title: Compounds from Geijera parviflora with prostaglandin E2 inhibitory activity may explain its traditional use for pain relief.
abstract: BACKGROUND
  Australian Aboriginal people used crushed leaves of Geijera parviflora Lindl. both internally and externally for pain relief, including for toothache (Cribb and Cribb, 1981). This study tested the hypothesis that this traditional use might be at least in part explained by the presence of compounds with anti-inflammatory activity.
  
  
  METHODS
  A crude extract (95% EtOH) was prepared from powdered dried leaves. From the CH3Cl fraction of this extract compounds were isolated by bioassay-guided fractionation and tested for: (1) cytotoxicity in RAW 264.7 murine leukemic monocyte-macrophages, (2) prostaglandin E2 (PGE2) inhibitory activity in 3T3 Swiss albino mouse embryonic fibroblast cells, as well as (3) nitric oxide (NO) and (4) tumour necrosis factor alpha (TNFα) inhibitory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Isolated compounds were also tested for (5) antibacterial activity against a panel of Gram-positive (Staphylococcus aureus ATCC 29213 and ATCC 25923, Staphylococcus epidermidis ATCC 35984, biofilm-forming) and Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) strains by broth microdilution.
  
  
  RESULTS
  Eleven compounds were isolated, including one new flavone and one new natural product, with a further four compounds reported from this species for the first time. Some of the compounds showed good anti-inflammatory activity in vitro. In particular, flindersine (1) and N-(acetoxymethyl) flindersine (3) inhibited PGE2 release with IC50 values of 5.0μM and 4.9μM, respectively, without any significant cytotoxicity. Several other compounds showed moderate inhibition of NO (5, 6, 7) and TNF-α (6), with IC50 in the low micromolar range; however much of this apparent activity could be accounted for by the cytotoxicity of these compounds. None of the compounds showed anti-bacterial activity.
  
  
  CONCLUSIONS
  The inhibition of PGE2, an important mediator of inflammation and pain, by flindersine and a derivative thereof, along with the moderate anti-inflammatory activity shown by several other compounds isolated from Geijera parviflora leaf extract, support the traditional use of this plant for pain relief by Australian Aboriginal people.
authors: Southern Cross Plant Science, Southern Cross University, PO Box 157, Lismore, NSW 2480, Australia. Electronic address: lkbanbury63@gmail.com.
authors: Linda K
authors: LK
authors: Banbury
authors: Southern Cross Plant Science, Southern Cross University, PO Box 157, Lismore, NSW 2480, Australia. Electronic address: sanqi_0617@126.com.
authors: Qingyao
authors: Q
authors: Shou
authors: Southern Cross Plant Science, Southern Cross University, PO Box 157, Lismore, NSW 2480, Australia. Electronic address: dane@rkeenanconsult.com.au.
authors: Dane E
authors: DE
authors: Renshaw
authors: Southern Cross Plant Science, Southern Cross University, PO Box 157, Lismore, NSW 2480, Australia. Electronic address: eleanore.lambley@scu.edu.au.
authors: Eleanore H
authors: EH
authors: Lambley
authors: Mawson Institute, University of South Australia, Mawson Lakes SA 5095, Australia. Electronic address: hans.griesser@unisa.edu.au.
authors: Hans J
authors: HJ
authors: Griesser
authors: Mawson Institute, University of South Australia, Mawson Lakes SA 5095, Australia. Electronic address: htwe.mon@unisa.edu.au.
authors: Htwe
authors: H
authors: Mon
authors: Integria Healthcare, Gallans Rd, Ballina, NSW 2478, Australia. Electronic address: hans.wohlmuth@scu.edu.au.
authors: Hans
authors: H
authors: Wohlmuth
mesh_terms: D016475:3T3 Cells; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001315:Australia; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects; D008070:Lipopolysaccharides; D008519:Medicine, Traditional; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010146:Pain / Q000188:drug therapy; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D027821:Rutaceae; D013210:Staphylococcus / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D015232:Dinoprostone
keywords: Anti-inflammatory; Flavones; Flindersine; Geijera parviflora; Pain relief; Prostaglandin E(2)