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Sesquiterpene lactones from Ambrosia arborescens Mill. inhibit pro-inflammatory cytokine expression and modulate NF-κB signaling in human skin cells

Svensson, Daniel LU ; Lozano, Maribel LU ; Almanza, Giovanna R. ; Nilsson, Bengt Olof LU ; Sterner, Olov LU and Villagomez, Rodrigo LU (2018) In Phytomedicine 50. p.118-126
Abstract

Background: Ambrosia arborescens has been used in Andean traditional medicine to reduce problems associated with various inflammatory diseases and conditions, although the underlying mechanism is unknown. Hypothesis/purpose: The sesquiterpene lactones (SLs) coronopilin and damsin, which are major secondary metabolites of A. arborescens, have anti-inflammatory activity by attenuation of IL-6 and MCP-1 expression and inhibition of NF-κB in human dermal fibroblasts (HDFa) and human keratinocytes (HaCaT). Study design: In order to confirm a high concentration of damsin and coronopilin in the plant material, a quantitative method was developed. The effect of the pure compounds on cytokine and NF-κB expression was examined, as well as their... (More)

Background: Ambrosia arborescens has been used in Andean traditional medicine to reduce problems associated with various inflammatory diseases and conditions, although the underlying mechanism is unknown. Hypothesis/purpose: The sesquiterpene lactones (SLs) coronopilin and damsin, which are major secondary metabolites of A. arborescens, have anti-inflammatory activity by attenuation of IL-6 and MCP-1 expression and inhibition of NF-κB in human dermal fibroblasts (HDFa) and human keratinocytes (HaCaT). Study design: In order to confirm a high concentration of damsin and coronopilin in the plant material, a quantitative method was developed. The effect of the pure compounds on cytokine and NF-κB expression was examined, as well as their effects on HDFa and HaCaT cell morphology and viability. Methods: Coronopilin and damsin were quantified by HPLC-DAD analysis, from EtOAc extracts of the aerial parts of A. arborescens. Cell morphology was investigated by phase-contrast microscopy and cell viability by the MTT assay. IL-6 and MCP-1 cytokine gene expression was assessed by quantitative real-time RT-PCR in LPS stimulated cells. The NF-κB pathway was studied through western blotting of the phosphorylated forms of p65 and p50/p105, as well as the non-phosphorylated IκB. Dexamethasone was used as positive control. Results: Dry aerial parts contained 12.3 mg/g and 13.4 mg/g of coronopilin and damsin, respectively. Treatment with either compound (1–10 µM) for 24 h attenuated LPS-induced mRNA expression of the pro-inflammatory cytokine IL-6 and the chemokine MCP-1 in HDFa cells. The down-regulation of MCP-1 mRNA induced by coronopilin and damsin was confirmed on the protein level. Damsin reduced phosphorylated p65 and p105 subunits in HDFa cells. Neither coronopilin nor damsin affected HDFa cell morphology and viability within the used concentration range (1–10 µM). Also, in HaCaT cells, treatment with damsin (1–10 µM) for 24 h inhibited the MCP-1 expression, and damsin thereby attenuated cytokine expression both in HDFa and HaCaT cells. Conclusion: We show that coronopilin and damsin from A. arborescens inhibit pro-inflammatory IL-6 and MCP-1 expression in human skin cells via NF-κB inhibition, suggesting that they may be useful for antagonizing inflammatory conditions of the human skin.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Andean medicine, Dermal fibroblasts, Inflammation, NF-κB, NSAID, Pseudoguaianolides
in
Phytomedicine
volume
50
pages
9 pages
publisher
Urban & Fischer Verlag
external identifiers
  • pmid:30466970
  • scopus:85054568243
ISSN
0944-7113
DOI
10.1016/j.phymed.2018.04.011
language
English
LU publication?
yes
id
e45db9ed-5e29-493d-b17a-9aa8b96a593c
date added to LUP
2018-10-29 14:16:52
date last changed
2020-09-16 03:59:20
@article{e45db9ed-5e29-493d-b17a-9aa8b96a593c,
  abstract     = {<p>Background: Ambrosia arborescens has been used in Andean traditional medicine to reduce problems associated with various inflammatory diseases and conditions, although the underlying mechanism is unknown. Hypothesis/purpose: The sesquiterpene lactones (SLs) coronopilin and damsin, which are major secondary metabolites of A. arborescens, have anti-inflammatory activity by attenuation of IL-6 and MCP-1 expression and inhibition of NF-κB in human dermal fibroblasts (HDFa) and human keratinocytes (HaCaT). Study design: In order to confirm a high concentration of damsin and coronopilin in the plant material, a quantitative method was developed. The effect of the pure compounds on cytokine and NF-κB expression was examined, as well as their effects on HDFa and HaCaT cell morphology and viability. Methods: Coronopilin and damsin were quantified by HPLC-DAD analysis, from EtOAc extracts of the aerial parts of A. arborescens. Cell morphology was investigated by phase-contrast microscopy and cell viability by the MTT assay. IL-6 and MCP-1 cytokine gene expression was assessed by quantitative real-time RT-PCR in LPS stimulated cells. The NF-κB pathway was studied through western blotting of the phosphorylated forms of p65 and p50/p105, as well as the non-phosphorylated IκB. Dexamethasone was used as positive control. Results: Dry aerial parts contained 12.3 mg/g and 13.4 mg/g of coronopilin and damsin, respectively. Treatment with either compound (1–10 µM) for 24 h attenuated LPS-induced mRNA expression of the pro-inflammatory cytokine IL-6 and the chemokine MCP-1 in HDFa cells. The down-regulation of MCP-1 mRNA induced by coronopilin and damsin was confirmed on the protein level. Damsin reduced phosphorylated p65 and p105 subunits in HDFa cells. Neither coronopilin nor damsin affected HDFa cell morphology and viability within the used concentration range (1–10 µM). Also, in HaCaT cells, treatment with damsin (1–10 µM) for 24 h inhibited the MCP-1 expression, and damsin thereby attenuated cytokine expression both in HDFa and HaCaT cells. Conclusion: We show that coronopilin and damsin from A. arborescens inhibit pro-inflammatory IL-6 and MCP-1 expression in human skin cells via NF-κB inhibition, suggesting that they may be useful for antagonizing inflammatory conditions of the human skin.</p>},
  author       = {Svensson, Daniel and Lozano, Maribel and Almanza, Giovanna R. and Nilsson, Bengt Olof and Sterner, Olov and Villagomez, Rodrigo},
  issn         = {0944-7113},
  language     = {eng},
  month        = {11},
  pages        = {118--126},
  publisher    = {Urban & Fischer Verlag},
  series       = {Phytomedicine},
  title        = {Sesquiterpene lactones from Ambrosia arborescens Mill. inhibit pro-inflammatory cytokine expression and modulate NF-κB signaling in human skin cells},
  url          = {http://dx.doi.org/10.1016/j.phymed.2018.04.011},
  doi          = {10.1016/j.phymed.2018.04.011},
  volume       = {50},
  year         = {2018},
}