title: Opuntia dillenii cladode: Opuntiol and opuntioside attenuated cytokines and eicosanoids mediated inflammation.
abstract: CONCLUSIONS
  Opuntia dillenii Haw (Nagphana) traditionally used against inflammation. The present study addressed the anti-inflammatory activity of O. dillenii derived methanol extract, fractions and pure compounds and their underlying mechanism of action.
  
  
  METHODS
  O. dillenii cladode methanol extract was subjected to vacuum liquid chromatography (VLC) furnishing two main fractions viz (T-1 and -2) leading to isolation of opuntiol (aglycone) and opuntioside (O-glucoside), respectively. Anti-inflammatory activity of extract, fractions, pure compounds and reference drugs were evaluated using: (1) arachidonic acid (AA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ear edema accompanied by histological studies of mice ear sections and phospholipase A2 (PLA2)-induced mice paw edema. (2) Carrageenan and glycogen-induced peritonitis in rodents. In parallel levels of leukotriene B4 (LTB4) and reactive oxygen species (ROS) were also determined via HPLC and fluoroemetrically using 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA) dye, respectively. Additionally, levels of prostaglandin E2 (PGE2), tumor necrosis factor (TNF-α), interleukins IL-1β and -6 were measured by ELISA assay.
  
  
  RESULTS
  O. dillenii methanol extract, fractions and pure compounds reduced AA and TPA-induced ear punch weight in a dose dependent fashion. The corresponding IC50 values obtained also suppressed inflammatory features observed histologically. Furthermore, paw edema and peritonitis were also attenuated. Similar to indomethacin and diclofenac sodium, opuntioside reduced PGE2 levels of inflamed ear which was comparatively 1.3× better than opuntiol. However, opuntiol was more potent in reducing LTB4 levels in rat neutrophils with an IC50 value of 19±3.3μΜ, while opuntioside was ineffective. Opuntiol also effectively suppressed ROS (37%) and cytokine levels (TNF-α, IL-1β and -6) by ~50% and comparable to dexamethasone.
  
  
  CONCLUSIONS
  O. dillenii cladodes possess anti-inflammatory properties via inhibition of arachidonic acid metabolites and cytokines. Opuntiol (aglycone) emerged as a dual inhibitor of cyclooxygenase (COX) and lipooxygenase (LOX) pathways. It also suppressed ROS and cytokine levels. However, opuntioside manifested its selectivity towards COX (PGE2) pathway without affecting LTB4 levels. The present report describing the anti-inflammatory activity of opuntiol and opuntioside for the first time thereby, supporting and justifying the traditional use of O. dillenii against inflammation and may serve as lead compound in designing of new anti-inflammatory agents.
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: faheemasiddiqi@hotmail.com.
authors.forename: Faheema
authors.initials: F
authors.lastname: Siddiqui
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: naqvi_sabira@yahoo.com.
authors.forename: Sabira
authors.initials: S
authors.lastname: Naqvi
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Chemistry, Jinnah University for Women, Karachi 74600, Pakistan. Electronic address: sci423@hotmail.com.
authors.forename: Lubna
authors.initials: L
authors.lastname: Abidi
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: shaheenfaizi@hotmail.com.
authors.forename: Shaheen
authors.initials: S
authors.lastname: Faizi
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: lubnazaheer_789@hotmail.com.
authors.lastname: Lubna
authors.affiliation: Pathology Department, Dow International Medical College (DIMC), Dow University of Health Sciences, Karachi 74200, Pakistan. Electronic address: lubna.avesi@hotmail.com.
authors.forename: Lubna
authors.initials: L
authors.lastname: Avesi
authors.affiliation: Pathology Department, Dow International Medical College (DIMC), Dow University of Health Sciences, Karachi 74200, Pakistan. Electronic address: talat.mirza@duhs.edu.pk.
authors.forename: Talat
authors.initials: T
authors.lastname: Mirza
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: ahsanadar@hotmail.com.
authors.forename: Ahsana Dar
authors.initials: AD
authors.lastname: Farooq
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016718:Arachidonic Acid; D002199:Capillary Permeability / Q000187:drug effects; D002351:Carrageenan; D003373:Coumaric Acids / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004423:Ear / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005528:Foot / Q000473:pathology; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D051379:Mice; D009005:Monosaccharides / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D029747:Opuntia; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy; D054467:Phospholipases A2; D008517:Phytotherapy; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate
chemical_list: D000893:Anti-Inflammatory Agents; D003373:Coumaric Acids; D016207:Cytokines; D009005:Monosaccharides; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C519456:opuntiol; C519457:opuntioside; D007975:Leukotriene B4; D016718:Arachidonic Acid; D002351:Carrageenan; D054467:Phospholipases A2; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate
keywords: Anti-inflammatory; Arachidonic acid metabolites; Cytokines; Opuntia dillenii; Opuntiol; Opuntioside