Downregulation of pro-inflammatory mediators by a water extract of Schisandra chinensis (Turcz.) Baill fruit in lipopolysaccharide-stimulated RAW 264.7 macrophage cells

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• 作者：Matharage Gayani Dilshara ; Rajapaksha Gedara Prasad Tharanga Jayasooriya ; Chang-Hee Kang ; Seungheon Lee ; Sang Rul Park ; Jin-Woo Jeong ; Yung Hyun Choi ; Yong Taek Seo ; Young Pyo Jang ; Gi-Young Kim
• 关键词：Schisandra chinensis ; Nitric oxide ; Prostaglandin E2 ; Tumor necrosis factor-¦Á ; Nuclear factor-¦ÊB ; Akt
• 刊名：Environmental Toxicology and Pharmacology
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：36
• 期：2
• 页码：256-264
• 全文大小：1717 K

文摘

Schisandra chinensis has a long-standing history of medicinal use as a tonic, a sedative, an anti-tussive, and an anti-aging drug. Nevertheless, the antagonistic effects of S. chinensis against lipopolysaccharide (LPS)-stimulated responses have not yet been studied. In this study, we investigated whether water extract of S. chinensis fruit (WESC) has the ability to attenuate the expression of pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E₂ (PGE₂), and tumor necrosis factor-¦Á (TNF-¦Á) in LPS-stimulated RAW 264.7 macrophage cells. WESC inhibited the expression of LPS-induced pro-inflammatory mediators, namely, NO, PGE₂, and TNF-¦Á. Furthermore, gene expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-¦Á was inhibited both at mRNA and protein synthesis levels, without any cytotoxic effect. Moreover, WESC significantly suppressed LPS-induced DNA-binding activity of NF-¦ÊB by inhibiting degradation of I¦ÊB¦Á. It was found that pyrrolidine dithiocarbamate (PDTC), a specific NF-¦ÊB inhibitor, downregulates the expression of these pro-inflammatory genes to be closely regulated by NF-¦ÊB activity. Furthermore, we found that WESC retains dephosphorylation of Akt in response to LPS, and consequently suppressed the DNA-binding activity of NF-¦ÊB in RAW 264.7 macrophage cells. LY294002, a specific Akt inhibitor, attenuated LPS-induced pro-inflammatory gene expression via suppression of NF-¦ÊB activity. Taken together, our results indicate that WESC downregulates the expression of pro-inflammatory genes involved in the synthesis of NO, PGE₂, and TNF-¦Á in LPS-stimulated RAW 264.7 macrophage cells by suppressing Akt-dependent NF-¦ÊB activity.