Capparis ovata treatment suppresses inflammatory cytokine expression and ameliorates experimental allergic encephalomyelitis model of multiple sclerosis in C57BL/6 mice.
Since ancient times, Capparis species have been widely used in traditional medicine to treat various diseases. Our recent investigations have suggested Capparis ovata's potential anti-neuroinflammatory application for the treatment of multiple sclerosis (MS). The present study was designed to precisely determine the underlying mechanism of its anti-neuroinflammatory effect in a mouse model of MS. C. ovata water extract (COWE) was prepared using the plant's fruit, buds, and flower parts (Turkish Patent Institute, PT 2012/04,093). We immunized female C57BL/6J mice with MOG35-55/CFA. COWE was administered at a daily dose of 500mg/kg by oral gavage either from the day of immunization (T1) or at disease onset (T2) for 21days. Gene expression analysis was performed using a Mouse Multiple Sclerosis RT² Profiler PCR Array, and further determinations and validations of the identified genes were performed using qPCR. Whole-genome transcriptome profiling was analyzed using Agilent SurePrint G3 Mouse GE 8X60K microarrays. Immunohistochemical staining was applied to brain sections of the control and treated mice to examine the degree of degeneration. COWE was further fractionated and analyzed phytochemically using the Zivak Tandem Gold Triple Quadrupole LC/MS-MS system. COWE remarkably suppressed the development of EAE in T1, and the disease activity was completely inhibited. In the T2 group, the maximal score was significantly reduced compared with that of the parallel EAE group. The COWE suppression of EAE was associated with a significantly decreased expression of genes that are important in inflammatory signaling, such as TNFα, IL6, NF-κB, CCL5, CXCL9, and CXCK10. On the other hand, the expression of genes involved in myelination/remyelination was significantly increased. Immunohistochemical analysis further supported these effects, showing that the number of infiltrating immune cells was decreased in the brains of COWE-treated animals. In addition, differential expression profiling of the transcriptome revealed that COWE treatment caused the down regulation of a group of genes involved in the immune response, inflammatory response, antigen processing and presentation, B-cell-mediated immunity and innate immune response. Collectively, these results suggest anti-neuroinflammatory mechanisms by which COWE treatment delayed and suppressed the development of EAE and ameliorated the disease in mice with persistent clinical signs.
Department of Biology, Faculty of Arts and Sciences, Pamukkale University, 20070 Kınıklı, Denizli, Turkey.
Ozden
O
Ozgun-Acar
Department of Biology, Faculty of Arts and Sciences, Pamukkale University, 20070 Kınıklı, Denizli, Turkey.
Gurbet
G
Celik-Turgut
Department of Analytical Chemistry, Faculty of Pharmacy, Bezmialem Vakif University, 34093 Fatih, Istanbul, Turkey.
Isil
I
Gazioglu
Department of Analytical Chemistry, Faculty of Pharmacy, Istanbul University, 34116 Beyazit, Istanbul, Turkey.
Ufuk
U
Kolak
Department of Histology and Embryology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
Seda
S
Ozbal
Department of Histology and Embryology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
Bekir U
BU
Ergur
Department of Biology, Faculty of Arts and Sciences, Pamukkale University, 20070 Kınıklı, Denizli, Turkey.
Sevki
S
Arslan
Department of Biology, Faculty of Arts and Sciences, Pamukkale University, 20070 Kınıklı, Denizli, Turkey. Electronic address: sena@pau.edu.tr.
Alaattin
A
Sen
Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Bezmialem Vakif University, 34093 Fatih, Istanbul, Turkey.
Gulacti
G
Topcu
D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D031484:Capparis / Q000737:chemistry*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010936:Plant Extracts; C445081:myelin oligodendrocyte glycoprotein (35-55)
Anti-neuroinflammatory; Capparis ovata; Cytokine expression; Experimental allergic encephalomyelitis; Immunohistochemistry; LC–MS–MS; Multiple sclerosis; Transcriptome profiling