Screening and promoting effect of grow-promoting fungi in rhizosphere of Angelica dahurica var. formosana / 中国中药杂志

Excessive application of chemical fertilizer has caused many problems in Angelica dahurica var. formosana planting, such as yield decline and quality degradation. In order to promote the green cultivation mode of A. dahurica var. formosana and explore rhizosphere fungus resources, the rhizosphere fungi with nitrogen fixation, phosphorus solubilization, potassium solubilization, iron-producing carrier, and IAA-producing properties were isolated and screened in the rhizosphere of A. dahurica var. formosana from the genuine and non-genuine areas, respectively. The strains were identified comprehensively in light of the morphological characteristics and ITS rDNA sequences, and the growth-promoting effect of the screened strains was verified by pot experiment. The results showed that 37 strains of growth-promoting fungi were isolated and screened from the rhizosphere of A. dahurica var. formosana, mostly belonging to Fusarium. The cultured rhizosphere growth-promoting fungi of A. dahurica var. formosana were more abundant and diverse in the genuine producing areas than in the non-genuine producing areas. Among all strains, Aspergillus niger ZJ-17 had the strongest growth promotion potential. Under the condition of no fertilization outdoors, ZJ-17 inoculation significantly promoted the growth, yield, and accumulation of effective components of A. dahurica var. formosana planted in the soil of genuine and non-genuine producing areas, with yield increases of 73.59% and 37.84%, respectively. To a certain extent, it alleviated the restriction without additional fertilization on the growth of A. dahurica var. formosana. Therefore, A. niger ZJ-17 has great application prospects in increasing yield and quality of A. dahurica var. formosana and reducing fertilizer application and can be actually applied in promoting the growth of A. dahurica var. formosana and producing biofertilizer.

Chemical characterization, antioxidant activity, -amylase and acetylcholinesterase inhibitory potential of Angelica pancicii Vandas ex Velen / Caracterización química, actividad antioxidante, potencial inhibidor de -amilasa y acetilcolinesterasa de Angelica pancicii Vandas ex Velen

Abstract: Comparative study GC - FID /M S of essential oils of fruits, leaves and roots of the endemic plant Angelica pancicii Vandas ex Velen. revealed a significant difference in their chemical composition. The enantiomeric purity of the main component in the fruit oil (+) - ß - phellandrene was a lso confirmed. In addition, imperatorin, isoimperatorin, oxypeucedanin, oxypeucedanin hydrate, angeloylpangelin and umbelliprenin were isolated from the fruit hexane extract. The content of these coumarins in the hexane extracts from different plant parts was further determined by HPLC. The essential oils and hexane extracts were assessed for their antioxidant potential and inhibitory effect towards  - amylase and acetylcholinesterase enzymes. The fruit and leaf essential oils (> 80%) as well as the fruit he xane extract (> 62%) significantly inhibited acetylcholinesterase enzyme. Distinguish free radical scavenging properties were detected for the leaf (Inh. 95.0 ± 2.2 %) and the root (Inh. 66.0 ± 2.4 %) extracts.

Resumen: Estudio comparativo GC - FID / MS de aceites esenciales de frutas, hojas y raíces de la planta endémica Angelica pancicii Vandas ex Velen revelaron una dife rencia significativa en su composición química. También se confirmó la pureza enantiomérica del componente principal del aceite de fruta (+) - ß - felandreno. Además, se aislaron imperatorina, isoimperatorina, oxipeucedanina, hidrato de oxipeucedanina, angeloi lpangelina y umbeliprenina del extracto de hexano del fruto. El contenido de estas cumarinas en los extractos de hexano de diferentes partes de la planta se determinó adicionalmente mediante HPLC. Los aceites esenciales y extractos de hexano se evaluaron p or su potencial antioxidante efecto inhibidor de las enzimas -  - amilasa y acetilcolinesterasa. Los aceites esenciales de frutas y hojas (> 80%), así como el extracto de hexano de frutas (> 62%) inhibieron significativamente la enzima acetilcolinesterasa. Se detectaron propiedades de captación de radicales libres diferenciadas para los extractos de hoja (Inh. 95,0 ± 2,2%) y de raíz (Inh. 66,0 ± 2,4%).

Bioinformatics and expression analysis on MYB-related family in Angelica dahurica var. formosana / 中国中药杂志

In recent years, the MYB-related gene family has been found pivotal in plant growth and development. MYB-related gene family in Angelica dahurica var. formosana was systematically investigated based on "Chuanzhi No. 2" through transcriptome database search and bioinformatics and the temporal and spatial expression patterns were analyzed through real-time fluorescence-based quantitative polymerase chain reaction(PCR). The results showed that 122 MYB-related proteins family were identified, mainly including the unstable hydrophilic proteins with good thermal stability. Most of the proteins were located in nuclei. The majority of the proteins had the structures of random coil and α-helix. Five MYB-related proteins family of A. dahurica var. formosana had membrane-binding domains. The conserved domain analysis of MYB-related proteins family of A. dahurica var. formosana showed that the MYB domains of genes in five subgroups, similar to 2 R-, 3 R-, and 4 R-MYB proteins, contained three evenly distributed Trp(W) residues in the MYB repeat sequence. The phylogenetic analysis of MYB-related proteins family in A. dahurica var. formosana and Arabidopsis thaliana showed that the MYB-related members were unevenly distributed in five subgroups, and A. thaliana and A. dahurica var. formosana had almost the same number of genes in the CCA1-like subgroup. There were differences in the number, type, and distribution of motifs contained in 122 encoded proteins. Transcription factors with similar branches had similar domains and motifs. The expression pattern analysis showed that the transcription factors AdMYB53, AdMYB83, and AdMYB89 responded to hormones to varying degrees, and they were highly expressed in leaves and responded quickly in roots. This study lays a foundation for further investigating the function of MYB-related transcription factors of A. dahurica var. formosana and solving the corresponding biological problems such as bolting early.

Analysis of volatile constituents and chemical relationship of cultivated and wild Angelica dahurica / 南方医科大学学报

OBJECTIVE@#To determine the volatile constituents and their contents in the roots of 5 cultivated Angelica dahurica and one wild A. dahurica and analyze the chemical relationship among the plants of A. dahurica.@*METHODS@#The essential oil was extracted from the roots of 5 cultivated plants of Angelica dahurica and one wild A. dahurica by water steam distillation. Gas chromatography-mass spectrometry (GC-MS) was used to separate and identify all the volatile oil components in the extracts, and their relative contents were calculated with area normalization method. We also conducted clustering analysis and principal component analysis of the volatile oil components.@*RESULTS@#We identified a total of 81 compounds from the roots of the 6 plants of Angelica dahurica, including 27 in Chuanbaizhi (Angelica dahurica cv. 'Hangbaizhi'), 34 in Hangbaizhi (Angelica dahurica cv. 'Hangbaizhi'), 24 in Qibaizhi (Angelica dahurica cv. 'Qibaizhi'), 32 in Yubaizhi (Angelica dahurica cv.'Qibaizhi'), 28 in Bobahizhi (Angelica dahurica cv.'Qibaizhi'), and 34 in Xinganbaizhi (Angelica dahuirca). These compounds included, in the order of their relative contents (from high to low), alkanes, olefins, esters, organic acids and alcohols. Among the common components found in the roots of all the plants of A. dahurica, nonylcyclopropane, cyclododecane and hexadecanoic acid were identified as the volatile oil components that showed the highest relative contents. Clustering analysis of the volatile oil components showed that wild Angelica dahurica (Xing'anbaizhi) and the 5 cultivated Angelica dahurica (Chuanbaizhi, Hangbaizhi, Qibaizhi, Yubaizhi, Bobaizhi) could be divided into two groups, and the cultivated Angelica dahurica could be divided into two subgroups: Chuanbaizhi, Yubaizhi and Hangbahizhi were clustered in one subgroup, and Qibaizhi and Bobaizhi in another. The results of principal component analysis was consistent with those of clustering analysis.@*CONCLUSION@#The main volatile oil components and their contents vary among the 6 plants of A. dahurica. Nonylcyclopropane, cyclododecane and hexadecanoic acid are the most abundant volatile oil components in all the plants of A. dahurica, which can be divided into two clusters.

Studies on absorption and transportation of coumarins in Angelica dahurica 'Yubaizhi' across human intestinal epithelial by using human Caco-2 cell monolayers / 中国中药杂志

The absorption is the key to the resulted efficacy of orally administered drugs and the small intestine is the main site to absorb the orally administered drug. In this paper, internationally recognized human colon adenocarcinoma cell line(Caco-2) monola-yer model which can simulate small intestinal epithelial cell was used to comparatively study the absorption and transportation diffe-rences of total coumarins and main individual coumarin in Angelica dahurica 'Yubaizhi' by separately using 6-and 12-well plates. It was found that apparent permeability coefficient(P_(app)) values of oxypeucedanin hydrate, byakangelicin and phellopterin were at the quantitative degree of 1 × 10~(-5) cm·s~(-1) when the individual administration was conducted independently, indicating that they were well-absorbed compounds. P_(app) ratio of their bi-directional transportation was close to 1, indicating that they can be absorbed across Caco-2 monolayer by passive diffusion mechanism without carrier mediation during the transportation. The similar trend of transportation was also observed for imperatorin, isoimperatorin and bergapten. The P_(app) values of oxypeucedanin hydrate, byakangelicin and bergapten were at quantitative degree of 1 × 10~(-5) cm·s~(-1) when the administration of total coumarins in Angelica dahurica 'Yubaizhi' was conducted, indicating that they were well-absorbed compounds. The results were consistent with those of independent administration of individual coumarins. Whereas, the P_(app) values of imperatorin, phellopterin and isoimperatorin in the total coumarins decreased, indicating that the interaction between compounds may exist although the P_(app) value ratio of bi-directional transportation was between 0.5 and 1.5. The results laid the foundation for intestinal absorption study of Angelica dahurica 'Yubaizhi' coumarins in compound Chinese medicine.

Bioinformatics analysis and expression pattern of NAC transcription factor family of Angelica dahurica var. formosana from Sichuan province / 中国中药杂志

NAC(NAM/ATAF/CUC) protein plays an important role in plant growth and development, secondary cell wall formation and stress response. In this study, based on the sequencing data of Angelica dahurica, the NAC family was systematically analyzed using bioinformatics methods and its expression pattern was analyzed. Studies showed that 75 candidate genes had been selected from the NAC transcription factor family of A. dahurica, with the protein size of 148-641, all of which were unstable hydrophilic proteins. Most NAC proteins were localized in the nucleus, and had complete NAC domain. Phylogenetic analysis of NAC family proteins of A.dahurica and Arabidopsis thaliana showed that among the 17 subfamilies, NAC members were unevenly distributed in each subfamily, indicating that the evolution of species is developing in multiple directions. Among them, ANAC063 subfamily contained no NAC sequence of A. dahurica, which might be due to the functional evolution of the species. Analysis of protein transmembrane structure and signal peptide showed that NAC transcription factor could carry out transmembrane transportation, but its signal peptide function had not been found. Expression analysis showed that most transcription factors responded to abiotic stress and hormones to varying degrees, and the effects of hormones were obvious, especially ABA and IAA. In different organs of A. dahurica, most members of the NAC family had higher expression in root phloem, followed by root xylem. This study lays a foundation for further research on the function of A. dahurica NAC transcription factor and for solving the biological problems of A. dahurica.

Quality evaluation of angelica broken wall powder based on QbD concept of traditional Chinese medicine / 中国中药杂志

In this paper, angelica broken wall powder(ABWP) was taken as the research object, HPLC fingerprint combined with multi-component determination(ferulic acid, senkyunolide I, coniferyl ferulate, ligustilide and 3-butylidenephthalide), physical fingerprint(D_(90), particle size distribution range, particle size distribution width, bulk density, tap density, inter-particle porosity, Carr index, specific surface area, pore volume, angle of repose, Hausner ratio, loss on drying and hygroscopicity)were used to characterize the quality attribute of ABWP; similarity analysis, cluster analysis, principal component analysis and orthogonal partial least squares discriminant analysis were conducted to construct the quality evaluation method of holographic analysis based on traditional Chinese medicine QbD "4 H mode", in order to evaluate the quality of ABWP from different sources and find out differentiated indicators. The quality evaluation method could be used for scientific, comprehensive evaluation of the quality attribute of ABWP, and the quality consistency evaluation of cell-wall-broken powder of different sources or different processes.It provides new ideas for quality control and research of ultrafine granular powders of traditional Chinese medicine.

Habitat suitability evaluation for Angelica dahurica planting in Yanting county,Sichuan province based on GIS / 中国中药杂志

It is of great significance to analyze habitable suitability of genuine medicinal materials for Chinese herbal medicine planting according to local environment,for medicinal resources protecting and for reasonable planning introduction. Based on GIS technology,the analytic hierarchy process was applied to analyze the spatial differentiation of habitat suitability of Angelica dahurica in Yanting county of Sichuan province. The evaluation combined local geographical environment characteristics and habitat requirements for A. dahurica planting and adopted the expert experience method to screen out the evaluation index for establishing evaluation system.With the established evaluation system,the index weight of evaluating index was determined by analytic hierarchy process and their grouping values were assigned by Delphi method. The all evaluating index were translated into index distribution maps using Arc GIS software. Using the comprehensive factor weighted evaluating model and spatial index distribution map,the evaluation was obtained by means of the overlay analysis function of Arc GIS 10. 3 software. RESULTS:: showed that A. dahurica had a wide range of suitable planting areas in Yanting county. Highly suitable areas amounted to 165. 01 km2,and mainly distributed in the low hilly area with moderate elevation and fertile soil. Moderately suitable areas amounted to 798. 92 km2 which had extensive distribution in middle and west part of the county. Marginally suitable areas amounted to 0. 33 km2,where the soil was highly viscous with high altitude and low temperature that was not conducive to the growth and development of A. dahurica. Adapting to local conditions and scientific planning plays an important role in the development of local characteristic planting industry of genuine medicinal materials.

Quantitative determination of nine furanocoumarins for quality evaluation of Angelica dahurica from different habitats / 中国中药杂志

A UPLC method has been developed for simultaneous determination of nine furanocoumarins of Angelica dahurics,and was used for quality evaluation of A. dahurica from different habitats. ACQUITY UPLC BEH C18 chromatographic column was employed,the separation was performed with the mobile phase consisting of acetonitrile and water,and the detection wavelength was set at254 nm. This method was used to simultaneously determine the content of xanthotoxol,oxypeucedaninhydrate,byak-angelicin,psoralen,xanthotoxin,bergapten,oxypeucedanin,imperatorin and isoimperatorin in A. dahurica from different habitats. Then,the further quality assessment of the drug was carried out by similarity evaluation,cluster analysis( CA),principal component analysis( PCA),and orthogonal partial least squares discriminant analysis( OPLS-DA). The content order of measured furanocoumarins from high to low was: oxypeucedanin>imperatorin>isoimperatorin>oxypeucedaninhydrate>bergapten>byak-angelicin>xanthotoxin>xanthotoxol>psoralen,with the mean content 2. 844,1. 277,0. 649 2,0. 216 2,0. 129 8,0. 062 68,0. 052 68,0. 019 30,0. 018 19 mg·g-1,respectively. There were difference between the batches of the drug,and the quality was influenced by smouldering sulphur based on the results of chemical pattern recognition and content determination. Finally,six active ingredients were recognized as the quality makers using OPLS-DA method. The validated UPLC fingerprint combined with chemical pattern recognition method can be used in the quality control and evaluation of A. dahurica.

Angelica Polysaccharide Resists Platelets Apoptosis Induced by LY294002 / 中国实验血液学杂志

OBJECTIVE@#To investigate the anti-apoptotic effect of Angelica polysaccharide (APS) on cryopreservated platelets and its mechanism.@*METHODS@#The platelets were divided into 4 group: control group(4 ℃ stored platelets),APS group (APS-treated platelets stored at 4 ℃), LY294002 group (LY294002-treated platelets stored at 4 ℃) and LY294002+APS group(LY294002+APS treated platelets stored at 4 ℃ ). The expression of platelet membrane glycoprotein CD41 and CD61, as well as the platelet apoptotic rate, Caspase 3 expression and mitochondrial membrane potential (MMP) were detected by flow cytometry; the anti-apoptotic mechanism of APS by PI3K /AKT signaling pathway was analyzed by Western blot assay.@*RESULTS@#The apoptosis rate of platelets in LY294002 group obviously increased, the activity of CD41 and CD61 expression gradually decreased along with the enhancement of LY294002 concentrations (r=-0.953)； compared with control group, the apoptosis rate of platelets in LY294002 group was enhanced significantly(P<0.05)，while the apoptosis rate of platelets in LY294002+APS group significantly was reduced(P<0.05) as compare with LY294002 group, which suggest that APS has an anti-apoptotic effect on the cryopreserved platelets. APS decreased the expression of Caspase-3 and inhibited the reduction of mitochondrial membrane potential induced by LY294002, moreover, APS could increase the activation of PI3K /AKT pathway in Plt.@*CONCLUSION@#APS has an anti-apoptotic effect on the cryopreserved platelets through activating the PI3K /AKT pathway, decreasing the expression of apoptosis protease Caspase-3 and inhibiting the reduction of MMP.

Spectrum-effect relationships on enriching blood activities of aerial parts of Angelica sinenis / 中国中药杂志

Ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to establish the chromatography fingerprint for aerial parts of Angelica sinenis(AAS) from 10 different places. Acetyl-phenyl-hydrazine(APH) was used to duplicate the mouse model of blood deficiency. Then partial least squares regression was used to investigate the spectrum-effect relationship between the relative contents and the data of enriching blood pharmacodynamics efficacy. The results showed that the three groups of high, medium and low doses of AAS had certain enriching blood activities(P<0.05), and the high dose group had the best effect(P<0.01). The contribution degree of the AAS to enriching blood activities of each common peaks were determined by PLS regression coefficient. Among them, 7 common peaks, including P17(unknown), P18(unknown), P19(unknown), P28(alisol B 23-acetate or its isomer), N5(luteolin), N11(1-caffeoylquinicacid,1-O-caffeoylquinic acid) and N14(unknown), contributed significantly to the effect of enriching blood activities. This paper dealed with the investigation on the spectrum-effect relationship between enriching blood activities and LC-MS chromatography fingerprint of AAS, and determination of the effective compositions of AAS with enriching blood activities. It provided theoretical foundation for the comprehensive development and utilization of AAS.

Photosynthetic physiological characteristics of Angelica dahurica var.formosana from Sichuan province in different growth years / 中国中药杂志

In this study,the leaves of autumn-sown Angelica dahurica var. formosana from Sichuan province in different growth years was used to explore the fitting model of photosynthetic response curve and the different photosynthetic physiological characteristics between annual and biennial A. dahurica var. formosana from Sichuan province. The results showed that the fitting model of the optimum light response curve of the leaves of A. dahurica var. formosana from Sichuan province with different growth years was all rectangular hyperbolic correction model. The light saturation points were 1 600,1 700 μmol·m-2·s-1,the light compensation points were17. 98,52. 23 μmol·m-2·s-1 in the leaves of annual and biennial plant,respectively. The diurnal variation curves of net photosynthetic rate,transpiration rate and stomatal conductance in the leaves all acted as a single peak value wave. The daily mean values of net photosynthetic rate and transpiration rate in the leaves of biennial plant were significantly higher than that of annual plant. There was no significant difference in daily mean stomatal conductance. The net photosynthetic rate was significantly positively correlated with stomatal conductance in both of the different growth years. The net photosynthetic rate of annual and biennial A. dahurica var. formosana from Sichuan province had extremely significant and significantly negative correlation with the intercellular CO2 respectively. The transpiration rate of annual plant was positively correlated with the effective photosynthetic radiation intensity and air temperature,but had significantly negative correlation with the intercellular CO2 concentration. The transpiration rate of biennial plant had extremely positive correlation with the effective photosynthetic radiation intensity,and negatively correlated with the intercellular CO2 concentration. In conclusion,the photosynthetic efficiency of the leaves in biennial plant of A. dahurica var. formosana from Sichuan province was higher than that in annual plant,but the ability to utilize weak light was lower than that of annual plant. It should be planted in the sunny field.

Pharmaceutical Studies on “Dang-Gui” in Korean Journals

A crude drug “Dang-Gui”, belonging to the genus Angelica, has been used as a traditional herbal medicine in Asia. Various studies have investigated the chemical components and pharmacological activities of Dang-Gui worldwide. However, domestic research results published in Korean are undervalued in international academia due to language barriers. Therefore, it is necessary to summarize the domestic research findings systematically for greater accessibility. This review focuses on the results published in four Korean pharmaceutical journals between 1970 and 2018, which detail the botanical, phytochemical, and pharmacological properties of three Angelica species (A. gigas, A. sinensis, and A. acutiloba) used as “Dang-Gui” in Korea, China, and Japan.

Decursinol Angelate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Modulating Type 17 Helper T Cell Responses

Angelica gigas has been used as a Korean traditional medicine for pain relief and gynecological health. Although the extracts are reported to have an anti-inflammatory property, the bioactive compounds of the herbal plant and the effect on T cell responses are unclear. In this study, we identified decursinol angelate (DA) as an immunomodulatory ingredient of A. gigas and demonstrated its suppressive effect on type 17 helper T (Th17) cell responses. Helper T cell culture experiments revealed that DA impeded the differentiation of Th17 cells and IL-17 production without affecting the survival and proliferation of CD4 T cells. By using a dextran sodium sulfate (DSS)-induced colitis model, we determined the therapeutic potential of DA for the treatment of ulcerative colitis. DA treatment attenuated the severity of colitis including a reduction in weight loss, colon shortening, and protection from colonic tissue damage induced by DSS administration. Intriguingly, Th17 cells concurrently with neutrophils in the colitis tissues were significantly decreased by the DA treatment. Overall, our experimental evidence reveals for the first time that DA is an anti-inflammatory compound to modulate inflammatory T cells, and suggests DA as a potential therapeutic agent to manage inflammatory conditions associated with Th17 cell responses.

Ethnobotany, Phytochemistry, and Pharmacology of Angelica decursiva Fr. et Sav

Angelica decursiva Fr. et Sav. (Umbelliferae) has traditionally been used to treat different diseases due to its antitussive, analgesic, and antipyretic activities. It is also a remedy for thick phlegm, asthma, and upper respiratory infections. Recently, the leaf of A. decursiva has been consumed as salad without showing any toxicity. This plant is a rich in different types of coumarin derivatives, including dihydroxanthyletin, psoralen, dihydropsoralen, hydroxycoumarin, and dihydropyran. Its crude extracts and pure constituents possess anti-inflammatory, anti-diabetic, anti-Alzheimer disease, anti-hypertension, anti-cancer, antioxidant, anthelmintic, preventing cerebral stroke, and neuroprotective activities. This valuable herb needs to be further studied and developed not only to treat these human diseases, but also to improve human health. This review provides an overview of current knowledge of A. decursiva metabolites and their biological activities to prioritize future studies.

Decursin induces apoptosis in glioblastoma cells, but not in glial cells via a mitochondria-related caspase pathway

Decursin is a major biological active component of Angelica gigas Nakai and is known to induce apoptosis of metastatic prostatic cancer cells. Recently, other reports have been commissioned to examine the anticancer activities of this plant. In this study, we evaluated the inhibitory activity and related mechanism of action of decursin against glioblastoma cell line. Decursin demonstrated cytotoxic effects on U87 and C6 glioma cells in a dose-dependent manner but not in primary glial cells. Additionally, decursin increased apoptotic bodies and phosphorylated JNK and p38 in U87 cells. Decursin also down-regulated Bcl-2 as well as cell cycle dependent proteins, CDK-4 and cyclin D1. Furthermore, decursin-induced apoptosis was dependent on the caspase activation in U87 cells. Taken together, our data provide the evidence that decursin induces apoptosis in glioblastoma cells, making it a potential candidate as a chemotherapeutic drug against brain tumor.

Angelica tenuissima Nakai Ameliorates Cognitive Impairment and Promotes Neurogenesis in Mouse Model of Alzheimer's Disease / 中国结合医学杂志

<p><b>OBJECTIVE</b>To research Angelica tenuissima Nakai (ATN) for use in novel Alzheimer's disease (AD) therapeutics.</p><p><b>METHODS</b>The effect of a 30% ethanol extract of ATN (KH032) on AD-like cognitive impairment and neuropathological and neuroinflammatory changes induced by bilateral intracerebroventricular injections of β-amyloid (Aβ) peptide (Aβ) was investigated. Male C57Bl/6 mice were randomly divided into 4 groups, 10 in each group. KH032-treated groups were administrated with a low or high dose of KH032 (50 and 200 mg/kg, respectively), intragastrically for 16 days; distilled water was applied in the sham and negative groups. Open fifield test, Y maze and Morris water maze test were used for behavior test and cognitive ability. In addition, the neuroprotective effects of KH032 in Aβ-infused mice on the histopathological markers [neuronspecific nuclear protein (NeuN), Aβ] of neurodegeneration were examined. The levels of glial fibrillary acidic protein (GFAP), NeuN, phosphorylation extracellular signal-regulated kinase (ERK)/ERK, brain-derived neurotrophic factor (BDNF), phosphorylation cAMP response element-binding (CREB)/CREB protein expression were measured by Western blot.</p><p><b>RESULTS</b>KH032 treatment ameliorated cognitive impairments, reduced the overexpression of Aβ, and inhibited neuronal loss and neuroinflammatory response in the Aβ-infused mice. Moreover, KH032 treatment enhanced BDNF expression levels in the hippocampus. Finally, KH032 treatment increased phosphorylation of ERK1/2 and CREB, vital for ERK-CREB signaling.</p><p><b>CONCLUSIONS</b>KH032 attenuated cognitive defificits in the Aβ-infused mice by increasing BDNF expression and ERK1/2 and CREB phosphorylation and inhibiting neuronal loss and neuroinflflammatory response, suggesting that KH032 has therapeutic potential in neurodegenerative disorders such as AD.</p>

Preclinical safety assessment of Angelica acutiloba using a 13-week repeated dose oral toxicity study in rats / 한국실험동물학회지

Angelica acutiloba (AA), a Japanese species of Danggui, has been used worldwide as a traditional herbal medicine with several bioactivities including anti-diabetic, anti-allergic, anti-inflammatory, anti-tumor, and anti-obesity. However, there is lack of toxicological data available to evaluate potential long-term toxicity and the no-observed-adverse-effect level (NOAEL) of AA extract in accordance with the test guidelines published by the Organization for Economic Cooperation and Development. In the 14-day repeat-dose toxicity study, no adverse effects on mortality, body weight change, clinical signs, and organ weights was found following repeat oral administration to rats for 14 days (125, 250, 500, 1000, and 2000 mg/kg body weight), leading that 2000 mg/kg is the highest recommended dose of AA extract for the 13-week repeat-dose oral toxicity study. In the 13-week repeat-dose oral toxicity study, the AA extract was orally administered to groups of rats for 13 weeks (125, 250, 500, 1000, and 2000 mg/kg body weight) to compare between control and AA extract groups. The administration of AA extract did not produce mortality or remarkable clinical signs during this 13-week study. And, the data revealed that there were no significant differences in food/water consumption, body weight, hematological parameters, clinical chemistry parameters, gross macroscopic findings, organ weight and histopathology in comparison to the control group. On the basis of these results, the subchronic NOAEL of the AA extract was more than 2000 mg/kg/day when tested in rats. And, the AA extract is considered safe to use orally as a traditional herbal medicine.

Evaluation of in vitro and in vivo genotoxicity of Angelica acutiloba in a standard battery of assays / 한국실험동물학회지

Among three representative species of Angelica found in Asian countries, including Korea, China, and Japan, Angelica acutiloba (AA) has been used as traditional herbal medicine with antitumor, anti-inflammatory, anti-obesity, and anti-diabetes activities. In this study, the potential genotoxicity and mutagenicity of the AA extract were examined in a battery of in vitro and in vivo tests (bacterial reverse mutation assay, in vitro chromosomal aberrations assay, and in vivo micronucleus assay) in accordance with the test guidelines for toxicity testing developed by the Organization for Economic Cooperation and Development. Upon testing in the bacterial mutation assay (Ames test) using five Salmonella typhimurium TA98, TA100, TA102, TA1535 and TA1537, no significant increase the number of revertant colonies in the metabolic activation system and non-activation system was noted in the AA extract groups. Also, in the chromosome aberration test, the AA extract did not cause chromosomal aberration with or without metabolic activation by S9 mix. A bone marrow micronucleus test of mice demonstrated that the incidence of micronucleated polychromatic erythrocytes in the AA extract groups (500, 1000 and 2000 mg/kg BW) was equivalent to that of the negative control group. Based on these results from a standard battery of assays, the AA extract was concluded to have no genotoxic at the proper dose.

Effects of Nodakenin, Columbianadin, and Umbelliferone Isolated from the Roots of Angelica decursiva on the Gene Expression and Production of MUC5AC Mucin from Human Airway Epithelial NCI-H292 Cells

Angelica decursiva has been utilised as remedy for controlling the airway inflammatory diseases in folk medicine. We investigated whether nodakenin, columbianadin, and umbelliferone isolated from the roots of Angelica decursiva inhibit the gene expression and production of MUC5AC mucin from human airway epithelial cells. Confluent NCI-H292 cells were pretreated with nodakenin, columbianadin or umbelliferone for 30 min and then stimulated with epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA) or tumor necrosis factor-α (TNF-α) for 24 h. The MUC5AC mucin gene expression was measured by reverse transcription - polymerase chain reaction (RT-PCR). Production of MUC5AC mucin protein was measured by enzyme-linked immunosorbent assay (ELISA). The results were as follows: (1) Nodakenin did not affect the expression of MUC5AC mucin gene induced by EGF, PMA or TNF-α. Columbianadin inhibited the expression of MUC5AC mucin gene induced by EGF or PMA. However, umbelliferone inhibited the expression of MUC5AC mucin gene induced by EGF, PMA or TNF-α; (2) Nodakenin also did not affect the production of MUC5AC mucin protein induced by EGF, PMA or TNF-α. Columbianadin inhibited the production of MUC5AC mucin protein induced by PMA. However, umbelliferone inhibited the production of MUC5AC mucin protein induced by EGF, PMA or TNF-α. These results suggest that, among the three compounds investigated, umbelliferone only inhibits the gene expression and production of MUC5AC mucin stimulated by various inducers, by directly acting on airway epithelial cells, and the results might explain the traditional use of Angelica decursiva as remedy for diverse inflammatory pulmonary diseases.