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Downregulation of pro-inflammatory mediators by a water extract of Schisandra chinensis (Turcz.) Baill fruit in lipopolysaccharide-stimulated RAW 264.7 macrophage cells.
Environ Toxicol Pharmacol 2013; 36(2):256-264ET

Abstract

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-α (TNF-α) in LPS-stimulated RAW 264.7 macrophage cells. WESC inhibited the expression of LPS-induced pro-inflammatory mediators, namely, NO, PGE2, and TNF-α. Furthermore, gene expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α was inhibited both at mRNA and protein synthesis levels, without any cytotoxic effect. Moreover, WESC significantly suppressed LPS-induced DNA-binding activity of NF-κB by inhibiting degradation of IκBα. It was found that pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, downregulates the expression of these pro-inflammatory genes to be closely regulated by NF-κB activity. Furthermore, we found that WESC retains dephosphorylation of Akt in response to LPS, and consequently suppressed the DNA-binding activity of NF-κB in RAW 264.7 macrophage cells. LY294002, a specific Akt inhibitor, attenuated LPS-induced pro-inflammatory gene expression via suppression of NF-κB activity. Taken together, our results indicate that WESC downregulates the expression of pro-inflammatory genes involved in the synthesis of NO, PGE2, and TNF-α in LPS-stimulated RAW 264.7 macrophage cells by suppressing Akt-dependent NF-κB activity.

Authors+Show Affiliations

Division of Marine Biomedical Sciences, Jeju National University, Jeju 690-756, Republic of Korea.Division of Marine Biomedical Sciences, Jeju National University, Jeju 690-756, Republic of Korea.Division of Marine Biomedical Sciences, Jeju National University, Jeju 690-756, Republic of Korea.Division of Marine Biomedical Sciences, Jeju National University, Jeju 690-756, Republic of Korea.Division of Marine Biomedical Sciences, Jeju National University, Jeju 690-756, Republic of Korea.Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-051, Republic of Korea.Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-051, Republic of Korea.Department of Oriental Pharmaceutical Science, College of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.Department of Oriental Pharmaceutical Science, College of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.Division of Marine Biomedical Sciences, Jeju National University, Jeju 690-756, Republic of Korea. Electronic address: immunkim@jejunu.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23686005

Citation

Dilshara, Matharage Gayani, et al. "Downregulation of Pro-inflammatory Mediators By a Water Extract of Schisandra Chinensis (Turcz.) Baill Fruit in Lipopolysaccharide-stimulated RAW 264.7 Macrophage Cells." Environmental Toxicology and Pharmacology, vol. 36, no. 2, 2013, pp. 256-264.
Dilshara MG, Jayasooriya RGPT, Kang CH, et al. Downregulation of pro-inflammatory mediators by a water extract of Schisandra chinensis (Turcz.) Baill fruit in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Environ Toxicol Pharmacol. 2013;36(2):256-264.
Dilshara, M. G., Jayasooriya, R. G. P. T., Kang, C. H., Lee, S., Park, S. R., Jeong, J. W., ... Kim, G. Y. (2013). Downregulation of pro-inflammatory mediators by a water extract of Schisandra chinensis (Turcz.) Baill fruit in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Environmental Toxicology and Pharmacology, 36(2), pp. 256-264. doi:10.1016/j.etap.2013.04.005.
Dilshara MG, et al. Downregulation of Pro-inflammatory Mediators By a Water Extract of Schisandra Chinensis (Turcz.) Baill Fruit in Lipopolysaccharide-stimulated RAW 264.7 Macrophage Cells. Environ Toxicol Pharmacol. 2013;36(2):256-264. PubMed PMID: 23686005.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Downregulation of pro-inflammatory mediators by a water extract of Schisandra chinensis (Turcz.) Baill fruit in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. AU - Dilshara,Matharage Gayani, AU - Jayasooriya,Rajapaksha Gedara Prasad Tharanga, AU - Kang,Chang-Hee, AU - Lee,Seungheon, AU - Park,Sang Rul, AU - Jeong,Jin-Woo, AU - Choi,Yung Hyun, AU - Seo,Yong Taek, AU - Jang,Young Pyo, AU - Kim,Gi-Young, Y1 - 2013/04/19/ PY - 2013/01/29/received PY - 2013/04/11/revised PY - 2013/04/12/accepted PY - 2013/5/21/entrez PY - 2013/5/21/pubmed PY - 2014/3/13/medline KW - Akt KW - Nitric oxide KW - Nuclear factor-κB KW - Prostaglandin E2 KW - Schisandra chinensis KW - Tumor necrosis factor-α SP - 256 EP - 264 JF - Environmental toxicology and pharmacology JO - Environ. Toxicol. Pharmacol. VL - 36 IS - 2 N2 - 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-α (TNF-α) in LPS-stimulated RAW 264.7 macrophage cells. WESC inhibited the expression of LPS-induced pro-inflammatory mediators, namely, NO, PGE2, and TNF-α. Furthermore, gene expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α was inhibited both at mRNA and protein synthesis levels, without any cytotoxic effect. Moreover, WESC significantly suppressed LPS-induced DNA-binding activity of NF-κB by inhibiting degradation of IκBα. It was found that pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, downregulates the expression of these pro-inflammatory genes to be closely regulated by NF-κB activity. Furthermore, we found that WESC retains dephosphorylation of Akt in response to LPS, and consequently suppressed the DNA-binding activity of NF-κB in RAW 264.7 macrophage cells. LY294002, a specific Akt inhibitor, attenuated LPS-induced pro-inflammatory gene expression via suppression of NF-κB activity. Taken together, our results indicate that WESC downregulates the expression of pro-inflammatory genes involved in the synthesis of NO, PGE2, and TNF-α in LPS-stimulated RAW 264.7 macrophage cells by suppressing Akt-dependent NF-κB activity. SN - 1872-7077 UR - https://www.unboundmedicine.com/medline/citation/23686005/Downregulation_of_pro_inflammatory_mediators_by_a_water_extract_of_Schisandra_chinensis__Turcz___Baill_fruit_in_lipopolysaccharide_stimulated_RAW_264_7_macrophage_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1382-6689(13)00088-4 DB - PRIME DP - Unbound Medicine ER -