• Toxicological Research
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• v.33 no.1
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• pp.71-77
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• 2017

Hormone replacement therapy (HRT) consists of highly effective prescription medications for treating menopausal symptoms; however, these agents have exhibited side effects including the risk of estrogen-induced carcinogenesis. Therefore, interest in phytotherapy-based materials as a natural source of alternatives to estrogen therapy has increased. However, some of these herbal medicines have been reported to increase the risk of estrogen-induced cancer. Herbal formulations composed of a combination of Cynanchum wilfordii Hemsley (CW), Phlomis umbrosa Turczaninow (PU), and Angelica gigas Nakai (AG) extracts (CPAE) have been used for treating menopausal symptoms. Therefore, in this study, we aimed to examine the safety of CPAE by determining its potential adverse estrogenic activity using the Organization for Economic Cooperation and Development (OECD) test guideline 455 (TG455) in a stably transfected transcriptionally activated human estrogen receptor ${\alpha}$ ($hER{\alpha}$)-HeLa9903 cell model. We found that CPAE did not how any estrogenic activity or stimulate promoters containing estrogen response elements in MCF-7 cells. In addition, CPAE showed no significant selective activity against $hER{\alpha}$ and $hER{\beta}$, non-selective activity against the ER, or effects on ER target gene expression. Furthermore, CPAE did not significantly induce MCF-7 cell proliferation and uterine weight increase in ovariectomized rats. These results demonstrate that CPAE can be used as beneficial herbal drug for prevention and therapeutic intervention of estrogen carcinogenesis in menopausal women.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.38 no.4
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• pp.317-323
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• 1993

In order to clarify the contents of active principles in floral inhibition cultured Angelica gigas roots, the amounts of crude extract and the contents of decursin and decursinol angelate in the yearly roots were analyzed and compared with respect to the root age, root part and growth stage. The woody cell, weight and width of pith and cortex were also investigated at different growth stage to observe the developmental characteristics of lignification in the roots as bolting and flowering in normal cultured Angelica gigas. The amount of crude extracts did not differ with plant ages, whereas the contents of decursin and decursinol angelate were differed and the highest in 3 year old roots. The contents of decursin in 1, 2 and 3 year old roots were 3.71, 4.76 and 8.20% and those of decursinol angel ate were 2.84, 3.40 and 5.01%, respectively. The amount of crude extracts, and the contents of decursin and decursinol angelate were the highest in fine roots, followed by the lateral roots and the lowest in the primary roots. On the other hand, the amount of the constituents in the cortex were much higher than those in the pith of the root. The amounts of crude extract, and the contents of decursin and decursinol angelate showed the highest value at the vagetative stage and decreased with development to bolting and blooming stage. Woody cells were accumulated in the pith of the root as advancing growth stage, so that the weight and radius of the pith increased, whereas the relative weight and width of the cortex decreased slightly.

• Journal of Life Science
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• v.28 no.6
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• pp.726-732
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• 2018

The purpose of this study was to investigate the effects of Bacillus polyfermenticus KJS-2 (B. polyfermenticus KJS-2) and Angelica gigas Nakai extracts (AGNE) on hyperlipidermia. The purity of the major decursin and decursinol angelate (D/DA) in the AGNE were analyzed at 78%. Increased concentrations of AGNE (0.1-20 mg/ml) showed a higher 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibition activity. Endospore-forming B. polyfermenticus KJS-2 ($1{\times}10^9CFU/ml$) exhibited good bile tolerance (0.3 mm) on an agar plate. An animal study was carried out using different groups, including a normal control, positive control (atorvastatin), negative control (triton WR-1339), AGNE group, B. polyfermenticus KJS-2 group, AGNE + B. polyfermenticus KJS-2 group, and Atorvastatin + AGNE + B. polyfermenticus KJS-2 group to determine the effect of hyperlipidemia. There were no significant changes in body weight, kidney weight, or liver weight except for the liver weight of the triton WR-1339-treated group. Groups with AGNE and B. polyfermenticus KJS-2 had increased HDL-cholesterol and decreased total cholesterol and triglycerides. The liver histopathological results also showed that all AGNE and B. polyfermenticus KJS-2-treated groups contained lower fat accumulation in the liver tissues. The findings of this study verified that AGNE and Endospore-forming B. polyfermenticus KJS-2 combination materials have a hyperlipidemic effect.

• Archives of Pharmacal Research
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• v.28 no.7
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• pp.848-853
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• 2005

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1 % inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7 -day model of multiple treatment of TPA (38.1 % inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin $E_2$ production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.3
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• pp.419-427
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• 2016

There is a high association of heat shock on the alteration of energy and lipid metabolism. The alterations associated with thermal stress are composed of gene expression changes and adaptation through biochemical responses. Previous study showed that Angelica gigas Nakai (AGN) root extract promoted adipogenic differentiation in murine 3T3-L1 preadipocytes under the normal temperature condition. However, its effect in heat shocked 3T3-L1 cells has not been established. In this study, we investigated the effect of AGN root hot water extract in the adipogenic differentiation of murine 3T3-L1 preadipocytes following heat shock and its possible mechanism of action. Thermal stress procedure was executed within the same stage of preadipocyte confluence (G0) through incubation at $42^{\circ}C$ for one hour and then allowed to recover at normal incubation temperature of $37^{\circ}C$ for another hour before AGN treatment for both cell viability assay and Oil Red O. Cell viability assay showed that AGN was able to dose dependently (0 to $400{\mu}g/mL$) increase cell proliferation under normal incubation temperature and also was able to prevent cytotoxicity due to heat shock accompanied by cell proliferation. Confluent preadipocytes were subjected into heat shock procedure, recovery and then AGN treatment prior to stimulation with the differentiation solution. Heat shocked preadipocytes exhibited reduced differentiation as supported by decreased amount of lipid accumulation in Oil Red O staining and triglyceride measurement. However, those heat shocked preadipocytes that then were given AGN extract showed a dose dependent increase in lipid accumulation as shown by both evaluation procedures. In line with these results, real-time polymerase chain reaction (RT-PCR) and Western blot analysis showed that AGN increased adipogenic differentiation by upregulating heat shock protection related genes and proteins together with the adipogenic markers. These findings imply the potential of AGN in heat shock amelioration among 3T3-L1 preadipocytes through heat shock factor and proteins augmentation and enhanced adipogenic marker expression.

• Journal of Life Science
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• v.29 no.10
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• pp.1086-1095
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• 2019

This research was performed to develop a new material consisting of a mixture of Red Allium cepa (RA) Cucurbita moschata duch (CM), and Angelica gigas Nakai (AG). RA and CM have low storage stability because of their high moisture content. Therefore, their major components were extracted and used for the research after a content analysis. In order to overcome these limitations, the quercetin from RA, ${\beta}-carotene$ from CM, and decursin/decursinol angelate (D/DA) from AG were separately extracted, and the biochemical activity of each extract and mixture was compared. RA was bioconverted by the Bacillus subtillis KJ-3 (BS3) after ethanol extraction. After bioconversion, the quercetin content of RA was increased by 128.9%. ${\beta}-carotene$ was detected in the CM ethanol extract and its content was very low concentrations at 0.2 mg/g. The AG ethanol extract (1 mg) contained 0.4146 mg and 0.3659 mg of D/DA, respectively. The purity of the D/DA was found to be about 78%. The flavonoid and polyphenol content of each extract and their mixtures (mixture 1 (RA:CM:AG = 5:2:3), mixture 2 (RA:CM: AG = 3:5:2), and mixture 3 (RA:CM:AG = 3:2:5)) were measured. In addition, the cell survival rate, anti-inflammatory activity, and antioxidant ability were also evaluated. In all the results, the antioxidant activity of mixture 3 was most effective. Therefore, these findings provide basic data for future food development using a 3:2:5 mixture of RA, CM, and AG.

• The Journal of Korean Medicine
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• v.29 no.2
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• pp.133-150
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• 2008

Objective: This study was performed to examine Danggui (DG, Angelica gigas Nakai)'s potential activity for promoting axonal regeneration in the injured peripheral nerve. Methods: Using the sciatic nerve in the rats, DG extract 5 ${\mu}l$(10 mg/ml in 0.5% saline) was dripped into the injury site of the nerve. Results: DG treatment facilitated axonal elongation responses in the distal portion to the injury site. GAP-43 protein levels were upregulated by DG treatment in the injured nerve and also in the DRG, suggesting the induction of GAP-43 expression at gene expression level after nerve injury. Phospho-Erk1/2 protein levels were upregulated in the injured nerve area and also in the DRG, suggesting retrograde transport of phospho-Erk1/2 protein from the injury area to the cell body. Cdc2 protein levels were slightly upregulated by DG treatment. DG treatment increased the number of non-neuronal cells in the distal portion to the injury site. Conclusions: The present data suggest that DG is effective for enhanced axonal regrowth after sciatic nerve injury.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.40 no.1
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• pp.1-8
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• 1995

This study was carried out to investigate the effects of floral inhibition of An-gelica gigas NAKAI in the hilly altitude located in the Northern Gyeongbuk Province from Feb. 1992 to Nov. 1994. The results obtained were as follows ： As the cultivated areas are high, rate of bolting was significantly decreased, having high yield, good growth, and medicinal quality. It is considered that the optimal cultivating area was at least above 600m altitude. In the hilly altitude, the more shorten nursery period was, the more decreased rate of bolting was, it results in decreased yield, having no significant differences in contents such as extracts and decursin. In bolting response from temperature treatment of the seedlings, treatment of high temperature was significantly decreased floral induction, but rate of establishment was decreased by decayed root. Bolting rate at different organic resources has more reduced in single fertilization than that of in organic application, but among organic resources, compost of rice straw has the lowest bolting rate. As a result, yield and medicinal qualities at various organic resources were increased in application of organic resources which was no con-siderable tendency among organic resources.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.4
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• pp.177-183
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• 2020

The Hippo-YAP signaling pathway is critical for cell proliferation, survival, and self-renewal in both Drosophila and mammals. Disorder of Hippo-YAP pathway leads to tumor development, progression and poor prognosis in various cancers. YAP/TAZ are the key downstream effectors of the Hippo pathway and they can be inhibited through LATS1/2, core kinases in the Hippo pathway, mediated phosphorylation. In this study, we investigated the effect of Angelica gigas Nakai extract (AGNE) on Hippo-YAP/TAZ pathway. First, ANGE induced YAP/TAZ phosphorylation and dissociation of the YAP/TAZ-TEAD transcription complex. By qRT-PCR, we found that ANGE inhibits the expression of YAP/TAZ-TEAD target gene, CTGF and CYR61. In addition, the transcriptional activity of YAP/TAZ was not suppressed significantly in LATS1/2 double-knockout (DKO) cells by ANGE compared to LATS1/2 wild-type (WT) cells, which means AGNE inhibits YAP/TAZ signaling through direct action on LATS1/2. Further, it was confirmed that AGNE-induced activation of LATS1/2 inhibited the migration potential of the vector-expressing cells by suppressing YAP/TAZ activity. The reduced migration potential was restored in active YAP-TEAD expressing cells. Taken together, the results of this study indicate that ANGE downregulates YAP/TAZ signaling in cells through the activation of LATS1/2.

• Journal of Life Science
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• v.20 no.5
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• pp.750-759
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• 2010

The bioactive materials (phenolic compounds, flavonoids, minerals, decursin and decursinol angelate) and biological activities (DPPH [$\alpha,\alpha$'-diphenyl-$\beta$-picrylhydrazyl] free radical scavenging capability, reducing power, and tyrosinase activity) in the extracts of leaf, stem mixture (AGLS), and root (AGR) from Angelica gigas Nakai were examined by using water, hot water and ethanol solvent. The highest extract yield (21.89%) was found in the water extract of AGR. The highest concentrations of phenolic compounds and flavonoids in the ethanol extracts of AGLS and AGR were 14.99% and 14.79%. Major minerals of AGLS and AGR were K, Mg, Fe, Na and Ca. Decursin and decursinol angelate were the major ingredients of Angelica gigas, detected at 18.71 and 18.89 min of retention time by HPLC analysis, respectively. The highest concentrations of decursin and decursinol angelate in the Angelica gigas ethanol extract were found in root ($41.7\;{\mu}g/g$) and leaf ($34.04\;{\mu}g/g$). The highest free radical scavenging activity was found in the hot water extracts of AGLS and AGR, and its activity was stronger in all extracts of AGLS than AGR. The highest reducing power was found in the ethanol extracts of AGLS and AGR and this was dependent on the sample concentration. The hot water extracts of AGLS and AGR revealed the highest inhibition activity on tyrosinase. Overall, these results may provide the basic data needed to understand the biological activities of bioactive materials derived from Angelica gigas.