Decursinol

The roots of Angelica gigas

In vitro metabolism of pyranocoumarin isomers decursin and decursinol angelate by liver microsomes from man and rodents.[Pubmed:24026903]

Planta Med. 2013 Nov;79(16):1536-44.

The aim of this study is to investigate and compare the metabolic rate and profiles of pyranocoumarin isomers decursin and Decursinol angelate using liver microsomes from humans and rodents, and to characterize the major metabolites of decursin and Decursinol angelate in human liver microsomal incubations using LC-MS/MS. First, we conducted liver microsomal incubations of decursin and Decursinol angelate in the presence or absence of NADPH. We found that in the absence of NADPH, decursin was efficiently hydrolyzed to Decursinol by hepatic esterase(s), but Decursinol angelate was not. In contrast, formation of Decursinol from Decursinol angelate was mediated mainly by cytochrome P450(s). Second, we measured the metabolic rate of decursin and Decursinol angelate in liver S9 fractions from mice and humans. We found that human liver S9 fractions metabolized both decursin and Decursinol angelate more slowly than those of the mouse. Third, we characterized the major metabolites of decursin and Decursinol angelate from human liver microsomes incubations using HPLC-UV and LC-MS/MS methods and assessed the in vivo metabolites in mouse plasma from a one-dose PK study. Decursin and Decursinol angelate have different metabolite profiles. Nine metabolites of decursin and nine metabolites of Decursinol angelate were identified in human liver microsome incubations besides Decursinol using a hybrid triple quadruple linear ion trap LC-MS/MS system, and many of them were later verified to be also present in plasma samples from rodent PK studies.

Single oral dose pharmacokinetics of decursin and decursinol angelate in healthy adult men and women.[Pubmed:25695490]

PLoS One. 2015 Feb 19;10(2):e0114992.

UNLABELLED: The ethanol extract of Angelica gigas Nakai (AGN) root has promising anti-cancer and other bioactivities in rodent models. It is currently believed that the pyranocoumarin isomers decursin (D) and Decursinol angelate (DA) contribute to these activities. We and others have documented that D and DA were rapidly converted to Decursinol (DOH) in rodents. However, our in vitro metabolism studies suggested that D and DA might be metabolized differently in humans. To test this hypothesis and address a key question for human translatability of animal model studies of D and DA or AGN extract, we conducted a single oral dose human pharmacokinetic study of D and DA delivered through an AGN-based dietary supplement Cogni.Q (purchased from Quality of Life Labs, Purchase, NY) in twenty healthy subjects, i.e., 10 men and 10 women, each consuming 119 mg D and 77 mg DA from 4 vegicaps. Analyses of plasma samples using UHPLC-MS/MS showed mean time to peak concentration (Tmax) of 2.1, 2.4 and 3.3 h and mean peak concentration (Cmax) of 5.3, 48.1 and 2,480 nmol/L for D, DA and DOH, respectively. The terminal elimination half-life (t1/2) for D and DA was similar (17.4 and 19.3 h) and each was much longer than that of DOH (7.4 h). The mean area under the curve (AUC0-48h) for D, DA and DOH was estimated as 37, 335 and 27,579 hnmol/L, respectively. Gender-wise, men absorbed the parent compounds faster and took shorter time to reach DOH peak concentration. The human data supported an extensive conversion of D and DA to DOH, even though they metabolized DA slightly slower than rodents. Therefore, the data generated in rodent models concerning anti-cancer efficacy, safety, tissue distribution and pharmacodynamic biomarkers will likely be relevant for human translation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02114957.

Single oral dose pharmacokinetics of decursin, decursinol angelate, and decursinol in rats.[Pubmed:23364885]

Planta Med. 2013 Mar;79(3-4):275-80.

Decursin and Decursinol angelate are the major components in the alcoholic extract of the root of Angelica gigas Nakai. Our previous work convincingly demonstrated that both decursin and Decursinol angelate were rapidly converted to Decursinol in mice after administration by either oral gavage or i. p. injection. In the current study, we compared for the first time the plasma profiles of Decursinol, when equal moles of decursin/Decursinol angelate or Decursinol were given to rats by oral gavage, and investigated the effect of different formulas and other chemicals in Angelica gigas extract on the bioavailability of Decursinol. Our results show that gavage of Decursinol led to a faster attainment of plasma Decursinol peak (Tmax ~ 0.7 h) and much higher peak levels than an equal molar amount administered as decursin/Decursinol angelate mixture or as Angelica gigas ethanol extract, resulting in 2-3 fold higher bioavailability as estimated by the area under the curve of the respective regimens (65 012 vs. 27 033 h . ng/mL for Decursinol and decursin/Decursinol angelate treatment groups, respectively). Compared to a formula based on ethanol-PEG400-Tween80, carboxyl methyl cellulose was a less optimized vehicle. In addition, we detected peak levels of decursin and Decursinol angelate in the plasma of rats administered with decursin/Decursinol angelate or Angelica gigas extract in the nM range (Tmax ~ 0.5 h) with a newly established sensitive UHPLC-MS/MS method. Furthermore, our data support the liver, instead of intestine, as a major organ site where decursin and Decursinol angelate were hydrolyzed to Decursinol with a S9 microsomal in vitro metabolism assay. Taken together, our study provided important PK, LC-MS/MS methodology, formulation and metabolism insights in a rodent model for the rational design of in vivo efficacy studies of the corresponding chemicals in the future.

Decursin and decursinol from Angelica gigas inhibit the lung metastasis of murine colon carcinoma.[Pubmed:21170925]

Phytother Res. 2011 Jul;25(7):959-64.

The principal objective of the present study was to evaluate the antimetastatic activity of decursin and Decursinol isolated from Angelica gigas. Decursin and Decursinol inhibited the proliferation and invasion of CT-26 colon carcinoma cells. The expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in cells and the activities in the culture medium were also reduced by decursin and Decursinol treatment. In CT-26 cells, the extracellular signal-regulated kinase (ERK) inhibitor inhibited cell proliferation, invasion and MMP-9 expression, and the c-Jun N-terminal kinase (JNK) inhibitor suppressed the expression of both MMPs, as well as cell proliferation and cell invasion. The phosphatidylinositol-3 kinase (PI3K) inhibitor reduced only the expression of MMP-2. In addition, the invasion of CT-26 cells was inhibited by the treatment with anti-MMP-9 antibody, rather than anti-MMP-2 antibody. These results indicate that MMP-9 expression via ERK and JNK plays a critical role for the invasion of CT26 cells. Decursin and Decursinol downregulated ERK and JNK phosphorylation. Moreover, oral administration of decursin and Decursinol reduced the formation of tumor nodules in the lungs and the increase in lung weight caused by CT-26 metastases. Therefore, both decursin and Decursinol may be beneficial antimetastatic agents, targeting MMPs and their upstream signaling molecules.

Decursinol, isolated from the roots of Angelica gigas, possesses antinociceptive effect with orally bioavailability. Decursinol possesses anti-tumor and anti-metastasis activity.

Decursinol,23458-02-8,Smyrinol,Natural Products, buy Decursinol , Decursinol supplier , purchase Decursinol , Decursinol cost , Decursinol manufacturer , order Decursinol , high purity Decursinol