title: Diterpenoid alkaloids of Aconitum laciniatum and mitigation of inflammation by 14-O-acetylneoline in a murine model of ulcerative colitis.
abstract: Aconitum laciniatum is used in Bhutanese traditional medicine for treating various chronic infections and inflammatory conditions. We carried out in-depth isolation and characterization of the phytochemicals from the root component and determined the anti-inflammatory effects of the isolated compounds against chemically-induced colitis in mice. Five diterpenoid alkaloids - pseudaconitine, 14-veratroylpseudaconine, 14-O-acetylneoline, neoline, and senbusine A - were isolated from A. laciniatum for the first time. Two of the alkaloids were tested for anti-inflammatory properties in the TNBS-induced colitis model in mice. Various parameters were measured to assess pathology including weight loss, clinical and macroscopic scores, histological structure and IFN-γ production in the gut. Of the two alkaloids tested, 14-O-acetylneoline showed significant protection against different parameters of colitic inflammation. Compared to control mice that received TNBS alone, mice treated with 14-O-acetylneoline experienced significantly less weight loss and had significantly lower clinical scores, macroscopic pathology and grades of histological inflammation. Moreover, colonic IFN-γ mRNA levels were significantly reduced in mice that received 14-O-acetylneoline compared to control mice that received TNBS alone. This alkaloid is now considered a novel anti-colitis drug lead compound.
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.|School of Chemistry, University of Wollongong, Wollongong, NSW, Australia.
authors.forename: Phurpa
authors.initials: P
authors.lastname: Wangchuk
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.
authors.forename: Severine
authors.initials: S
authors.lastname: Navarro
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Shepherd
authors.affiliation: School of Chemistry, University of Wollongong, Wollongong, NSW, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Keller
authors.affiliation: School of Chemistry, University of Wollongong, Wollongong, NSW, Australia.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Pyne
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D031841:Aconitum / Q000737:chemistry*; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis; D014302:Trinitrobenzenesulfonic Acid; D015431:Weight Loss / Q000187:drug effects
chemical_list: C000609448:14-O-acetylneoline; D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D010936:Plant Extracts; D012333:RNA, Messenger; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid; D000157:Aconitine