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Docking study and antiosteoporosis effects of a dibenzylbutane lignan isolated from Litsea cubeba targeting Cathepsin K and MEK1

  • Wei Peng
  • Hui Shen
  • Bing Lin
  • Ping Han
  • Changhui Li
  • Qiaoyan Zhang
  • Bingzhu Ye
  • Khalid Rahman
  • Hailiang Xin
  • Luping Qin
  • Ting Han
Original Research
  • 9 Downloads

Abstract

Litsea cubeba (Lour.) Pers. (Lauraceae family) has been used as a folk prescription in China for the treatment of rheumatic diseases for a long time. Previous studies of our laboratory have indicated that 9′-O-di-(E)-feruloyl-meso-5, 5′-dimethoxy-secoisolariciresinol (FCL) which is a dibenzylbutane lignan enriched in L. cubeba displayed anti-inflammatory activity in LPS induced RAW264.7 cells. The present study was aimed to investigate anti-osteoporosis/anti-rheumatoid arthritis (RA) properties of FCL and explore its potential molecular targets. The anti-RA and anti-osteoporosis properties were evaluated by determination of cell proliferation, alkaline phosphatase (ALP) activity and calcium deposition formation on osteoblasts. Meanwhile, the Tartaric Resistnt Acid Phosphatase (TRAP) inhibitory activity of FCL was evaluated on the macrophage colony-stimulating factor (M-CSF) and soluble receptor activator of nuclear factor kappa-B ligand (sRANKL) induced bone marrow cells (BMCs). Furthermore, molecular docking was carried out to predict the molecular targets of FCL, and cellular thermal shift assay (CETSA) was carried out to verify the in silico molecular docking results. The present results revealed that FCL promoted osteoblastogenesis and bone formation whereas suppressed osteoclastogenesis, and importantly, FCL showed strong binding activities to the cathepsin K and mitogen-activated proteinkinase kinase 1 (MEK1) based on the results of molecular docking and CETSA. Taken together, our results indicated that FCL may possess the anti-osteoporosis potential through acting on the targets of cathepsin K and MEK1.

Keywords

Rheumatoid arthritis Osteoporosis Molecular docking Cellular thermal shift assay 9,9′-O-di-(E)-feruloyl-meso-5,5′-dimethoxy-secoisolariciresinol Litsea cubeba 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 81573696) and the Foundation of Science and Technology Commission of Shanghai (Grant No. 14401902900).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Wei Peng
    • 1
    • 2
  • Hui Shen
    • 1
  • Bing Lin
    • 1
  • Ping Han
    • 3
  • Changhui Li
    • 1
  • Qiaoyan Zhang
    • 1
  • Bingzhu Ye
    • 1
  • Khalid Rahman
    • 4
  • Hailiang Xin
    • 1
  • Luping Qin
    • 1
    • 5
  • Ting Han
    • 1
  1. 1.Department of Pharmacognosy, School of PharmacySecond Military Medical UniversityShanghaiChina
  2. 2.School of PharmacyChengdu University of Traditional Chinese MedicineChengduChina
  3. 3.Jinan Center for Disease Control and Prevention of PLAJinanChina
  4. 4.Faculty of Science, School of Biomolecular SciencesLiverpool John Moores UniversityLiverpoolUK
  5. 5.College of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhouChina

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