Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan, inhibits MAP kinases and AP-1 activation via potent MKK inhibition: the role in TNF-α inhibition

Cho, Min Kyung; Jang, Young Pyo; Kim, Young Choong; Kim, Sang Geon

doi:10.1016/j.intimp.2004.06.011

Cited by 123 publications

(75 citation statements)

References 34 publications

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“…In addition, arctigenin strongly inhibited the expression of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and IL-6, in LPS-stimulated RAW264.7 cells, THP-1 human monocyte-macrophage and differentiated human macrophage U937 (Cho et al, 2002;Zhao et al, 2009). Further study showed that arctigenin-induced inhibition of TNF-α production might be mediated by arctigenin's potent inactivation of mitogen-activated protein (MAP) kinases including ERK1/2, p38 kinase and JNK through the inhibition of MAP kinase kinase (MKK) activity, leading to inactivation of activator protein-1 (AP-1) (Cho et al, 2004;Zhao et al, 2009). …”

Section: Anti-inflammatory Effectsmentioning

confidence: 99%

A review of the pharmacological effects of Arctium lappa (burdock)

et al. 2010

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Abstract. Arctium lappa, commonly known as burdock, is being promoted/recommended as a healthy and nutritive food in Chinese societies. Burdock has been used therapeutically in Europe, North America and Asia for hundreds of years. The roots, seeds and leaves of burdock have been investigated in view of its popular uses in Traditional Chinese Medicine (TCM). In this review, the reported therapeutic effects of the active compounds present in the different botanical parts of burdock are summarized. In the root, the active ingredients have been found to "detoxify" blood in TCM term and promote blood circulation to the skin surface, improving the skin quality/texture and curing skin diseases like eczema. Antioxidants and anti-diabetic compounds have also been found in the root. In the seeds, some active compounds possess anti-inflammatory effects, and potent inhibitory effects on the growth of tumors such as the pancreatic carcinoma. In the leaf extract, the active compounds isolated can inhibit the growth of micro-organisms in the oral cavity. The medicinal uses of burdock in treating chronic diseases like cancers, diabetes and AIDS have been reported. However, it is also essential to be aware of the side-effects of burdock including contact dermatitis and other allergic/inflammatory responses that might be evoked by burdock.

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Section: Anti-inflammatory Effectsmentioning

confidence: 99%

A review of the pharmacological effects of Arctium lappa (burdock)

et al. 2010

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“…Fructus arctii have been reported to have antimicrobial, antioxidant, and anti-inflammatory activities (Lin et al, 1996;Huang et al, 2010). Research on the chemical compositions of Fructus arctii has shown that the most active ingredient of Fructus arctii is arctigenin (C 21 H 24 O 6 with a molecular weight of 372.41), a phenylpropanoid dibenzylbutyrolactone lignan (Hirose et al, 2000;Cho et al, 2004;Huang et al, 2004). Because of its anti-cancer and anti-viral activities and low toxicity, Fructus arctii should be tested for chemoprevention of different cancers.…”

Section: Introductionmentioning

confidence: 99%

Arctigenin Anti‐Tumor Activity in Bladder Cancer T24 Cell Line Through Induction of Cell‐Cycle Arrest and Apoptosis

Yang

Xiao

et al. 2012

The Anatomical Record

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Bladder cancer is the most common neoplasm in the urinary system. This study assesses arctigenin anti-tumor activity in human bladder cancer T24 cells in vitro and the underlying molecular events. The flow cytometry analysis was used to detect cell-cycle distribution and apoptosis. Western blotting was used to detect changes in protein expression. The data showed that arctigenin treatment reduced viability of bladder cancer T24 cells in a dose-and time-dependent manner after treatment with arctigenin (10, 20, 40, 80, and 100 lmol/L) for 24 hr and 48 hr. Arctigenin treatment clearly arrested tumor cells in the G1 phase of the cell cycle. Apoptosis was detected by hoechst stain and flow cytometry after Annexin-V-FITC/PI double staining. Early and late apoptotic cells were accounted for 2.32-7.01% and 3.07-7.35%, respectively. At the molecular level, arctigenin treatment decreased cyclin D1 expression, whereas CDK4 and CDK6 expression levels were unaffected. Moreover, arctigenin selectively altered the phosphorylation of members of the MAPK superfamily, decreasing phosphorylation of ERK1/2 and activated phosphorylation of p38 significantly in a dose-dependent manner. These results suggest that arctigenin may inhibit cell viability and induce apoptosis by direct activation of the mitochondrial pathway, and the mitogen-activated protein kinase pathway may play an important role in the anti-tumor effect of arctigenin. The data from the current study demonstrate the usefulness of arctigenin in bladder cancer T24 cells, which should further be evaluated in vivo before translation into clinical trials for the chemoprevention of bladder cancer. Anat

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“…Arctigenin also has various other biological functions, such as antiproliferative (Matsumoto et al 2006;Ryu et al 1995), hepatoprotective (Kim et al 2003), anti-inflammatory, and analgesic activities (Fan et al 2006;Kang et al 2008). It also suppresses the heat shock response in mammalian cells (Ishihara et al 2006), inhibits mitogen-activated protein kinases (Cho et al 2004) and cyclic AMP phosphodiesterase (Nikaido et al 1981), and has a relaxation effect on histamine-induced contraction of tracheal muscles (Fujimoto et al 1992).…”

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confidence: 99%

A lignan O-methyltransferase catalyzing the regioselective methylation of matairesinol in Carthamus tinctorius

Umezawa

Ragamustari

Nakatsubo

et al. 2013

Plant Biotechnology

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Lignans are a group of plant phenolic compounds with various biological activities, including antitumor and antioxidant properties. O-Methylation is a critical step in biosynthesis of these compounds. However, little is known about the O-methyltransferase (OMT) enzymes that catalyze lignan O-methylation. We discovered a highly regioselective OMT activity in safflower (Carthamus tinctorius) seeds that catalyzed the methylation of matairesinol, a dibenzylbutyrolactone lignan, into 4′-O-methylmatairesinol (arctigenin) but not 4-O-methylmatairesinol (isoarctigenin). By examining such OMT activity in correlation with OMT transcript abundances during seed development, we cloned a few putative OMT cDNAs and produced their recombinant proteins in Escherichia coli. Among them, one protein exhibited O-methylation activity for matairesinol with the regioselectivity identical to that of the plant protein, and was named C. tinctorius matairesinol OMT (CtMROMT). CtMROMT did not show any detectable OMT activities towards phenylpropanoid monomers under the reaction conditions tested, while it methylated flavonoid apigenin efficiently into 4′-O-methylapigenin (acacetin). However, quantitative real-time polymerase chain reaction analysis demonstrated that expression of the CtMROMT gene was synchronized with the CtMROMT activity profile and arctigenin accumulation in the plant. These results demonstrated that CtMROMT is a novel plant OMT for lignan methylation.

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Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan, inhibits MAP kinases and AP-1 activation via potent MKK inhibition: the role in TNF-α inhibition

Cited by 123 publications

References 34 publications

A review of the pharmacological effects of Arctium lappa (burdock)

A review of the pharmacological effects of Arctium lappa (burdock)

Arctigenin Anti‐Tumor Activity in Bladder Cancer T24 Cell Line Through Induction of Cell‐Cycle Arrest and Apoptosis

A lignan O-methyltransferase catalyzing the regioselective methylation of matairesinol in Carthamus tinctorius

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