RESUMO
Osteoarthritis (OA), characterized by chronic pain and joint degradation, is a progressive joint disease primarily induced by age-related systemic inflammation. Angelica gigas Nakai (AG), a medicinal plant widely used in East Asia, exhibits promising results for such conditions. This study aimed to evaluate the potential of AG as a drug candidate for modulating the multifaceted pathology of OA based on its anti-inflammatory properties. We evaluated the efficacy of AG in pain relief, functional improvement, and cartilage erosion delay using monosodium iodoacetate-induced OA rats and acetic acid-induced writhing mice, along with its anti-inflammatory effects on multiple targets in the serum and cartilage of in vivo models and lipopolysaccharide-stimulated RAW 264.7 cells. In vivo experiments demonstrated significant analgesic and chondroprotective effects of AG, along with functional recovery, in model animals compared with the active controls. AG dose-dependently modulated inflammatory OA pathology-related targets, including interleukin-1ß, tumor necrosis factor-α, matrix metalloproteinase-13, and cyclooxygenase-2, both in vitro and in vivo. In conclusion, AG could be a potential drug candidate for modulating the multifaceted pathology of OA. Nevertheless, further comprehensive investigations, involving a broader range of compounds, pathologies, and mechanisms, are warranted to validate these findings.
Assuntos
Angelica , Anti-Inflamatórios , Osteoartrite , Extratos Vegetais , Animais , Angelica/química , Anti-Inflamatórios/farmacologia , Camundongos , Osteoartrite/tratamento farmacológico , Masculino , Extratos Vegetais/farmacologia , Células RAW 264.7 , Ratos , Analgésicos/farmacologia , Modelos Animais de Doenças , Ratos Sprague-Dawley , Dor/tratamento farmacológico , Ciclo-Oxigenase 2/metabolismoRESUMO
Statins are cholesterol-lowering drugs with a mechanism of inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase, but long-term use can cause side effects. An example of a plant capable of reducing cholesterol levels is Angelica keiskei (ashitaba). Therefore, this study aimed to obtain suitable compounds with inhibitory activity against the HMG-CoA reductase enzyme from ashitaba through in silico tests. The experiment began with screening and pharmacophore modeling, followed by molecular docking on ashitaba's compounds, statins groups, and the native ligand was (3R,5R)-7-[4-(benzyl carbamoyl)-2-(4-fluorophenyl)-5-(1-methylethyl)-1H-imidazole-1-yl]-3,5-dihydroxyheptanoic acid (4HI). Based on the results of the molecular docking simulations, 15 hit compounds had a small binding energy (ΔG). Pitavastatin, as the comparator drug (ΔG = -8.24 kcal/mol; Ki = 2.11 µM), had a lower ΔG and inhibition constant (Ki) than the native ligand 4HI (ΔG = -7.84 kcal/mol; Ki = 7.96µM). From ashitaba's compounds, it was found that 4'-O-geranylnaringenin, luteolin, isobavachalcone, dorsmannin A, and 3'-carboxymethyl-4,2'-dihydroxy-4'-methoxychalcone have low ΔG of below -6 kcal/mol. The lowest ΔG value was found in 3'-carboxymethyl-4,2'-dihydroxy-4'-methoxy chalcone with a ΔG of -6.67 kcal/mol and Ki value of 16.66 µM, which was lower than the ΔG value of the other comparator drugs, atorvastatin (ΔG = -5.49 kcal/mol; Ki = 1148.17 µM) and simvastatin (ΔG = -6.50 kcal/mol; Ki = 22.34 µM). This compound also binds to the important amino acid residues, including ASN755D, ASP690C, GLU559D, LYS735D, LYS691C, and SER684C, through hydrogen bonds. Based on the results, the compound effectively binds to six important amino acids with good binding affinity and only requires a small concentration to reduce half of the enzyme activity.
Assuntos
Angelica , Hidroximetilglutaril-CoA Redutases , Simulação de Acoplamento Molecular , Angelica/química , Hidroximetilglutaril-CoA Redutases/metabolismo , Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Metabolismo Secundário , Ligação Proteica , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ligantes , FarmacóforoRESUMO
Angelica dahurica var. formosana (ADF), which belongs to the Umbelliferae family, is one of the original plants of herbal raw material Angelicae Dahuricae Radix. ADF roots represent an enormous biomass resource convertible for disease treatment and bioproducts. But, early bolting of ADF resulted in lignification and a decrease in the coumarin content in the root, and roots lignification restricts its coumarin for commercial utility. Although there have been attempts to regulate the synthesis ratio of lignin and coumarin through biotechnology to increase the coumarin content in ADF and further enhance its commercial value, optimizing the biosynthesis of lignin and coumarin remains challenging. Based on gene expression analysis and phylogenetic tree profiling, AdNAC20 as the target for genetic engineering of lignin and coumarin biosynthesis in ADF was selected in this study. Early-bolting ADF had significantly greater degrees of root lignification and lower coumarin contents than that of the normal plants. In this study, overexpression of AdNAC20 gene plants were created using transgenic technology, while independent homozygous transgenic lines with precise site mutation of AdNAC20 were created using CRISPR/Cas9 technology. The overexpressing transgenic ADF plants showed a 9.28% decrease in total coumarin content and a significant 12.28% increase in lignin content, while knockout mutant plants showed a 16.3% increase in total coumarin content and a 33.48% decrease in lignin content. Furthermore, 29,671 differentially expressed genes (DEGs) were obtained by comparative transcriptomics of OE-NAC20, KO-NAC20, and WT of ADF. A schematic diagram of the gene network interacting with AdNAC20 during the early-bolting process of ADF was constructed by DEG analysis. AdNAC20 was predicted to directly regulate the transcription of several genes with SNBE-like motifs in their promoter, such as MYB46, C3H, and CCoAOMT. In this study, AdNAC20 was shown to play a dual pathway function that positively enhanced lignin formation but negatively controlled coumarin formation. And the heterologous expression of the AdNAC20 gene at Arabidopsis thaliana proved that the AdNAC20 gene also plays an important role in the process of bolting and flowering.
Assuntos
Angelica , Cumarínicos , Regulação da Expressão Gênica de Plantas , Lignina , Raízes de Plantas , Lignina/biossíntese , Cumarínicos/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Angelica/genética , Angelica/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , FilogeniaRESUMO
BACKGROUND: Angelica Gigas (Purple parsnip) is an important medicinal plant that is cultivated and utilized in Korea, Japan, and China. It contains bioactive substances especially coumarins with anti-inflammatory, anti-platelet aggregation, anti-cancer, anti-diabetic, antimicrobial, anti-obesity, anti-oxidant, immunomodulatory, and neuroprotective properties. This medicinal crop can be genetically improved, and the metabolites can be obtained by embryonic stem cells. In this context, we established the protoplast-to-plant regeneration methodology in Angelica gigas. RESULTS: In the present investigation, we isolated the protoplast from the embryogenic callus by applying methods that we have developed earlier and established protoplast cultures using Murashige and Skoog (MS) liquid medium and by embedding the protoplast in thin alginate layer (TAL) methods. We supplemented the culture medium with growth regulators namely 2,4-dichlorophenoxyaceticacid (2,4-D, 0, 0.75, 1.5 mg L- 1), kinetin (KN, 0, 0.5, and 1.0 mg L- 1) and phytosulfokine (PSK, 0, 50, 100 nM) to induce protoplast division, microcolony formation, and embryogenic callus regeneration. We applied central composite design (CCD) and response surface methodology (RSM) for the optimization of 2,4-D, KN, and PSK levels during protoplast division, micro-callus formation, and induction of embryogenic callus stages. The results revealed that 0.04 mg L- 1 2,4-D + 0.5 mg L- 1 KN + 2 nM PSK, 0.5 mg L- 1 2,4-D + 0.9 mg L- 1 KN and 90 nM PSK, and 1.5 mg L- 1 2,4-D and 1 mg L- 1 KN were optimum for protoplast division, micro-callus formation and induction embryogenic callus. MS basal semi-solid medium without growth regulators was good for the development of embryos and plant regeneration. CONCLUSIONS: This study demonstrated successful protoplast culture, protoplast division, micro-callus formation, induction embryogenic callus, somatic embryogenesis, and plant regeneration in A. gigas. The methodologies developed here are quite useful for the genetic improvement of this important medicinal plant.
Assuntos
Angelica , Reguladores de Crescimento de Plantas , Técnicas de Embriogênese Somática de Plantas , Protoplastos , Angelica/embriologia , Reguladores de Crescimento de Plantas/farmacologia , Técnicas de Embriogênese Somática de Plantas/métodos , Protoplastos/efeitos dos fármacos , Divisão Celular/efeitos dos fármacosRESUMO
BACKGROUND: The Xin-yi-san herbal decoction (XYS) is commonly used to treat patients with allergic rhinitis in Taiwan. Theophylline is primarily oxidized with high affinity by human cytochrome P450 (CYP)1A2, and has a narrow therapeutic index. PURPOSE: This study aimed to investigate the inhibition of human CYP1A2-catalyzed theophylline oxidation (THO) by XYS and its adverse effects in patients. METHODS: Human CYPs were studied in recombinant enzyme systems. The influence of concurrent XYS usage in theophylline-treated patients was retrospectively analyzed. RESULTS: Among the major human hepatic and respiratory CYPs, XYS inhibitors preferentially inhibited CYP1A2 activity, which determined the elimination and side effects of theophylline. Among the herbal components of XYS decoction, Angelicae Dahuricae Radix contained potent THO inhibitors. Furanocoumarin imperatorin was abundant in XYS and Angelicae Dahuricae Radix decoctions, and non-competitively inhibited THO activity with Ki values of 77â84 nM, higher than those (20â52 nM) of fluvoxamine, which clinically interacted with theophylline. Compared with imperatorin, the intestinal bacterial metabolite xanthotoxol caused weaker THO inhibition. Consistent with the potency of the inhibitory effects, the docking analysis generated Gold fitness values in the order-fluvoxamine > imperatorin > xanthotoxol. During 2017â2018, 2.6 % of 201,093 theophylline users consumed XYS. After inverse probability weighting, XYS users had a higher occurrence of undesired effects than non-XYS users; in particular, there was an approximately two-fold higher occurrence of headaches (odds ratio (OR), 2.14; 95 % confidence interval (CI), 1.99â2.30; p < 0.001) and tachycardia (OR, 1.83; 95 % CI, 1.21â2.77; p < 0.05). The incidence of irregular heartbeats increased (OR, 1.36; 95 % CI, 1.07â1.72; p < 0.05) only in the theophylline users who took a high cumulative dose (≥ 24 g) of XYS. However, the mortality in theophylline users concurrently taking XYS was lower than that in non-XYS users (OR, 0.24; 95 % CI, 0.14â0.40; p < 0.001). CONCLUSION: XYS contains human CYP1A2 inhibitors, and undesirable effects were observed in patients receiving both theophylline and XYS. Further human studies are essential to reduce mortality and to adjust the dosage of theophylline in XYS users.
Assuntos
Angelica , Inibidores do Citocromo P-450 CYP1A2 , Citocromo P-450 CYP1A2 , Medicamentos de Ervas Chinesas , Furocumarinas , Teofilina , Teofilina/farmacologia , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Citocromo P-450 CYP1A2/metabolismo , Inibidores do Citocromo P-450 CYP1A2/farmacologia , Angelica/química , Furocumarinas/farmacologia , Masculino , Interações Ervas-Drogas , Estudos Retrospectivos , Feminino , Taiwan , Pessoa de Meia-Idade , Adulto , Oxirredução , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/induzido quimicamenteRESUMO
Using (S)-decursinol isolated from root of Angelica gigas Nakai (AGN), we semi-synthesized and evaluated a series of both enantiomerically pure decursin derivatives for their antiproliferative activities against A549 human lung cancer cells. All synthesized compounds showed a broad spectrum of inhibitory activities against the growth of A549 cells. Especially, compound (S)-2d with (E)-(furan-3-yl)acryloyl group showed the most potent activity (IC50: 14.03 µM) against A549 cancer cells as compared with the reference compound, decursin (IC50: 43.55 µM) and its enantiomer, (R)-2d (IC50: 151.59 µM). Western blotting assays indicated that (S)-2d more strongly inhibited Janus kinase 1 (JAK1) and signal transducer and activator of transcription activation 3 (STAT3) phosphorylation than decursin in a dose-dependent manner, while having no effect on CXCR7 overexpression and total STAT3 level. In addition, (S)-2d induced cell cycle arrest at G1 phase and subsequent apoptotic cell death in A549 cancer cells. Our combined analysis of molecular docking studies and biological data suggests that the inhibition of JAK1 with (S)-2d resulted in loss of STAT3 phosphorylation and inhibition of cell growth in A549 cancer cells. These overall results strongly suggest that (S)-2d (MRC-D-004) as a novel JAK1 inhibitor may have therapeutic potential in the treatment of A549 human lung cancers by targeting the JAK1/STAT3 signaling pathway.
Assuntos
Apoptose , Benzopiranos , Butiratos , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Fator de Transcrição STAT3 , Humanos , Proliferação de Células/efeitos dos fármacos , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Benzopiranos/farmacologia , Benzopiranos/química , Benzopiranos/síntese química , Butiratos/farmacologia , Butiratos/química , Butiratos/síntese química , Apoptose/efeitos dos fármacos , Células A549 , Estereoisomerismo , Relação Dose-Resposta a Droga , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Relação Estrutura-Atividade , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 1/metabolismo , Estrutura Molecular , Angelica/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/químicaRESUMO
Development of high-performance joint injection lubricants has become the focus in the field of osteoarthritis treatment. Herein, natural product of angelica essential oil combined with the graphene oxide were prepared to the stable Pickering emulsion as a biological lubricant. The tribological properties of the Pickering emulsion under different friction conditions were studied. The lubricating mechanism was revealed and the biological activities were evaluated. Results showed that the prepared Pickering emulsion displayed superior lubrication property at the Ti6Al4V biological material interface. The maximum friction reduction and anti-wear abilities of the Pickering emulsion were improved by 36% and 50% compared to water, respectively. This was primarily due to the action of the double-layer lubrication films composed of the graphene oxide and angelica essential oil molecules. It was worth noting that the friction reduction effect of the Pickering emulsion at the natural cartilage interface was higher about 19% than that of HA used in clinic for OA commonly. In addition, the Pickering emulsion also displayed antioxidant activity and cell biocompatibility, showing a good clinical application prospect in the future.
Assuntos
Angelica , Emulsões , Lubrificação , Óleos Voláteis , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Emulsões/química , Angelica/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Grafite/química , Grafite/farmacologia , Lubrificantes/química , Lubrificantes/farmacologia , Humanos , Propriedades de Superfície , Tamanho da Partícula , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacosRESUMO
The objective of our study was to analyse the extracts from six medicinal herb roots (marshmallow, dandelion, liquorice, angelica, burdock, and comfrey) in terms of antioxidant capacity (ABTS, DPPH) and inhibition of advanced glycation end product (AGEs) formation. The quantification of phenolic acids and flavonoids was analysed using the UHPLC-DAD-MS method. Fifteen polyphenolic compounds were detected in the studied herbs. The higher number of polyphenols were found in marshmallows (ten polyphenols), while the lowest was in comfrey (five compounds). Liquorice root revealed the highest individual phenolic concentration (382 µg/g dm) with the higher contribution of kaempferol-3-O-rutinoside. Comfrey root extract was characterised by the most abundant TPC (Total Phenolic Content) value (29.79 mg GAE/ g dm). Burdock and comfrey showed the strongest anti-AGE activity studies with the BDA-GLU model. Burdock root was also characterised by the highest anti-AGE activity in the BSA-MGO model. The highest antioxidant capacity was determined by ABTS (72.12 µmol TE/g dw) and DPPH (143.01 µmol TE/g dw) assays for comfrey extract. The p-coumaric acid content was significantly correlated with anti-AGE activity determined by the BSA-MGO model. This research sheds new light on the bioactivity of root herbs, explaining the role of p-coumaric acid in preventing diabetes.
Assuntos
Antioxidantes , Flavonoides , Produtos Finais de Glicação Avançada , Extratos Vegetais , Raízes de Plantas , Plantas Medicinais , Polifenóis , Antioxidantes/análise , Antioxidantes/farmacologia , Polifenóis/análise , Polifenóis/farmacologia , Raízes de Plantas/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/análise , Plantas Medicinais/química , Flavonoides/análise , Flavonoides/farmacologia , Angelica/química , Glycyrrhiza/química , Arctium/química , Propionatos , Ácidos Cumáricos/análise , Ácidos Cumáricos/farmacologia , Hidroxibenzoatos/análise , Cromatografia Líquida de Alta PressãoRESUMO
HemoHIM is a standardized medicinal herbal preparation consisting of extracts of Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia lactiflora Pallas that possesses immune regulatory activities. This study aimed to research the potential antioxidant effects of HemoHIM and its capacity for reducing fatigue in aged mice subjected to forced exercise. After administering HemoHIM 125 (500 mg/kg orally) for 4 weeks in 8-month-old female C57BL/6 mice (4 groups of 10 mice), various parameters were evaluated. The analyses revealed that HemoHIM enhanced swimming time and grip strength. In addition, it significantly reduced serum lactate levels and increased liver glutathione peroxidase (GPx) levels after exercise challenge. The expression levels of antioxidant enzymes and factors, including nuclear factor erythroid 2-related factor-2 (Nrf-2), heme oxygenase 1, superoxide dismutase, GPx, and glutathione reductase, were significantly higher in liver and muscle tissues of mice treated with HemoHIM. These results indicate that HemoHIM might function as an anti-fatigue and antioxidant agent by modulating the Nrf-2 signaling pathway.
Assuntos
Angelica , Antioxidantes , Fadiga , Glutationa Peroxidase , Fígado , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2 , Extratos Vegetais , Superóxido Dismutase , Animais , Antioxidantes/farmacologia , Fadiga/tratamento farmacológico , Feminino , Angelica/química , Camundongos , Glutationa Peroxidase/metabolismo , Superóxido Dismutase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Fator 2 Relacionado a NF-E2/metabolismo , Cnidium/química , Paeonia/química , Condicionamento Físico Animal , Glutationa Redutase/metabolismo , Humanos , Envelhecimento/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Estresse Oxidativo/efeitos dos fármacosRESUMO
Phytopathogenic bacteria (MAFF 302110T and MAFF 302107) were isolated from lesions on Japanese angelica trees affected by bacterial soft rot in Yamanashi Prefecture, Japan. The strains were Gram-reaction-negative, facultatively anaerobic, motile with peritrichous flagella, rod-shaped, and non-spore-forming. The genomic DNA G+C content was 51.1 molâ% and the predominant cellular fatty acids included summed feature 3 (C16â:â1 ω7c and/or C16â:â1 ω6c), C16â:â0, summed feature 8 (C18â:â1 ω7c and/or C18â:â1 ω6c), summed feature 2 (comprising any combination of C12â:â0 aldehyde, an unknown fatty acid with an equivalent chain length of 10.928, C16â:â1 iso I, and C14â:â0 3OH), and C12â:â0. Phylogenetic analyses based on 16S rRNA and gyrB gene sequences, along with phylogenomic analysis utilizing whole-genome sequences, consistently placed these strains within the genus Pectobacterium. However, their phylogenetic positions did not align with any known species within the genus. Comparative studies involving average nucleotide identity and digital DNA-DNA hybridization with the closely related species indicated values below the thresholds employed for the prokaryotic species delineation (95-96â% and 70â%, respectively), with the highest values observed for Pectobacterium polonicum DPMP315T (92.10 and 47.1â%, respectively). Phenotypic characteristics, cellular fatty acid composition, and a repertoire of secretion systems could differentiate the strains from their closest relatives. The phenotypic, chemotaxonomic, and genotypic data obtained in this study show that MAFF 302110T/MAFF 302107 represent a novel species of the genus Pectobacterium, for which we propose the name Pectobacterium araliae sp. nov., designating MAFF 302110T (=ICMP 25161T) as the type strain.
Assuntos
Angelica , Pectobacterium , Japão , Filogenia , RNA Ribossômico 16S/genética , Composição de Bases , Ácidos Graxos/química , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , BactériasRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Angelica roots are a significant source of traditional medicines for various cultures around the northern hemisphere, from indigenous communities in North America to Japan. Among its many applications, the roots are used to treat type 2 diabetes mellitus; however, this application is not mentioned often. Ethnopharmacological studies have reported the use of A. japonica var. hirsutiflora, A. furcijuga, A. shikokiana, and A. keiskei to treat diabetes symptoms, and further reports have demonstrated the three angelica roots, i.e., A. japonica var. hirsutiflora, A. reflexa, and A. dahurica, exhibit insulin secretagogue activity. AIM OF THE STUDY: This study aimed to phytochemically characterize and compare angelica roots monographed in the European Pharmacopeia 11th, isolate major plant metabolites, and assess extracts and isolates' capability to modulate pancreatic ß-cell function. MATERIALS AND METHODS: Root extracts of Angelica archangelica, Angelica dahurica, Angelica biserrata, and Angelica sinensis were phytochemically profiled using liquid chromatography method coupled with mass spectrometry. Based on this analysis, simple and furanocoumarins were isolated using chromatography techniques. Extracts (1.6-50 µg/mL) and isolated compounds (5-40 µmol/L) were studied for their ability to modulate insulin secretion in the rat insulinoma INS-1 pancreatic ß-cell model. Insulin was quantified by the homogeneous time-resolved fluorescence method. RESULTS: Forty-one secondary metabolites, mostly coumarins, were identified in angelica root extracts. A. archangelica, A. dahurica, and A. biserrata root extracts at concentration of 12.5-50 µg/mL potentiated glucose-induced insulin secretion, which correlated with their high coumarin content. Subsequently, 23 coumarins were isolated from these roots and screened using the same protocol. Coumarins substituted with the isoprenyl group were found to be responsible for the extracts' insulinotropic effect. CONCLUSIONS: Insulinotropic effects of three pharmacopeial angelica roots were found, the metabolite profiles and pharmacological activities of the roots were correlated, and key structures responsible for the modulation of pancreatic ß-cell function were identified. These findings may have implications for the traditional use of angelica roots in treating diabetes. Active plant metabolites may also become lead structures in the search for new antidiabetic treatments.
Assuntos
Angelica , Células Secretoras de Insulina , Compostos Fitoquímicos , Extratos Vegetais , Raízes de Plantas , Angelica/química , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Animais , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/análise , Ratos , Insulina/metabolismo , Secreção de Insulina/efeitos dos fármacos , Cumarínicos/farmacologia , Cumarínicos/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/químicaRESUMO
Angelica sinensis is a perennial herb widely distributed around the world, and angelica polysaccharide (APS) is a polysaccharide extracted from Angelica sinensis. APS is one of the main active components of Angelica sinensis. A large number of studies have shown that APS has hematopoietic, promoting blood circulation, radiation resistance, lowering blood glucose, enhancing the body immunity and other pharmacological effects in a variety of diseases. However, different extraction methods and extraction sites greatly affect the efficacy of APS. In recent years, with the emerging of new technologies, there are more and more studies on the combined application and structural modification of APS. In order to promote the comprehensive development and in-depth application of APS, this narrative review systematically summarizes the effects of different drying methods and extraction sites on the biological activity of APS, and the application of APS in the treatment of diseases, hoping to provide a scientific basis for the experimental study and clinical application of APS.
Assuntos
Angelica sinensis , Polissacarídeos , Humanos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/uso terapêutico , Animais , Angelica sinensis/química , Angelica/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêuticoRESUMO
Crude drug Angelicae acutilobae radix is one of the most important crude drugs in Japanese traditional medicine and is used mainly for the treatment of gynecological disorders. In the listing in the Japanese Pharmacopoeia XVIII, Angelicae acutilobae radix is defined as the root of Angelica acutiloba (Apiaceae), which has long been produced on an industrial scale in Japan. With the aging of farmers and depopulation of production areas, the domestic supply has recently declined and the majority of the supply is now imported from China. Due to having only slightly different morphological and chemical characteristics for the Apiaceae roots used to produce dried roots for Chinese medicines, the plant species originating the crude drug Apiaceae roots may be incorrectly identified. In particular, Angelicae sinensis radix, which is widely used in China, and Angelicae acutilobae radix are difficult to accurately identify by morphology and chemical profiles. Thus, in order to differentiate among Angelicae acutilobae radix and other radixes originated from Chinese medicinal Apiaceae plants, we established DNA markers. Using DNA sequences for the chloroplast psbA-trnH intergenic spacer and nuclear internal transcribed spacer regions, Angelicae acutilobae radix and other Chinese Apiaceae roots, including Angelicae sinensis radix, can be definitively identified.
Assuntos
Angelica sinensis , Angelica , Código de Barras de DNA Taxonômico , Raízes de Plantas , Angelica/genética , Angelica/química , Angelica/classificação , Angelica sinensis/genética , Raízes de Plantas/genética , Apiaceae/genética , Apiaceae/classificação , DNA de Plantas/genética , Plantas Medicinais/genética , Plantas Medicinais/classificação , Medicamentos de Ervas Chinesas/química , Filogenia , ChinaRESUMO
Microbiomes are the most important members involved in the regulation of soil nitrogen metabolism. Beneficial interactions between plants and microbiomes contribute to improving the nitrogen utilization efficiency. In this study, we investigated the Apiaceae medicinal plant Angelica dahurica var. formosana. We found that under a low-nitrogen treatment, the abundance of carbon metabolites in the rhizosphere secretions of A. dahurica var. formosana significantly increased, thereby promoting the ratio of C to N in rhizosphere and nonrhizosphere soils, increasing carbon sequestration, and shaping the microbial community composition, thus promoting a higher yield and furanocoumarin synthesis. Confirmation through the construction of a synthetic microbial community and feedback experiments indicated that beneficial plant growth-promoting rhizobacteria play a crucial role in improving nitrogen utilization efficiency and selectively regulating the synthesis of target furanocoumarins under low nitrogen conditions. These findings may contribute additional theoretical evidence for understanding the mechanisms of interaction between medicinal plants and rhizosphere microorganisms.
Assuntos
Angelica , Apiaceae , Furocumarinas , Plantas Medicinais , Desenvolvimento Vegetal , Solo , Nitrogênio , Raízes de Plantas , Rizosfera , Microbiologia do SoloRESUMO
OBJECTIVE: Angelica keiskei is a medicinal and edible plant that has been reported to possess potent antioxidant properties in several in vitro models, but its effectiveness on naturally aging organisms is still lacking. This study explores the antioxidant and health-promoting effects of Angelica keiskei in naturally aging mice. METHODS: We treated 48-week-old mice with Angelica keiskei water extract (AKWE) 30 days, and measured indicators related to aging and antioxidants. In addition, we conducted network pharmacology analysis, component-target molecular docking, real-time PCR, and MTS assays to investigate relevant factors. RESULTS: The results indicated that administration of AKWE to mice led to decrease blood glucose levels, improve muscle fiber structure, muscle strength, gait stability, and increase levels of glutathione and superoxide dismutase in serum. Additionally, it decreased pigmentation of the heart tissues. Angelica keiskei combats oxidative stress by regulating multiple redox signaling pathways, and its ingredients Coumarin and Flavonoids have the potential to bind to SIRT3 and SIRT5. CONCLUSIONS: Our findings indicated the potential of Angelica keiskei as a safe and effective dietary supplement to combat aging and revealed the broad prospects of medicinal and edible plants for addressing aging and age-related chronic diseases.
Assuntos
Angelica , Antioxidantes , Camundongos , Animais , Angelica/química , Simulação de Acoplamento Molecular , Suplementos Nutricionais , Estresse Oxidativo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/químicaRESUMO
Angelica gigas (A. gigas) is traditional medicinal herb that mainly exists in Korea and northeastern China. There have been relatively few studies conducted thus far on its polysaccharides and their bioactivities. We purified and described a novel water-soluble polysaccharide derived from A. gigas and investigated its immunoenhancing properties. The basic components of crude and purified polysaccharides (F1 and F2) were total sugar (41.07% - 70.55%), protein (1.12-10.33%), sulfate (2.9-5.5%), and uronic acids (0.5-31.05%) in total content. Our results demonstrated that the crude and fractions' molecular weights (Mw) varied from 42.2 to 285.2 × 103 g/mol. As the most effective polysaccharide, F2 significantly stimulated RAW264.7 cells to release nitric oxide (NO) and express several cytokines. Furthermore, F2 increased the expression of tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-É£), natural killer cytotoxicity receptors (NKp44), and granzyme-B in NK-92 cells and enhanced the cytotoxicity against HCT-116 cells. In our experiments, we found that F2 stimulated RAW264.7 cells and NK-92 cells via MAPK and NF-κB pathways. The monosaccharide and methylation analysis of the high immunostimulant F2 polysaccharide findings revealed that the polysaccharide was primarily composed of 1 â 4, 1 â 6, 1 â 3, 6, 1 â 3 and 1 â 3, 4, 6 galactopyranose residues, 1 â 3 arabinofuranose residues, 1 â 4 glucopyranose residues. These results demonstrated that the F2 polysaccharide of A. gigas which possesses potential immunostimulatory attributes, could be used to create a novel functional food.
Assuntos
Angelica , NF-kappa B , Animais , Camundongos , Humanos , NF-kappa B/metabolismo , Células HCT116 , Ativação de Macrófagos , Células RAW 264.7 , Transdução de Sinais , Células Matadoras Naturais/metabolismo , Polissacarídeos/químicaRESUMO
In traditional Chinese medicine, Angelica dahurica is a valuable herb with numerous therapeutic applications for a range of ailments. There have not yet been any articles on the methodical assessment and choice of the best reference genes for A. dahurica gene expression studies. Real-time quantitative PCR (RT-qPCR) is widely employed as the predominant method for investigating gene expression. In order to ensure the precise determination of target gene expression outcomes in RT-qPCR analysis, it is imperative to employ stable reference genes. In this study, a total of 11 candidate reference genes including SAND family protein (SAND), polypyrimidine tract-binding protein (PTBP), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), TIP41-like protein (TIP41), cyclophilin 2 (CYP2), elongation factor 1 α (EF1α), ubiquitin-protein ligase 9 (UBC9), tubulin ß-6 (TUB6), thioredoxin-like protein YLS8 (YLS8), and tubulin-α (TUBA) were selected from the transcriptome of A. dahurica. Subsequently, three statistical algorithms (geNorm, NormFinder, and BestKeeper) were employed to assess the stability of their expression patterns across seven distinct stimulus treatments. The outcomes obtained from these analyses were subsequently amalgamated into a comprehensive ranking using RefFinder. Additionally, one target gene, phenylalanine ammonia-lyase (PAL), was used to confirm the effectiveness of the selected reference genes. According to the findings of this study, the two most stable reference genes for normalizing the expression of genes in A. dahurica are TIP41 and UBC9. Overall, our research has determined the appropriate reference genes for RT-qPCR in A. dahurica and provides a crucial foundation for gene screening and identifying genes associated with the biosynthesis of active ingredients in A. dahurica.
Assuntos
Angelica , Angelica/genética , Tubulina (Proteína) , Actinas , Reação em Cadeia da Polimerase em Tempo Real , Estresse FisiológicoRESUMO
Imperatorin (IMP) is the main bioactive furanocoumarin of Angelicae dahuricae radix, which is a well-known traditional Chinese medicine. The purpose of this study was to elucidate the role of IMP in promoting absorption and the possible mechanism on the compatible drugs of Angelicae dahuricae radix. The influence of IMP on drugs' intestinal absorption was conducted by the Caco-2 cell model. The mechanism was studied by investigating the transcellular transport mode of IMP and its influence on P-glycoprotein (P-gp)-mediated efflux, protein expression of P-gp and tight junction, and cell membrane potential. The result showed IMP promoted the uptake of osthole, daidzein, ferulic acid, and puerarin and improved the transport of ferulic acid and puerarin in Caco-2 cells. The absorption-promoting mechanism of IMP might involve the reduction of the cell membrane potential, decrease of P-gp-mediated drug efflux and inhibition of the P-gp expression level in the cellular pathway, and the loosening of the tight junction protein by the downregulation of the expression levels of occludin and claudin-1 in the paracellular pathway. This study provides new insights into the understanding of the improved bioavailability of Angelicae dahuricae radix with its compatible drugs.
Assuntos
Angelica , Ácidos Cumáricos , Cumarínicos , Furocumarinas , Absorção Intestinal , Isoflavonas , Furocumarinas/farmacologia , Humanos , Células CACO-2 , Angelica/química , Absorção Intestinal/efeitos dos fármacos , Isoflavonas/farmacologia , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Junções Íntimas/metabolismo , Junções Íntimas/efeitos dos fármacos , Transporte Biológico , Ocludina/metabolismo , Raízes de PlantasRESUMO
Duhuo, a member of the Angelica family, is widely used to treat ailments such as rheumatic pain. It possesses a diverse array of bioactivities, including anti-tumor, anti-inflammatory, and analgesic properties, as recent pharmacological research has revealed. Nevertheless, the mtDNA of Angelica species remains relatively unexplored. To address this gap, we sequenced and assembled the mtDNA of A. biserrata to shed light on its genetic mechanisms and evolutionary pathways. Our investigation indicated a distinctive multi-branched conformation in the A. biserrata mtDNA. A comprehensive analysis of protein-coding sequences (PCGs) across six closely related species revealed the presence of 11 shared genes in their mitochondrial genomes. Intriguingly, positive selection emerged as a significant factor in the evolution of the atp4, matR, nad3, and nad7 genes. In addition, our data highlighted a recurring trend of homologous fragment migration between chloroplast and mitochondrial organelles. We identified 13 homologous fragments spanning both chloroplast and mitochondrial genomes. The phylogenetic tree established a close relationship between A. biserrata and Saposhnikovia divaricata. To sum up, our research would contribute to the application of population genetics and evolutionary studies in the genus Acanthopanax and other genera in the Araliaceae family.