Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 167
Filtrar
1.
Phytomedicine ; 81: 153436, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33360346

RESUMO

BACKGROUND: Depression is a pervasive or persistent mental disorder that causes mood, cognitive and memory deficits. Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history, although its efficacy and potential mechanism are still uncertain. PURPOSE: The present study aimed to investigate anti-depression effect and potential mechanism of U. rhynchophylla extract (URE). STUDY DESIGN AND METHODS: A mouse depression model was established using unpredictable chronic mild stress (UCMS). Effects of URE on depression-like behaviours, neurotransmitters, and neuroendocrine hormones were investigated in UCMS-induced mice. The potential target of URE was analyzed by transcriptomics and bioinformatics methods and validated by RT-PCR and Western blot. The agonistic effect on 5-HT1A receptor was assayed by dual-luciferase reporter system. RESULTS: URE ameliorated depression-like behaviours, and modulated levels of neurotransmitters and neuroendocrine hormones, including 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), corticosterone (CORT), corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH), in UCMS-induced mice. Transcriptomics and bioinformatics results indicated that URE could regulate glutamatergic, cholinergic, serotonergic, and GABAergic systems, especially neuroactive ligand-receptor and cAMP signaling pathways, revealing that Htr1a encoding 5-HT1A receptor was a potential target of URE. The expression levels of downstream proteins of 5-HT1A signaling pathway 5-HT1A, CREB, BDNF, and PKA were increased in UCMS-induced mice after URE administration, and URE also displayed an agonistic effect against 5-HT1A receptor with an EC50 value of 17.42 µg/ml. CONCLUSION: U. rhynchophylla ameliorated depression-like behaviours in UCMS-induced mice through activating 5-HT1A receptor.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Uncaria/química , Hormônio Adrenocorticotrópico/sangue , Animais , Antidepressivos/química , Biologia Computacional , Corticosterona/sangue , Hormônio Liberador da Corticotropina/sangue , Depressão/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Extratos Vegetais/farmacologia , Receptor 5-HT1A de Serotonina , Serotonina/metabolismo , Estresse Psicológico
2.
Int J Biol Macromol ; 144: 289-295, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31838069

RESUMO

The present study was intended to prepare and optimize the mucoadhesive buccal patch of gambier leaf extract using chitosan (CH) and tapioca starch (TS) composite as the polymer complexes. The patch formulation was designed based on 22 factorial design in order to optimize the composition of CH and TS. The physical and chemical characteristics of the prepared patches, including mass and thickness uniformity, folding endurance, surface pH, swelling index, percent of elongation, and mucoadhesive time were successfully evaluated. Based on statistical analysis, the optimum concentration of CH and TS was 900 mg and 300 mg, respectively, with desirability percent of 0.968. The characterization of the optimum patch showed that the variability coefficient of the mass and thickness uniformity was 0.4805 ± 0.1887% and 0.9716 ± 1.2026%, surface pH of the patch was 6, folding endurance >300 times, elongation percent was 53.333 ± 0.1082%, and mucoadhesive time was 320 ± 1.1547 min. The catechin content, as the active agent of the gambier leaf extract, was 92.1667 ± 0.3626%, and the FT-IR characterization indicated that there are no chemical interactions between each patch component.


Assuntos
Catequina/química , Quitosana/química , Gengivite/terapia , Manihot/química , Amido/química , Uncaria/química , Concentração de Íons de Hidrogênio , Extratos Vegetais/química , Folhas de Planta/química , Polímeros/química , Adesivo Transdérmico
3.
J Sep Sci ; 43(6): 1043-1050, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31858716

RESUMO

Source authentication of herbal medicines was essential for ensuring their safety, efficacy and quality consistency, especially those with multiple botanical origins. This study proposed a metabolomics strategy for species discrimination and source recognition. Uncariae Rammulus Cum Uncis, officially stipulating the stems with hooks of five Uncaria species as its origins, was taken as a case study. Firstly, an untargeted MSE method was developed by ultra-high performance liquid chromatography hyphenated with quadrupole time-of-flight mass spectrometry for global metabolite characterization. Subsequently, data pretreatment was conducted by using Progenesis QI software and screening rules. The obtained metabolite features were defined as variables for statistical analyses. Principal component analysis and chemical fingerprinting spectra suggested that five official species were differentiated from each other except for Uncaria hirsuta and Uncaria sinensis. Furthermore, orthogonal partial least squares discrimination analysis was performed to discriminate confused two species, and resulted in the discovery of nine contributing markers. Ultimately, a Support Vector Machine model was developed to recognize five species and predict origins of commercial materials. The study demonstrated that the developed strategy was effective in discrimination and recognition of confused species, and promising in tracking botanical origins of commercial materials.


Assuntos
Medicamentos de Ervas Chinesas/metabolismo , Metabolômica , Plantas Medicinais/metabolismo , Uncaria/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Espectrometria de Massas , Medicina Tradicional Chinesa , Caules de Planta/química , Caules de Planta/metabolismo , Plantas Medicinais/química , Análise de Componente Principal , Uncaria/metabolismo
4.
J Nat Prod ; 82(12): 3302-3310, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31789520

RESUMO

Nine new monoterpenoid indole alkaloids, uncarialins A-I (1-9), were isolated from Uncaria rhynchophylla as well as 14 known analogues (10-23). Their structures were determined by HRESIMS, 1D and 2D NMR, and experimental and calculated electronic circular dichroism data. Compounds 5, 7, 15, and 22 displayed significant agonistic effects against the 5-HT1A receptor with EC50 values of 2.2 ± 0.1, 0.1 ± 0.1, 1.6 ± 0.3, and 2.0 ± 0.5 µM, respectively. The mechanisms of action of these four compounds with the 5-HT1A receptor were investigated by molecular docking, and the results suggested that amino acid residues Asp116, Thr196, Asn386, and Tyr390 played critical roles in the observed activity of the above-mentioned compounds.


Assuntos
Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Alcaloides de Triptamina e Secologanina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Uncaria/química , Animais , Células CHO , Cricetulus , Simulação de Acoplamento Molecular , Estrutura Molecular , Alcaloides de Triptamina e Secologanina/química , Alcaloides de Triptamina e Secologanina/isolamento & purificação , Agonistas do Receptor de Serotonina/química , Agonistas do Receptor de Serotonina/isolamento & purificação , Análise Espectral/métodos
5.
J Nat Prod ; 82(12): 3288-3301, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31804070

RESUMO

Twenty-six glucoconjugated monoterpene indole alkaloids, including 12 new compounds, rhynchophyllosides A-L (1-12), and 14 known ones, 13-26, were obtained from the hook-bearing stems of Uncaria rhynchophylla (Miq.) Miq. ex Havil. Their structures were unambiguously elucidated by analyses of UV, MS, NMR, ECD, and single-crystal X-ray diffraction data. The ESI-MSn behavior of the new glucoalkaloids was also elucidated. Although comprising the same glucosyl moiety, the aglycone skeletons and glucosidic numbers and linkage varied greatly, implying the diversity in biosynthetic pathways. This is the first report of such structurally diverse glucoconjugated monoterpene indole alkaloids from U. rhynchophylla. Compound 1 represents a new subtype of oxindole alkaloid with a seven-membered D-ring, 10 is a rare monoterpene indole alkaloid with the glucosyl moiety located at C-9, 4 and 5 are the first two oxindole alkaloid diglycosides, and 11 and 12 represent the first two examples of alkaloids with a quinolone nucleus from the genus Uncaria. Compound 10 exhibited moderate acetylcholinesterase (AChE) inhibitory activity with an IC50 value of 10.5 µM. Molecular docking was performed to explore the binding mode of inhibitor 10 at the active site of AChE.


Assuntos
Glicoconjugados/química , Alcaloides de Triptamina e Secologanina/química , Uncaria/química , Linhagem Celular Tumoral , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Alcaloides de Triptamina e Secologanina/farmacologia , Análise Espectral/métodos
6.
Chin J Nat Med ; 17(12): 928-934, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31882048

RESUMO

Two new folate-derived analogues, named uncarophyllofolic acids A (1) and B (2), respectively, were isolated from the Uncaria rhynchophylla hook bearing stem (Gouteng in Chinese). The distinct stereochemical structures of 1 and 2 were determined by spectroscopic data analysis in combination with acidic hydrolysis and Marfey's derivatization, along with comparison of their specific rotation and Cotton effect (CE) data with those of the biogenetically related known derivatives as well as theoretical calculations of electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway of 1 and 2, associating to folate metabolism and the previously reported orychophragines A-C from Orychophragmus violaceus, is discussed.


Assuntos
Ácido Fólico/química , Extratos Vegetais/química , Uncaria/química , China , Cromatografia Líquida de Alta Pressão , Ácido Fólico/análogos & derivados , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Caules de Planta/química
7.
J Nat Prod ; 82(11): 2933-2940, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31686505

RESUMO

The structure elucidation of three new alkaloids named isoformosaninol (1), formosaninol (2), and longiflorine (3), isolated from the leaves of Uncaria longiflora var. pteropoda (Miq.) Ridsdale, along with their biosynthetic pathways are discussed. Their absolute structures were determined through a combination of physical data interpretation and quantum chemical calculations using the time-dependent density functional theory (TDDFT) method.


Assuntos
Alcaloides/química , Uncaria/química , Biologia Computacional , Teoria da Densidade Funcional , Alcaloides Indólicos/análise , Malásia , Estrutura Molecular , Folhas de Planta/química , Teoria Quântica
8.
Environ Toxicol ; 34(10): 1114-1120, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31231976

RESUMO

The aim of this study was designed to investigate the effects of rhynchophyllin (RH) on neuroinflammation in Tourette syndrome (TS) rats. TS model was established in rats by the injection of selective 5-HT2A/2C agonist 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Behavior in DOI-induced rats was tested. Inflammatory cytokines levels such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum and striatum were detected. The expression levels of janus kinase 2 (JAK2)/signal transducer and transcription activator 3 (STAT3) and nuclear factor (NF)-κB pathways in striatum were measured by Western blot. Data indicated that RH can significantly reduce the numbers of nodding experiment of TS rats. RH significantly decreased IL-6, IL-1ß, and TNF-α in serum and striatum of TS rats, with altered expression of P-JAK2, P-STAT3, P-NF-κBp65, and P-IκBα in TS rats, as evidenced by Western blot analysis and immunohistochemistry, suggesting that the regulation of JAK2/STAT3 and NF-κB pathways might be involved in the mechanism of RH on TS.


Assuntos
Corpo Estriado/imunologia , Medicamentos de Ervas Chinesas/administração & dosagem , Janus Quinase 2/imunologia , Oxindois/administração & dosagem , Síndrome de Tourette/tratamento farmacológico , Uncaria/química , Animais , Corpo Estriado/efeitos dos fármacos , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Janus Quinase 2/genética , Masculino , NF-kappa B/genética , NF-kappa B/imunologia , Propano/efeitos adversos , Propano/análogos & derivados , Ratos , Ratos Wistar , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Transdução de Sinais/efeitos dos fármacos , Síndrome de Tourette/induzido quimicamente , Síndrome de Tourette/genética , Síndrome de Tourette/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
9.
Braz J Med Biol Res ; 52(6): e8273, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116257

RESUMO

Excessive pro-inflammatory cytokines result in adverse pregnancy outcomes, including preeclampsia-like phenotypes, and fetal growth restriction. Anti-inflammation might be an effective therapy. The aim of this research was to investigate whether Uncaria rhynchophylla alkaloid extract (URE), a highly safe anti-inflammation constituent of the herb, can inhibit inflammation and improve clinical characteristics of preeclampsia in a lipopolysaccharide (LPS)-induced preeclampsia rat model. The rat model was established by daily administration of LPS (1 µg/kg body weight per day) from gestational day (GD) 14 to 19. Different doses of URE (35, 70, and 140 mg/kg body weight per day) were administered from GD 14 to GD 19. The effects of URE on proteinuria, maternal hypertension, pregnancy outcomes, as well as pro-inflammatory cytokines levels in serum and placenta were measured. High-dose URE (HURE) treatment decreased LPS-induced mean 24-h proteinuria and systolic blood pressure, and increased fetal weight, placental weight, and the number of live pups (P<0.05). Moreover, increased serum and placental levels of interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, and interferon-γ in the LPS-treated group were obviously inhibited after HURE administration (P<0.01). URE improved preeclampsia symptoms and mitigated inflammatory responses in the LPS-induced preeclampsia rat model, which suggests that the anti-inflammation effect of URE might be an alternative therapy for preeclampsia.


Assuntos
Anti-Inflamatórios/administração & dosagem , Inflamação/prevenção & controle , Extratos Vegetais/administração & dosagem , Pré-Eclâmpsia/prevenção & controle , Uncaria/química , Animais , Citocinas/sangue , Citocinas/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Lipopolissacarídeos , Pré-Eclâmpsia/induzido quimicamente , Gravidez , Ratos
10.
Toxicol Appl Pharmacol ; 376: 95-106, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31145917

RESUMO

Medical therapy of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) targets smooth muscle contraction in the prostate, for which α1A-adrenoceptor (α1A-AR) antagonists have been considered to be the primary therapeutic method. We investigated the effects and underlying mechanisms of isocorynoxeine (ICN), one of indole alkaloids from Uncaria, on the treatment of LUTS secondary to BPH via α1A-ARs in mice. The effect of ICN on prostatic contractility was studied via myographic measurements in the prostates of rabbits. The effects of ICN on bladder function, serum-hormone levels, bladder histology, and prostate histology were determined in testosterone propionate-induced prostatic hyperplasic wild-type (WT) and α1A-AR knockout (α1A-KO) mice. The cytotoxicity of ICN in cultured human prostatic stromal cells (WPMY-1) was assessed by the following: a cell-counting kit, measuring the relaxant effect on WPMY-1 by a collagen gel contraction assay, intracellular Ca2+ mobilization indicated by Fluo-4, cytoskeletal organization by phalloidin staining, and expressions of α1A-AR-mediated key messengers by western blot analyses. ICN non-competitively antagonized the contractions of prostates induced by α1A-AR agonists. ICN treatment improved bladder functions in prostatic hyperplasic WT mice, whereas it failed to ameliorate bladder functions in prostatic hyperplasic α1A-KO mice. In WPMY-1, ICN relaxed cell contractions on collagen gels, disrupted F-actin organization, inhibited α1A-AR agonist-stimulated Ca2+ mobilization, and antagonized α1A-ARs via the RhoA/ROCK2/MLC signaling pathway. Our results suggest that ICN may be a promising therapeutic drug for targeting α1A-ARs in the treatment of BPH/LUTS.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Alcaloides Indólicos/uso terapêutico , Hiperplasia Prostática/complicações , Uncaria/química , Doenças Urológicas/tratamento farmacológico , Doenças Urológicas/etiologia , Animais , Linhagem Celular , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiopatologia , Próstata/efeitos dos fármacos , Próstata/fisiopatologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/fisiopatologia , Coelhos , Receptores Adrenérgicos alfa 1/genética , Receptores Adrenérgicos alfa 1/fisiologia , Células Estromais , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia
11.
Life Sci ; 223: 137-145, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30858121

RESUMO

AIMS: Excessive inflammatory response and oxidative stress are considered as important pathogenic factors in the development of acute lung injury. Isorhynchophylline (IRN), a tetracyclic oxindole alkaloid isolated from Uncaria rhynchophylla, possesses anti-inflammatory and anti-oxidant activities. Our study aimed to investigate the effects and potential mechanisms of IRN on lipopolysaccharide (LPS)-stimulated murine alveolar macrophage cell lines MH-S and NR8383. MAIN METHODS: CCK-8 assay was used to evaluate the cytotoxicity of IRN and LPS. Inflammatory response was assessed by detecting the mRNA expressions and release of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-6, and plasminogen activator inhibitor-1 (PAI-1) using qRT-PCR and ELISA. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were examined by qRT-PCR and western blot. Oxidative stress was evaluated by detecting malondialdehyde (MDA) level and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). The changes of the toll like receptor (TLR4)/nuclear factor-kappa B (NF-κB)/nod-like receptor protein 3 (NLRP3) inflammasome pathway was detected by western blot. KEY FINDINGS: Treatment with LPS or IRN for 24 h showed no cytotoxicity on MH-S and NR8383 cells. IRN pretreatment inhibited LPS-induced production of inflammatory cytokines, expressions of iNOS and COX-2, and oxidative stress in murine alveolar macrophages. Additionally, IRN inhibited LPS-induced activation of TLR4/NF-κB/NLRP3 inflammasome pathway in MH-S cells. Mechanistically, inhibition of TLR4/NF-κB/NLRP3 inflammasome pathway by si-TLR4 suppressed LPS-induced inflammation and oxidative stress in murine alveolar macrophages. SIGNIFICANCE: IRN exerted anti-inflammatory and anti-oxidant effects on LPS-stimulated murine alveolar macrophages via inhibition of the TLR4/NF-κB/NLRP3 inflammasome pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Macrófagos Alveolares/efeitos dos fármacos , Oxindois/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Citocinas/genética , Lipopolissacarídeos/farmacologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Oxindois/isolamento & purificação , Ratos , Uncaria/química
12.
Xenobiotica ; 49(12): 1494-1503, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30741064

RESUMO

1. Yokukansankachimpihange (YKSCH), a Kampo formulation combining Citrus unshiu peel (CUP) and Pinellia tuber (PT) with yokukansan (YKS), has been recently used to treat the behavioral and psychological symptoms of dementia. Several flavonoids derived from CUP and PT reportedly exhibit psychopharmacological activity, but it remains unclear whether these flavonoids reach the brain after oral administration of YKSCH. 2. In this study, we first measured eight target flavonoids in the plasma and brain in rats orally administered YKSCH. Among these flavonoids, hesperidin, narirutin, nobiletin, and heptamethoxyflavone (HMF) were detected in the plasma, and nobiletin and HMF were detected in the brain. 3. Next, to clarify whether CUP and PT affect the pharmacokinetics of YKS ingredients in YKSCH, the plasma pharmacokinetics of geissoschizine methyl ether (GM) as a representative active ingredient in YKS was examined in rats orally administered YKSCH or YKS. There was no significant difference between the two groups, inferring that the pharmacokinetics of GM may not be affected by the two additional crude drugs. 4. Taken together, this study suggests that the CUP-derived flavonoids nobiletin and HMF may be responsible for the psychopharmacological effects of YKSCH in addition to YKS ingredients.


Assuntos
Encéfalo/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Flavonoides/metabolismo , Administração Oral , Animais , Encéfalo/efeitos dos fármacos , Citrus/química , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Flavonoides/sangue , Alcaloides Indólicos/sangue , Ratos Sprague-Dawley , Distribuição Tecidual , Uncaria/química
13.
Molecules ; 24(1)2019 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-30621230

RESUMO

The genus Uncaria is an important source of traditional Chinese medicines with multiple therapeutic effects. The identification of the correct species and accurate determination of the contents of bioactive constituents are important for quality control of Uncaria medicinal materials. Here, an integrated evaluation system based on DNA barcoding for species identification and quantitative analysis by LC-MS/MS has been established. DNA barcoding based on the ITS2 barcode region showed sufficient discriminatory power to precisely identify 24 samples from seven Uncaria species. The length of the 24 ITS2 sequences of Uncaria samples is 227 bp, and 17 variation sites were detected. Additionally, the results of qualitative and quantitative chemical analyses by LC-MS/MS indicated that the chemical compositions of all Uncaria samples were similar; while their contents of targeted alkaloids in samples from different species and origin areas were different. The contents of rhynchophylline (RC) and isorhynchophylline (IRC) were 2.9⁻1612 mg/kg and 2.60⁻1299 mg/kg in all tested samples, respectively. This study concludes that DNA barcoding should be used as the first screening step for Uncaria medicinal materials. Then, integration of DNA barcoding with chemical analyses should be applied in quality control of Uncaria medicinal materials in the medicinal industry.


Assuntos
Alcaloides/genética , Código de Barras de DNA Taxonômico , DNA de Plantas/genética , Uncaria/genética , Alcaloides/química , Cromatografia Líquida , DNA de Plantas/química , Alcaloides Indólicos/química , Medicina Tradicional Chinesa , Espectrometria de Massas em Tandem , Uncaria/química
14.
Zhongguo Zhong Yao Za Zhi ; 44(23): 5118-5123, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-32237347

RESUMO

The aim of this study was to study the effects of different light intensity on the growth,biomass accumulation and distribution,chlorophyll content and effective components of Uncaria rhynchophylla seedlings,and explore the suitable light intensity conditions for artificial cultivation of U. rhynchophylla seedlings. Three-year-old U. rhynchophylla seedlings were used as experimental materials. Four light intensity levels( 100%,70%-75%,30%-35%,5%-10%) were set up with different layers of black shading net. With the decrease of light intensity,the results showed that the plant height,basal diameter and biomass( root,stem,leaf and hook) of U.rhynchophylla seedlings exhibited the trend of " increase-decrease". Under 70%-75% light intensity,the plant height,basal diameter,biomass( root,stem,leaf,hook) of U. rhynchophylla seedlings were significantly higher than those of other treatments( P< 0. 05);under 5%-10% light intensity,the plant height,basal diameter and biomass( root,hook) of U. rhynchophylla seedlings were significantly lower than those of other treatments( P<0. 05). With the decrease of light intensity,the chlorophyll content of U. rhynchophylla seedlings increased gradually: under 100% light intensity,the chlorophyll content of U. rhynchophylla seedlings were the smallest,while under 100% light intensity,its chlorophyll content was the highest. With the decrease of light intensity,the contents of rhynchophylline and isorhynchophylline in different organs of U. rhynchophylla seedlings varied: under 30%-35% light intensity,the contents of rhynchophylline and isorhynchophylline in hooks and rhynchophylline content in stems were the highest; under 5%-10% light intensity,the contents of rhynchophylline and isorhynchophylline in leaves and stems of U. rhynchophylla were the highest. In conclusion,70%-75% light intensity is suitable for seedling growth and biomass accumulation,and 30%-35% light intensity is suitable for the accumulation of effective components in U. rhynchophylla seedlings.


Assuntos
Compostos Fitoquímicos/análise , Uncaria/química , Uncaria/crescimento & desenvolvimento , Uncaria/efeitos da radiação , Biomassa , Clorofila/análise , Luz , Oxindois/análise , Plântula/química , Plântula/crescimento & desenvolvimento , Plântula/efeitos da radiação
15.
Phytomedicine ; 51: 120-127, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30466609

RESUMO

BACKGROUND: Carboxylesterases (CEs) belong to the serine hydrolase family, and are in charge of hydrolyzing chemicals with carboxylic acid ester and amide functional groups via Ser-His-Glu. Uncaria rhynchophylla (Miq.) Miq. ex Havil. is a famous traditional Chinese medicine used in managing hyperpyrexia, epilepsy, preeclampsia, and hypertension in China. HYPOTHESIS/PURPOSE: To discover the potential natural human carboxylesterase 2 (hCE 2) inhibitors from U. rhynchophylla. METHODS: Compounds were obtained from the hooks of U. rhynchophylla by silica gel and preparative HPLC. Their structures were elucidated by using HRESIMS, 1D and 2D NMR spectra. Their inhibitory activeties and inhibition kinetics against hCE 2 were assayed by the fluorescent probe, and potential mechanisms were also investigated by molecular docking. RESULTS: Twenty-three compounds, including a new phenolic acid uncariarhyine A (1), eight known triterpenoids (2-9), and ten known aromatic derivatives (10, 13-16, and 19-23), were isolated from U. rhynchophylla. Compounds 1-5, 7, 9, and 15 showed significant inhibitory activities against hCE 2 with IC50 values from 4.01  ±â€¯0.61 µM to 18.60 ±â€¯0.21 µM, and their inhibition kinetic analysis results revealed that compounds 1, 5, 9, and 15 were non-competitive; compounds 3 and 4 were mixed-type, and compounds 2 and 7 were uncompetitive. Molecular docking studies indicated inhibition mechanisms of compounds 1-5, 7, 9, and 15 against hCE 2. CONCLUSION: Our present findings highlight potential natural hCE 2 inhibitors from U. rhynchophylla.


Assuntos
Carboxilesterase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Compostos Fitoquímicos/farmacologia , Triterpenos/farmacologia , Uncaria/química , China , Cromatografia Líquida de Alta Pressão , Humanos , Hidroxibenzoatos/isolamento & purificação , Hidroxibenzoatos/farmacologia , Cinética , Simulação de Acoplamento Molecular , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação
16.
PLoS One ; 13(10): e0205667, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30365495

RESUMO

Uncaria guianensis is native to the Amazon and is used traditionally as an anti-inflammatory. Natural populations of the species have declined markedly in recent times because of strong anthropic pressure brought about by deforestation and indiscriminate collection. The aim of the present study was to assess the genetic and chemical diversity among eight natural populations of U. guianensis located in the Brazilian states of Acre, Amapá and Amazonas. A set of four primer combinations was employed in sequence-related amplified polymorphism (SRAP) amplifications of leaf DNA, and the fragments were analyzed in an LI-COR model 4300 DNA Analyzer. Genetic variability within the populations (81%) was substantially greater than that detected between them (19%). The highest percentage of polymorphic loci (90.21%) and the largest genetic variability were observed in the population located in Mazagão, Amapá. Genetic differentiation between populations was high (Fst = 0.188) and the studied populations formed three distinct genetic groups (K = 3). The population located in Assis Brasil, Acre, presented the highest average content of the mitraphylline (0.60 mg/g dry weight,). However, mitraphylline and isomitraphylline not detected in most individuals in the studied populations, and it is questionable whether they should be considered as chemical markers of the species. The genetic data confirm the urgent need for conservation programs for U. guianensis, and for further studies aimed at ascertaining the genetic basis and heritability of alkaloid accumulation.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais , Extratos Vegetais/análise , Polimorfismo Genético , Uncaria/genética , Brasil , Etnofarmacologia , Alcaloides Indólicos/análise , Medicina Tradicional/métodos , Oxindois/análise , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/genética , Plantas Medicinais/química , Plantas Medicinais/genética , Uncaria/química
17.
Cell Physiol Biochem ; 47(4): 1453-1464, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29940559

RESUMO

BACKGROUND/AIMS: Uncaria rhynchophylla, known as "Gou-teng", is a traditional Chinese medicine (TCM) used to extinguish wind, clear heat, arrest convulsions, and pacify the liver. Although U. rhynchophylla has a long history of being often used to treat central nervous system (CNS) diseases, its efficacy and potential mechanism are still uncertain. This study investigated neuroprotective effect and the underlying mechanism of U. rhynchophylla extract (URE) in MPP+-induced SH-SY5Y cells and MPTP-induced mice. METHODS: MPP+-induced SH-SY5Y cells and MPTP-induced mice were used to established Parkinson's disease (PD) models. Quantitative proteomics and bioinformatics were used to uncover proteomics changes of URE. Western blotting was used to validate main differentially expressed proteins and test HSP90 client proteins (apoptosis-related, autophagy-related, MAPKs, PI3K, and AKT proteins). Flow cytometry and JC-1 staining assay were further used to confirm the effect of URE on MPP+-induced apoptosis in SH-SY5Y cells. Gait analysis was used to detect the behavioral changes in MPTP-induced mice. The levels of dopamine (DA) and their metabolites were examined in striatum (STR) by HPLC-EC. The positive expression of tyrosine hydroxylase (TH) was detected by immunohischemical staining and Western blotting. RESULTS: URE dose-dependently increased the cell viability in MPP+-induced SH-SY5Y cells. Quantitative proteomics and bioinformatics results confirmed that HSP90 was an important differentially expressed protein of URE. URE inhibited the expression of HSP90, which further reversed MPP+-induced cell apoptosis and autophagy by increasing the expressions of Bcl-2, Cyclin D1, p-ERK, p-PI3K p85, PI3K p110α, p-AKT, and LC3-I and decreasing cleaved caspase 3, Bax, p-JNK, p-p38, and LC3-II. URE also markedly decreased the apoptotic ratio and elevated mitochondrial transmembrane potential (DΨm). Furthermore, URE treatment ameliorated behavioral impairments, increased the contents of DA and its metabolites and elevated the positive expressions of TH in SN and STR as well as the TH protein. CONCLUSIONS: URE possessed the neuroprotective effect in vivo and in vitro, regulated MAPK and PI3K-AKT signal pathways, and inhibited the expression of HSP90. U. rhynchophylla has potentials as therapeutic agent in PD treatment.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas de Choque Térmico HSP90/biossíntese , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos , Uncaria/química , Animais , Linhagem Celular Tumoral , Medicamentos de Ervas Chinesas/química , Humanos , Camundongos , Fármacos Neuroprotetores/química , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia , Proteômica
18.
PLoS One ; 13(6): e0199259, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29953548

RESUMO

Uncaria macrophylla Wall. is an important Chinese medicinal herb. Rhynchophylline (RIN) and isorhynchophylline (IRN) are its major active compounds. We investigated the influence of genetic differentiation and environmental factors on the RIN and IRN to find the main influencing factors of their contents and lay the foundation for the following cultivation and breeding. We used inter-simple sequence repeat (ISSR) markers to investigate the genetic diversity, and high-performance liquid chromatography (HPLC) to measure the contents of RIN and IRN in 200 samples of U. macrophylla obtained from nine natural populations, and then to analyze the correlation between genetic differentiation, environmental factors of sampling sites and the contents of RIN and IRN. We found that High intra-population (80.05%) and low inter-population (19.95%) genetic diversity existed in the samples of U. macrophylla. To some extent, genetic differentiation and the contents of RIN and IRN had correlation in individual populations (such as JH, MH, XM, and ML). The RIN and IRN contents were significant negatively correlated with the precipitation in May (RIRN = -0.771, p = 0.015) and June (RRIN = -0.814, p = 0.008; RIRN = -0.921, p = 0.000), indicating that precipitation was the main affecting factor of their contents. Interestingly, the analysis results showed that the RIN content had a significant positive correlation (r = 0.585, p = 0.000) with the IRN content (they are isomers); the proportion of RIN had a significant negative correlation with the sum of the two (r = -0.390, p<0.0001), while the proportion of IRN had a significant positive correlation (r = 0.390, p<0.0001). It meant that, with the total quantity of the two compounds increased, the proportion of RIN decreased and the proportion of IRN increased, illustrating that their conversion exist some regularity. Moreover, the content ratio of RIN and IRN was significant positively correlated with the January precipitation (r = 0.716, p = 0.030), implying that January may be the key period for the mutual transformation of RIN and IRN.


Assuntos
Parede Celular/metabolismo , Meio Ambiente , Variação Genética , Oxindois/metabolismo , Uncaria/genética , Uncaria/metabolismo , Parede Celular/química , China , DNA de Plantas , Geografia , Filogenia , Compostos Fitoquímicos/metabolismo , Uncaria/química , Uncaria/classificação
19.
J Chromatogr A ; 1563: 124-134, 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-29880214

RESUMO

Comprehensive chemical profiling is of great significance for understanding the therapeutic material basis and quality control of herbal medicines, which is challenging due to its inherent chemical diversity and complexity, as well as wide concentration range. In this study, we introduced an enhanced strategy integrating offline two-dimensional (2D) separation and the step-wise precursor ion list-based raster-mass defect filter (step-wise PIL-based raster-MDF) scan by tandem LTQ-Orbitrap mass spectrometer. A comprehensive analysis of indole alkaloids in five botanical origins of Uncariae Ramulus Cum Unicis (Gou-Teng) was used as an exemplary application. A positively charged reversed phase (PR) × conventional RP LC system in different pH conditions was constructed with the orthogonality of 74%. A theoretical step-wise PIL among 310-950 Da with the step-size of 2 Da was developed to selectively trigger fragmentations and extend the coverage of potential indole alkaloids. Simultaneously, by defining parent mass width (PMW) of the step-wise PIL to ±55 mDa, a raster-MDF screening was achieved in the acquisition process. Additionally, subtype classification and structural elucidation were facilitated by a four-step interpretation strategy. As a result, a total of 1227 indole alkaloids were efficiently exposed and characterized from five botanical origins of Gou-Teng, which showed high chemical diversity. A systematic comparison among five species was first performed and only 66 indole alkaloids were common. For method validation, three new alkaloid N-oxides were isolated and unambiguously identified by NMR. The present study provides a novel data-dependent acquisition method with improved target coverage and high selectivity. The integrated strategy is practical to efficiently expose and comprehensively characterize complex components in herbal medicines.


Assuntos
Cromatografia Líquida de Alta Pressão , Alcaloides Indólicos/análise , Espectrometria de Massas em Tandem , Cromatografia de Fase Reversa , Medicamentos de Ervas Chinesas/química , Concentração de Íons de Hidrogênio , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Conformação Molecular , Peso Molecular , Uncaria/química , Uncaria/metabolismo
20.
Phytomedicine ; 43: 120-125, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29747744

RESUMO

BACKGROUND: We recently focused on alkaloids in Uncaria hook (a constituent of the Kampo medicine, yokukansan) and identified the pharmacological action of geissoschizine methyl ether on several G protein-coupled receptors. However, the functions of other identified alkaloids in Uncaria hook, including hirsutine, hirsuteine, rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine, are not clear. PURPOSE: To evaluate the effect of seven alkaloids in Uncaria hook (hirsutine, hirsuteine, rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine and geissoschizine methyl ether) on the hydroxytryptamine type-3 (5-HT3) receptor ion channel. STUDY DESIGN: We examined the effect of these alkaloids on the current of human 5-HT3 receptors expressed in Xenopus laevis oocytes. METHODS: The human 5-HT3A subunit alone for the 5-HT3A receptor, or 5-HT3A and 5-HT3B subunits for the 5-HT3AB receptor, were expressed in Xenopus laevis oocytes. The 5-HT current was measured with or without alkaloid application using a two-electrode voltage clamp. RESULTS: Each alkaloid, except for geissoschizine methyl ether, weakly inhibited the 5-HT-mediated 5-HT3A and/or 5-HT3AB receptor current, but co-application of these seven alkaloids inhibited the current strongly. CONCLUSION: Each alkaloid contributes to antagonism of the 5-HT3 receptor.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Alcaloides Indólicos/farmacologia , Antagonistas do Receptor 5-HT3 de Serotonina/farmacologia , Alcaloides/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Medicamentos de Ervas Chinesas/química , Feminino , Humanos , Alcaloides Indólicos/química , Medicina Kampo , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Oxindois , Receptores 5-HT3 de Serotonina/genética , Receptores 5-HT3 de Serotonina/metabolismo , Uncaria/química , Xenopus laevis
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...