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

Abstract

<?tex id="Q1" staff-cmt="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 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.

Antimelanogenesis Effects of Theasinensin A

“…B16F10 cells were treated with TSA (12.5–25 µM) or arbutin (1 mM) with μ-MSH (100 nM) for 48 h. We prepared the total cell lysates, as previously described [ 62 , 63 ]. Cells (1 × 10 6 cells/mL) were washed with cold PBS and lysed with buffer (20 mM Tris-HCl, pH 7.4, 2 mM EDTA, 2 mM EGTA, 50 mM glycerol phosphate, 1 mM DTT, 2 µg/mL aprotinin, 2 µg/mL leupeptin, 1 µg/mL pepstatin, 50 µM PMSF, 1 mM benzamide, 2% Triton X-100, 10% glycerol, 0.1 mM sodium vanadate, 1.6 mM pervanadate, and 20 mM NaF).…”

Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1

“…Upon stimulation, TAK1 could activate the MAPKKs (MKK3/6 and MKK4/7) to transduce the signal to MAPKs (p38, JNK, and ERK) [ 23 ], although this protein is also involved in the activation of the NF-κB pathway. In addition, anti-inflammatory remedies derived from compounds or plant extracts that target TAK1 have been reported to inhibit inflammatory responses via a blockade of AP-1 pathways [ 24 , 25 , 26 ]. Using overexpression strategies and CETSA assays, we confirmed that Src and TAK1 were targeted by Cs-EE as well as gained insight into the interaction of Cs-EE with its target proteins.…”

“…Using overexpression strategies and CETSA assays, we confirmed that Src and TAK1 were targeted by Cs-EE as well as gained insight into the interaction of Cs-EE with its target proteins. Following previous studies, Src- or TAK1-overexpressing HEK293 cells expressed autophosphorylation events of Src and TAK1, respectively [ 24 , 26 ]. Treatment with Cs-EE reduced protein expression of phosphorylated Src and TAK1 as well as led to the thermo-stabilization of Src and TAK1.…”

Identification of a mitogen‐activated protein kinase kinase (AccMKK4) from Apis cerana cerana and its involvement in various stress responses

“…We then conducted further experiments to further study the functional mechanism of AccMKK4. Yeast two‐hybrid interaction experiments showed that AccMKK4 interacts with Accp38b, and similar results were also obtained in some recent studies (Li et al ., 2018b, Wang et al ., 2018; Shin et al ., 2019). Subsequently, we successfully silenced the AccMKK4 gene, and after the silencing of AccMKK4 , we detected the expression level of Accp38b and found that the expression level of Accp38b was significantly reduced.…”