Anti-Inflammatory Effects of Licania macrocarpa Cuatrec Methanol Extract Target Src- and TAK1-Mediated Pathways

Author:

Shin Kon Kuk1ORCID,Park Jae Gwang12ORCID,Hong Yo Han1,Aziz Nur1ORCID,Park Sang Hee3ORCID,Kim Sunggyu34ORCID,Kim Eunji1ORCID,Cho Jae Youl13ORCID

Affiliation:

1. Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea

2. Division of Translational Science, Research Institute, National Cancer Center, Goyang 10408, Republic of Korea

3. Department of Biocosmetics, Sungkyunkwan University, Suwon 16419, Republic of Korea

4. Research and Business Foundation, Sungkyunkwan University, Suwon 16419, Republic of Korea

Abstract

It is very important for the corresponding author to have a linked ORCID (Open Researcher and Contributor ID) account on MTS. To register a linked ORCID account, please go to the Account Update page (http://mts.hindawi.com/update/) in our Manuscript Tracking System and after you have logged in click on the ORCID link at the top of the page. This link will take you to the ORCID website where you will be able to create an account for yourself. Once you have done so, your new ORCID will be saved in our Manuscript Tracking System automatically."?>In this study, we investigated the anti-inflammatory effects of Licania macrocarpa Cuatrec methanol extract (Lm-ME) in vitro and in vivo and found pharmacological target proteins of Lm-ME in TLR4-mediated inflammatory signaling. This extract reduced NO production and mRNA expression of inflammatory cytokines such as iNOS, COX-2, IL-6, and IL-1β. In the NF-κB- and AP-1-mediated luciferase reporter gene assay, transcription factor activities decreased under cotransfection with MyD88 or TRIF. Phosphorylated protein levels of Src, PI3K, IKKα/β, and IκBα as well as p50 and p65 in the NF-κB signal pathway were downregulated, and phosphorylation of TAK1, MEK1/2, MKK4/7, and MKK3/6 as well as ERK, JNK, and p38 was decreased in the AP-1 signal pathway. Through overexpression of HA-Src and HA-TAK1, respectively, Lm-ME inhibited autophosphorylation of overexpressed proteins and thereby activated fewer downstream signaling molecules. Lm-ME also attenuated stomach ulcers in an HCl/EtOH-induced acute gastritis model mice, and COX-2 mRNA expression and phosphorylated TAK1 levels in gastric tissues were diminished. The flavonoids kaempferol and quercetin were identified in the HPLC analysis of Lm-ME; both are actively anti-inflammatory. Therefore, these results suggest that Lm-ME can be used for anti-inflammatory remedy by targeting Src and TAK1.

Funder

Ministry of Education

Publisher

Hindawi Limited

Subject

Complementary and alternative medicine

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