Angelica Dahurica Research Articles

An Exploration in the potential substance basis and mechanism of Chuanxiong Rhizoma and Angelicae Dahuricae Radix on analgesia based on network pharmacology and molecular docking

Objective: The objective was to study the potential substance basis and action mechanism of Chuanxiong Rhizoma (CX) and Angelicae Dahuricae Radix (AD) on analgesia through network pharmacology and molecular docking. Materials and Methods: The active components and targets of CX and AD and pain-related genes were retrieved through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and GeneCards database. Then, the co-action targets were found, protein–protein interaction network was constructed by the String database. The Cytoscape 3.7.1 was used to construct “CX-AD-active components-pain” network. Further enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was carried out to predict its mechanism of action, the top four active components in the network were docked with the targets. Results: There are 26 compounds, 45 targets in the network. Among them, (Z)-ligustilide and beta-sitosterol, respectively, have more potential targets in CX and AD, and prostaglandin-endoperoxide synthase (PTGS2), PTGS1 have more ligands. GO analysis shows that molecular functions of CX and AD mainly performed through the G protein-coupled amine receptor activity, adrenergic receptor activity, and catecholamine binding. KEGG analysis indicates that they could exert analgesic effect on the pathways of regulating neuroactive ligand-receptor interaction, serotonergic synapse, and cGMP-PKG signaling pathway. Molecular docking results show that the active compounds are highly compatible with the structure of the protein receptor, and they interact through the hydrogen bond and π–π bond between the ligand and the active site residues. Conclusions: Through network pharmacology and molecular docking, this study preliminarily revealed the main active components, targets, and potential regulation network of CX and AD, providing a reference for the subsequent experimental research.

Angelica dahurica and Rheum officinale Facilitated Diabetic Wound Healing by Elevating Vascular Endothelial Growth Factor.

Traditional Chinese medicine (TCM) provides alternative treatment choices for diabetic wounds. The aim of this study was to evaluate the effects of Angelica dahurica and Rheum officinale (ARE) on diabetic wounds and its underlying action mechanism. Atotal of 36 healthy male Sprague-Dawley rats were randomly divided into three groups: diabetes mellitus (DM) rats treated with ARE (DM-ARE), DM rats treated with 0.9% saline (DM-NS), and non-DM rats treated with 0.9% saline (NDM-NS). DM was induced by intraperitoneal administration of 40 mg/kg of streptozotocin after a 2-week high-fat diet feeding. After excisional skin wounds and treatments, the remaining wound area (RWA) in each group was measured. The RWA in the DM-NS group (69.60% ± 2.35%) was greater than that in the DM-ARE (55.70% ± 1.85%) and NDM-NS groups (52.50% ± 2.77%) on day 6. Besides, the DM-ARE group showed higher vascular endothelial growth factor (VEGF), higher inducible nitric oxide synthase (iNOs), higher [Formula: see text]-smooth muscle actin ([Formula: see text]-SMA), and lower nuclear factor kappa-light-chain-enhancer of activated B cell (NF-[Formula: see text]B) expression in the wound skin tissue. These results showed that treatment with ARE shifted the recovery pattern of diabetic rats to the pattern of nondiabetic rats, indicating that ARE may improve wound healing in diabetic conditions.

Imperatorin ameliorates mast cell-mediated allergic airway inflammation by inhibiting MRGPRX2 and CamKII/ERK signaling pathway

BackgroundAllergic asthma is a common inflammatory lung disease associated with complex pathogenesis. Mast cell (MC) is one of the key drivers of allergic asthma, Mas-related G protein-coupled receptor X2 (MRGPRX2) on the MC could mediate MC activation and trigger a pseudo-allergic reaction. Imperatorin (IMP), the main active compound of Radix Angelicae Dahuricae, has been reported to exert various pharmacological effects. In this study, we focused on the therapeutical mechanism of IMP on MRGPRX2-induced pseudo-allergy and allergic asthma. MethodsWe examined the effect of IMP on MRGPRX2 related mast cell activation in mouse peritoneal MC (MPMC), Human Laboratory of Allergic Disease 2 MCs (LAD2 cells) and Mrgprx2-expressing HEK293 cells. Molecular docking and Surface plasmon resonance (SPR) were taken to reveal the binding character between IMP and MRPGRX2. MRGPRX2 downstream proteins were also detected by western blotting. IgE-independent responses was evaluated by using passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) models. The therapeutic effect of IMP on asthma was evaluated by a lung inflammation mouse model which was induced by ovalbumin (OVA). ResultsIMP was found to reduce substance P (SP) induced calcium flux and suppressed degranulation of MC. SP can promote the phosphorylation of ERK and CamKII, which regulates the synthesis of inflammatory factors such as MIP-2 and TNF-α in MC. In vivo assays revealed that IMP can mitigate SP-induced mouse PCA and ASA. IMP could also mitigate lung inflammation in an OVA induced mice model by inhibiting MC activation in the lung tissue. Furthermore, IMP binds well to MRGPRX2 protein. The binding constant (KD) is 4.48 ± 0.49 × 10−7 M. The data suggeste that IMP is a novel inhibitor of MRGPRX2 to treat allergic asthma.

Phytochemical components and biological activities of essential oils from three selected medicinal plants

Essential oils extracted from herbs have been utilized in food and medicine on the account of their increasing physicochemical characteristics. This present study aimed to investigate the phytochemical components, anti-inflammatory, cytotoxic, anti-microbial and anti-oxidant activities of essential oils from Pogostemon cablin (P. cablin), Angelica dahurica (A. dahurica) and Myristica fragrans (M. fragrans), all belong to “medicine food homology” herbs. Approximately 107 components were identified by gas chromatography mass spectrometry (GC–MS) from these essential oils. The main compounds of P. cablin essential oils (PCEOs) were patchouli alcohol (27.72%), α-buaiacene (17.94%) and α-guaiene (14.15%); in A. dahurica essential oils (ADEOs) were anethole (24.91%) and cinnamaldehyde (18.35%); and in M. fragrans essential oils (MFEOs) were (1S)-(-)-α-pinene (23.39%), α-terpineol (18.60%) and caryophyllene (10.34%). These essential oils were found to have strong anti-inflammatory activities through decreasing the production of cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), nuclear factor-kappa B p65 (P65) and tumor necrosis factor-α (TNF-α). These essential oils also had significant anti-bacterial activities against both Gram-negative and Gram-positive strains and anti-fungal activities. Moreover, effective anti-oxidant properties of three essential oils were estimated (0.001962%-0.19%). The study also explored the effect of these essential oils on the survival of Brain microglia (BV2) microglial cells (IC50 = 145.50–281.52 μg/mL). Based on these bioactivities, these essential oils could be used as food additives, fragrances, cosmetics and health products.

Selection principles and analysis of common prescriptions in clinical practice guidelines of traditional Chinese medicine--case example of migraine

In this study, common prescriptions were retrieved from existing data in multiple ways to determine the selection principle of common formulas in traditional Chinese medicine(TCM) clinical practice guidelines. Taking the selection of common prescriptions in the clinical practice guidelines of TCM for migraine as an example, we searched common prescriptions for migraines from National Essential Medicine List, the National Drug Catalog for Basic Medical Insurance, Work-related Injury Insurance, and Maternity Insurance, Chinese Pharmacopoeia, three teaching materials and two clinical practice guidelines, and we also electronically searched CNKI, VIP, WanFang about famous clinical experience for migraine published from 1990 to 2019. At the same time, 32 prescriptions commonly used by experts in the clinical questionnaire survey were collected to summarize and analyze the TCM clinically applicable syndrome types and medication rules of the included prescriptions and medicines. From the National Essential Medicine List, the National Drug Catalog for Basic Medical Insurance, Work-related Injury Insurance, and Maternity Insurance, Chinese Pharmacopoeia, we got 12 Chinese patent medicines. From the teaching materials, we got 9 prescriptions. From the clinical practice guidelines, we got 8 prescriptions. We got 3 prescriptions from the experience of famous experts and got 4 prescriptions from experts in the clinical questionnaire survey. A total of 24 prescriptions were included from the above results. External wind syndrome, syndrome of blood stasis and brain blocking, and syndrome of liver Yang transforming into wind were the common syndrome types in the treatment of migraine. Chuanxiong Rhizoma and Angelicae Dahuricae Radix were the most common Chinese herbs in the prescriptions. Chuanxiong Rhizoma-Angelicae Dahuricae Radix was the most common drug pair for the treatment of migraine. By retrieving the data such as the famous clinical experience and teaching materials, we systematically summarized the prescriptions in the treatment of migraine in this study, which can provide a basis for the selection of traditional Chinese medicines in clinical practice guidelines.

Observation of the therapeutic effect and prognosis analysis of Yiqijiebiao prescription for the treatment of children with influenza B

To observe the efficacy of Yiqijiebiao prescription in treating children with influenza B infection (flu). A total of 120 children with influenza B infection who were treated at the Traditional Chinese Medicine (TCM) Clinic of Tianjin Children's Hospital from October to December 2019 were enrolled. According to different treatments, the children were divided into Yiqijiebiao prescription treatment group and Western medicine treatment control group, with 60 cases in each group. Yiqijiebiao prescription treatment group was orally given Yiqijiebiao prescription plus and minus treatment (composition: perilla leaf, kudzu root, Bupleurum, Qing Pinellia, Scutellaria baicalensis Georgi each 6 g, tangerine peel, nepeta panicle, Divaricate Saposhniovia root, praecupura, almond, ginseng, platycodon, roasted licorice each 4 g, add plaster and cooked rhubarb for dry stools, add pre-bait, honey loquat leaves for severe cough, add Angelica dahurica and flos magnoliae for runny nose), take 1 dose a day, twice a day; Western medicine treatment control group was orally given Ribavirin, 10 mg/kg each time, 3 times a day. After 7 days of treatment, the changes in clinical symptoms, laboratory results and clinical efficacy of the two groups were observed, and the changes in prognostic indexes of the two groups were analyzed. The numbers of children with normal body temperature and improved or partially improved symptoms such as cough, sore throat, and runny nose in the Yiqijiebiao prescription treatment group were significantly higher than those in the control group (normal body temperature: 49 cases vs. 44 cases, cough relieved: 33 cases vs. 25 cases, sore throat relieved: 27 cases vs. 23 cases, runny nose relieved: 47 cases vs. 42 cases, all P < 0.05). The numbers of children whose nasopharyngeal swabs with influenza B virus antibody (IBV-Ag) turned negative and serum amyloid A (SAA) and C-reactive protein (CRP) in the normal reference value range (< 10 mg/L) were significantly higher than those in Western medicine treatment control group (IBV-Ag negative: 36 cases vs. 31 cases, SAA in the normal reference value range: 49 cases vs. 46 cases, CRP in the normal reference value range: 50 cases vs. 46 cases, all P < 0.05). The total effective rate of Yiqijiebiao prescription treatment group after treatment was significantly higher than that of control group [81.67% (49/60) vs. 75.00% (45/60), P < 0.05]. The numbers of children with constipation, loss of appetite and diarrhea in the Yiqijiebiao prescription treatment group were significantly less than those in the control group (constipation: 11 cases vs. 14 cases, loss of appetite: 8 cases vs. 11 cases, diarrhea: 6 cases vs. 8 cases, all P < 0.05). Yiqijiebiao prescription can significantly improve the clinical symptoms and laboratory results of children with influenza B infection and increase the total effective rate, and have a definite effect.

Wound healing at the body wall of the sea cucumber Apostichopus japonicus by Chinese herbal treatment

The leading cause of death for sea cucumbers in aquaculture is damage to the body wall. Large-scale use of antibiotics to treat such wounds is undesirable because this treatment leaves a drug residue in the animal's body as well as posing increased pathogen resistance in the environment. In this study, both naturally and artificially occurring wound sea cucumber were used as the experimental animals. Compound Chinese herbal medicines were then selected and evaluated for wound healing effects. The results showed that Chinese herbal medicine mixtures I (Angelica dahurica, Geosaurus, Rhus chinensis and Dark plum fruit), II (Angelica dahurica, Geosaurus and Taraxacum mongolicum Hand) and III (Angelica dahurica, Geosaurus, Taraxacum mongolicum Hand, Rhus chinensis and Dark plum fruit) significantly improved wound healing of artificially injured sea cucumbers. After 1 week of treatment, histological analysis showed that the epidermal layer was completely restored, indistinguishable from the control. Cyclin B, Protease inhibitor Epi11 and PCSK9 expression in immune coelomocytes showed a tendency to increase at first and then decrease at different time points of herbal treatment. Results of companion treatment trials for naturally wounded sea cucumbers showed that after 1 week in the treatment group, the skin ulcer areas of sea cucumbers were reduced, and the survival rate was significantly improved. The results of this study provide a scientific basis for the treatment and prevention of sea cucumber skin ulcerations and body wall damage. This treatment may provide an important natural healing modality for sea cucumbers in an aquaculture system.

Angelica dahurica promoted angiogenesis and accelerated wound healing in db/db mice via the HIF-1α/PDGF-β signaling pathway

Impaired angiogenesis is crucial for impeding the wound healing process in diabetic foot ulcers (DFUs). In this study, we found that Angelica dahurica (A. dahurica) stimulated angiogenesis and benefited wound healing in genetic mouse models of diabetes. In HUVECs, A. dahurica promoted cell proliferation and tube formation, which was accompanied by increased nuclear translocation of HIF-1α under hypoxic conditions and led to elevated PDGF-β protein expression. A. dahurica activated the PI3K/AKT signaling pathway in human umbilical vein endothelial cells (HUVECs), which was abrogated by the PI3K inhibitor LY294002. Furthermore, the cellular expression of PDGF-β decreased significantly after treatment with a HIF-1α-siRNA, and PDGF-β expression was increased in HIF-1α-overexpressing cells. In a full-thickness cutaneous wound healing db/db mouse model, A. dahurica accelerated wound closure, which was reflected by a significantly reduced wound area and an increase in neovascularization, as well as by elevated PDGF-β expression and increased capillary formation. In addition, A. dahurica activated the PI3K/AKT signaling pathway and enhanced HIF-1α synthesis in wounds. In summary, A. dahurica promoted angiogenesis of HUVECs in vitro by promoting signaling via the HIF-1α/PDGF-β pathway, efficiently enhancing vascularization in regenerated tissue and facilitating wound healing in vivo. The results revealed that A. dahurica has potential as a therapy for vessel injury-related wounds.

日本薬局方に見られた向精神・神経薬の変遷(その 21)ヨーロッパ薬局方(EP4.0(2002)~EP9.0(2017))および英国薬局方(BP2002~BP2018)におけるアンゲリカ根,白芷,唐独活,唐当帰の規格・試験法の変遷,ならびに対比について

日本薬局方に見られた向精神・神経薬の変遷(その 21)ヨーロッパ薬局方(EP4.0(2002)~EP9.0(2017))および英国薬局方(BP2002~BP2018)におけるアンゲリカ根,白芷,唐独活,唐当帰の規格・試験法の変遷,ならびに対比について

Simultaneous analysis of ten components in patch preparation of Wan-Yin-Gau by high performance liquid chromatography

A facile HPLC method for the reduction and quantitative measurement of ten marker substances, the active ingredients in formula preparation of Wan-Yin-Gau, was established under the gradient elution in the reversed-phase mode. These marker substances included cinnamic acid, cinnamaldehyde (Cinnamomi Cortex), isoimperatorin (Angelicae Dahuricae Radix and Notopterygii Rhizoma), ferulic acid (Angelicae Sinensis Radix), paeoniflorin (Paeoniae Radix), glycyrrhizin (Glycyrrhizae Radix), harpagoside (Scrophulariae Radix), emodin, sennoside A, and sennoside B (Rhei Rhizoma). The ingredients in the water-based and oil-based patches from different manufactures were also analyzed for quality evaluation. Extracted samples were analyzed with reverse-phase column (Inertsil 5 ODS-2, 4.6 i.d. × 250 mm) at 30°C, eluted with a mixture of 20% and 70% acetonitrile aqueous solution in gradient manner at a flow rate of 1.0 mL/min, and detected at 250 nm. Relative coefficients of variation of intra- and inter-day analysis were less than 5%. All the recoveries were 96.29-103.46%. This method could be applied for the simultaneous determination of ten marker substances in "Wan-Yin-Gau".

Transporters (OATs and OATPs) contribute to illustrate the mechanism of medicinal compatibility of ingredients with different properties in yuanhuzhitong prescription

Various medicinal ingredients with different tastes are combined according to the theory of compatibility in Chinese materia medica to achieve a better efficacy, while the mechanism was not very clear. Here, the authors studied the interaction between ingredients and human transporters such as the kidney transporters OAT1 and OAT3, the liver transporters OATP1B1 and OATP1B3, and the intestine transporter OATP2B1 to discern the compatibility mechanism of ingredients with different tastes in the Yuanhuzhitong preparation (YHP) comprising Corydalis yanhusuo (CYH) and Angelica dahurica (AD), which could relieve pain by restraining the central system. The results show that tetrahydropalmatine (TDE), the major component of CYH, could be transported by OAT3 into kidney, OATP1B1 and OATP1B3 into liver, while imperatorin (IPT) and isoimperatorin (ISP), the two key components of AD, and AD extract showed strong inhibition to OAT1 and OAT3. What's more, AD extract also exerted strongly inhibition to human transporters OATP1B1 and OATP1B3. It was also detected that IPT, ISP, and AD extract significantly downregulated the expression of Oatp1a1, Oatp1a4, and Oatp1b2 of liver in mice. The in vivo results show that the concentration of TDE in liver and kidney significantly decreased, while the TDE concentration in blood and brain were both significantly enhanced in the presence of IPT, ISP, and AD extract. These results suggest that the ingredients in AD with pungent taste could enhance the exposure of TDE in blood and brain by inhibiting the uptake of TDE in liver and kidney. That is to say, TDE with bitter taste could “flood up” into the central nervous system to play its therapeutic effect by the cut-off of that into liver and kidney in the presence of ingredients within AD. This paper not only proves the meridian distribution of CYH in liver and kidney with the role of OAT3, OATP1B1, and OATP1B3, but also illustrates how to improve the efficacy of CYH by reasonable compatibility with AD. This study may offer a valuable clue to illustrate the mechanism of compatibility theory.

Byakangelicin inhibits IL-1β–induced mouse chondrocyte inflammation in vitro and ameliorates murine osteoarthritis in vivo

Osteoarthritis (OA) is a chronic musculoskeletal degeneration disease, resulting in severe consequences such as chronic pain and functional disability. Owing to the complex pathology, there are currently available preventative clinical therapies for OA. Several studies have reported the potential anti-inflammatory effects of byakangelicin (BYA), a component of the Angelica dahurica root extract; however, the effects of BYA in OA remain unknown. In this study, we investigated the protective effects of BYA in interleukin (IL)-1β–induced mouse chondrocytes in vitro and on surgical destabilization in a medial meniscus (DMM) mouse OA model in vivo. In vitro, BYA treatment inhibited IL-1β–mediated inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-alpha, and IL-6 expression. Moreover, BYA promoted the expression of type two collagen and aggrecan but inhibited the expression of thrombospondin motifs 5 and matrix metalloproteinases, leading to degradation of the extracellular matrix. In addition, BYA mechanistically suppressed nuclear factor-kappa B signaling in the IL-1β–induced chondrocytes. The protective effects of BYA in OA development were also observed in vivo using the DMM model. In conclusion, our results highlight BYA as a candidate for OA treatment and prevention.

Antiviral activity of furanocoumarins isolated from Angelica dahurica against influenza a viruses H1N1 and H9N2

Ethnopharmacological relevanceAngelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav. (Umbelliferae family) is an herbaceous, perennial plant native to northern and eastern Asia. The root of A. dahurica has traditionally been used under the name “Bai Zhi” as a medicinal plant for colds, dizziness, ulcers, and rheumatism. Moreover, it is also an important ingredient of various prescriptions, such as Gumiganghwal-Tang, for the common cold and influenza. Aim of the studyEven though various biological activities of the root of A. dahurica have been reported along with its chemical components, the detailed mechanism of how it exerts anti-influenza activity at the compound level has not been studied. Therefore, we investigated the anti-influenza properties of furanocoumarins purified by bioactivity-guided isolation. Materials and methodsBioactivity-guided isolation from a 70% EtOH extract of the root of A. dahurica was performed to produce four active furanocoumarins. The inhibition of cytopathic effects (CPEs) was evaluated to ascertain the antiviral activity of these compounds against influenza A (H1N1 and H9N2) viruses. The most potent compound was subjected to detailed mechanistic studies such as the inhibition of viral protein synthesis, CPE inhibition in different phases of the viral replication cycle, neuraminidase (NA) inhibition, antiapoptotic activity using flow cytometry, and immunofluorescence. ResultsThe bioactivity-guided isolation produced four active furanocoumarins, isoimperatorin (1), oxypeucedanin (2), oxypeucedanin hydrate (3) and imperatorin (4) from the n-BuOH fraction. Among them, compound 2 (followed by compounds 1, 4 and 3) showed a significant CPE inhibition effect, which was stronger than that of the positive control ribavirin, against both H1N1 and H9N2 with an EC50 (μM) of 5.98 ± 0.71 and 4.52 ± 0.39, respectively. Compound 2 inhibited the synthesis of NA and nucleoprotein (NP) in a dose-dependent manner. In the time course assays, the cytopathic effects of influenza A-infected MDCK cells were reduced by 80–90% when treated with compound 2 for 1 and 2 h after infection and declined drastically 3 h after infection. The level of viral NA and NP production was markedly reduced to less than 20% for both proteins in compound 2 (20 μM)-treated cells compared to untreated cells at 2 h after infection. In the molecular docking analysis, compound 2 showed a stronger binding affinity for the C-terminus of polymerase acidic protein (PAC; −36.28 kcal/mol) than the other two polymerase subunits. Compound 2 also exerted an antiapoptotic effect on virus infected cells and significantly inhibited the mRNA expression of caspase-3 and Bax. ConclusionOur results suggest that compound 2 might exert anti-influenza A activity via the inhibition of the early phase of the viral replication cycle, not direct neutralization of surface proteins, such as hemagglutinin and NA, and abnormal apoptosis induced by virus infection. Taken together, these findings suggest that furanocoumarins predominant in A. dahurica play a pivotal role in its antiviral activity. These findings can also explain the reasons for the ethnopharmacological uses of this plant as an important ingredient in many antiviral prescriptions in traditional Chinese medicine (TCM).

Imperatorin alleviates the abnormal proliferation, migration, and foaming of ox-LDL-induced VSMCs through regulating PI3K/Akt/mTOR signaling pathway

• IMP regulates cell cycle of ox-LDL-stimulated VSMCs. • IMP reduces intracellular lipid accumulation and slows foaming process of VSMCs. • IMP attenuates expressions of PCNA, MMP-2 and LOX-1 in ox-LDL-induced VSMCs. • IMP mitigates VSMCs proliferation, migration and foaming by inhibiting PI3K/Akt/mTOR pathway. Abnormal proliferation, migration and foaming of vascular smooth muscle cells (VSMCs) are involved in atherosclerosis (AS) process. Imperatorin (IMP) is a coumarin compound mainly originated from angelica dahurica in natural plants. In this study, effects of IMP on proliferation, migration and foaming of oxidized low-density lipoprotein (ox-LDL)-induced VSMCs were investigated. The results showed that IMP regulated cell cycle in S ~ G2/M phase and down-regulated the proliferating cell nuclear antigen (PCNA), and then exerted anti-proliferation effect. IMP might have a repressive effect on migration in ox-LDL-stimulated VSMCs through inhibiting the metalloproteinase-2 (MMP-2). Oil red O staining showed IMP suppressed lipid accumulation in ox-LDL-induced-VSMCs. This was consistent with the determination of Lectin-like oxidation of lectin-like ox-LDL receptor-1 (LOX-1) and total cholesterol (TC). IMP also reduced the expression of p-PI3K, p-Akt and p-mTOR in ox-LDL-treated VSMCs. These results suggested that IMP might play an anti-lesion role in ox-LDL-stimulated-VSMCs by inhibiting the PI3K/Akt/mTOR pathway.

Effect of co-administration of Acori Tatarinowii Rhizoma volatile oil on pharmacokinetic fate of xanthotoxol, oxypeucedanin hydrate, and byakangelicin from Angelicae Dahuricae Radix in rat.

A combination of Angelicae Dahuricae Radix and Acori Tatarinowii Rhizoma has been widely used as the herb pair in traditional Chinese medicine to treat stroke, migraine, and epilepsy. However, the underlying synergistic mechanism of the herb pair remains unknown. This study was aimed at investigating the effects of Acori Tatarinowii Rhizoma volatile oil on the pharmacokinetic parameters of xanthotoxol, oxypeucedanin hydrate, and byakangelicin from Angelicae Dahuricae Radix in rat, and in vitro absorption behavior of the three compounds using rat everted gut sac, in situ single-pass intestinal perfusion, and Caco-2 cell monolayer models. The pharmacokinetic study exhibited clear changes in the key pharmacokinetic parameters of the three main coumarins through co-administering with Acori Tatarinowii Rhizoma volatile oil (50mg/kg), the area under curve and the maximum plasma concentration of xanthotoxol increased 1.36 and 1.31 times; the area under curve, the maximum plasma concentration, mean residence time, half-life of elimination, and the time to reach peak concentration of oxypeucedanin hydrate increased by 1.35, 1.18, 1.24, 1.19 and 1.49 times, respectively; the area under curve, mean residence time, half-life of elimination, and time to reach peak concentration of byakangelicin climbed 1.29, 1.27, 1.37, and 1.28 times, respectively. The three coumarin components were absorbed well in the jejunum and ileum in the intestinal perfusion model, when co-administered with Acori Tatarinowii Rhizoma volatile oil (100 μg/mL). The in vivo and in vitro experiments showed good relevance and consistency. The results demonstrated that the three coumarin compounds from Angelicae Dahuricae Radix were absorbed through the active transportation, and Acori Tatarinowii Rhizoma volatile oil could promote the intestinal absorption and transport of these compounds by inhibiting P-glycoprotein (P-gp)-mediated efflux.

Development and characterization of 16 novel microsatellite markers by Transcriptome sequencing for Angelica dahurica and test for cross-species amplification

BackgroundAngelica dahurica (Apiaceae) is an important herb in traditional Chinese medicine. Because of its important medicinal and economic values, its wild resources were over-exploited and increasingly reduced. Meanwhile, the diversity of cultivars of A. dahurica has decreased as a result of long-term artificial cultivation. However, there are no population genetics studies of natural A. dahurica reported yet, especially for using microsatellite markers (SSRs) to investigate population genetics of the species.ResultsSixteen polymorphic EST-SSR loci were isolated from A. dahurica with transcriptome sequencing technology (RNA-Seq). The number of alleles varied from 2 to 15 per polymorphic locus over populations with the observed and expected heterozygosities ranging from 0.000 to 1.000 and from 0.000 to 0.829, respectively. Significant deviations from Hardy–Weinberg equilibrium were observed at 8 loci. Tests of linkage disequilibrium showed 11 informative locus pairs were significant across all populations. Cross-species amplification showed that 14 out of 16 SSR loci have the transferability in cultivar-A. dahurica cv. ‘Hangbaizhi’ and A. decursiva.ConclusionsThe 16 newly developed loci microsatellite primers with RNA-Seq will be useful for further investigating population genetics of A. dahurica, cultivars and other members of this genus.

Inhibitory Effects of Furanocoumarins From the Roots of Angelica dahurica on Ionizing Radiation-Induced Migration of A549 Human Non-Small Cell Lung Cancer Cells

Radiation therapy is a very effective tool for the treatment of advanced human lung cancers. However, as one of its malignancy-promoting behaviors, ionizing radiation (IR) increases cell migration and radiation resistance in several lung cancer cells, including non-small cell lung cancer (NSCLC) cells. As part of our ongoing search for potent radiotherapy enhancers from medicinal herbs, a chloroform-soluble fraction of the roots of Angelica dahurica was subjected to phytochemical investigation, leading to the isolation of 8 furanocoumarins. Of these, psoralen (1), xanthotoxin (2), and bergapten (3) inhibited IR-induced migration at a non-cytotoxic concentration (50 μM) in human NSCLC A549 cells. This study is the first to report on the inhibitory activities of these constituents of A. dahurica against IR-induced cancer metastasis.

Antioxidant Activity and Sensory Improvement of Angelica dahurica cv. Yubaizhi Essential Oil on Sunflower Oil during High-temperature Storage

The oxidative state of sunflower oil during high-temperature storage has been facing large challenges. In the study, the antioxidant effect of the essential oil of Angelica dahurica cv. Yubaizhi (ADEO) in sunflower oil was explored. In the high-temperature storage for 24 days at 65 °C, ADEO (800 ppm) was able to markedly inhibit the development of the acid value (AV), peroxide value (PV), p-anisidine value (AnV), total oxidation value (TOTOX), thiobarbituric acid reactive substances (TBARS), total polar compounds (TPC), and the absorbance at 232 and 268 nm (p &lt; 0.01 or p &lt; 0.05) of sunflower oil and to prominently inhibit the transformation between unsaturated fatty acids (UFA) and saturated fatty acids (SFA). Interestingly, the synergistic effect of ADEO (400 ppm) and tert-butyl hydroquinone (TBHQ, 100 ppm) was demonstrated. Furthermore, the sensory attributes such as flavor, taste, and overall acceptability of oxidized sunflower oil added by ADEO at 200, 400, and 800 ppm were memorably elevated (p &lt; 0.05). Besides, one of its main compounds, myrcene, was demonstrated to be its active compound during the whole investigation. Consequently, TBHQ at 200 ppm could be substituted by ADEO at 800 ppm and myrcene at 69.8 ppm in the high-temperature storage at 65 °C of sunflower oil.

Antimicrobial and anti-inflammatory potential of Angelica dahurica and Rheum officinale extract accelerates wound healing in Staphylococcus aureus-infected wounds

Wound infection is a serious clinical problem, and the most common infection-causing bacteria are Staphylococcus aureus and Pseudomonas aeruginosa. Angelica dahurica and Rheum officinale extract (ARE) was reported to accelerate excisional wound healing in rats. In this study, we investigated the therapeutic effects of ARE on bacterial-infected wounds. Thirty Sprague-Dawley rats were divided into three groups: normal saline (NS), ARE, and biomycin ointment (BO). Full-thickness dorsal excisions in all the rats were infected with 108 colony-forming units of S. aureus; the treatments were applied once daily for 7 days. Results showed that the residual wound area in ARE group was smaller than those in NS and BO groups. TBCs on wound sites gradually decreased in ARE and BO groups. The body temperature and plasma inflammatory cytokines (TNF-α, IL-6) levels increased after bacterial infection at 24 h in all groups. After treatment, BT and inflammatory cytokines levels decreased in ARE group. Histological observations showed ARE group exhibited earlier scab formation, denser dermal granulation tissue, thicker epidermis, and more angiogenesis markers than the other groups. In conclusion, ARE accelerated wound healing in S. aureus-infected wounds. We proposed ARE exhibited potential antimicrobial and anti-inflammatory effects and stimulated angiogenesis, thus improving healing in infected wounds.

Simultaneous Determination of Three Coumarins in Angelica dahurica by 1H-qNMR Method: A Fast and Validated Method for Crude Drug Quality Control.

In this study, a quantitative 1H NMR method (1H-qNMR) for determining the contents of imperatorin, byakangelicin, and oxypeucedanin in A. dahurica in traditional Chinese medicine (TCM) has been established. Dried plant material was extracted exhaustively with methanol by an ultrasonication-assisted extraction method. The 1H-qNMR measurements were performed on a 600 -MHz spectrometer with hydroquinone as the internal standard reference in deuterated dimethyl sulfoxide (DMSO-d6) solvent. Quantification was carried out using the 1H resonance signals at 6.55 ppm for hydroquinone and 7.68, 7.38-7.39, and 6.38-6.39 ppm for imperatorin, byakangelicin, and oxypeucedanin, respectively. The linearity, limit of detection (LOD), limit of quantitation (LOQ), precision, reproducibility, stability, and recovery of the methodology were evaluated, and results were good. The newly developed method has been applied to determine the three coumarins in A. dahurica.