title: β Mangostin suppress LPS-induced inflammatory response in RAW 264.7 macrophages in vitro and carrageenan-induced peritonitis in vivo.
abstract: BACKGROUND
  The fruit hull of Garcinia mangostana Linn. has been used in traditional medicine for treatment of various inflammatory diseases. Hence, this study aims to investigate the in vitro and in vivo anti-inflammatory effect of β mangostin (βM), a major compound present in Garcinia mangostana.
  
  
  METHODS
  The in silico analysis of inflammatory mediators such as cyclooxygenase (COX) and nuclear factor-kappa B (NF-kB) were performed via molecular docking. Further evaluation of anti-inflammatory effect was conducted in lipopolysaccharide (LPS) induced RAW 264.7 macrophages. Suppression of activated NF-kB was analyzed by high content screening. βM triggered inhibition of COX-1 and COX-2 in vitro were studied using biochemical kit. The in vivo model used in this study was carrageenan-induced peritonitis model, where reduction in carrageenan-induced peritonitis is measured by leukocyte migration and vascular permeability. In addition, the evaluation of βM׳s effect on carrageenan induced TNF-α and IL-1β release on peritoneal fluid was also carried out.
  
  
  RESULTS
  Treatment with βM could inhibit the LPS-induced NO production but not the viability of RAW 264.7. Similarly, βM inhibited PGE2 production and the cytokines: TNF-α and IL-6. The COX catalyzed prostaglandin biosynthesis assay had showed selective COX-2 inhibition with a 53.0±6.01% inhibition at 20 µg/ml. Apart from this, βM was capable in repressing translocation of NF-kB into the nucleus. These results were concurrent with molecular docking which revealed COX-2 selectivity and NF-kB inhibition. The in vivo analysis showed that after four hours of peritonitis, βM was unable to reduce vascular permeability, yet could decrease the total leukocyte migration; particularly, neutrophils. Meanwhile, dexamethasone 0.5 mg/kg, successfully reduced vascular permeability. The levels of TNF-α and IL-1β in peritoneal fluid was reduced significantly by βM treatment.
  
  
  CONCLUSIONS
  The current study supports the traditional use of Garcinia mangostana fruit hull for treatment of inflammatory conditions. In addition, it is clear that the anti-inflammatory efficacy of this plant is not limited to the presence of α and γ, but β also with significant activity.
authors.affiliation: UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia; Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: suvithaavs@gmail.com.
authors.forename: Suvitha
authors.initials: S
authors.lastname: Syam
authors.affiliation: UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Bustamam
authors.affiliation: Department of Veterinary Pathology and Microbiology, Faculty of Veterinary, University Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Rasedee
authors.initials: R
authors.lastname: Abdullah
authors.affiliation: Department of Chemistry, Faculty of Science, University Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Mohamed Aspollah
authors.initials: MA
authors.lastname: Sukari
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Najihah Mohd
authors.initials: NM
authors.lastname: Hashim
authors.affiliation: Medical Research Centre, Jazan University, PO Box 114, Jazan, Saudi Arabia.
authors.forename: Syam
authors.initials: S
authors.lastname: Mohan
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Chung Yeng
authors.initials: CY
authors.lastname: Looi
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Won Fen
authors.initials: WF
authors.lastname: Wong
authors.affiliation: Institute of Bioproduct Developments, Universiti Teknologi Malaysia, Malaysia.
authors.forename: Maizatul Akmal
authors.initials: MA
authors.lastname: Yahayu
authors.affiliation: Medical Research Centre, Jazan University, PO Box 114, Jazan, Saudi Arabia.
authors.forename: Siddig Ibrahim
authors.initials: SI
authors.lastname: Abdelwahab
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000633:toxicity*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D062105:Molecular Docking Simulation; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D044004:Xanthones; D002351:Carrageenan; C021053:mangostin
keywords: COX-2; Cytokines; Garcinia mangostana; NF-kB; iNOS; β Mangostin