Decursinol angelate

Biochem Biophys Res Commun. 2018 May 23;499(4):979-984.

Decursin and decursinol angelate improve wound healing by upregulating transcription of genes encoding extracellular matrix remodeling proteins, inflammatory cytokines, and growth factors in human keratinocytes.[Pubmed: 29626469 ]

The coumarins decursin and Decursinol angelate, which are found in Angelica gigas Nakai, have a variety of biological functions.
METHODS AND RESULTS:
Here, we show that treatment with these compounds improves wound healing by HaCaT human keratinocytes. Wound healing was increased by treatment with up to a threshold concentration of decursin, Decursinol angelate, a mixture of both, and a nano-emulsion of these compounds, but inhibited by treatment with higher concentrations. Immunoblotting and fluorescence imaging of cells expressing an epidermal growth factor receptor (EGFR) biosensor demonstrated that these compounds did not stimulate wound healing by inducing EGFR phosphorylation. Rather, transcriptional analysis revealed that decursin and Decursinol angelate improved wound healing by upregulating the expression of genes encoding extracellular matrix remodeling proteins, inflammatory cytokines, and growth factors.

Arch Pharm Res. 2003 Sep;26(9):727-30.

Anti-tumor activities of decursinol angelate and decursin from Angelica gigas.[Pubmed: 14560921]

The in vivo anti-tumor activities of Decursinol angelate (1) and decursin (2) isolated from the roots of Angelica gigas were investigated.
METHODS AND RESULTS:
These two compounds, when administered consecutively for 9 days at 50 and 100 mg/kg i.p. in mice, caused a significant increase in the life span and a significant decrease in the tumor weight and volume of mice inoculated with Sarcoma-180 tumor cells.
CONCLUSIONS:
These results suggest that Decursinol angelate (1) and decursin (2) from A. gigas have anti-tumor activities.

Pesticide Biochemistry & Physiology, 2011, 101(2):118-124.

In vitro and in vivo antifungal activities of decursin and decursinol angelate isolated from Angelica gigas against Magnaporthe oryzae, the causal agent of rice blast[Reference: WebLink]

Blast is considered the most important fungal disease of rice due to its wide distribution and destructiveness under favorable conditions. Development of new effective and environmentally benign agents against the causal pathogen, Magnaporthe oryzae, is of great interest. In the course of a search for natural antifungal compounds in medicinal plants, we found that the methanol extract of Angelica gigas roots showed a potent control efficacy against rice blast caused by M. oryzae.
METHODS AND RESULTS:
We isolated antifungal coumarins from the extract, and they were identified as decursin and Decursinol angelate. Antifungal activities of these compounds, along with kasugamycin, were tested on M. oryzae in vivo and in vitro. In an in vivo assay, the three compounds effectively suppressed the development of rice blast at concentrations more than 100μg/mL. Coumarins showed relatively weak inhibitory effect on fungal mycelial growth when compared to kasugamycin. However, they strongly inhibited M. oryzae spore germination, which was not observed in kasugamycin treatments. This is the first report demonstrating that Decursinol angelate can provide control against rice blast and that the two coumarins inhibit M. oryzae spore germination. In addition, the wettable powder formulation of the crude extract of A. gigas prohibited the development of blast symptoms on rice plants more effectively than liquid concentrate formulation of kasugamin, a commercial fungicide.
CONCLUSIONS:
Based on our study, we propose that coumarin compounds as well as the A. gigas root crude extract can be used as natural, benign fungicides for controlling rice blast.

Carcinogenesis. 2009 Apr;30(4):655-61.

Decursin and decursinol angelate inhibit VEGF-induced angiogenesis via suppression of the VEGFR-2-signaling pathway.[Pubmed: 19228635 ]

Inhibition of angiogenesis is an attractive approach for the treatment of angiogenic diseases, such as cancer. Vascular endothelial growth factor (VEGF) is one of the most important activators of angiogenesis and interacts with the high-affinity tyrosine kinase receptors, VEGFR-1 and VEGFR-2. The pyranocoumarin compounds decursin and Decursinol angelate isolated from the herb, Angelica gigas, are known to possess potent anti-inflammatory activities. However, little is known about their antiangiogenic activity or their underlying mechanisms.
METHODS AND RESULTS:
Here, we show the antiangiogenic effects of decursin and Decursinol angelate using in vitro assays and in vivo animal experiments. Decursin and Decursinol angelate inhibited VEGF-induced angiogenic processes in vitro, including proliferation, migration and tube formation of human umbilical vein endothelial cells. Decursin and Decursinol angelate significantly suppressed neovessel formation in chick chorioallantoic membrane and tumor growth in a mouse model. The microvessel density in tumors treated with decursin for 14 days was significantly decreased compared with a vehicle control group. Decursin and Decursinol angelate inhibited VEGF-induced phosphorylation of VEGFR-2, extracellular signal-regulated kinases and c-Jun N-terminal kinase mitogen-activated protein kinases.
CONCLUSIONS:
Taken together, these results demonstrate that decursin and Decursinol angelate are novel candidates for inhibition of VEGF-induced angiogenesis.

Cancer Lett. 2010 Oct 1;296(1):35-42.

Decursinol angelate blocks transmigration and inflammatory activation of cancer cells through inhibition of PI3K, ERK and NF-kappaB activation.[Pubmed: 20381234 ]

The protective effects of decursin (D) and Decursinol angelate (DA) purified from Angelica gigas Nakai on amyloid β-protein (Aβ)-induced neurotoxicity and the underlying mechanisms were investigated.
METHODS AND RESULTS:
Aβ plays a major role in the pathogenesis of Alzheimer's disease (AD) by eliciting oxidative stress. It significantly increased cytotoxicity and lipid peroxidation, but decreased glutathione contents and antioxidant enzyme activities. All of these results were markedly reversed by pretreatment with D or DA. Nuclear transcription factor Nrf2, which regulates the expression of antioxidant enzymes, was significantly increased by D or DA pretreatment. Furthermore, D and DA suppressed Aβ aggregation.
CONCLUSIONS:
These results suggest that D and DA increase cellular resistance to Aβ-induced oxidative injury in the rat pheochromocytoma (PC12) cells, presumably through not only the induction of Nrf2 and related antioxidant enzymes, but also the anti-aggregation of Aβ. Thus D and DA have therapeutic potential in treating AD and other oxidative stress-related diseases.

Natural Product Sciences,2003,9(3):170-3.

Antioxidant activities of decursinol angelate and decursin from Angelica gigas roots[Reference: WebLink]

METHODS AND RESULTS:
The anti-oxidant activities of Decursinol angelate (1) and decursin (2) isolated from Angelica gigas were investigated. These two coumarins exhibited decrease in serum transaminase activities elevated by hepatic damage induced by in rats. They also showed increase in anti-oxidant enzyme such as hepatic cytosolic superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-px) in rats.
CONCLUSIONS:
These results suggest that Decursinol angelate (1) and decursin (2) from A. gigas possess not only the anti-oxidant, but also the hepatoprotective activities in rats.