Anti-inflammatory effect of Ailanthus altissima (Mill.) Swingle leaves in lipopolysaccharide-stimulated astrocytes.
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.
['Kim|Sung Rae|SR|', 'Park|Yongun|Y|', 'Li|Mo|M|', 'Kim|Yeong Kyeong|YK|', 'Lee|Sunmin|S|', 'Son|Su Young|SY|', 'Lee|Sarah|S|', 'Lee|Jong Seok|JS|', 'Lee|Choong Hwan|CH|', 'Park|Hyun Ho|HH|', 'Lee|Ji-Yun|JY|', 'Hong|Sungguan|S|', 'Cho|Young-Chang|YC|', 'Kim|Jung-Woong|JW|', 'Yoo|Hee Min|HM|', 'Cho|Namki|N|', 'Lee|Hyun-Shik|HS|', 'Lee|Sung Hoon|SH|']
MAPK Ailanthus altissima, astrocytes Behaviors Neuroinflammation Nuclear factor kappa-light-chain-enhancer of activated B cells Pathway