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Diterpenoid alkaloids of Aconitum laciniatum and mitigation of inflammation by 14-O-acetylneoline in a murine model of ulcerative colitis
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Diterpenoid alkaloids of Aconitum laciniatum and mitigation of inflammation by 14-O-acetylneoline in a murine model of ulcerative colitis
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Diterpenoid alkaloids of Aconitum laciniatum and mitigation of inflammation by 14-O-acetylneoline in a murine model of ulcerative colitis
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Journal Article
Diterpenoid alkaloids of Aconitum laciniatum and mitigation of inflammation by 14-O-acetylneoline in a murine model of ulcerative colitis
2015
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/106
/ 13/21
/ 13/51
/ 14/63
/ 38/77
/ 82/58
/ Aconitine - analogs & derivatives
/ Aconitine - isolation & purification
/ Alkaloids - isolation & purification
/ Animals
/ Anti-Inflammatory Agents, Non-Steroidal - isolation & purification
/ Anti-Inflammatory Agents, Non-Steroidal - pharmacology
/ Colitis, Ulcerative - chemically induced
/ Colitis, Ulcerative - drug therapy
/ Colitis, Ulcerative - metabolism
/ Colitis, Ulcerative - pathology
/ Colon
/ Diterpenes - isolation & purification
/ Epithelial Cells - drug effects
/ Epithelial Cells - metabolism
/ Epithelial Cells - pathology
/ Humanities and Social Sciences
/ Interferon-gamma - biosynthesis
/ Male
/ Mice
/ mRNA
/ RNA, Messenger - biosynthesis
/ Rodents
/ Science
