title: Serrulatane Diterpenoid from Eremophila neglecta Exhibits Bacterial Biofilm Dispersion and Inhibits Release of Pro-inflammatory Cytokines from Activated Macrophages.
abstract: The purpose of this study was to assess the biofilm-removing efficacy and inflammatory activity of a serrulatane diterpenoid, 8-hydroxyserrulat-14-en-19-oic acid (1), isolated from the Australian medicinal plant Eremophila neglecta. Biofilm breakup activity of compound 1 on established Staphylococcus epidermidis and Staphylococcus aureus biofilms was compared to the antiseptic chlorhexidine and antibiotic levofloxacin. In a time-course study, 1 was deposited onto polypropylene mesh to mimic a wound dressing and tested for biofilm removal. The ex-vivo cytotoxicity and effect on lipopolysaccharide-induced pro-inflammatory cytokine release were studied in mouse primary bone-marrow-derived macrophage (BMDM) cells. Compound 1 was effective in dispersing 12 h pre-established biofilms with a 7 log10 reduction of viable bacterial cell counts, but was less active against 24 h biofilms (approximately 2 log10 reduction). Compound-loaded mesh showed dosage-dependent biofilm-removing capability. In addition, compound 1 displayed a significant inhibitory effect on tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) secretion from BMDM cells, but interleukin-1 beta (IL-1β) secretion was not significant. The compound was not cytotoxic to BMDM cells at concentrations effective in removing biofilm and lowering cytokine release. These findings highlight the potential of this serrulatane diterpenoid to be further developed for applications in wound management.
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, SA 5000, Australia.|Wound Management Innovation Cooperative Research Centre , Toowong, QLD 4066, Australia.
authors.forename: Htwe H
authors.initials: HH
authors.lastname: Mon
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, SA 5000, Australia.|Experimental Therapeutics Laboratory, Hanson Institute , Adelaide, SA 5000, Australia.
authors.forename: Susan N
authors.initials: SN
authors.lastname: Christo
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, SA 5000, Australia.
authors.forename: Chi P
authors.initials: CP
authors.lastname: Ndi
authors.affiliation: Future Industries Institute, University of South Australia , Mawson Lakes, SA 5095, Australia.
authors.forename: Marek
authors.initials: M
authors.lastname: Jasieniak
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, SA 5000, Australia.
authors.forename: Heather
authors.initials: H
authors.lastname: Rickard
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, SA 5000, Australia.|Experimental Therapeutics Laboratory, Hanson Institute , Adelaide, SA 5000, Australia.
authors.forename: John D
authors.initials: JD
authors.lastname: Hayball
authors.affiliation: Wound Management Innovation Cooperative Research Centre , Toowong, QLD 4066, Australia.|Future Industries Institute, University of South Australia , Mawson Lakes, SA 5095, Australia.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Griesser
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia , Adelaide, SA 5000, Australia.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Semple
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001315:Australia; D018441:Biofilms / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D041621:Eremophila Plant / Q000737:chemistry*; D053583:Interleukin-1beta / Q000187:drug effects; D015850:Interleukin-6; D064704:Levofloxacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D028083:Scrophulariaceae; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
chemical_list: C524231:8-hydroxyserrulat-14-en-19-oic acid; D000900:Anti-Bacterial Agents; D016207:Cytokines; D004224:Diterpenes; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D064704:Levofloxacin