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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
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
9.
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
10.
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
11.
Chem Pharm Bull (Tokyo) ; 66(5): 527-534, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29503397

RESUMO

Uncaria rhynchophylla is woody climber plant distributed mainly in China and Japan, the stems and hooks of which can be collected as "Gou-Teng" for the treatment of hyperpyrexia, epilepsy and preeclampsia. Fudan University first manufactured KHR98, the extract of Uncaria rhynchophylla. In order to study the active components and structural information of KHR98, we established a HPLC coupled with quadrupole time-of-flight (Q-TOF)-MS method for rapid analysis of alkaloids. In qualitative analysis, a total of eight compounds, including four known alkaloids and four unknown components, were detected and identified. The fragmentation behaviors, such as the fragment ion information and the fragmentation pathways of the eight components were summarized simultaneously, and the concentration of the above components was determined by HPLC-MS method. The quantitative method was proved to be reproducible, precise and accurate. This study shed light on the standardization and quality control of the KHR98 and provided a foundation for the further research on pharmacology, follow-up clinical research and New Drug Applications.


Assuntos
Alcaloides/análise , Uncaria/química , Cromatografia Líquida de Alta Pressão , Conformação Molecular , Espectrometria de Massas em Tandem
12.
Fitoterapia ; 127: 47-55, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29373834

RESUMO

Four new zwitterionic monoterpene indole alkaloids, rhynchophyllioniums A-D (1-4), together with eight known alkaloids (5-12), were isolated from the hook-bearing stems of Uncaria rhynchophylla. Their structures were elucidated by extensive spectroscopic data analysis of MS, 1D and 2D NMR, and ECD, and the zwitterionic forms and absolute configurations of 1 and 2 were unambiguously confirmed by single crystal X-ray diffraction analysis. All the isolates, including the monoterpene indole alkaloids with free C-22 carboxyl group and those with C-22 carboxyl methyl ester, were proved to be naturally coexisting in the herb by LC-MS analysis. This is the first report of monoterpene indole alkaloids that exist in the form of zwitterion. Additionally, the cytotoxic activities of all isolates against A549, HepG2, and MCF-7 cell lines are reported.


Assuntos
Alcaloides Indólicos/isolamento & purificação , Monoterpenos/isolamento & purificação , Caules de Planta/química , Uncaria/química , Linhagem Celular Tumoral , Humanos , Estrutura Molecular
13.
Biomed Chromatogr ; 32(3)2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29034541

RESUMO

Uncaria is a multi-source herb and its species identification has become a bottleneck in quality control. To study the identification method of different Uncaria species herbs through HPLC-MS coupled with rDNA Internal Transcribed Spacer (rDNA ITS) sequence, both plant morphological traits and molecular identification were used to determine the species of every collected Uncaria herb. The genetic analysis of different Uncaria species was performed using their rDNA ITS sequence as a molecular marker. Meanwhile, the phylogenetic relationships of 22 samples from six Uncaria species were divided and classified clearly. By optimizing the chromatographic conditions, a practical HPLC method to differentiate various varieties of Uncaria herbs was set up based on a set of characteristic components across each species. A high-performance liquid chromatography-photodiode array detector tandem ion trap and time of flight mass spectrometry technique combined with reference substances was utilized to derive 21 characteristic compounds containing six groups of six Uncaria species in China. Thus, this study provides a feasible method to solve the current problem of confusion in Uncaria species, and makes a significant step forward in the appropriate clinical use, in-depth research and further utilization of different Uncaria species.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , DNA de Plantas/genética , Espectrometria de Massas por Ionização por Electrospray/métodos , Uncaria , DNA Intergênico/genética , DNA de Plantas/análise , Filogenia , Extratos Vegetais/análise , Extratos Vegetais/química , Folhas de Planta/química , Análise de Sequência de DNA , Uncaria/química , Uncaria/classificação , Uncaria/genética
14.
Acta Pharmacol Sin ; 39(3): 345-356, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29119967

RESUMO

Autophagy plays an important role in alleviating oxidative stress and stabilizing atherosclerotic plaques. However, the potential role of autophagy in endothelial vasodilation function has rarely been studied. This study aimed to investigate whether rhynchophylla total alkaloid (RTA) has a positive role in enhancing autophagy through decreasing oxidative stress, and improving endothelial vasodilation. In oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs), RTA (200 mg/L) significantly suppressed ox-LDL-induced oxidative stress through rescuing autophagy, and decreased cell apoptosis. In spontaneous hypertensive rats (SHR), administration of RTA (50 mg·kg-1·d-1, ip, for 6 weeks) improved endothelin-dependent vasodilation of thoracic aorta rings. Furthermore, RTA administration significantly increased the antioxidant capacity and alleviated oxidative stress through enhancing autophagy in SHR. In ox-LDL-treated HUVECs, we found that the promotion of autophagy by RTA resulted in activation of the AMP-activated protein kinase (AMPK) signaling pathway. Our results show that RTA treatment rescues the ox-LDL-induced autophagy impairment in HUVECs and improves endothelium-dependent vasodilation function in SHR.


Assuntos
Alcaloides/farmacologia , Autofagia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Uncaria/química , Vasodilatação/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Aorta/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Lipoproteínas LDL/metabolismo , Masculino , Ratos , Transdução de Sinais/efeitos dos fármacos
15.
Xenobiotica ; 48(10): 990-998, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28990840

RESUMO

1. The objective was to investigate the underlying mechanism of the stereoselectivity in the metabolism of rhynchophylline (RIN) and isorhynchophylline (IRN) epimers in rat liver microsomes (RLM). 2. After incubation, eight metabolites of RIN (M1-5) and IRN (M6-8) reacted at A- and C-ring were identified using LC-Q-TOF/MS. Metabolic pathways included oxidation, hydroxylation, N-oxidation and dehydrogenation. In addition, hydroxylation at A-ring was the major metabolic pathway for RIN whereas the oxidation at C-ring was the major one for IRN. 3. Enzyme kinetics showed that the intrinsic clearance (CLint) for IRN elimination was 1.9-fold higher than RIN and the degradation half-life (T1/2) of RIN was 4.7-fold higher than that of IRN, indicating IRN was more favorable to be metabolized than RIN in RLM. 4. Data from chemical inhibition study demonstrated CYP3A was the predominant isoform involved in the metabolic elimination of both epimers, as well as the formation of M1-8. 5. In conclusion, data revealed that due to the spatial configurations at C-7 position, RIN and IRN epimers possessed different hepatic metabolic pathways and elimination rates which were mainly mediated by CYP3A.


Assuntos
Alcaloides Indólicos/química , Alcaloides Indólicos/metabolismo , Microssomos Hepáticos/metabolismo , Uncaria/química , Animais , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Hidroxilação , Cinética , Metaboloma/efeitos dos fármacos , Metabolômica , Microssomos Hepáticos/efeitos dos fármacos , Oxirredução , Oxindois , Ratos , Estereoisomerismo
16.
Planta Med ; 84(6-07): 449-456, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29216668

RESUMO

It remains a challenge to establish new monographs for herbal drugs derived from multiple botanical sources. Specifically, the difficulty involves discriminating and quantifying these herbs with components whose levels vary markedly among different samples. Using Uncaria stem with hooks as an example, a characteristic chromatogram was proposed to discriminate its five botanical origins and to quantify its characteristic components in the chromatogram. The characteristic chromatogram with respect to the components of Uncaria stem with hooks with the five botanical origins was established using 0.02% diethylamine and acetonitrile as the mobile phase. The total analysis time was 50 min and the detection wavelength was 245 nm. Using the same chromatogram parameters, the single standard to determine multicomponents method was validated to simultaneously quantify nine indole alkaloids, including vincosamide, 3α-dihydrocadambine, isocorynoxeine, corynoxeine, isorhynchophylline, rhynchophylline, hirsuteine, hirsutine, and geissoschizine methyl ether. The results showed that only the Uncaria stem with hooks from Uncaria rhynchophylla, the most widely used in the herbal market, showed the presence of these nine alkaloids. The conversion factors were 1.27, 2.32, 0.98, 1.04, 1.00, 1.02, 1.26, 1.33, and 1.25, respectively. The limits of quantitation were lower than 700 ng/mL. The total contents of 31 batches of Uncaria stem with hooks were in the range of 0.1 - 0.6%, except for Uncaria hirsuta Havil and Uncaria sinensis (Oliv.) Havil. The results also showed that the total content of indole alkaloids tended to decrease with an increase in the hook diameter. This showed that the characteristic chromatogram is practical for controlling the quality of traditional Chinese medicines with multiple botanical origins.


Assuntos
Caules de Planta/química , Uncaria/química , Cromatografia Líquida de Alta Pressão/métodos , Medicina Herbária/métodos , Alcaloides Indólicos/análise , Controle de Qualidade
17.
J Sep Sci ; 41(7): 1532-1538, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29274199

RESUMO

Uncaria rhynchophylla (Gou-Teng) as the monarch herb of many formulae (Fufang), e.g. "Tian-Ma-Gou-Teng-Yin," "Ling-Jiao-Gou-Teng-Yin," and "Yi-Gan-San", is a famous traditional Chinese medicine documented in the Chinese pharmacopoeia for mental and cardiovascular diseases. In the traditional Chinese medicine system, only the hook-bearing stems are used as the crude materials for Gou-Teng, and the hooks are always considered more effective than the stems. Focusing on the mono-herb and its active constituents from combinatorial formulae is the core idea of reductionism of traditional Chinese medicine theory. Detailed liquid chromatography with mass spectrometry analysis on the hooks of U. rhynchophylla was performed to profile the chemical constituents based on tandem mass spectrometry fragmentation and UV absorption. Under the guidance of liquid chromatography with ion trap/time-of-flight mass spectrometry, one new indole alkaloid triglycoside (1), together with five known compounds 2-6 as the main constituents, were isolated from the hooks of U. rhynchophylla by various column chromatography methods. Compound 1 showed moderate activity on MT1 and MT2 melatonin receptors with agonistic rates of 79.6 and 46.3% at the concentration of 1 mM. This dereplication strategy can be equally applicable to rapidly disclose the active constituents of other Chinese herbs through targeted purification.


Assuntos
Glicosídeos/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Estruturas Vegetais/química , Uncaria/química , Cromatografia Líquida , Glicosídeos/química , Alcaloides Indólicos/química , Espectrometria de Massas , Fatores de Tempo
18.
Curr Med Chem ; 25(9): 1036-1045, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28322152

RESUMO

BACKGROUND: Geissoschizine methyl ether (GM) is one of the indole alkaloids in Uncaria hook, and an active ingredient of yokukansan (YKS) that improves behavioral and psychological symptoms of dementia (BPSD) in patients with several types of dementia. The pharmacological action of GM has been related to various serotonin (5-HT) receptor subtypes. OBJECTIVE: The aim of this article is to review the binding characteristics of GM to the 5-HT receptor subtypes in the brains using our own data and previous findings. METHOD: Competitive receptor-binding and agonist/antagonist activity assays for several 5-HT receptor subtypes were performed. Moreover, the articles describing pharmacokinetics and brain distribution of GM were searched in PubMed. RESULTS: GM bound the following 5-HT receptor subtypes: 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5- HT4, 5-HT5A, 5-HT6, and 5-HT7. Among these receptors, GM had partial agonistic activity for 5-HT1A receptors and antagonistic activity for 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT7 receptors. Also, GM was metabolized by various CYP isoforms, mainly CYP3A4. Parent/unchanged GM was detected in both the blood and brain of rats after oral administration of YKS. In the brains, GM was presumed to bind to 5- HT1A, 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT7 receptors on neuron-like large cells mainly in the frontal cortex. CONCLUSION: These results suggest that GM is a pharmacologically important alkaloid that regulates various serotonergic activities or functions by binding to multiple 5-HT receptor subtypes. Thus, this review provides recent 5-HT receptor-related evidence that GM is partly responsible for pharmacological effects of YKS.


Assuntos
Alcaloides Indólicos/metabolismo , Receptores de Serotonina/metabolismo , Uncaria/química , Animais , Ligação Competitiva , Encéfalo/metabolismo , Medicamentos de Ervas Chinesas/química , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Ligação Proteica , Ratos , Receptores de Serotonina/química
19.
Zhongguo Zhong Yao Za Zhi ; 42(1): 94-99, 2017 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-28945031

RESUMO

Using four Uncariae Cum Uncis materials including Uncaria sinensis (HGT), U. hirsutea (MGT), Jianhe U. rhynchophylla (JHGT) and U. rhynchophylla(GT) as the research objects, the correlations between medicinal materials' yield and photosynthetic ecophysiology-factors in the plant exuberant growth period were studied. Results showed that the Uncaria plants net photosynthetic rate (Pn) changed by unimodal curve. There was not "midday depression" phenomenon. There was a different relationship among the photosynthetic ecophysiology-factors and between photosynthetic ecophysiology-factors and medicinal materials' yield. Pn,Tl,Gs had a significant correlation with medicinal materials' yield(M)and were the most important factors of growth.


Assuntos
Fotossíntese , Uncaria/fisiologia , Folhas de Planta/fisiologia , Plantas Medicinais/química , Plantas Medicinais/fisiologia , Uncaria/química
20.
Phytother Res ; 31(11): 1676-1685, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28872719

RESUMO

Herbal medications are commonly used to manage symptoms associated with osteoarthritis (OA). This systematic review evaluated the effectiveness and safety of oral medications used in Brazil for the treatment of OA. Randomized clinical trials involving adults with OA treated by a herbal medicine or a control group were eligible. The primary outcomes measured were pain, physical function, swelling, stiffness and quality of life; and the secondary outcomes were adverse events, activity limitations and treatment satisfaction. Sixteen studies were included (n = 1,741 patients) in the systematic review and nine studies in the meta-analysis, representing 6 of the 13 herbal medicines studied: Boswellia serrata (n = 2), Curcuma longa (n = 3), Harpagophytum procumbens (n = 1), Salix daphnoides (n = 3), Uncaria guianensis (n = 2) and Zingiber officinale (n = 5). B. serrata was more effective than both placebo and valdecoxib for improvement of pain and physical function. No difference was observed for H. procumbens, C. longa and U. guianensis compared with control. Z. officinale showed improvement of pain over placebo. The evidence was insufficient to support the effective and safe use of these herbal medicines, because the quality of evidence of studies was low. This study guides managers of the Brazilian public health system and prescribers in decision-making regarding the use of these herbal medicines for OA. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Osteoartrite/tratamento farmacológico , Fitoterapia , Preparações de Plantas/uso terapêutico , Boswellia/química , Brasil , Curcuma/química , Gengibre/química , Harpagophytum/química , Medicina Herbária , Humanos , Plantas Medicinais/química , Ensaios Clínicos Controlados Aleatórios como Assunto , Salix/química , Uncaria/química
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