• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.447-456
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• 2022

The present study was carried out to investigate the effect of Arctigenin on cell growth and the mechanism of cell death elicited by Arctigenin were examined in FaDu human pharyngeal carcinoma cells. To determine the apoptotic activity of Arctigenin in FaDu human pharyngeal carcinoma cells, cell viability assay, DAPI staining, caspase activation analysis, and immunoblotting were performed. Arctigenin inhibited the growth of cells in a dose-dependent manner and induced nuclear condensation and fragmentation. Arctigenin-treated cells showed caspase-3/7 activation and increased apoptosis versus control cells. FasL, a death ligand associated with extrinsic apoptotic signaling pathways, was up-regulated by Arctigenin treatment. Moreover, caspase-8, a part of the extrinsic apoptotic pathway, was activated by Arctigenin treatments. Expressions of anti-apoptotic factors such as Bcl-2 and Bcl-xL, components of the mitochondria-dependent intrinsic apoptosis pathway, significantly decreased following Arctigenin treatment. The expressions of pro-apoptotic factors such as BAX, BAD and caspase-9, and tumor suppressor -53 increased by Arctigenin treatments. In addition, Arctigenin activated caspase-3 and poly (ADP-ribose) polymerase (PARP) induced cell death. Arctigenin also inhibited the proliferation of FaDu cells by the suppression of p38, NF-κB, and Akt signaling pathways. These results suggest that Arctigenin may inhibit cell proliferation and induce apoptotic cell death in FaDu human pharyngeal carcinoma cells through both the mitochondria-mediated intrinsic pathway and the death receptor-mediated extrinsic pathway.

• Biomolecules & Therapeutics
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• v.22 no.6
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• pp.497-502
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• 2014

In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-1 promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat primary astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-1 expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-1 expression by arctigenin via modulation of Nrf2/ARE axis in rat primary astrocytes.

• YAKHAK HOEJI
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• v.56 no.6
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• pp.395-400
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• 2012

To investigate the possibility of development as a whitening agent using arctigenin, we measured DPPH assay, NBT/XO assay, intracellular ROS scavenging assay, tyrosinase assay and MSH-induced melanin production in B16 melanoma cells. Arctigenin dose-dependently had anti-oxidant activity in DPPH, NBT/XO and intracellular ROS assay. Although arctigenin did not inhibit purified tyrosinase activity, it dose-dependently inhibited tyrosinase activity and melanin production in B16 melanoma cells stimulated by $1{\mu}M$ ${\alpha}$-MSH. In particular, arctigenin at a concentration $100{\mu}M$ inhibited ${\alpha}$-MSH-stimulated tyrosinase activity and melanin production by $50.9{\pm}2.9%$ and $69.0{\pm}6.5%$ respectively. And typical tyrosinase inhibitor, arbutin, inhibited $57.7{\pm}2.9%$ and $65.1{\pm}5.0%$ respectively. Such an similar inhibitory effect of arctigenin and arbutin in B16 melanoma cells may be due to the inhibition of MSH signal pathway rather than the direct inhibition of tyrosinase. Therefore, these results suggest that arctigenin may be useful for the development as whitening agents.

• Journal of the Korean Applied Science and Technology
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• v.32 no.3
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• pp.505-511
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• 2015

In this study, Arctigenin was obtained by using supercritical fluid extraction and bio-conversion process from Arctii Fructus. Arctigenin is efficacious in anti-inflammatory and anti-influenza. For this reason, Arctigenin is studied in various field. It was identified as 4-[(3,4-Dimethoxyphenyl)methyl)]dihydro-3-[(4-hydroxy-3-methoxyphenyl)methyl]-2(3H)-furanone (arctigenin) by FT-IR, $^1H$-NMR and the purity of it was 95.1 % by HPLC analysis. Arctigenin inhibited tyrosinase (up to $85.06{\pm}0.9%$ at $260{\mu}g/m{\ell}$ concentration) and melanin synthesis in a dose dependent manner (up to $51.1{\pm}3.7%$ at the concentration of $3.0{\mu}g/m{\ell}$). The results were better than arbutin. Therefore, it is expected that manufactured Arctigenin is useful for whitening cosmetics.

• Mass Spectrometry Letters
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• v.8 no.2
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• pp.23-28
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• 2017

Arctigenin is the main active ingredient of Fructus Arctii, which has been reported with a variety of therapeutic activities including anti-cancer, anti-inflammation, anti-virus, and anti-obesity effects. In this study, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of arctigenin in rat plasma. The assay utilized a simple protein precipitation with methanol and the mobile phase consisted of 100% methanol and water containing 0.1% formic acid (65:35 v/v). Arctigenin and the internal standard (psoralen) were monitored using a positive electrospray turbo ionspray mode with multiple reaction monitoring transitions of m/z $373.2{\rightarrow}136.9$ and m/z $187.2{\rightarrow}130.9$, respectively, and total chromatographic run time was within 5 min. The lower limit of quantification (LLOQ) of arctigenin was 5 ng/mL in the rat plasma. The intra- and inter-day accuracy of arctigenin at LLOQ and matrix-matched quality control samples ranged 97.4 - 104.8% and 97.2 - 102.0%, respectively. The intra-day precision was within 4.80% and the inter-day precision was within 5.92%. Application of the present method was demonstrated through a pharmacokinetic study after intravenous and oral administration of arctigenin in male Sprague Dawley rats.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.425-430
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• 2011

In this study, we found that Forsythiae fructus (FF) and one of its main compounds, arctigenin, significantly inhibited nitric oxide production in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Arctigenin also suppressed the expression of inducible nitric oxide synthase and cyclooxygenase-2, and inhibited the activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38. Moreover, it also reduced levels of proinflammatory cytokines, interleukin $1{\beta}$, tumor necrosis factor ${\alpha}$ and prostaglandin E2, and inhibited neuronal death in LPS-treated organotypic hippocampal cultures. Therefore, we suggest that arctigenin may confer a neuroprotective effect via the inhibition of neuroinflammation.

• Journal of Microbiology and Biotechnology
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• v.29 no.4
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• pp.571-576
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• 2019

Microenvironmental stress, which is naturally observed in solid tumors, has been implicated in anticancer drug resistance. This tumor-specific stress causes the degradation of topoisomerase $II{\alpha}$, rendering cells resistant to topoisomerase $II{\alpha}$-targeted anticancer agents. In addition, microenvironmental stress can induce the overexpression of 78kDa glucose regulated protein (GRP78), which can subsequently block the activation of apoptosis induced by treatment with anticancer agents. Therefore, inhibition of topoisomerase $II{\alpha}$ degradation and reduction in GRP78 expression may be effective strategies for inhibiting anticancer drug resistance. In this study, we investigated the active compound arctigenin, which inhibited microenvironmental stress-induced etoposide resistance in HT-29 cells. Arctigenin was also highly toxic to etoposide-resistant HT-29 cells, with an $IC_{50}$ value of $10{\mu}M$ for colony formation. We further showed that arctigenin inhibited the degradation of topoisomerase $II{\alpha}$ and reduced the expression of GRP78. Thus, these results suggest that arctigenin is a novel therapeutic agent that inhibits resistance to etoposide associated with microenvironmental stress conditions.

• Journal of Microbiology and Biotechnology
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• v.15 no.2
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• pp.269-273
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• 2005

Five dibenzylbutyrolactones were isolated from a methanol extract of Arctii fructus (Arctium lappa L.) by bioassay-guided isolation, using the interleukin-l $\beta$ converting enzyme (caspase-l, ICE) production inhibitory assay in vitro. These compounds were spectroscopically identified as lappaol E (1), lappaol A (2), matairesinol (3), arctigenin (4), and arctiin (5). Among the compounds tested, arctigenin (4) showed the strongest inhibitory activity for ICE production in IL-$\beta$-induced proliferation of D 1 OS cells. Western blot analysis demonstrated that the arctigenin suppressed the expression of ICE protein in a dose-dependent manner. To estimate the biotransformation of Arctii fructus in vivo by human intestinal bacteria, we carried out an anaerobic incubation of the Arctii fructus extract with a human fecal suspension. From the HPLC analysis of metabolites, Arctiin (IC$_{50}$=74.2$\mu$g/ml), a major component of Arctii fructus, was transformed to aglycone, arctigenin (IC$_{50}$=12.5$\mu$g/ml), by human intestinal bacteria. The ICE production inhibitory activity of Arctii fructus would be much stronger in vivo than in vitro due to the biotransformation by human intestinal bacteria.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.139-139
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• 2001

Arctigenin and demethyltraxillagenin, dibenzylbutyrolactone lignans, are phenylpropanoid plant metabolites with antioxidative and anti-inflammatory activities. The effects of arctigenin and demethyltraxillagenin on the nuclear factor-kB (NF-kB)-mediated inducible nitric oxide synthase (iNOS) gene expression were studied in Raw264.7 cells.(omitted)

• Korean Journal of Plant Resources
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• v.5 no.1
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• pp.49-56
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• 1992

In the preliminary antitumor screening tests of Crude Drugs and collected plants, the methanol ic extract of Forsythia Fruits in Korean marcket showed signif icant cytotoxic activity against Chinese hamster V-79 cells, but that in Japanese market did not. The former was identifid as Forsythia viridissima Lindley and latter as F.suspensa Vahl on the basis of the morphological observation. When an aqueous solution of the extract prepared from the fruits of F. viridissima (Oleaceae) was partitioned successively with n-hexane, methylene chloride, n-butanol, the cytoyoxic activitywas concetrated in the methylene chloride extract. Fractionation of the extract was made with the guidance of bioassay against V-79 cells to give cytotoxic lignans, matariresiol (1) and arctigenin (2). Their ICso values of compounds 1 and 2 were respectively $7.8{\;}\mu\textrm{g}/ml$ 1 and $1.65{\;}\mu\textrm{g}/ml$. Also, their structures were confirmed by comparison of physical and spectral data in the literature.