title: Compounds from Caesalpinia sappan with anti-inflammatory properties in macrophages and chondrocytes.
abstract: The heartwood of Caesalpinia sappan is a traditional ingredient of food and beverages in South East Asia and has been used in traditional medicine as an analgesic and anti-inflammatory drug or to promote blood circulation. Scientific studies have confirmed different bioactivities associated with its use. Here, five fractions were isolated from the ethanolic extract of C. sappan heartwood, including episappanol (1), protosappanin C (2), brazilin (3), (iso-)protosappanin B (4) and sappanol (5) using high-performance liquid chromatography (HPLC). All compounds were tested for their anti-inflammatory effects in two different cell lines. Cytokine concentrations in the cell supernatant were determined using enzyme-linked immunosorbent assay (ELISA), and mRNA levels were measured using reverse-transcription quantitative polymerase chain reaction (RT-qPCR). In lipopolysaccharide-stimulated macrophages, all compounds significantly inhibited the secretion of the pro-inflammatory cytokines interleukin (IL-6) and tumor necrosis factor-alpha (TNF-α). Sappanol (5) increased the secretion of the anti-inflammatory IL-10. In IL-1β-stimulated chondrocytes, all fractions reduced the mRNA expression and the secretion of the pro-inflammatory cytokines IL-6 and TNF-α. The highest anti-inflammatory effect was found for brazilin (3) in both cell lines. Of note, this is the first study which shows the anti-inflammatory effect of sappanol and episappanol. This study provides evidence for the efficacy of the traditional use of C. sappan as an anti-inflammatory remedy. Given the high prevalence of inflammation-related pathologies including arthritis, and the urgent need to clinically intervene with these diseases, the anti-inflammatory activity of diverse compounds from C. sappan may be of interest for the development of complementary and alternative treatment strategies.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria. monika.mueller@univie.ac.at.
authors.forename: Monika
authors.initials: M
authors.lastname: Mueller
authors.affiliation: Karl Chiari Lab for Orthopaedic Biology, Department of Orthopaedics, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Weinmann
authors.affiliation: Karl Chiari Lab for Orthopaedic Biology, Department of Orthopaedics, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Toegel
authors.affiliation: Department of Pharmaceutical Chemistry - Division of Drug Synthesis, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Holzer
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria. monika.mueller@univie.ac.at.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Unger
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria. monika.mueller@univie.ac.at.
authors.forename: Helmut
authors.initials: H
authors.lastname: Viernstein
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000494:pharmacology*; D029911:Caesalpinia / Q000737:chemistry*; D002460:Cell Line; D019902:Chondrocytes / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10