title: Topical anti-inflammatory and analgesic activities of standardized pomegranate rind extract in comparison with its marker compound ellagic acid in vivo.
abstract: BACKGROUND
  In Chinese traditional medicine, the peels of Punica granatum L. have been used to treat traumatic hemorrhage, burn, and ulcers.
  
  
  OBJECTIVE
  This study aimed to assess the topical anti-inflammatory and analgesic activities of a standardized pomegranate rind extract (SPRE) of which ellagic acid (EA) was the major antioxidant constituent and the marker compound.
  
  
  METHODS
  The topical anti-inflammatory effects of SPRE were evaluated against acute models (croton oil-induced mouse ear edema and carrageenan-induced rat paw edema) and chronic model (complete Freund's adjuvant (CFA)-induced polyarthritis). The topical analgesic activities of SPRE were investigated in the rat punctuate mechanical hyperalgesia test and in the mouse formalin test. All studies of SPRE were carried out in parallel with its marker compound EA.
  
  
  RESULTS
  SPRE (5%, 2.5%, and 1%, w/w) and the equivalent EA (0.65%, 0.325%, and 0.13%, w/w) dose-dependently reduced the croton oil-induced mouse ear edema with a maximal inhibition of 86.30% and 80.82%, respectively. SPRE dose-dependently attenuated the inflammatory responses in the carrageenan-induced rat paw edema and in the CFA-induced polyarthritis but the equivalent EA were effective only at the doses of 0.65% and 0.325%. Both SPRE (5%) and EA (0.65%) showed significant topical analgesic activities in the rat punctuate mechanical hyperalgesia test and in the mouse formalin test.
  
  
  CONCLUSIONS
  SPRE was more active as an anti-inflammatory agent than EA. The anti-inflammatory and analgesic effects of SPRE were achieved through inhibiting the leukocyte infiltration and modulating the pro-inflammatory cytokines IL-β and TNF-α. These results clearly demonstrated that SPRE is a promising phytomedicine that could find use in the treatment of inflammatory diseases.
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90110 Thailand.
authors.forename: Jiao
authors.initials: J
authors.lastname: Mo
authors.forename: Pharkphoom
authors.initials: P
authors.lastname: Panichayupakaranant
authors.forename: Nattha
authors.initials: N
authors.lastname: Kaewnopparat
authors.forename: Anupong
authors.initials: A
authors.lastname: Nitiruangjaras
authors.forename: Wantana
authors.initials: W
authors.lastname: Reanmongkol
mesh_terms: D000287:Administration, Topical; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000843:Ankle Joint / Q000473:pathology; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D002351:Carrageenan; D003436:Croton Oil; D004423:Ear / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D004610:Ellagic Acid / Q000627:therapeutic use*; D005528:Foot / Q000473:pathology; D005557:Formaldehyde; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D029561:Lythraceae; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D004610:Ellagic Acid; D005557:Formaldehyde; D003436:Croton Oil; D002351:Carrageenan; D005620:Freund's Adjuvant
keywords: Arthritis; CFA; CIA; COX; DF; EA; Ear edema; HTAB; IL-1β; Inflammation; LPS; MPO; NF-κB; NGF; NO; NSAIDs; PBS; PEG; PGE(2); Pain; Punica granatum; SPRE; TA; TMB; TNF-α; Topical administration; collagen-induced arthritis; complete Freund's adjuvant; control; ctrl; cyclooxygenase; diclofenac; ellagic acid; hexadecyltrimethylammonium bromide; iNOS; inducible NO synthase; interleukin-1 beta; lipopolysaccharide; myeloperoxidase; nerve growth factor; nitric oxide; nml; non-steroidal anti-inflammatory drugs; normal control; nuclear factor kappa B; phosphate-buffered saline; polyethylene glycol; prostaglandin E(2); standardized pomegranate rind extract; tetramethylbenzidine HCl; triamcinolone; tumor necrosis factor-alpha