||Columbianadin has analgesic, anti-inflammatory, calcium-channel blocking, and platelet aggregation inhibiting functions. It can effectively suppress the growth of colon cancer cells, the induction of apoptosis was correlated with the modulation of caspase-9, caspase-3, Bax, Bcl-2, RIP-3, and caspase-8, Bim and Bid.|
||Caspase | Bcl-2/Bax | ROS | IL Receptor | NO | Calcium Channel | RIP-3 | SOD | GPx-1|
|Phytochemistry. 2012 Sep;81:109-16. |
|Biotransformation of columbianadin by rat hepatic microsomes and inhibition of biotransformation products on NO production in RAW 264.7 cells in vitro.[Pubmed: 22784551]|
|Columbianadin (CBN, 1), 1-[(8S)-8,9-dihydro-2-oxo-2H-furo[2,3-h]-1-benzopyran-8-yl]-1-methylethyl-[(2Z)-2-methyl-2-butenoic acid]ester is a coumarin-type compound and one of the main bioactive constituents of the underground part of Angelica pubescens Maxim. f. biserrata Shan et Yuan.
Although numerous investigations have been undertaken to study the biological activities of Columbianadin, such as analgesic, anti-inflammatory, calcium-channel blocking, and platelet aggregation inhibiting functions, little attention has been paid to its metabolism and/or biotransformation.
METHODS AND RESULTS:
Biotransformation of Columbianadin by rat liver microsomes in vitro was studied, and thirteen biotransformation products including eight hitherto unknown compounds [columbianadiratimetins A-H (3-10)] and five known compounds [Columbianadin oxide (2), (+)-2,3-dihydro-4-hydroxy-2-(1-hydroxy-1-methylethyl)-5-benzofurancarboxaldehyde (11), oroselol (12), columbianetin (13), and vaginol (14)] were produced by liver microsomes from rats pre-treated with sodium phenobarbital. The structures of these compounds were elucidated on the basis of extensive spectroscopic analyses which included IR, UV, EIMS, HRESIMS, 1D NMR and 2D NMR, respectively.
The inhibition of Columbianadin and its main biotransformation products on nitric oxide production induced by lipopolysaccharide was assayed in RAW 264.7 cells at concentrations ranging from 10 to 200 μM to evaluate the biological significance of biotransformation.
|J Ethnopharmacol. 2014 Sep 11;155(2):1353-61. |
|Inhibition of airway inflammation by the roots of Angelica decursiva and its constituent, columbianadin.[Pubmed: 25068578]|
|The roots of Angelica decursiva Fr. Et Sav (Umbelliferae) have been frequently used in traditional medicine as anti-inflammatory, antitussive, analgesic agents and expectorant, especially for treating cough, asthma, bronchitis and upper respiratory tract infections. To establish the scientific rationale for the clinical use of Angelica decursiva and to identify new agents for treating inflammatory lung disorders, pharmacological evaluation of the roots of Angelica decursiva and the isolated constituents was performed.
METHODS AND RESULTS:
In vitro study was carried out using two lung cells, lung epithelial cells (A549) and alveolar macrophages (MH-S). The inflammatory markers such as IL-6 and nitric oxide (NO) for each cell line were examined. For in vivo study, a mouse model of lipopolysaccharide (LPS)-induced acute lung injury was used and the effects on lung inflammation were established by measuring the cell numbers in bronchoalveolar lavage fluid (BALF) and by histological observation. Water and 70% ethanol extracts of the roots of Angelica decursiva showed considerable inhibitory activity against LPS-induced lung inflammation in mice following oral administration at a dose of 400 mg/kg. Five coumarin derivatives including Columbianadin, umbelliferone, umbelliferone 6-carboxylic acid, nodakenin and nodakenetin were isolated. Among the isolated compounds, Columbianadin was found to possess strong inhibitory activity against the inflammatory response of IL-1β-treated A549 cells and LPS-treated MH-S cells. Columbianadin was found to inhibit NO production by down-regulation of inducible NO synthase. Moreover, Columbianadin was also proved to possess significant inhibitory activity against LPS-induced lung inflammation following oral administration at a dose of 20-60 mg/kg.
The roots of Angelica decursiva were proved to be effective in the treatment of lung inflammation. Columbianadin can be a potential new agent for treating inflammatory lung disorders.