plant Extracts/isolation & purification ; Plant Leaves

Ethnopharmacological Relevance: Activated astrocytes are involved in the progression of neurodegenerative diseases. Traditionally, Ailanthus altissima (Mill.) Swingle, widely distributed in East Asia, has been used as a medicine for the treatment of fever, gastric diseases, and inflammation. Although A. altissima has been reported to play an anti-inflammatory role in peripheral tissues or cells, its role in the central nervous system (CNS) remains unclear.
Aim of the Study: In the present study, we investigated the anti-inflammatory effects and mechanism of action of A. altissima in primary astrocytes stimulated by lipopolysaccharide (LPS).
Materials and Methods: A nitrite assay was used to measure nitric oxide (NO) production, and the tetrazolium salt 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to determine cytotoxicity. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) were determined with western blotting. Reverse-transcription PCR was used to assess the expression of inflammatory cytokines. The levels of reactive oxygen species were measured using 2,7-dichlorodihydrofluorescein diacetate. Luciferase assay and immunocytochemistry were used for assessing nuclear factor-kappa B (NF-κB) transcription and p65 localization, respectively. Memory and social interaction were analyzed using the Y-maze and three-chamber tests, respectively.
Results: The ethanol extract of A. altissima leaves (AAE) inhibited iNOS and COX-2 expression in LPS-stimulated astrocytes. Moreover, AAE reduced the transcription of various proinflammatory mediators, hindered NF-κB activation, and suppressed extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activation without p38 activation. Ultra-high performance liquid chromatography with mass spectrometry analysis revealed that AAE comprised ethyl gallate, quercetin, and kaempferol, along with luteolin, which has anti-inflammatory properties, and repressed LPS-induced nitrite levels and the nuclear translocation of p65. Finally, oral administration of AAE attenuated LPS-induced memory and social impairment in mice and repressed LPS-induced ERK and JNK activation in the cortices of mice.
Conclusion: AAE could have therapeutic uses in the treatment of neuroinflammatory diseases via suppression of astrocyte activation.
(Copyright © 2021 Elsevier B.V. All rights reserved.)

Keywords: Ailanthus altissima, astrocytes; Behaviors; MAPK; Neuroinflammation; Nuclear factor kappa-light-chain-enhancer of activated B cells Pathway

0 (Anti-Inflammatory Agents)
0 (Cytokines)
0 (Lipopolysaccharides)
0 (Plant Extracts)
31C4KY9ESH (Nitric Oxide)

Date Created: 20210716 Date Completed: 20220224 Latest Revision: 20220224

20240628

10.1016/j.jep.2021.114258

34271112