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TLR-4 may mediate signaling pathways of Astragalus polysaccharide RAP induced cytokine expression of RAW264.7 cells
Wei Wei1; Hai-Tao Xiao1; Wan-Rong Bao1; Dik-Lung Ma2; Chung-Hang Leung3; Xiao-Qiang Hand4; Chun-Hay Ko4; Clara Bik-San Lau4; Chun-Kwok WONG4; Kwok-Pui Fung4; Ping-Chung Leung4; Zhao-Xiang Bian1; Quan-Bin Han1
2016-02-17
Source PublicationJournal of Ethnopharmacology
ISSN0378-8741
Volume179Pages:243-252
Abstract

Ethnopharmacological relevance Polysaccharides of Radix Astragali (Astragalus membranaceus (Fisch) Bge.; Huangqi) are able to induce cytokine production of macrophages and are considered the main active ingredient for the immune-enhancing effect of this commonly used medicinal herb. Aim of study To investigate the molecular mechanism of immunomodulating activities of a reported Astragalus polysaccharide, RAP, which is a hyperbranched heteroglycan with average molecular weight of 1334 kDa. Materials and methods The cytokine production of RAW264.7 cells were analyzed by using ELISA assays while cell viability was assessed by MTT method. Western blot analysis was used for determining protein contents of mitogen-activated protein kinases (MAPKs). In addition, the level of IL-6, iNOS, and TNF-α mRNA was determined by RT-PCR. Results It has been found that RAP itself did not have any cytotoxic effect on mouse mammary carcinoma 4T1 cells, but it significantly enhanced cytotoxicity of the supernatant of RAW264.7cells on 4T1 cells. Furthermore, RAP enhanced the production of NO and cytokines in RAW264.7 cells, and significantly up-regulated gene expressions of TNF-α, IL-6, iNOS. All these bioactivities were blocked by the inhibitor of TLR4 (Toll-like receptor 4), suggesting that TLR4 is a receptor of RAP and mediates its immunomodulating activity. Further analyses demonstrated that RAP rapidly activated TLR4-related MAPKs, including phosphorylated ERK, phosphorylated JNK, and phosphorylated p38, and induced translocation of NF-κB as well as degradation of IκB-α. These results are helpful to better understand the immunomodulating effects of Radix Astragali. Conclusions RAP may induce cytokine production of RAW264.7 cells through TLR4-mediated activation of MAPKs and NF-κB. 

KeywordAstragalus Polysaccharides Mapks Nf-κb Raw264.7macrophages
DOIhttps://doi.org/10.1016/j.jep.2015.12.060
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaPlant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
WOS SubjectPlant Sciences ; Chemistry, Medicinal ; Integrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS IDWOS:000370884400025
The Source to ArticleScopus
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Cited Times [WOS]:83   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorZhao-Xiang Bian; Quan-Bin Han
Affiliation1.School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
2.Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
3.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
4.State Key Laboratory of Phytochemistry and Plant Resources in West China, Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
Recommended Citation
GB/T 7714
Wei Wei,Hai-Tao Xiao,Wan-Rong Bao,et al. TLR-4 may mediate signaling pathways of Astragalus polysaccharide RAP induced cytokine expression of RAW264.7 cells[J]. Journal of Ethnopharmacology,2016,179:243-252.
APA Wei Wei,Hai-Tao Xiao,Wan-Rong Bao,Dik-Lung Ma,Chung-Hang Leung,Xiao-Qiang Hand,Chun-Hay Ko,Clara Bik-San Lau,Chun-Kwok WONG,Kwok-Pui Fung,Ping-Chung Leung,Zhao-Xiang Bian,&Quan-Bin Han.(2016).TLR-4 may mediate signaling pathways of Astragalus polysaccharide RAP induced cytokine expression of RAW264.7 cells.Journal of Ethnopharmacology,179,243-252.
MLA Wei Wei,et al."TLR-4 may mediate signaling pathways of Astragalus polysaccharide RAP induced cytokine expression of RAW264.7 cells".Journal of Ethnopharmacology 179(2016):243-252.
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