Anti-proliferative effect of Euphorbia stenoclada in human airway smooth muscle cells in culture.
The ethanolic extract of a Malagasy species Euphorbia stenoclada (ES) (Euphorbiaceae), traditionally used as a herbal remedy against asthma and acute bronchitis, was tested to evaluate possible anti-proliferative activity on human airway smooth muscle cells (HASMC). The ES ethanolic extract totally abolished the interleukin-1beta (IL-1beta) induced proliferation of HASMC (IC(50)=0.73+/-0.08 microg/mL). No cytotoxic effect was observed up to 20 microg/mL. A bioassay-guided fractionation of the ethanolic extract was performed by reversed-phase (RP) flash chromatography, giving five fractions (FA to FE) where fraction FE was the only active one (IC(50)=0.38+/-0.02 microg/mL). The purification of this bioactive fraction FE was carried out by RP-HPLC affording six sub-fractions 1-6, and only sub-fraction 5 kept the anti-proliferative activity. Its major constituent was identified as quercetin (IC(50)=0.49+/-0.12 microg/mL) by means of HPLC/UV/MS and co-elution with the authentic standard. Quercitrin was also identified in the fraction FE but was inactive. A structure-activity relationship with flavonols determined that methylation reduced the anti-proliferative activity whereas glycosylation abolished it. The present study shows that the anti-proliferative properties of Euphorbia stenoclada are mediated through the presence of quercetin that may explain the traditional use of this plant as a remedy against asthma.
Chaabi
M
M
UMR/CNRS 7175 Pharmacognosie et Molécules Naturelles Bioactives, Faculté de Pharmacie, Université Louis Pasteur, Strasbourg I, Illkirch, France.
Freund-Michel
V
V
Frossard
N
N
Randriantsoa
A
A
Andriantsitohaina
R
R
Lobstein
A
A
D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D028481:Euphorbia / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008270:Madagascar; D013058:Mass Spectrometry; D008745:Methylation; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts
D018927:Anti-Asthmatic Agents; D053583:Interleukin-1beta; D010936:Plant Extracts; D013778:Tetrazolium Salts; C059087:2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide; D011794:Quercetin