Diterpenoid alkaloids of Aconitum laciniatum and mitigation of inflammation by 14-O-acetylneoline in a murine model of ulcerative colitis

Wangchuk, Phurpa, Navarro, Severine, Shepherd, Catherine, Keller, Paul A., Pyne, Stephen G., and Loukas, Alex (2015) Diterpenoid alkaloids of Aconitum laciniatum and mitigation of inflammation by 14-O-acetylneoline in a murine model of ulcerative colitis. Scientific Reports, 5. pp. 1-10.

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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.

Item ID: 40037
Item Type: Article (Refereed Research - C1)
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This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.

ISSN: 2045-2322
Funders: Australian Government (AG), National Health and Medical Research Council (NHMRC), James Cook University, University of Wollongong
Projects and Grants: AG Australian Endeavour Award, NHMRC Peter Doherty Early Career Fellowship Grant, NHMRC Principal Research Fellowship
Date Deposited: 13 Aug 2015 00:05
FoR Codes: 03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030401 Biologically Active Molecules @ 50%
03 CHEMICAL SCIENCES > 0305 Organic Chemistry > 030502 Natural Products Chemistry @ 40%
03 CHEMICAL SCIENCES > 0301 Analytical Chemistry > 030108 Separation Science @ 10%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920105 Digestive System Disorders @ 50%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 40%
92 HEALTH > 9299 Other Health > 929999 Health not elsewhere classified @ 10%
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