4.7 Article

First Report on Inhibitory Effect against Osteoclastogenesis of Dihydro-β-agarofuran-Type Sesquiterpenoids

Journal

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 70, Issue 2, Pages 554-566

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c06862

Keywords

Celastraceae; Celastrus monospermus Roxb; osteoclastogenesis; dihydro-beta-agarofuran sesquiterpenoid

Funding

  1. Shanghai Sailing Program [20YF1418300]
  2. Shanghai Municipal Health Commission [20184Y0138]
  3. Teacher's Professional Development Project of Shanghai Municipal Education Commission [A3-2601-20-311001-8]
  4. Science and Technology Commission of Shanghai Municipality [21S11907700]
  5. Shanghai Municipal Science Technology Major Project

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Dihydro-beta-agarofuran-type sesquiterpenoids are characteristic metabolites of Celastraceae plants, and extracts from these plants have been developed into botanical pesticides. In this study, eight new dihydro-beta-agarofuran-type sesquiterpenoids were identified from the stems of Celastrus monospermus Roxb. Three of these compounds showed inhibitory activities against osteoclastogenesis and affected the expression of genes and proteins related to bone metabolism. This is the first report on the potential medical applications of dihydro-beta-agarofuran-type sesquiterpenoids in bone metabolic diseases.
Dihydro-beta-agarofuran-type sesquiterpenoids are characteristic metabolites of Celastraceae plants, and the extracts of these plants have been developed into botanical pesticides. In the course of our efforts to find novel natural biologically active products, eight new dihydro-beta-agarofuran-type sesquiterpenoids (1-8) were identified from the stems of Celastrus monospermus Roxb. Their structures were elucidated by extensive spectroscopic analysis, single crystal X-ray crystallography, and electronic circular dichroism (ECD) calculations. In consideration of the efficacy of certain Celastrus plants for the treatment of arthritis and arthralgia in folk medicine, the isolates were evaluated for their inhibitory activities against osteoclastogenesis. As a result, compounds 4, 6, and 7 were found to restrain osteoclastogenesis induced by receptor activator of nuclear factor-kappa B ligand (RANKL) with IC50 values of 0.58, 1.2, and 6.1 mu M, respectively. Furthermore, compound 4 was found to inhibit osteoclastogenesis-related gene (c-Fos, MMP-9, CTSK, TRAP) expression and block c-Fos protein expression and inhibited bone resorption of mature osteoclasts induced by M-CSF and RANKL in a dose dependent manner. This is the first report of dihydro-beta-agarofuran-type sesquiterpenoid for their potential medical applications in bone metabolic diseases.

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