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Compounds DRG and DAG, Two Phenol Glycosides, Inhibit TNF-α-stimulated Inflammatory Response through Blocking NF-kB/AKT/JNK Signaling Pathways in MH7A Cells

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Abstract

Fourteen constituents were recently isolated from the roots of Dendropanax dentiger with cyclooxygenase-2 (COX-2) inhibitory effects. However, the effect of 14 constituents on rheumatoid arthritis (RA) and their action mechanism remain unclear. The study aimed to explore the anti-RA effect and potential mechanism of these constituents in tumor necrosis factor α (TNF-α)–stimulated human RA fibroblast-like synoviocytes (MH7A cells). The cell viability, nitric oxide (NO) production, inflammatory cytokine levels, and protein expressions were measured by cell counting kit-8 (CCK-8), Griess reagent, ELISA, and Western blot assays, respectively. Results showed that 14 constituents (40 μM) have no cytotoxicity for MH7A cells. Among them, two phenols including 3,4-dimethoxyphenyl-1-O-α-l-rhamnopyranosyl-(1→6)-O-β-d-glucopyranoside (DRG) and 3,4-dimethoxyphenol-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (DAG) were shown to significantly inhibit the NO production with IC50 values of 5.25±0.34 and 5.35±0.31 μM, respectively. They also remarkably decreased the release of interleukin (IL)-2, 6, 8, and interferon (IFN)-γ, as well as prominently reduced the phosphorylation protein levels of p65, IkBα, AKT, and JNK at a concentration of 10 μM. Taken together, DRG and DAG could inhibit TNF-α-induced inflammatory response through blocking NF-kB/AKT/JNK signaling pathways in MH7A cells, thus could be promising against RA and other inflammation-related agents.

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DATA AVAILABILITY

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

Abbreviations

COX-2:

Cyclooxygenase-2

RA:

Rheumatoid arthritis

IL:

Interleukin

IFN:

Interferon

TNF-α:

Tumor necrosis factor α

NO:

Nitric oxide

FLS:

Fibroblast-like synoviocyte

DRG:

3,4-dimethoxyphenyl-1-O-α-l-rhamnopyranosyl-(1→6)-O-β-d-glucopyranoside

DAG:

3,4-dimethoxyphenol-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside

TCM:

Traditional Chinese medicine

RIPA:

Radioimmunoprecipitation assay

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ACKNOWLEDGMENTS

Not applicable.

Funding

This project was financially supported by the National Natural Science Foundation of China (No. 81760705) and the Natural Science Foundation of Jiangxi Province (Nos. 2020BCJL23047, 20192BBHL80008, and 20171BAB215063), and the Jiangxi University of Traditional Chinese Medicine (Nos. s202010412063 and 202010412047).

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Authors and Affiliations

  1. Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, People’s Republic of China

    Li Yang

  2. College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, People’s Republic of China

    Ronghua Liu, Sheng Ouyang, Meng Zou, Yelin Duan, Longmei Li, Tao Guan & Ting Zhang

  3. Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, People’s Republic of China

    Junwei He

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  1. Li Yang
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  4. Meng Zou
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  9. Junwei He
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Contributions

J.H. designed the study. L.Y., J.H., M.Z., Y.D., L.L., T.G., and T.Z. performed the study and analyzed the data. L.Y. and J.H. drafted the paper. J.H, R.L., and S.O. edited the manuscript.

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Correspondence to Junwei He.

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Yang, L., Liu, R., Ouyang, S. et al. Compounds DRG and DAG, Two Phenol Glycosides, Inhibit TNF-α-stimulated Inflammatory Response through Blocking NF-kB/AKT/JNK Signaling Pathways in MH7A Cells. Inflammation 44, 1762–1770 (2021). https://doi.org/10.1007/s10753-021-01452-9

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