Lignan from Alnus japonica Inhibits Adipocyte Differentiation via Cell Cycle and FOXO1 Regulation

Lee, Hye-Jin; Jeong, Ji Hye; Ryu, Jae‐Ha

doi:10.3390/molecules25153346

Cited by 11 publications

(10 citation statements)

References 26 publications

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“…To investigate the myogenic effect of ((-)-(2R,3R-1,4-O-diferuloylsecoisolarciresinol, DFS) (Fig. 1a) isolated from Alnus japonica (AJ) [19], mouse myoblast C2C12 cells were treated with non-toxic concentrations of DFS (1, 10, 100, or 1000 nM) during myogenesis.…”

Section: Resultsmentioning

confidence: 99%

“…AJ contains numerous active compounds such as diarylheptanoids, triterpenoids, and flavonoids [16]. We have previously isolated a lignan compound ((-)-(2R,3R-1,4-O-diferuloylsecoisolarciresinol, DFS) from the stem of AJ and reported its anti-cancer [17,18] and anti-obesity activities [19]. As muscle atrophy is accompanied by chronic diseases including cancer, aging, and obesity, an antimyopathy activity of DFS can be expected based on results of our previous studies.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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A Lignan from Alnus japonica Activates Myogenesis and Alleviates Dexamethasone-induced Myotube Atrophy

et al. 2022

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To find inhibitors against skeletal muscle loss, we isolated a lignan compound ((-)-(2 R ,3R-1,4-Ο-diferuloylsecoisolarciresinol, DFS) from the stem of Alnus japonica. C2C12 myoblasts were treated with DFS during differentiation. To induce an in vitro atrophic condition, differentiated myotubes were treated with dexamethasone (a synthetic glucocorticoid). DFS (10 nM) increased expression levels of myogenic factors and the number of multi-nucleated myotubes expressing myosin heavy chain (MHC). The myogenic potential of DFS could be attributed to p38 MAPK activation. DFS also protected against dexamethasone-induced damage showing increased expression of MHC and mammalian target of rapamycin (mTOR), a major anabolic factor. Under atrophic condition, the anti-myopathy effect of DFS was associated with inactivation of NF-κB signaling pathway and the subsequent suppression of muscle degradative E3 ligases and myostatin. DFS treatment also restored fast muscle fiber (type IIa, IIb, and IIx) known to be susceptible to dexamethasone. These results indicate that DFS isolated from A. japonica can stimulate myogenesis via p38 MAPK activation and alleviate muscle atrophy by modulating the expression of genes associated with muscle protein anabolism/catabolism. Thus, we propose that DFS can be used as a pharmacological and nutraceutical agent for increasing muscle strength or protecting muscle loss.

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Section: Resultsmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

A Lignan from Alnus japonica Activates Myogenesis and Alleviates Dexamethasone-induced Myotube Atrophy

et al. 2022

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“…DFS, a lignan isolated from a methanol extract of stems of A. japonica 24 . A. japonica is a plant widely used as both a food and a medicinal herb in east Asia 19 , 24 .…”

Section: Discussionmentioning

confidence: 99%

A lignan from Alnus japonica inhibits glioblastoma tumorspheres by suppression of FOXM1

Shim

Lim

Jeong

et al. 2022

Sci Rep

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Forkhead Box M1 (FOXM1) is known to regulate cell proliferation, apoptosis and tumorigenesis. The lignan, (−)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol (DFS), from Alnus japonica has shown anti-cancer effects against colon cancer cells by suppressing FOXM1. The present study hypothesized that DFS can have anti-cancer effects against glioblastoma (GBM) tumorspheres (TSs). Immunoprecipitation and luciferase reporter assays were performed to evaluate the ability of DFS to suppress nuclear translocation of β-catenin through β-catenin/FOXM1 binding. DFS-pretreated GBM TSs were evaluated to assess the ability of DFS to inhibit GBM TSs and their transcriptional profiles. The in vivo efficacy was examined in orthotopic xenograft models of GBM. Expression of FOXM1 was higher in GBM than in normal tissues. DFS-induced FOXM1 protein degradation blocked β-catenin translocation into the nucleus and consequently suppressed downstream target genes of FOXM1 pathways. DFS inhibited cell viability and ATP levels, while increasing apoptosis, and it reduced tumorsphere formation and the invasiveness of GBM TSs. And DFS reduced the activities of transcription factors related to tumorigenesis, stemness, and invasiveness. DFS significantly inhibited tumor growth and prolonged the survival rate of mice in orthotopic xenograft models of GBM. It suggests that DFS inhibits the proliferation of GBM TSs by suppressing FOXM1. DFS may be a potential therapeutic agent to treat GBM.

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“…A. japonica is a plant widely used as both a food and a medicinal herb in east Asia [19,42]. It is effective in various medical conditions, such as fever, diarrhea and hemorrhage, because it contains diverse pharmacologically active components.…”

Section: Discussionmentioning

confidence: 99%

“…It is effective in various medical conditions, such as fever, diarrhea and hemorrhage, because it contains diverse pharmacologically active components. DFS, a lignan isolated from a methanol extract of A. japonica stems [42], has shown anticancer activity in colon cancer by suppressing the nuclear translocation of βcatenin through lysosomal-dependent degradation of FOXM1 protein [19].…”

Section: Discussionmentioning

confidence: 99%

A lignan from Alnus japonica inhibits glioblastoma tumorspheres by suppression of FOXM1

Shim

Lim

Jeong

et al. 2021

Preprint

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Introduction Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Forkhead Box M1 (FOXM1) has been shown to regulate cell proliferation, apoptosis, angiogenesis, DNA damage repair and tumorigenesis. The lignin, (−)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol (DFS), from Alnus japonica (Betulaceae) has shown anti-cancer effects against colon cancer cells by suppressing FOXM1. However, the efficacy of DFS in GBM has not yet been determined. The present study hypothesized that DFS can have anti-cancer effects against GBM tumorspheres (TSs). Methods Immunoprecipitation and luciferase reporter assays were performed to evaluate the ability of DFS to suppress nuclear translocation of β-catenin through β-catenin/FOXM1 binding. GBM TSs were treated with DFS to assess the ability of DFS to inhibit GBM TSs and to evaluate their transcriptional profiles. The in vivo efficacy of DFS was examined in orthotopic xenograft models of GBM. Results Expression of FOXM1 was higher in GBM than in normal tissues. DFS-induced FOXM1 protein degradation blocked β-catenin translocation into the nucleus and consequently suppressed downstream target genes of FOXM1 pathways. DFS considerably inhibited cell viability and ATP levels in GBM TSs, while increasing the proportion of apoptotic cells. Treatment with DFS also reduced neurosphere formation and the invasive properties of GBM TSs. Transcriptome analyses showed that DFS reduced the activities of transcription factors related to tumorigenesis, stemness, and invasiveness. In addition, DFS significantly inhibited tumor growth and prolonged the survival rate of mice in orthotopic xenograft models of GBM. Conclusions DFS inhibits the proliferation of GBM TSs by suppressing FOXM1. These findings suggest that DFS may be a potential therapeutic agent to treat patients with GBM.

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Lignan from Alnus japonica Inhibits Adipocyte Differentiation via Cell Cycle and FOXO1 Regulation

Cited by 11 publications

References 26 publications

A Lignan from Alnus japonica Activates Myogenesis and Alleviates Dexamethasone-induced Myotube Atrophy

A Lignan from Alnus japonica Activates Myogenesis and Alleviates Dexamethasone-induced Myotube Atrophy

A lignan from Alnus japonica inhibits glioblastoma tumorspheres by suppression of FOXM1

A lignan from Alnus japonica inhibits glioblastoma tumorspheres by suppression of FOXM1

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