Anti-inflammatory and antiproliferative compounds from Sphaeranthus africanus
| Autor: | Olaf Kunert, Eva-Maria Pferschy-Wenzig, Pia Raab, Veronika Temml, Xuehong Gao, Huyen Thi Tran, Nadine Kretschmer, Daniela Schuster, Teresa Pirker, Rudolf Bauer, Loi Huynh |
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| Rok vydání: | 2019 |
| Předmět: |
medicine.drug_class
Anti-Inflammatory Agents Drug Evaluation Preclinical Pharmaceutical Science Asteraceae Isozyme Anti-inflammatory Cell Line 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Drug Discovery Gene expression medicine Animals Humans Cyclooxygenase Inhibitors Viability assay Cytotoxicity Medicinal plants 030304 developmental biology Pharmacology 0303 health sciences Plants Medicinal Molecular Structure Chemistry Macrophages Plant Components Aerial Antineoplastic Agents Phytogenic Molecular Docking Simulation Complementary and alternative medicine Biochemistry Cell culture Cyclooxygenase 2 030220 oncology & carcinogenesis Toxicity Molecular Medicine |
| Zdroj: | Phytomedicine : international journal of phytotherapy and phytopharmacology. 62 |
| ISSN: | 1618-095X |
| Popis: | Background Sphaeranthus africanus has been used in traditional Vietnamese medicine to treat sore throat, and to relieve pain and swelling. However, the anti-inflammatory activity of this plant had not yet been investigated. Previously, we isolated five carvotacetones (1–5) from this plant that displayed cytotoxicity against several cancer cell lines. Purpose The objective of this study was to isolate further constituents from S. africanus and to investigate the anti-inflammatory activity of all constituents. Furthermore, the anti-proliferative activity of the newly isolated compounds was evaluated. Study design and methods Compounds were isolated from the upper parts of S. africanus by chromatographic methods. Structures were determined using spectroscopic techniques, like NMR and MS. All nine compounds isolated from S. africanus were evaluated for inhibitory activity against COX-1 and COX-2 isoenzymes in-vitro, COX-2 mRNA expression and influence on NO production. The anti-proliferative activities of newly isolated compounds (6–9) were evaluated by XTT viability assay with four cancer cell lines, namely CCRF-CEM, MDA-MB-231, HCT-116, and U-251 cells. Results Two diastereomeric carvotacetones (3-angeloyloxy-5-[2″S,3″R-dihydroxy-2″-methyl-butanoyloxy]-7-hydroxycarvotacetone (6) and 3-angeloyloxy-5-[2″R,3″R-dihydroxy-2″-methyl-butanoyloxy]-7-hydroxycarvotacetone (7), asperglaucide (8) and chrysoplenol D (9) were isolated from S. africanus. COX-1 and COX-2 assays of compounds 1–9 revealed that compounds 1 and 2 possess potent and selective COX-2 inhibitory activity with IC50 values of 3.6 and 0.5 μM, respectively. COX-2 gene expression assay showed that some carvotacetones exhibited inhibitory effects on COX-2 gene expression in THP-1 macrophages. Compound 4 is the most active compound inhibiting the synthesis of COX-2 by 55% at 2.06 μM. In the iNOS assay, all seven carvotacetones inhibited NO production in BV2 and RAW cell lines with IC50 values ranging from 0.2 to 2.9 μM. Compound 4 showed potent inhibitory activity with IC50 values of 0.2 μM in both BV2 and RAW cell lines. Molecular docking studies revealed the binding orientations of 1 and 2 in the active sites of COX-2. XTT assay of the newly isolated compounds revealed that the two isomeric carvotacetones (6–7) exhibited considerable anti-proliferative activity against four cancer cell lines (CCRF-CEM, MDA-MB-231, HCT-116, U-251) with IC50 values ranging from 1.23 to 8 μM. Conclusion For the first-time, the diastereomeric carvotacetones (6–7) were isolated as separate compounds, and their anti-proliferative activity was determined. Selective COX-2 inhibitory, COX-2 mRNA expression and NO production inhibitory activities by some of the major constituents of S. africanus supports the traditional medical application of this plant for the treatment of inflammation-related disorders. |
| Databáze: | OpenAIRE |
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