Nodakenetin

Arch Pharm Res. 2012 Jan;35(1):179-92.

In vitro antioxidant and anti-inflammatory activities of Angelica decursiva.[Pubmed: 22297757 ]

Mounting evidences continue to support the involvement of oxidative/nitrosative stress and inflammation in the pathogenesis of many diseases. Plant constituents having antioxidant activities together with anti-inflammatory activities may provide better opportunities to develop anti-inflammatory agents.
METHODS AND RESULTS:
In view of this, we evaluated the antioxidant and antiinflammatory activities of methanolic extract of whole plants of Angelica decursiva, and its solvent soluble fractions via in vitro activities against lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 cells, as well as in vitro scavenging activities against 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid, NO, and peroxynitrite. Among the tested fractions, the ethyl acetate fraction was found as the most active antioxidant fraction together with significant anti-inflammatory effect. From the active ethyl acetate fraction, four coumarin derivatives consisting of nodakenin, Nodakenetin, umbelliferone, and umbelliferone-6-carboxylic acid, along with a phenolic compound, vanillic acid, were isolated. Among them, umbelliferone 6-carboxylic acid and vanillic acid were isolated for the first time from this plant. In all antioxidant assays, vanillic acid showed the highest antioxidant potential followed by umbelliferone 6-carboxylic acid among the isolated compounds. In the anti-inflammatory assay, umbelliferone 6-carboxylic acid exhibited the highest inhibitory activity against lipopolysaccharide-induced NO production in RAW 264.7 cells with an IC(50) value of 72.98 μg/mL.
CONCLUSIONS:
Therefore, the present study reveals the potential antioxidant and antiinflammatory activities of whole plants of A. decursiva and its constituents, mainly umbelliferone 6-carboxylic acid, which could be used in the development of therapeutic and preventive agents for oxidative stress-related inflammatory diseases.

J Asian Nat Prod Res. 2008 Jan-Feb;10(1-2):49-58.

Irritant and cytotoxic coumarins from Angelica glauca Edgew roots.[Pubmed: 18058380 ]

Irritant and cytotoxic potentiality of six coumarins, isolated for the first time from the roots of Angelica glauca identified as 5,6,7-trimethoxycoumarin, 6-methoxy-7,8-methylenedioxycoumarin, bergapten, decursinol angelate, decursin, and Nodakenetin, were investigated.
METHODS AND RESULTS:
The irritant potential was explored by open mouse ear assay, evaluating their ID(50) after acute and by IU (Irritant units) after chronic effects, while the cytotoxic capability was explored by their LC(50), using brine shrimp (Artemia salina) larvae (nauplii). All the coumarins exhibited well-defined irritancy on mouse's ears, compared with the positive controlled euphorbium reaction and cytotoxic response against brine shrimp larvae, compared with the positive control colchicine. Decursinol angelate and decursin were the most potent and persistent irritant compounds with least ID(50), whose reactions lasted for 48 h. 6-Methoxy-7,8-methylenedioxycoumarin and bergaten revealed an intermediate irritant reactions, while 5,6,7-trimethoxycoumarin and Nodakenetin displayed the least irritant and least persistent reactions on mouse ears. Both decursin and decursinol angelate also appeared to be the stronger cytotoxic agents than other coumarins.
CONCLUSIONS:
5,6,7-trimethoxycoumarin displayed an intermediate cytotoxic behaviour, while other three coumarins, i.e., 6-methoxy-7,8-methylenedioxycoumarin, bergapten, and Nodakenetin, exhibited the least cytotoxic capacity against brine shrimp larvae.

Biomed Chromatogr. 2010 Feb;24(2):216-21.

A new metabolite of nodakenetin by rat liver microsomes and its quantification by RP-HPLC method.[Pubmed: 19572262]

The biotransformation of Nodakenetin (NANI) by rat liver microsomes in vitro was investigated.
METHODS AND RESULTS:
Two major polar metabolites were produced by liver microsomes from phenobarbital-pretreated rats and detected by reversed-phase high-performance liquid chromatography (RP-HPLC) analysis. The chemical structures of two metabolites were firmly identified as 3'(R)-hydroxy-Nodakenetin-3'-ol and 3'(S)-hydroxy-Nodakenetin-3'-ol, respectively, on the basis of their (1)H-NMR, MS and optical rotation analysis. The latter was a new compound. A sensitive, selective and simple RP-HPLC method has been developed for the simultaneous determination of NANI and its two major metabolites in rat liver microsomes. Chromatographic conditions comprise a C(18) column, a mobile phase with MeOH-H(2)O (40 : 60, v/v), a total run time of 40 min, and ultraviolet absorbance detection at 330 nm. In the rat heat-inactivated liver microsomal supernatant, the lower limits of detection and quantification of metabolite I, metabolite II and NANI were 5.0, 2.0, 10.0 ng/mL and 20.0, 5.0, 50.0 ng/mL, respectively, and their calibration curves were linear over the concentration range 50-400, 20-120 and 150-24000 ng/mL, respectively.
CONCLUSIONS:
The results provided a firm basis for further evaluating the pharmacokinetics and clinical efficacy of NANI.

J. Raman Spectrosc., 2005, 36(1):63-72.

Near-infrared Fourier transform Raman, surface-enhanced Raman scattering and Fourier transform infrared spectra and ab initio calculations of the natural product nodakenetin angelate.[Reference: WebLink]

METHODS AND RESULTS:
Near-infrared Fourier transform Raman and Fourier transform infrared spectra of Nodakenetin angelate (C19H20O5), extracted from seeds of Heracleum candolleaum, were recorded and analysed. The root extract of this plant is used as an antiarthritic and nerve tonic. Ab initio SCF Hartree–Fock computations were performed employing the 6–31G basis set for geometry optimization for the prediction of IR and Raman spectral activities and wavenumber calculations. Parameters initially optimized using AM1 calculations were used as the input for ab initio computations.
CONCLUSIONS:
The computed results were used for the interpretation of the vibrational spectra. Important thermodynamic parameters were also provided. The strong band at 1712 cm−1 and medium-intensity band at 1731 cm−1 resulting from ester and lactone carbonyl vibrations, respectively, are identified in the Raman spectrum.