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Fargesin Exerts Anti-Inflammatory Effects in THP-1 Monocytes by Suppressing PKC-dependent AP-1 and NF-ĸB Signaling

Fargesin Exerts Anti-Inflammatory Effects in THP-1 Monocytes by Suppressing PKC-dependent AP-1 and NF-ĸB Signaling

Thu-Huyen Pham, Man-Sub Kim, Minh-Quan Le, Yong-Seok Song, Yesol Bak, Hyung-Won Ryu, Sei-Ryang Oh, Do-Young Yoon

Phytomedicine. 2017 Jan 15;24:96-103.

PMID: 28160867

Abstract:

Background:
Fargesin is a lignan from Magnolia fargesii, an oriental medicine used in the treatment of nasal congestion and sinusitis. The anti-inflammatory properties of this compound have not been fully elucidated yet.
Purpose:
This study focused on assessing the anti-inflammatory effects of fargesin on phorbal ester (PMA)-stimulated THP-1 human monocytes, and the molecular mechanisms underlying them.
Methods:
Cell viability was evaluated by MTS assay. Protein expression levels of inflammatory mediators were analyzed by Western blotting, ELISA, Immunofluorescence assay. mRNA levels were measured by Real-time PCR. Promoter activities were elucidated by Luciferase assay.
Results:
It was found that pre-treatment with fargesin attenuated significantly the expression of two major inflammatory mediators, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Fargesin also inhibited the production of pro-inflammation cytokines (IL-1β, TNF-α) and chemokine (CCL-5). Besides, nuclear translocation of transcription factors nuclear factor-kappa B (NF-ĸB) and activator protein-1 (AP-1), which regulate multiple pro-inflammatory genes, was suppressed by fargesin in a PKC-dependent manner. Furthermore, among the mitogen-activated protein kinases (MAPKs), only c-Jun N-terminal kinase (JNK) was downregulated by fargesin in a PKC-dependent manner, and this reduction was involved in PMA-induced AP-1 and NF-ĸB nuclear translocation attenuation, demonstrated using a specific JNK inhibitor.
Conclusion:
Taken together, our results found that fargesin exhibits anti-inflammation effects on THP-1 cells via suppression of PKC pathway including downstream JNK, nuclear factors AP-1 and NF-ĸB. These results suggest that fargesin has anti-inflammatory properties with potential applications in drug development against inflammatory disorders.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP31008192	Fargesin		31008-19-2	Price

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