N-trans-Feruloyltyramine

Chem Biol Interact. 2015 Jun 25;235:56-62.

N-trans-feruloyltyramine inhibits LPS-induced NO and PGE2 production in RAW 264.7 macrophages: Involvement of AP-1 and MAP kinase signalling pathways.[Pubmed: 25843058]

Mitogen-activated protein kinase (MAPK) signalling pathway can regulate inflammatory and immune responses. N-trans-Feruloyltyramine (FLA) is an active phenylpropanoid compound. It possesses antioxidant, antimicrobial, anti-melanogenesis, and anticancer activities. However, the precise molecular mechanisms underlying FLA modulation of cytokine expression in LPS-stimulated RAW 264.7 macrophages have not been fully investigated. In this study, we examined the mechanisms underlying the immunomodulative effects of FLA isolated from Arcangelisia gusanlung.
METHODS AND RESULTS:
FLA strongly suppressed mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), but not tumor necrosis factor (TNF)-α, thereby inhibiting the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Furthermore, FLA also inhibited nuclear translocation of activation protein (AP)-1, and simultaneously decreased the expression and phosphorylation of the c-Jun N-terminal kinase (JNK) protein.
CONCLUSIONS:
These results suggest that the anti-inflammatory effects of FLA might be attributed to downregulation of COX-2 and iNOS via suppression of AP-1 and the JNK signalling pathway in RAW 264.7 macrophages.

Fitoterapia. 2010 Mar;81(2):124-31.

Antioxidant and enzyme inhibition activities and chemical profiles of Polygonum sachalinensis F.Schmidt ex Maxim (Polygonaceae).[Pubmed: 19698767]

Polygonum sachalinensis is a widespread invasive plant in Europe. Chemical profiles of its different organs were studied by HPLC-UV-ESI/MS.
METHODS AND RESULTS:
Seven major constituents quercetin-3-O-beta-D-galactopyranoside, quercetin-3-O-arabinopyranoside, lapathoside D, N-trans-Feruloyltyramine, lapathoside C, hydropiperoside, and vanicoside B were isolated and identified. The free radical-scavenging, alpha/beta-glucosidase, and acetylcholinesterase inhibitory activities of crude MeOH extracts and isolated compounds were studied. The structure-activity relationships were discussed. The chemical profiles revealed flavonoids and phenylpropanoids are the major compounds of all the organs of this plant. Quercetin-3-O-arabinopyranoside, lapathoside D, N-trans-Feruloyltyramine, lapathoside C and hydropiperoside were isolated from this species for the first time. In the alpha-glucosidase bioassay, quercetin-3-O-beta-D-galactopyranoside, lapathoside D and N-trans-Feruloyltyramine demonstrated stronger activities than the positive reference acarbose.
CONCLUSIONS:
The trend in scavenging power showed no relation to enzyme inhibition in the test models.

Inflamm Res . 2018 Jan;67(1):67-75.

Nature is the best source of anti-inflammatory drugs: indexing natural products for their anti-inflammatory bioactivity[Pubmed: 28956064]

Abstract Objectives: The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs. Materials: A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes. Method: The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules. Results: By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab. Conclusion: The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity. Keywords: Anti-inflammatory; Bioactivity index; Chemoinformatics; Ligand-based modeling.

Biol Pharm Bull. 2007 Oct;30(10):1972-4.

N-trans-feruloyltyramine as a melanin biosynthesis inhibitor.[Pubmed: 17917275]

In this study, we examined the effect of N-trans-Feruloyltyramine (FA) on melanogenesis in mouse B16 melanoma cells.
METHODS AND RESULTS:
Melanogenesis was inhibited by FA in a dose-dependent manner. FA exhibited a greater potency than kojic acid as a standard inhibitor of melanogenesis. Moreover, treatment of B16 melanoma cells with FA was found to cause marked decreases in the expression levels of tyrosinase.
CONCLUSIONS:
FA-induced downregulation of tyrosinase resulted in suppression of melanin biosynthesis in murine B16 melanoma cells.

Neurosci Lett. 2012 Apr 4;513(2):229-32.

Protective role of N-trans-feruloyltyramine against β-amyloid peptide-induced neurotoxicity in rat cultured cortical neurons.[Pubmed: 22387154]

Enhanced oxidative stress and inflammation play important roles in the pathogenesis of Alzheimer's disease (AD). Amyloid β-peptide (Aβ), a major component of amyloid plaques, is considered to have a causal role in the development and progress of AD by being the initiator of a pathological cascade leading to oxidative stress. The present study investigated the effect of N-trans-Feruloyltyramine (NTF) purified from Polyalthia suberosa, an alkaloid shown to protect against oxidative stress and cell death.
METHODS AND RESULTS:
Pre-treatment of rat primary cortical cell cultures with 25-250μM NTF significantly attenuated 10μM Aβ(1-42)-induced neuronal death in a dose-dependent manner. Apoptotic cell death was demonstrated morphologically as well as by detection of the presence of activated caspase-3 and Bax, levels of which could be reduced by NTF pre-treatment. NTF also reduced production of reactive oxygen species induced by Aβ(1-42).
CONCLUSIONS:
These findings suggest that the protective effect of NTF against Aβ(1-42)-induced neuronal death might be due to its antioxidative property.