title: Isolation of xanthone and benzophenone derivatives from Cyclopia genistoides (L.) Vent. (honeybush) and their pro-apoptotic activity on synoviocytes from patients with rheumatoid arthritis.
abstract: A fast and efficient method for the isolation of the C-glucosidated xanthones mangiferin and isomangiferin from the South-African plant Cyclopia genistoides was developed for the first time. The procedure involved extraction, liquid-liquid partitioning with ethyl acetate and subsequent precipitation of mangiferin and isomangiferin from methanol and acetonitrile-water fractions, respectively. Additionally, two benzophenone derivatives: 3-C-β-glucosides of maclurin and iriflophenone, were isolated from C. genistoides extracts using semi-preparative HPLC. Apart from the above, the isolation procedure also yielded hesperidin and small amounts of luteolin. The structures of the compounds were determined by 1D and 2D NMR experiments and/or LC-DAD-ESI-MS. The selected Cyclopia constituents were screened for pro-apoptotic activity on TNF-α-stimulated synovial cells isolated from rheumatoid arthritis patients. The strongest effect, measured as percent of apoptotic cells, was recorded for isomangiferin (75%), followed by iriflophenone 3-C-β-glucoside (71%), hesperidin (67%) and mangiferin (65%). The results are encouraging for further studies on the use of the above compounds in the treatment of rheumatoid arthritis.
authors.affiliation: The Chair and Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Gdansk, al. gen. J. Hallera 107, 80-416 Gdansk, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Kokotkiewicz
authors.forename: Maria
authors.initials: M
authors.lastname: Luczkiewicz
authors.forename: Justyna
authors.initials: J
authors.lastname: Pawlowska
authors.forename: Piotr
authors.initials: P
authors.lastname: Luczkiewicz
authors.forename: Pawel
authors.initials: P
authors.lastname: Sowinski
authors.forename: Jacek
authors.initials: J
authors.lastname: Witkowski
authors.forename: Ewa
authors.initials: E
authors.lastname: Bryl
authors.forename: Adam
authors.initials: A
authors.lastname: Bucinski
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism; D007887:Fabaceae / Q000737:chemistry*; D005260:Female; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D006569:Hesperidin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D015394:Molecular Structure; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D037121:Plant Lectins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D044004:Xanthones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D005960:Glucosides; D010936:Plant Extracts; D037121:Plant Lectins; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones; C000588524:iriflophenone; C013592:mangiferin; C034551:maclurin; D006569:Hesperidin
keywords: AA; ADAMTS-4; AP-1; CD3; CIA; DAS28; DMEM; Disease Activity Score of 28 joints; Dulbecco's modified Eagle's medium; Fibroblast-like synovial cells; IFN-γ; IL-1β; Iriflophenone 3-C-β-glucoside; Isomangiferin; MMP; Mangiferin; NSAIDs; PBS; PGE(2); RA; Rheumatoid arthritis; SF; Semi-preparative HPLC; TNF-α; activator protein 1; adjuvant arthritis; aggrecanase-4; cluster of differentiation 3; collagen-induced arthritis; fibroblast-like synovial cells; interferon-gamma; interleukin-1 beta; matrix metalloproteinase; nonsteroidal anti-inflammatory drugs; phosphate buffered saline; prostaglandin E(2); rheumatoid arthritis; tumor necrosis factor-alpha