Arctiin is a pharmacological inhibitor of STAT3 phosphorylation at tyrosine 705 residue and potentiates bortezomib-induced apoptotic and anti-angiogenic effects in human multiple myeloma cells

Lee, Jong Hyun,Kim, Chulwon,Lee, Junhee,Um, Jae-Young,Sethi, Gautam,Ahn, Kwang Seok Elsevier 2019 Phytomedicine Vol.55 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Arctiin is a main component from the fruits of <I>Arctium lappa L</I>., that can be prescribed for cold or flu in East Asian countries; it has also been found to exert chemopreventive actions against various tumor cells.</P> <P><B>Hypothesis</B></P> <P>In view of this evidence, we examined arctiin for its ability to trigger apoptosis and inhibit the activation of signal transducer and activator of transcription 3 (STAT3) in human multiple myeloma (MM) cells.</P> <P><B>Methods</B></P> <P>We evaluated the effect of arctiin on STAT3 signaling cascades and its regulated functional responses in MM cells.</P> <P><B>Results</B></P> <P>Arctiin effectively blocked the constitutive activation of STAT3 phosphorylation in the residue of tyrosine 705. Arctiin also abrogated the constitutive activation of Src phosphorylation and Janus-activated kinases (JAKs) 1/2. Furthermore, it was found that arctiin treatment clearly enhanced the mRNA and protein levels of protein tyrosine phosphatase ε (PTPε), and the silencing of PTPε caused a reversal of the arctiin-induced PTPε expression and the blockadge of STAT3 phosphorylation. Interestingly, arctiin could not repress IL-6-induced STAT3 activation in serum-starved U266 cells and when arctiin was incubated with a complete culture medium in RPMI 8226 and MM.1S cells. Arctiin suppressed cell proliferation, accumulated cells in the G2/M cell-cycle phase, and induced apoptosis within U266 cells, although the knockdown of PTPε prevented PARP cleavage and caspase-3 activation induced by the arctiin. In addition, arctiin exerted cytotoxicity in MM cells, but did not do so in peripheral blood mononuclear cells. Arctiin down-modulated diverse oncogenic gene products regulated by STAT3, although the induction of apoptosis by arctiin was abrogated upon transfection with pMXs-STAT3C in mouse embryonic fibroblast (MEF) cells. Arctiin also potentiated bortezomib-induced antitumor effects in U266 cells.</P> <P><B>Conclusion</B></P> <P>On the whole, our results indicate that arctiin is a potentially new inhibitor of constitutive STAT3 activation through the induction of PTPε in MM, cells and therefore has great value in treating various tumors sheltering constitutively activated STAT3.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

P102 : Arctiin inhibits hydrogen peroxide-induced senescence and cell death in human dermal papilla cells

( Ho Jung Jung ),( Min Jung Kim ),( Hae Jeong Youn ),( Nam Kyung Roh ),( Soo Young Kim ),( Yu Ri Kim ),( Yu Na Lee ),( Jae Wook Jung ),( Yang Won Lee ),( Yong Beom Choe ),( Kyu Joong Ahn ),( In Sook A 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: Arctiin is an active lignin isolated from Arctium lappa and has anti-inflammation, antimicrobial, and anti-carcinogenic effects. Objectives: To find that arctiin exerts antioxidative effects on human hair dermal papilla cells (HHDPCs). Methods: To better understand the mechanism, we analyzed the level of hydrogen peroxide (H2O2)-induced cytotoxicity, cell death, ROS production and senescence after arctiin pretreatment of HHDPCs. Results: The results showed that arctiin pretreatment significantly inhibited the H2O2-induced reduction in cell viability. Moreover, H2O2-induced sub-G1 phase accumulation and G2 cell cycle arrest were also downregulated by arctiin pretreatment. The increase in intracellular ROS mediated by H2O2 was drastically decreased in HHDPCs cultured in the presence of arctiin. This effect was confirmed by senescence associated-beta galactosidase (SA-β-gal) assay results; we found that arctiin pretreatment impaired H2O2-induced senescence in HHDPCs. Using microRNA (miRNA) microarray and bioinformatic analysis, we showed that this anti-oxidative effect of arctiin in HHDPCs was related with mitogen-activated protein kinase (MAPK) and Wnt signaling pathways. Conclusion: Our data suggest that arctiin has a protective effect on ROS-induced cell dysfunction in HHDPCs and may therefore be useful for alopecia prevention and treatment strategies.

Collagen type 1α synthesis pathway induced by arctiin in human dermal fibroblast

( Ji Su Lee ),( Young Ah Cho ),( Sung Min Kim ),( Ji Youn Hong ),( Jin Hee Kim ),( Joo Ran Hong ),( Hye In Cheon ),( Byung Gon Choi ),( Yang Won Lee ),( Yong Beom Choe ),( Kyu Joong Ahn ) 대한피부과학회 2020 대한피부과학회 학술발표대회집 Vol.72 No.1

Background: Arctiin, which is known as extract of Arctium lappa, has recently been demonstrated to improve procollagen type I synthesis and exhibits a protective effect against ultraviolet B (UVB) radiation. However, the underlying mechanism of collagen synthesis, induced by arctiin treatment, remains unknown. Objectives: The purpose of this study was to find out which pathway is involved in the synthesis of collagen type 1α 1 chain (COL1A1) by arctiin at the mRNA level. Methods: Cell viability, microRNA-378b (miR-378b) expression, relative band intensity of sirtuin 6 (SIRT6) mRNA, and relative expression of COL1A1 mRNA were confirmed according to different combination of arctiin and miR-378b concentration in dermal fibroblast. For this study, western blotting and quantitative reverse transcription polymerase chain reaction were performed. Results: Arctiin downregulated the expression of miRNA 378b, and miR-378b upregulated the expression of SIRT6 mRNA. Finally, SIRT6 induced the expression of COL1A1 mRNA. Conclusion: This study demonstrated that the arctiin-induced upregulation of COL1A1 expression is regulated by the miR-378/SIRT6 signaling pathway.

LC-MS/MS를 이용한 S.D. Rat 혈장 중 Arctiin 분석법 개발

송병정,채정우,백현문,권광일 충남대학교 약학대학 의약품개발연구소 2014 藥學論文集 Vol.29 No.-

KIOM-MA128 is a novel oriental herbal medicine which is for atopic dermatitis and asthma. The purpose of this study was to develop on analytical method of arctiin in rat plasma after oral administration of KIOM-MA128. Analyte was separated on a Atlantis dC18 reverse phase column, using gradient mobile phase (A:B = acetonitrile: 0.1% formic acid in water) at a flow rate of 0.3 mL/min. Detection was performed by electrospray positive ionization mass spectrometry using multiple reaction monitoring of the transitions of arctiin at m/z 552.4 → 372.8 and internal standard (carbamazepine) at m/z 237.0 → 194.5. The limit of quantification was 1 ng/mL for arctiin. The precisions were lower than 15% and the accuracy was between – 12.21 and 3.2%. The maximum concentration found in plasma samples was 4.1 ng/mL. The present method was successfully developed for detecting arctiin in plasma and this results would be utilized to the further study.

Anti-wrinkle Compounds Isolated from the Seeds of Arctium lappa L.

Ju-Young Hwang(황주영),Tae-Soon Park(박태순),Dong-Hee Kim(김동희),Eun-Young Hwang(황은영),Jung-Noh Lee(이정노),Ji young Lee(이지영),Ghang-Tai Lee(이강태),Kunkook Lee(이건국),Jun-Ho Son(손준호) 한국생명과학회 2012 생명과학회지 Vol.22 No.8

본 연구에서는 우방자를 70% 에탄올로 추출하여 얻어진 추출물을 n-hexane, methylene chloride, ethyl acetate로 순차용매 분획하였다. 각 분획물에 대해 activity-guided isolation을 수행하여 활성물질의 분리 정제를 실시하였다. 활성을 나타내는 물질은 silica gel chromatography (230 mesh), sephadex LH 20, recrystallization method를 이용하여 분리하였다. 각 화합물의 화학구조는 NMR 스펙트럼 데이터 해석하였고 arctiin, arctigenin, diarctigenin, matairesinol 으로 동정하였다. 이들을 human dermal fibroblast HS68 세포에 처리하여 얻어진 상등액은 ELISA kit를 활용하여 procollagen type Ⅰ생합성과 MMP-1 저해활성을 측정하였다. 측정결과 procollagen type Ⅰ생합성과 MMP-1 저해활성 결과 모두 arctiin이 가장 우수한 결과를 보였다. 이와 같은 결과를 통해 우방자에서 분리한 리그난 화합물들을 이용하여 주름개선 소재로 개발할 수 있을 것으로 사료 된다. This study was carried out to discover the skin wrinkle reducing components in the seeds of Arctium lappa. The isolation of a methylene chloride-soluble fraction of 70% ethanol extract from the seeds of Arctium lappa using a procollagen type-1 synthesis and MMP-1 activity resulted in the isolation and identification of four lignin compounds: arctiin, arctigenin, matairesinol, and diarctigenin. All structures were confirmed via NMR and MS spectroscopic data. To determine cell viability and procollagen type-1 synthesis, human dermal fibroblasts were treated with 10-100 μM. As a result, none of the four compounds showed cytotoxicity up to 50 μM. We also investigated their procollagen type-1 synthesis and MMP-1 inhibition activity and found that arctiin had the highest activity in terms of both procollagen synthesis and MMP-1 inhibition among all four compounds. Putting all the data together, we suggest that arctiin be used in cosmetics as an anti-wrinkle material.

Arctiin inhibits adipogenesis in 3T3-L1 cells and decreases adiposity and body weight in mice fed a high-fat diet

Byulchorong Min,Heejin Lee,Ji Hye Song,Myung Joo Han,Jayong Chung 한국영양학회 2014 Nutrition Research and Practice Vol.8 No.6

BACKGROUND/OBJECTIVES: The purpose of this study was to examine the effects and associated mechanisms of arctiin, a lignan compound found in burdock, on adipogenesis in 3T3-L1 cells. Also, the effects of arctiin supplementation in obese mice fed a high-fat diet on adiposity were examined. MATERIALS/METHODS: 3T3-L1 cells were treated with arctiin (12.5 to 100 μM) during differentiation for 8 days. The accumulation of lipid droplets was determined by Oil Red O staining and intracellular triglyceride contents. The expressions of genes related to adipogenesis were measured by real-time RT-PCR and Western blot analyses. For in vivo study, C57BL/6J mice were first fed either a control diet (CON) or high-fat diet (HF) to induce obesity, and then fed CON, HF, or HF with 500 mg/kg BW arctiin (HF + AC) for four weeks. RESULTS: Arctiin treatment to 3T3-L1 pre-adipocytes markedly decreased adipogenesis in a dose-dependent manner. The arctiin treatment significantly decreased the protein levels of the key adipogenic regulators PPARγ and C/EBPα, and also significantly inhibited the expression of SREBP-1c, fatty acid synthase, fatty acid-binding protein and lipoprotein lipase. Also, arctiin greatly increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target phosphorylated-acetyl CoA carboxylase. Furthermore, administration of arctiin significantly decreased the body weight in obese mice fed with the high-fat diet. The epididymal, perirenal or total visceral adipose tissue weights of mice were all significantly lower in the HF + AC than in the HF. Arctiin administration also decreased the sizes of lipid droplets in the epididymal adipose tissue. CONCLUSIONS: Arctiin inhibited adipogenesis in 3T3-L1 adipocytes through the inhibition of PPARγ and C/EBPα and the activation of AMPK signaling pathways. These findings suggest that arctiin has a potential benefit in preventing obesity.

P260 : Photo-protective effect of arctiin by changes in microRNA expression against UVB-induced keratinocytes damage

( Min Jung Kim ),( Hae Jeong Youn ),( Soo Young Kim ),( Nam Kyung Roh ),( Ho Jung Jung ),( Yu Ri Kim ),( Yu Na Lee ),( Jae Wook Jung ),( Yang Won Lee ),( Yong Beom Choe ),( Kyu Joong Ahn ) 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: Arctiin has been isolated from several plants such as Arctium lappa and Forsythiae fructus. Previous studies demonstrated that arctiin exerted a protective effect against lipopolysaccharide (LPS)-induced inflammation and had anti-proliferative and anti-microbial functions. Objectives: In the present study, we demonstrated that photo-protective effect of arctiin on UVB-induced damaged keratinocyte though specific changes in miRNA expression. Methods: To determine the cytotoxicity of arctiin, a cell viability assay was performed using water-soluble tetrazolium salts. We performed the cell cycle distribution was examined by PI staining and flow cytometry to determine the protective effect of arctiin on UVB-irradiated HaCaT cells. To examine whether arctiin pretreatment induced UVB resistance through the regulation of the cell migration associated with wound healing, a series of scratch assays were performed in the HaCaT cells. Results: The cellular and molecular assays demonstrated a novel role for arctiin in UVB protection in keratinocytes, which was mediated by miRNA responses and the suppression of UVB-induced cell death. In addition, we demonstrated that arctiin is implicated as a potential chemo-preventive agent through UVB protection of keratinocytes. Conclusion: The photo-protective effects of arctiin were associated with changes in the expression levels of specific microRNAs (miRNAs) in HaCaT cells.

Antiproliferative effect of Arc-tigenin and Arctiin

Ryu, Shi-Yong,Ahn, Jong-Woong,Kang, Young-Hwa,Han, Byung-Hoon The Pharmaceutical Society of Korea 1995 Archives of Pharmacal Research Vol.18 No.6