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

• Published in: Journal of ethnopharmacology 2022-03, Vol.286, p.114258-114258, Article 114258
• Main Authors: Kim, Sung Rae, Park, Yongun, Li, Mo, Kim, Yeong Kyeong, Lee, Sunmin, Son, Su Young, Lee, Sarah, Lee, Jong Seok, Lee, Choong Hwan, Park, Hyun Ho, Lee, Ji-Yun, Hong, Sungguan, Cho, Young-Chang, Kim, Jung-Woong, Yoo, Hee Min, Cho, Namki, Lee, Hyun-Shik, Lee, Sung Hoon
• Format: Article
• Language: English
• Subjects: Ailanthus - chemistry; Ailanthus altissima, astrocytes; Animals; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Astrocytes - drug effects; Astrocytes - pathology; Behaviors; Cytokines - metabolism; Inflammation - drug therapy; Inflammation - pathology; Lipopolysaccharides; Male; MAPK; Mice; Mice, Inbred C57BL; Neuroinflammation; Neuroinflammatory Diseases - drug therapy; Nitric Oxide - metabolism; Nuclear factor kappa-light-chain-enhancer of activated B cells Pathway; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Leaves
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2021.114258

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. In the present study, we investigated the anti-inflammatory effects and mechanism of action of A. altissima in primary astrocytes stimulated by lipopolysaccharide (LPS). 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. 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. AAE could have therapeutic uses in the treatment of neuroinflammatory diseases via suppression of astrocyte activation. [Display omitted] •AAE regulates neuroinflammation in LPS-stimulated astrocytes.•AAE inhibits proinflammatory cytokines expressions in LPS-stimulated astrocytes.•