title: Anti-proliferative effects of Salacia reticulata leaves hot-water extract on interleukin-1β-activated cells derived from the synovium of rheumatoid arthritis model mice.
abstract: BACKGROUND
  Salacia reticulata (SR) is a plant native to Sri Lanka. In ayurvedic medicine, SR bark preparations, taken orally, are considered effective in the treatment of rheumatism and diabetes. We investigated the ability of SR leaves (SRL) to inhibit in vitro the interleukin-1β (IL-1β)-activated proliferation of synoviocyte-like cells derived from rheumatoid arthritis model mice.
  
  
  RESULTS
  Inflammatory synovial tissues were harvested from type II collagen antibody-induced arthritic mice. From these tissues, a synoviocyte-like cell line was established and named MTS-C H7. To determine whether SRL can suppress cell proliferation and gene expression in MTS-C H7 cells, fractionation of the SRL hot-water extract was performed by high-performance liquid chromatography (HPLC), liquid-liquid extraction, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and protease digestion.The 50% inhibitory concentration of the SRL hot-water extract against MTS-C H7 cells proliferation was ~850 μg/mL. Treatment with a low dose (25 μg dry matter per millilitre) of the extract inhibited IL-1β-induced cell proliferation and suppressed the expression of the matrix metalloproteinase (MMP) genes in MTS-C H7 cells. Various polyphenolic fractions obtained from HPLC and the fractions from liquid-liquid extraction did not affect cell proliferation. Only the residual water sample from liquid-liquid extraction significantly affected cell proliferation and the expression of MMP genes. The results of SDS-PAGE and protease digestion experiment showed that low molecular weight proteins present in SRL inhibited the IL-1β-activated cell proliferation.
  
  
  CONCLUSIONS
  We surmised that the residual water fraction of the SRL extract was involved in the inhibition of IL-1β-activated cell proliferation and regulation of mRNA expression in MTS-C H7 cells. In addition, we believe that the active ingredients in the extract are low molecular weight proteins.
authors.affiliation: Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors.forename: Yuusuke
authors.initials: Y
authors.lastname: Sekiguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mano
authors.forename: Sachie
authors.initials: S
authors.lastname: Nakatani
authors.forename: Jun
authors.initials: J
authors.lastname: Shimizu
authors.forename: Kenji
authors.initials: K
authors.lastname: Kobata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Wada
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D006358:Hot Temperature; D020128:Inhibitory Concentration 50; D053583:Interleukin-1beta / Q000378:metabolism*; D059625:Liquid-Liquid Extraction; D020782:Matrix Metalloproteinases / Q000235:genetics; D051379:Mice; D008811:Mice, Inbred DBA; D008970:Molecular Weight; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves; D010940:Plant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000378:metabolism; D049918:Salacia / Q000737:chemistry; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014867:Water / Q000737:chemistry*
chemical_list: D018501:Antirheumatic Agents; D053583:Interleukin-1beta; D010936:Plant Extracts; D010940:Plant Proteins; D012333:RNA, Messenger; D014867:Water; D020782:Matrix Metalloproteinases