Two-Dimensional High-Performance Thin-Layer Chromatography with Bioautography for Distinguishing Angelicae Dahuricae Radix Varieties: Chemical Fingerprinting and Antioxidant Profiling.

Angelicae Dahuricae Radix (ADR) holds a prominent place in traditional medicine for its remarkable antioxidative, anti-allergic, and antiproliferative capabilities. Recognized within the Korean Pharmacopoeia (KP 12th), Angelica dahurica (Hoffm.) Benth. and Hook.f. ex Franch. and Sav. (AD) and Angelica dahurica var. formosana (H. Boissieu) Yen (ADF) serve as the botanical origins for ADR. Differentiating these two varieties is crucial for the formulation and quality control of botanical drugs, as they are categorized under the same medicinal label. This research utilized two-dimensional high-performance thin-layer chromatography (2D-HPTLC) to effectively distinguish AD from ADF. Additionally, a quantitative analysis reveals significant differences in the concentrations of key active constituents such as oxypeucedanin, imperatorin, and isoimperatorin, with AD showing higher total coumarin levels. We further enhanced our investigative depth by incorporating a DPPH bioautography, which confirmed known antioxidant coumarins and unearthed previously undetected antioxidant profiles, including byakangelicin, byakangelicol, falcarindiol in both AD and ADF, and notably, 2-linoleoyl glycerol detected only in AD as an antioxidant spot. This comprehensive approach affords a valuable tool set for botanical drug development, emphasizing the critical need for accurate source plant identification and differentiation in ensuring the efficacy and safety of herbal medicine products.

Excavation of Ancient Prescription of Chinese Medicinals for Whitening and Freckle-Removing(Erbai Yixin)Based on the Theory of"Lung Governs the Skin and Hair" / 中药新药与临床药理

Objective Based on the theory of"lung governs the skin and hair"in"Yellow Emperor's Inner Classic",this paper analyzes the medication rules of whitening and freckle-removing.The aim of this study is to provide reference for the clinical practice of traditional Chinese medicine(TCM)theory and the medication in TCM cosmetics.Methods"Chinese Medical Classics"was used to search the records of whitening and freckle-related drugs.The frequency,nature,flavor,meridian tropism and compatibility laws of TCM for whitening and freckle-removal were analyzed by statistics and association rules.The network pharmacology research was used to analyze the whitening and freckle-removing effects and mechanisms of high-frequency drugs.Then,the potential active ingredients were analyzed.The whitening and anti-freckle effect was verified through cytotoxicity experiments and melanin content detection.Results A total of 171 external prescriptions were selected in eligible articles,including 261 Chinese medicinals,most of which were pungent and belong to the lung meridian.The most frequently used Chinese medicinals was"Erbai Yixin"(EBYX,Angelicae Dahuricae Radix,Typhonii Rhizoma,Asari Radix et Rhizoma).Network pharmacological analysis showed that the core targets of EBYX for whitening and removing freckles are TP53,EGFR,ALB,etc.,which are mainly involved in oxygen perception and response,skin immune regulation,skin cell growth,differentiation,stress,inflammatory response,and other biological processes.Based on the results of molecular docking,biological analysis proved that the active ingredients of EBYX are chrysophanol,gallic acid and caffeic acid,which have inhibitory effects on the proliferation of melanoma cells and melanin production.Conclusion Most of the ancient prescriptions for whitening and removing freckles are pungent and belong to the lung meridian,which embodies the theory of"lung governs the skin and hair".The high-frequency drug EBYX may play a role by regulating skin redox,immunity and inflammation.The active ingredients of EBYX have an inhibitory effect on melanin formation.This study enriches the scientific connotation of TCM whitening and freckle-removing prescriptions based on the theory of"lung governs the skin and hair",realizes interdisciplinary integration and provides support for the modernization of TCM.

Effect of Chuanxiong Rhizoma on the absorption and clearance of four coumarins in Angelicae Dahuricae Radix / 药学学报

To study the changes in the pharmacokinetic behavior of four coumarins (bergapten, oxypeucedanin, imperatorin and isoimperatorin) in rats before and after combinating Angelicae Dahuricae Radix with Chuanxiong Rhizoma. The plasma concentrations of the drugs were determined by ultra performance liquid chromatography-fluorescence detection (UPLC-FLD) for dose response and time dependent curves. The pharmacokinetic parameters were calculated by DAS 3.2.8, and SPSS 20.0 was used to analyze the differences of main pharmacokinetic parameters between the two groups. The result showed: comparing with Angelicae Dahuricae Radix group, the area under drug time curve (AUC0-24 h) of bergapten, oxypeucedanin and imperatorin increased by 177.2%, 97.14% and 54.43% respectively, AUC0-∞ increased by 282.3%, 104.2%, and 75.40% respectively, and clearance rate (CLZ/F) decreased by 68.26%, 51.08% and 43.98% respectively; the peak drug concentration (Cmax) of four coumarins was significantly increased; the distribution volume (VZ/F) of bergapten was significantly decreased. These data indicated that Chuanxiong Rhizoma can promote the absorption of coumarins in Angelicae Dahuricae Radix, slow down the elimination of coumarins, and increase their bioavailability in vivo. The animal experiment scheme in this study has been approved by the Experimental Animal Ethics Committee of Beijing University of Chinese Medicine (approval number: BUCM-4-2020083105-3072).

Investigation and Suggestions on Factors Affecting Quality of Angelicae Dahuricae Radix (Baizhi) in Some Post-harvest Processes / 中国实验方剂学杂志

Objective:To investigate the factors affecting the quality of post-harvest Angelicae Dahuricae Radix （Baizhi） and to provide the corresponding suggestions according to these factors. Method:A series of factors affecting the quality of Baizhi were analyzed comprehensively by visiting several origins， medicinal material markets， pharmacies， supermarkets and storehouses combined with plenty of literature reports. Result:The rot of Baizhi was the most common phenomenon after harvest， and mildew， discoloration and moth could occur during the processes of processing， storage and packaging. So the quality of Baizhi should be controlled strictly through the whole process. The roots of Baizhi should be harvested on sunny days to avoid mining damage and dried as soon as possible to prevent rotting. The drying methods included both traditional lime burial and modern ways such as sulfur fumigation， saline dehydration， sun drying method， and oven drying method. However， the water content should be strictly controlled. Furthermore， the storehouses should be disinfected firstly. The temperature and humidity of the storehouses should be controlled strictly. Some suitable ways could be adopted to prevent moth and discoloration during storage， which included airtight fumigation of aluminum phosphide， cold storage， air conditioning maintenance， antagonism storage with other Chinese medicinal materials， dry ice storage at room temperature， etc. Large quantities of Baizhi were generally packaged in woven bags. Otherwise， kraft paper bags， polyvinyl chloride plastic bags， glass bottles， aluminum foil composite film bags， and other packaging materials had been adopted for the retail. However， the packaging specification should be selected according to the situation. Conclusion:The quality of Baizhi can be directly affected by harvesting， drying， processing， storage and packaging. Scientific and reasonable methods should be adopted to ensure the quality of Baizhi.

Analysis of nationwide random inspection results of Angelicae dahurica and establishment of a quantitative analysis method of multi-component with a single-maker / 中草药

Objective: To analyze the quality of Angelicae Dahuricae Radix (ADR) from national drug evaluation sampling, continuously improve and revise the standard determination method, and ensure the safety of public drug use, six index components of ADR medicinal material and decoction pieces were determined by combining HPLC fingerprint chromatography and quantitative analysis of multi-components by single marker (QAMS). Methods: The determination and exploratory study were carried out according to the National Standard. The establishment of steamed Angelicae dahurica HPLC fingerprint, method for multiple assessment of six index components to conduct a methodological survey determination of multi-index component content of 20 batches of Angelicae dahurica tablets, the final determination of the quality of Angelicae dahurica. Result:s A total of 239 batches of ADR were received from 189 enterprises, in which 225 batches were qualified and 14 batches were unqualified. The qualified rate was 94%. A method that determined content of six kinds of coumarin in ADR decoction pieces using imperatorin as control was established, which could solve the problem of difficulty in obtaining control and consuming long determination time. It would better indicate the drug quality. Conclusio:n The method we had established could be used in qualitative and quantitative analysis of oxypeucedanin hydrate, byakangelicin, oxypeucedanin, berapten, imperatorin and isoimperatorin in ADR decoction pieces. Through this random inspection, it is found that there were still some quality problems in ADR decoction pieces. The quality supervision of traditional Chinese medicine should be strengthened further.

Effects of three aqueous extraction preprocessing methods on total coumarins extract of Angelicae dahuricae Radix / 中成药

AIM To investigate the effects of aqueous extraction at normal temperature,40 ℃,and water boiling on total coumarins extract of Angelicae dahuricae Radix.METHODS For the extracts Ⅰ-Ⅳ obtained by ethanol reflux extraction and three aqueous extraction preprocessing methods,respectively,UV and HPLC were adopted in the content determination of total coumarins and imperatorin,then the powder properties and dissolution rates were compared.RESULTS The contents of total coumarins in four extracts were 3.98％,6.03％,6.81％ and 4.46％,while those of imperatorin were 0.633％,0.540％,0.465％ and 0.155％,respectively.The angles of repose were 48.455°,42.587°,42.689° and 42.024° with the bulk densities of 0.214,0.324,0.316 and 0.354 g/cm3,respectively.Within 100 min,extract Ⅰ demonstrated higher moisture adsorption rate and equilibrium moisture absorption content than the other three extracts.The accumulative dissolution rates of various extracts were much higher than that of medicinal material fine powder within 120 min.CONCLUSION All the three aqueous extraction preprocessing methods can obviously improve the powder properties of total coumarins extract of A.dahuricae Radix and increase the dissolution rate of medicinal material fine powder.

Preventive effects of total coumarin and essential oil of Angelicae Dahuricae Radix on migraine rats and their mechanisms / 吉林大学学报(医学版)

Objective: To observe the preventive effects of combined application of total coumarin and essential oil of Angelicae Dahuricae Radix on the migraine rats induced by nitroglycerin, and to explore their mechanisms. Methods: A total of 56 Wistar rats were randomly divided into normal control group (saline 0. 1 mL · 10 g 1), migraine model group (saline 0. 1 mL · 10 g 1), total coumarin of Angelicae Dahuricae Radix group (100 mg · kg-1), essential oil of Angelicae Dahuricae Radix group (100 mg · kg-1), and low dose (25 mg · kg-1), middle dose (50 mg · kg-1) and high dose (100 mg · kg-1) of total coumarin and essential oil composition of Angelicae Dahuricae Radix groups (composition groups) (n=8). After continuously intragastric adminstration for 7 d, the rats were injected subcutaneously with nitroglycerin (10 mg · kg-1) for establishing the migraine models. The behavior of the rats were observed, the levels of nitric oxide (NO) in serum and brain tissue of rats, the levels of calcitonin gene related peptide (CGRP) and endothelin (ET) in plasma of the rats in various groups were detected. Results: Compared with normal control group, the frequencies of head shaking, the face shoting times of posterior legs and the scratching times of anterior limbs of the rats in migraine model group were increased (P<0. 05 or P<0. 01), and the levels of NO in serum and brain tissue of the rats were increased (P< 0. 01). Compared with migraine model group, the frequencies of head shaking, the face shoting times of posterior legs and scratching times of anterior limbs of the rats in total coumarin group, essential oil group, and composition groups were decreased (P<0. 05 or P<0. 01), and the levels of NO in serum and brain tissue of the rats were decreased (P<0. 05 or P<0. 01). Compared with migraine model group, the levels of CGRP and ET in plasma of the rats in essential oil group, total coumarin group and middle and high doses of composition groups were decreased (P<0. 05). Conclusion: The composition of two active ingredients of Angelicae Dahuricae Radix, total coumarin and essential oil, has preventive effects in the migraine rats induced by nitroglycerin, and their mechanisms may be related to regulation of the levels and function of vasoactive substances.

Development and in vitro evaluation of reservoir-type patch of coumarins in Angelicae Dahuricae Radix / 中草药

Objective To prepare the reservoir patch of coumarins in Angelicae Dahuricae Radix and investigate its release and transdermal absorption characteristics in vitro. The efficient enhancers were chosen to improve the drug’s permeation rate. Methods The reservoir patch was prepared using hydroxypropyl methylcellulose (HPMC) as medium and ethylene vinyl acetate (EVA) membrane to control the release of drug. The Franz diffusion cells were used and HPLC was used to determine imperatorin content and permeation rate. The content of imperatorin was determined by HPMC. The effect of the gel consumption, the content of coumarins and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model. The release of the selected patch in vitro was investigated. Results 1% HPMC, 1% coumarins in Angelicae Dahuricae Radix, 1% Isopropyl Myristate (IPM) and 3% Azone were the best permeation of the patch. The permeation rate reached 0.713 μg/(cm2•h). The release mechanisms of the patch in vitro coincided with zero-order kinetic. Conclusion The reservoir patch of coumarins in Angelicae Dahuricae Radix had high transdermal rate and complete in vitro release. It was indicated that the patch could be expected to be an effective transdermal drug delivery system.

Study on brain tissue distribution of compatibility of Yuanhu Zhitong Prescription in rat based on Q-marker / 中草药

Objective To investigate the effect of compatibility on brain tissue distribution in rat of corydaline, tetrahydropalmatine, protopine, imperatorin and isoimperatorin in Corydalis Rhizoma and Angelicae Dahuricae Radix, and to provide further experimental evidence for confirming the Q-marker of Yuanhu Zhitong Prescription. Methods After oral administration of Corydalis Rhizoma, Angelicae Dahuricae Radix, and Yuanhu Zhitong Prescription extracts respectively, the concentration of five compounds in brain tissue samples at different time points was determined by UPLC-MS/MS, and the effect of compatibility on brain tissue distribution was further evaluated by kinetic parameters. Results Compared with single-herb group, AUC and Cmax of corydaline, tetrahydropalmatine and protopine in Yuanhu Zhitong Prescription group were increased significantly, and MRT of imperatorin and isoimperatorin were prolonged at the same time. Conclusion Corydalis Rhizoma and Angelicae Dahuricae Radix exist synergistic effect, the compatibility of these two herbs promote brain tissue distribution of corydaline, tetrahydropalmatine, protopine, imperatorin and isoimperatorin, which can be used as Q-marker of Yuanhu Zhitong Prescription.

Chemical Composition and Antimigraine Activity of Essential Oil of Angelicae dahuricae Radix.

The aim of this study was to explore the chemical composition and the effect of essential oil of Angelicae dahuricae radix on a nitroglycerin (NTG)-induced rat model of migraine. The CO2 supercritical fluid extraction method was optimized for the extraction of essential oil of A. dahuricae radix (EOAD) and its chemical composition was determined. The migraine model was established by subcutaneous injection of NTG (10 mg/kg) 1 h after the last administration of EOAD. The therapeutic effect of EOAD and its underlying mechanism were assessed by monitoring behavioral changes, levels of nitric oxide (NO) in serum and brain tissues, plasma levels of calcitonin gene-related peptide (CGRP) and endothelin (ET), and ET/NO ratio. The optimal conditions for CO2 supercritical fluid extraction of EOAD, as determined by orthogonal test [L9(34)], were as follows: 2 h extraction time, 20 MPa pressure, 40°C temperature, and 30 mesh. The yield of EOAD was 1.8%. On gas chromatography-mass spectrometry, 45 peaks were found in EOAD, and 22 compounds were identified and quantified. The main constituents of EOAD were 1-dodecanol (13.71%), elemene (7.54%), palmitic acid ethyl ester (7.32%), α-pinene (6.25%), and 1-pentadecanol (6.08%). Compared with rat migraine model controls, EOAD (35, 70, and 140 mg/kg) significantly reduced the number of head shaking, head scratching, and hind leg shooting events, decreased serum and brain NO levels, decreased plasma CGRP, and increased ET levels in rats. ET/NO ratio was elevated to 28.68 in the EOAD high-dose group. EOAD ameliorates NTG-induced migraine in rats likely by modulating the levels of vasoactive substances.

Purification, characterization and procoagulant activity of polysaccharides from Angelica dahurice roots.

Five polysaccharides, namely ADPs-1a, ADPs-1b, ADPs-2, ADPs-3a and ADPs-3b, were extracted from Angelicae dahuricae Radix, purified, and identified by high performance gel permeation chromatography (HPSEC), gas chromatography (GC), Fourier transform infrared (FT-IR) spectrometer and nuclear magnetic resonance spectra (NMR), including the determination of procoagulant activity in vitro. The average molecular weight (Mw) of the polysaccharides was 153,800, 8312, 111,700, 3766 and 96,680 g/mol, respectively. Coagulation assays indicated that ADPs-1b, ADPs-2, ADPs-3a and ADPs-3b had procoagulant activities. ADPs-1b exerted the procoagulant activities through intrinsic pathway, extrinsic pathway and increased the content of FIB in vitro. ADPs-2 exerted the procoagulant activities through intrinsic pathway and extrinsic pathway. ADPs-3a had procoagulant activities and the activity was associated with the intrinsic pathway and increased the content of FIB. ADPs-3b exerted the activities through extrinsic pathway and increased the content of FIB.

Effects of Angelicae dahuricae Radix on 2, 4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions in mice model.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory, chronically relapsing, and intensively pruritic skin disease that affect 10-30% of the global population. Angelicae dahuricae Radix (ADR) has been reported to be anti-inflammatory in Korean Medicine. In the present study, we investigated whether ADR suppresses the progression of AD in animal model. METHODS: AD was induced by 2, 4-Dinitrochlorobenzene (DNCB). ADR was orally administered to mice to study the effect of ADR on AD. Histological Analysis, immunohistochemistry, blood analysis, RT-PCR, and ELISA assay were performed. RESULTS: ADR significantly suppressed AD-like symptoms in BALB/c mice: ADR decreased skin thickness and spleen weight of mice. ADR reduced infiltration of mast cells, inflammatory cells and CD4+ cells into mouse skin. ADR lowered the number of WBCs in the blood of mice. ADR reduced the levels of IgE, IL-6, IL-10 and IL-12 in mice serum. ADR down-regulated mRNA expression of IL-4, IL-6 and TNF-α in mouse skin tissue. CONCLUSION: Our present study clearly indicates that ADR suppresses the progression of AD induced by DNCB in BALB/c mice. This suggests that ADR might be a useful drug for the treatment of AD.

Simultaneous Quantification of Nine New Furanocoumarins in Angelicae Dahuricae Radix Using Ultra-Fast Liquid Chromatography with Tandem Mass Spectrometry.

A series of new furanocoumarins with long-chain hydrophobic groups, namely andafocoumarins A-H and J, have been isolated from the dried roots of Angelica dahurica cv. Hangbaizhi (Angelicae Dahuricae radix) in our previous study, among which andafocoumarins A and B were demonstrated to have better anti-inflammatory activity than the positive controls. In this work, a sensitive, accurate, and efficient ultra-fast liquid chromatography coupled with triple quadrupole mass spectrometer (UFLC-MS/MS) method was developed and validated for simultaneous quantification of above-mentioned nine compounds in four cultivars of Angelicae Dahuricae Radix. Chromatographic separation was performed on a Kinetex 2.6u C18 100 Å column (100 × 2.1 mm, 2.6 µm). The mobile phases were comprised of acetonitrile and water with a flow rate of 0.5 mL/min. Using the established method, all components could be easily separated within 12 min. With the multiple reaction monitor mode, all components were detected in positive electrospray ionization. The method was validated with injection precision, linearity, lower limit of detection, lower limit of quantification, precision, recovery, and stability, respectively. The final results demonstrated that the method was accurate and efficient, which could be used to simultaneously quantify the nine andafocoumarins in Angelicae Dahuricae Radix. The results also indicated that in different batches of Angelicae Dahuricae Radix, some of the andafocoumarins were significantly different in terms of content.

Fingerprint and multi-components content simultaneous determination for Liujing Toutong Tablets by HPLC / 中草药

Objective To establish the HPLC fingerprint of Liujing Toutong Tablets (LTT) and multi-wavelength method for determination of the contents of 3’-hydroxy puerarin, puerarin, daidzin, nuezhenide, and daidzein, so as to provide a reference for the quality control. Methods Using the method of HPLC, the fingerprint chromatography of high polarity and low polarity were established, with a mobile phase of acetonitrile-0.1% phosphoric acid and Diamonsil C18 column (250 mm × 4.6 mm, 5 μm). Furtherly, the Diamonsil C18 column was used with a mobile phase of acetonitrile-0.1% acetic acid gradient elution to determine the five contents. Results The fingerprint chromatography of high and low polarities with 11 batches of LTT were established, and the similarities of 11 batches were all over 0.90. The low polarity fingerprint chromatography included 16 mutual peaks, 12 of which belonged to herbs: No. 11, 12, 13 belonged to Angelicae Dahuricae Radix, No. 1, 2, 3, 7 belonged to Puerariae Lobatae Radix, No. 8 belonged to Ligustri Lucidi Fructus, No. 5, 6 belonged to Chuanxiong Rhizoma, No. 15 belonged to Ligustici Rhizoma et Radix and No. 4 belonged to Chuanxiong Rhizoma and Ligustici Rhizoma et Radix. Seven peaks including puerarin (No. 1), 3’-methoxy puerarin (No. 2), daidzin (No. 3), ferulic acid (No. 4), daidzein (No. 7), imperatorin (No. 11), and isoimperatorin (No. 13) were verified by standard compounds. The high polarity fingerprint chromatography included 10 mutual peaks, among them No. 2-9 belonged to Puerariae Lobatae Radix, No. 1, 10 belonged to Ligustri Lucidi Fructus. Five peaks including 3’-hydoxypuerarin (No. 2), puerarin (No. 3), 3’-methoxypuerarin (No. 4), daidzin (No. 7) and specnuezhenide (No. 10) were verified by standard compounds. The five active components were well separated and showed good lineaeity, such as 3’-hydroxy puerarin 71.60-716.00 ng (r = 0.999 1), puerarin 407.78-4 077.80 ng (r = 0.999 4), daidzin 90.72-907.20 ng (r = 0.999 9), nuezhenide 95.80-958.00 ng (r = 0.999 1), daidzein 21.98-219.80 ng (r = 0.999 9). The average recoveries and corresponding RSD values were 101.1% (1.38%), 97.8% (0.72%), 99.1% (0.75%), 97.8% (2.75%), and 98.7% (0.70%). The contents of 3’-hydoxypuerarin, puerarin, daidzin, specnuezhenide and daidzein in the 10 batches of sample were 3.08-3.84 mg/mL, 17.71-21.24 mg/mL, 3.51-4.71 mg/mL, 1.40-5.69 mg/mL, and 0.66-0.86 mg/mL, respectively. Conclusion The HPLC fingerprint combined with multi index determination method can reflect the intrinsic quality of LTT, which is stability, accurate, and reproducible, providing a scientific reference for quality control.

Study on compatibility rationality of Yuanhu Zhitong Dropping Pills for treatment of primary dysmenorrhea based on network pharmacology / 中草药

Objective: To explore the compatibility rationality of Yuanhu Zhitong Dropping Pills (YZDP) for the treatment of primary dysmenorrhea. Methods: The potential targets and pathways of tetrahydropalmatine, palmatine, glaucine, protopine, imperatorin, and isoimperatorin, selected as the representative compounds of alkaloid and coumarin from Corydalis Rhizoma and Angelicae Dahuricae Radix, were predicted by the methods of network pharmacology. The results were verified by docking and the mechanism and compatibility regularity of YZDP were analyzed by integrating all the data. Results: The in silico prediction results showed that the six compounds of YZDP affected 19 related pathways through 23 target proteins. The pathways were involved in central analgesia, hormonal regulation, spasmolysis, vasodilatation, inflammation, and immunoregulation. The alkaloid and coumarin showed common targets and pathways but also had their own emphasis. The pathways were connected by the common targets, showing the synergistic effect of different compounds by acting on multi-targets and multi-pathways. Conclusion: Corydalis Rhizoma acts as monarch drug, showing the effect of analgesia, regulating qi, and activating blood by acting on thromboxane receptors, angiotensin receptors, and targets related with central analgesia and spasmolysis. Angelicae Dahuricae Radix, showing the effect of regulating qi, and activating blood by regulating the pathways of spasm, inflammation, and so on, acts as ministerial drug to assist monarch drug to enhance treatment which reflected the compatibility rationality of Corydalis Rhizoma and Angelicae dahuricae Radix.

Simultaneous determination and pharmacokinetics of sixteen Angelicae dahurica coumarins in vivo by LC-ESI-MS/MS following oral delivery in rats.

BACKGROUND: The roots of Angelica dahurica cv. Qibaizhi is frequently used in clinical practice as a traditional Chinese medicine. However, a comprehensive study of the pharmacokinetics of this medicine has not been carried out. METHOD: A sensitive and specific liquid chromatographic-tandem mass (LC-MS/MS) spectrometric method was established to investigate pharmacokinetics of sixteen coumarins of Angelicae dahuricae Radix (ADR) in rat plasma, including xanthotoxol (1), oxypeucedanin hydrate (2), 5-hydroxy-8-methoxypsoralen (3), (-)-marmesin (4), byakangelicin (5), columbianetin (6), psoralen (7), xanthotoxin (8), neobyakangelicol (9), isoimpinellin (10), bergapten (11), heraclenin (12), oxypeucedanin ethanolate (13), imperatorin (14), phellopterin (15), isoimperatorin (16). Detection was performed on a triple quadrupole mass spectrometer in multiple-reaction-mode (MRM). RESULTS: The method established in this assay was successfully applied to the pharmacokinetic study of the selected coumarins in rat plasma after oral administration of the extract of ADR, and the pharmacokinetic characteristics of sixteen coumarins were clearly elucidated. CONCLUSION: This pharmacokinetic identification of multiple coumarins of ADR in rats provides a significant basis for better understanding the metabolic mechanism of the herb medicine.

[Determination of four coumarin constituents before and after Angelicae Dahuricae Radix stewed with yellow rice wine and research on its mutual transformation mechanism].

To determine the contents of oxypeucedanin, oxypeucedanin hydrate, byakangelicol and byak-angelicin both before and after Angelicae Dahuricae Radix was stewed with yellow rice wine by high-performance liquid chromatography, and study the mutual transformation mechanisms of oxypeucedanin into oxypeucedanin hydrate, as well as byakangelicol into byak-angelicin. The research results indicated that the contents of oxypeucedanin and byakangelicol were decreased, but the contents of oxypeucedanin hydrate and byak-angelicin were increased after Angelicae Dahuricae Radix was processed with yellow rice wine. The contents' changes of these chemical compounds were due to the ring opening reaction of epoxy compounds, such as oxypeucedanin and byakangelicol under the weak acidity and heating conditions of yellow rice wine. This research could provide a scientific basis for the processing mechanism of Angelicae Dahuricae Radix with yellow rice wine stewing.

Determination of four coumarin constituents before and after Angelicae Dahuricae Radix stewed with yellow rice wine and research on its mutual transformation mechanism / 中国中药杂志

To determine the contents of oxypeucedanin, oxypeucedanin hydrate, byakangelicol and byak-angelicin both before and after Angelicae Dahuricae Radix was stewed with yellow rice wine by high-performance liquid chromatography, and study the mutual transformation mechanisms of oxypeucedanin into oxypeucedanin hydrate, as well as byakangelicol into byak-angelicin. The research results indicated that the contents of oxypeucedanin and byakangelicol were decreased, but the contents of oxypeucedanin hydrate and byak-angelicin were increased after Angelicae Dahuricae Radix was processed with yellow rice wine. The contents' changes of these chemical compounds were due to the ring opening reaction of epoxy compounds, such as oxypeucedanin and byakangelicol under the weak acidity and heating conditions of yellow rice wine. This research could provide a scientific basis for the processing mechanism of Angelicae Dahuricae Radix with yellow rice wine stewing.

Correlation study on HPLC characteristic spectrum of raw herb-decoction pieces-extract-dispensing granules of Angelicae Dahuricae Radix / 中草药

Objective: To establish an HPLC characteristic spectrum of raw herbs-decoction pieces-extract-dispensing granules of Angelicae Dahuricae Radix (ADR) and evaluate the correlation among them. Methods: Gradient elution was performed with mobile phase of acetonitrile-water, detection wavelength of 320 nm, flow rate of 1.0 mL/min, and column temperature of 25℃, by setting the characteristic spectrum as control and evaluating the correlation of raw herbs-decoction pieces-extract-dispensing granules. Results: There were 10 common characteristic peaks in all characteristic spectra of 10 batches of raw herbs, decoction pieces, extract, and dispensing granules of ADR, presenting a good correlation. Conclusion: This study established an HPLC characteristic spectrum and reflected the whole picture of multi-component of raw herbs, decoction pieces, extract, and dispensing granules of ADR provides the reference for quality control of dispensing granules of ADR.

In vitro study on affinity of coumarins in Angelicae Dahuricae Radix and P-gp / 中草药

Objective: To study the effects of coumarins in Angelicae Dahuricae Radix (imperatorin, isoimperatorin, bergapten, and oxypeucedanin) on the activities of adenosine triphosphate (ATPase) in P-glycoprotein (P-gp) in vitro and to investigate the P-gp mediated meschanism in transport of drug. Methods: The ATPase activity assay was used to identify whether the coumarins in Angelicae Dahuricae Radix were P-gp substrates or not. Results: The average fluorescent values (ΔRLUTC) of imperation and oxypeucedanin at each concentration were greater than average basic fluorescence value (ΔRLUbasal). The average fluorescent values (ΔRLUTC) in medium and low concentration of isoimperatorin and bergapten groups were lower than average basic fluorescence value (ΔRLUbasal). Conclusion: Imperation and oxypeucedanun are non-concentration dependent P-gp ATP inhibitors. Isoimperatorin and bergamot lactones could inhibit the ATPase activity at low concentration and have the inhibitory effect on P-gp. At high concentration, the activity of ATPase can be induced so as to induce P-gp.