Anti-proliferative effect of Euphorbia stenoclada in human airway smooth muscle cells in culture

• Published in: Journal of ethnopharmacology 2007-01, Vol.109 (1), p.134-139
• Main Authors: Chaabi, M., Freund-Michel, V., Frossard, N., Randriantsoa, A., Andriantsitohaina, R., Lobstein, A.
• Format: Article
• Language: English
• Subjects: Airway smooth muscle; Anti-Asthmatic Agents - pharmacology; Asthma; Biochemistry, Molecular Biology; Biological and medical sciences; Bronchi - cytology; Bronchi - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Chromatography, High Pressure Liquid; Euphorbia - chemistry; Euphorbia stenoclada (Euphorbiaceae); Flavonoids; General pharmacology; Glycosylation; Humans; Interleukin-1beta - pharmacology; Life Sciences; Madagascar; Mass Spectrometry; Medical sciences; Methylation; Muscle, Smooth - cytology; Muscle, Smooth - drug effects; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant Extracts - pharmacology; Proliferation; Quercetin; Quercetin - chemistry; Quercetin - pharmacology; Spectrophotometry, Ultraviolet; Structure-Activity Relationship; Tetrazolium Salts
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2006.07.016

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-1β (IL-1β) induced proliferation of HASMC (IC 50 = 0.73 ± 0.08 μg/mL). No cytotoxic effect was observed up to 20 μg/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 μg/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 μg/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.