Short-term treatment with Uncaria tomentosa aggravates the injury phenotype in mdx mice

Introduction: Uncaria tomentosa (Willd. ex Roem. & Schult.) DC. (Rubiaceae) or UT is a medicinal plant with antiviral, antimutagenic, anti-inflammatory and antioxidant properties. Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by mutations in the dystrophin gene; this deficiency leads to sarcolemma instability, inflammation, muscle degeneration and fibrosis. Objective: Considering the importance of inflammation to dystrophy progression and the anti-inflammatory activity of UT, in the present study we evaluated whether oral administration of UT extract would ameliorate dystrophy in the mdx mice, a DMD model. Methods: Eight-week-old male mdx mice were submitted to 200 mg/kg body weight daily UT oral administration for 6 weeks. General histopathology was analysed, and muscle tumor necrosis factor α, transforming growth factor-ß, myostatin and osteopontin transcript levels were assessed. The ability of mice to sustain limb tension to oppose their gravitational force was measured. Data were analysed with the unpaired Student's t-test. Results: Morphologically, both untreated and UT-treated animals exhibited internalised nuclei, increased endomysial connective tissue and variations in muscle fibre diameters. Body weight and muscle strength were significantly reduced in the UT-treated animals. Blood creatine kinase was higher in UT-treated compared to untreated animals. In tibialis anterior, myostatin, transcript was more highly expressed in the UT-treated while in the diaphragm muscle, transforming growth factor-ß transcripts were less expressed in the UT-treated. Conclusion: While previous studies identified anti-inflammatory, antiproliferative and anticarcinogenic UT effects, the extract indicates worsening of dystrophic muscles phenotype after short-term treatment in mdx mice.

Minor triterpenoid acids from an aqueous extract of Uncaria rhynchophylla / 药学学报

Seventeen minor triterpenoid acids (1-17) were isolated from an aqueous decoction of Uncaria rhynchophylla by a combinatory application of column chromatography using multiple stationary phases, including macroporous adsorbent resin, MCI resin, Sephadex LH-20, Toyopearl HW-40C, silica gel, and C18 reversed phase silica gel, combined with separation techniques of flash chromatography (FC) and high performance liquid chromatography (HPLC). Their structures were determined by analysis of HR-ESI-MS, UV, CD, and IR as well as 1D and 2D NMR spectroscopic data, of which eight new compounds (1-8) are named successively uncarinic acids Q-X, while the structures of 2 and 7 were confirmed by single crystal X-ray diffraction. In the in vitro assays, 27-hydroxyolean-12-en-28-oic acid (17) inhibited TGF-β-induced HSC-T6 cell activation at the concentration of 5 μmol·L-1.

Uncária Tomentosa (Wild.) D.C. em processos inflamatórios na doença de Alzheimer / Uncária Tomentosa (Wild.) D.C. en procesos inflamatorios en la enfermedad de Alzheimer / Uncária Tomentosa (Wild.) D.C. in inflammatory processes in Alzheimer's disease

Objetivo: explorar os mecanismos envolvidos no desencadeamento e progressão da Doença de Alzheimer (DA) de forma a embasar a sugestão da planta Uncaria Tomentosa (Wild.) como mais uma possiblidade terapêutica coadjuvante para prevenção e tratamento da DA. Método: Trata-se de uma revisão narrativa da literatura realizada com busca de artigos publicados em bases indexadas e diretamente nas revistas de interesse, utilizando-se como descritores "Uncária Tomentosa", "Doença de Alzheimer", e os respectivos termos em inglês. Resultados: com os avanços para a compreensão dos mecanismos moleculares que desencadeiam os efeitos apresentados no desenvolvimento da DA, os diversos mecanismos dos fitocompostos presentes na planta sugerem sua utilização como neuroprotetor, por mecanismos anti-inflamatórios, imunomoduladores e antioxidantes, cujas evidências em literatura são apresentadas para defesa de sua utilização nesta patologia. Conclusão: foram encontradas evidências para sugerir a inclusão da Uncaria tomentosa (Wild.) como possível terapêutica complementar no tratamento da DA. Sua utilização deve ser melhor explorada para aplicação como tratamento complementar as terapêuticas convencionais para a DA

Objective: to explore the mechanisms involved in the triggering and progression of Alzheimer's disease (AD) in order to support the suggestion of the Uncaria Tomentosa (Wild.) plant as another adjuvant therapeutic possibility for the prevention and treatment of AD. Method: This is a narrative review of the literature conducted with a search for articles published on indexed bases and directly in the journals of interest, using as descriptors "Uncária Tomentosa", "Alzheimer's disease", and the respective terms in English. Results: with advances to understand the molecular mechanisms that trigger the effects presented in the development of AD, the various mechanisms of phytocompounds present in the plant suggest its use as neuroprotector, by anti-inflammatory, immunomodulatory and antioxidant mechanisms, whose evidence in the literature is presented to defend its use in this pathology. Conclusion: evidence was found to suggest the inclusion of Uncaria tomentosa (Wild.) as a possible complementary therapy in the treatment of AD. Its use should be better explored for application as a complementary treatment to conventional therapies for AD.

Objetivo: explorar los mecanismos implicados en el desencadenamiento y progresión de la enfermedad de Alzheimer (EA) con el fin de apoyar la sugerencia de la planta Uncaria Tomentosa (silvestre) como otra posibilidad terapéutica adyuvante para la prevención y tratamiento de la EA. Método: Se trata de una revisión narrativa de la literatura realizada con una búsqueda de artículos publicados en bases indexadas y directamente en las revistas de interés, utilizando como descriptores "Uncária Tomentosa", "Alzheimer's disease", y los términos respectivos en inglés. Resultados: con los avances para comprender los mecanismos moleculares que desencadenan los efectos presentados en el desarrollo de la EA, los diversos mecanismos de fitocompuestos presentes en la planta sugieren su uso como neuroprotector, por mecanismos antiinflamatorios, inmunomoduladores y antioxidantes, cuya evidencia en la literatura se presenta para defender su uso en esta patología. Conclusión: se encontró evidencia que sugiere la inclusión de Uncaria tomentosa (Silvestre) como una posible terapia complementaria en el tratamiento de la EA. Su uso debe explorarse mejor para su aplicación como tratamiento complementario a las terapias convencionales para la EA.

Content determination of four kinds of alkaloids in Uncaria by HPLC-MS-AIS / 四川精神卫生

ObjectiveTo determine the contents of four kinds of indole alkaloids （rhynchophylline， isorhynchophylline， corynoxeine， isocorynoxeine） in Uncaria by high-performance liquid chromatography-mass spectrometry-automatic internal standard （HPLC-MS-AIS）. MethodsChromatographic separation was performed using C18 column （3.0 mm×50 mm， 3.3 μm）， and the mobile phase， comprising 0.1% formic acid aqueous solution-acetonitrile （82∶18， V/V）， was eluted at a flow rate of 0.5 mL/min and column temperature of 30℃. Mass spectrometric detection was performed using an electrospray ionization source and positive multiple-reaction monitoring mode at a voltage capillary of 4 000 V. The mass-to-charge ratio （m/z） transition was 385.25/160.10 for rhynchophylline， 385.30/160.10 for isorhynchophylline， 383.25/160.15 for corynoxeine and 383.25/160.15 for isocorynoxeine， respectively. The injection volume was kept constant at 2 μL. ResultsThe linear concentration ranges of rhynchophylline， isorhynchophylline， corynoxeine and isocorynoxeine were 2.30~600.00 ng/mL （r=0.999 3）， 2.30~600.00 ng/mL （r=0.999 2）， 2.47~650.00 ng/mL （r=0.999 4） and 2.47~650.00 ng/mL （r=0.999 2）， respectively. The relative standard deviation （RSD） of precision and stability were all lower than 5.00%， the accuracy ranged from 92.40% to 104.10%， and the average recovery was 95.90%~104.60%. ConclusionHPLC-MS-AIS method is simple and accurate for the determination of four kinds of alkaloids in Uncaria， and can be used as a new method for quality control of Uncaria.

Megastigmanes from an aqueous extract of Uncaria rhynchophylla / 药学学报

Five new megastigmanes (1-5) were isolated from a decoction of Uncaria rhynchophylla by separation techniques of column chromatography using a combination of multiple stationary phases, including macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and Toyopearl HW-40F, and reversed phase HPLC. Their structures were characterized by spectroscopic data analysis of HR-ESI-MS, NMR, and CD, in combination with Mosher's mothed as well as ECD and NMR calculations. The new compounds were named uncarphyllonone A (1), uncarphyllonols A (2) and B (3), and uncarphabscisic acids A (4) and B (5). Although the structures of 3 and 4 were previously reported, the reported NMR spectroscopic data were incorrect or do not support the assigned structures in literatures. This is also the first report of discovery of new megastigmane natural products from the Uncaria genus.

Steroids from Uncaria rhynchophylla / 中国中药杂志

Thirteen steroids(1-13) were isolated from the non-alkaloid constituents of Uncaria rhynchophylla by column chromatography on silica gel, ODS, Sephadex LH-20, and preparative HPLC chromatography, and their structures were elucidated by analyses of the MS and NMR spectral data. All the compounds were isolated from the genus Uncaria for the first time, and 1 was a new compound. The ~1H-NMR and ~(13)C-NMR data of two compounds(12 and 13) in deuteron-chloroform were completely assigned. This study enriched the steroid constituents of U. rhynchophylla and provided scientific references for the elucidation of active constituents and further development and utilization of U. rhynchophylla.

Cloning and analysis of STR gene and its promoter from Uncaria / 药学学报

On the basis of the Uncaria transcriptome, specific primers were designed for UrSTR. The full-length cDNA of UrSTR (GeneBank: OL310251) was 1 541 bp, encoding 345 amino acid residues, and the promoter region sequence of UrSTR (GeneBank: OL310252) was 1 179 bp. Phylogenetic tree is revealed that UrSTR had a closest relationship with STR from Ophiorrhiza pumila and Ophiorrhiza japonica. Localization of UrSTR protein is revealed located in the vacuole membrane. Plant-care analysis indicated that the promoter region sequence of UrSTR, covering multiple light, stress and hormone-response cis-regulatory elements, and verified transcriptional activity. The results of SDS-PAGE show that pET-28a-UrSTR recombinant protein was successfully expressed, and the size was anticipated. The UrSTR prokaryotic expression system needs to be optimized in the later stage. The research lays the foundation for further purification to study its structure and functional characterization of the UrSTR protein.

High antibacterial properties of green synthesized gold nanoparticles using Uncaria gambir Roxb. leaf extract and triethanolamine

The development of antibacterial agents is increasingly gaining much attention due to the expansion activity ofmulti-drug resistant bacteria in causing many diseases. Metallic nanoparticles especially gold nanoparticles in thefield of nanotechnology is one of the new and significant materials to be developed as antibacterial agents. Goldnanoparticles have been successfully synthesized using Uncaria gambir Roxb. leaf extract as a bioreducing agent andtriethanolamine as a capping agent, through reduction of Au+3 by flavonoid compound in the leaf extract. The effect oftriethanolamine and hydrogen tetrachloroaurate (III) acid concentration on the stability and size of nanoparticles wasstudied. The presence of triethanolamine 1% as a capping agent successfully maintained the stability of colloidal goldnanoparticles with a concentration of hydrogen tetrachloroaurate (III) acid at 100 ppm. X-Ray Diffraction analysisshowed peak patterns corresponding to the metallic gold standard with a crystallite size of 32.52 nm. TransmissionElectron Microscope analysis showed that particles were spherical, hexagonal, and triangular, where the smallestparticle size was 7 nm. Synthesized gold nanoparticles showed great antibacterial activity against E. coli and S. aureus.The stability and antibacterial activity of synthesized gold nanoparticles showed good potential to be developed inbiomedical applications

Lipidomics study on intervention by Uncaria on hepatic metabolic disorder in spontaneously hypertensive rats / 药学学报

In this paper, the lipidomics was used to analyze the changes to address how Uncaria interrupts lipid metabolism in the liver of spontaneously hypertensive rats, and to explore the mechanism of action of Uncaria. All the experiments were approved by the animal protection and use committee of Shandong University of Traditional Chinese Medicine. UHPLC-Q Extractive orbitrap high-resolution mass spectrometry was used to collect lipid metabolite information of the rat livers. Through pattern recognition, matters with noticeable differences were recognized. Mass spectrum and data base searching helped to identify the potential biomarkers. Pattern recognition results indicated that the rats from control versus SHR group showed clear differences. Compared with the rats from the control group, there are decreases in sphosphatidylcholine, phosphatidic acid, diacylglycerol and sphingomyelin in rats from the SHR group, however lysophosphatidylcholine, triglyceride, linoleic acid, arachidonic acid and ceramide are increased. Uncaria could regulate the disorder of lipid metabolism by interfering with glycerophospholipid, sphingolipid, linoleic acid, and arachidonic acid metabolic pathways. This study provided the mechanistic understanding of the impact of Uncaria on lipid metabolism and revealed the lipid metabolism pathways affected to offer the explanation for the complex mechanism of action.

Alkaloids from an aqueous extract of Uncaria rhynchophylla / 药学学报

Five alkaloids were isolated from a decoction of Uncaria rhynchophylla by a combination of various chromatographic techniques, including macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and reversed phase HPLC. Their structures were characterized by comprehensive analyses of spectroscopic data as monoterpene indole alkaloids (+)-(7R)-3-oxo-7-hydroxy-3,7-seco-dihydrorhynchohylline (1), (+)-(7S)-3-oxo-7-hydroxy-3,7-seco-dihydrorhyncho-hylline (2), (+)-(7R)-3-oxo-7-hydroxy-3,7-seco-rhynchohylline (3) and (+)-(7S)-3-oxo-7-hydroxy-3,7-seco-rhynchohylline (4), and a β-carboline alkaloid 1,2,3,4-tetrahydro-1-oxo-β-carboline (5). Among them, 1 and 2 are new compounds, 3 and 4 are new natural products that were semi-synthesized from isorhynchohylline with incorrect specific rotations, and 5 is isolated for the first time from the genus Uncaria.

Advances in indole alkaloids from traditional Chinese medicine of Uncariae Ramulus Cum Uncis documented in Chinese Pharmacopoeia / 中国中药杂志

Uncaria genus( Rubiaceae) contains 34 species all over the world,of which 11 species and one variant are present in China. Five species,namely U. rhynchophylla,U. macrophylla,U. hirsuta,U. sinensis and U. sessilifructus,are documented in Chinese Pharmacopoeia as the raw materials of Uncariae Ramulus Cum Uncis. Indole alkaloids are the characteristic constituents of Uncaria plants,in addition to triterpenes,lignans and flavones. This paper reviews the progress of indole alkaloids and their distribution within the five Uncaria species documented in Chinese Pharmacopoeia for better understanding the active constituents of Uncariae Ramulus Cum Uncis.

Effects of light intensity on growth and content of active components of Uncaria rhynchophyll / 中国中药杂志

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.

Two folate-derived analogues from an aqueous decoction of Uncaria rhynchophylla / 中国天然药物

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.

Evaluation of the effects of Uncaria rhynchophylla alkaloid extract on LPS-induced preeclampsia symptoms and inflammation in a pregnant rat model

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-1β, 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.

Chemical constituents from stems of Uncaria scandens / 中草药

Objective: To study the chemical constituents from the stems of Uncaria scandens. Methods: The compounds were isolated and purified by silica gel column chromatography, Sephadex LH-20, RP18, and HPLC. The structures were identified by spectroscopic methods and physicochemical properties. The contents of rhynchophylline and isorhynchophylline were detected by HPLC method. Results: Seventeen compounds were isolated and identified from 95% ethanol extract of the stems of U. scandens and characterized as 5α-carboxystrictosidine (1), 3β-isodihydrocadambine (2), strictosamide (3), 3α-dihydrocadambine (4), mitraphylline (5), uncarine F (6), 3β-isodihydrocadambine 4-oxide (7), isodihydrocdambine (8), nauclefine (9), cadambine (10), calyxamine B (11), methyl chlorogenate (12), 3,4,5-trimethoxyphenol (13), α-tocopherylquinone (14), quinovic acid (15), methyl caffeate (16), and hyperoside (17). The contents of rhynchophylline and isorhynchophylline from U. scandens were 0.72 and 0.38 μg/g. Conclusion: Compounds 7-9 and 11-14 are isolated from Uncaria genus for the first time. Compounds 1-6 and 16, 17 are isolated from U.scandens for the first time. The contents of rhynchophylline and isorhynchophylline is low and the reasonable use of them as U. scandens in some areas needs to be further verified.

Chemical constituents from stems of Uncaria lancifolia / 中草药

Objective To study the chemical constituents from the stems of Uncaria lancifolia. Methods The isolation and purification were carried out by silica gel column chromatography, RP18, Sephadex LH-20, and preparative HPLC. The structures of the isolated compounds were elucidated by physical and chemical properties, and spectroscopic methods. Results Eighteen compounds were isolated and identified from 95% ethanol extract from the stems of U. lancifolia and characterized as uncarine A (1), uncarine E (2), isomitraphylline (3), tetrahydroalstonine (4), strictosidine (5), cadambine (6), glabratine (7), strictosamide (8), (13R)-hydroxy- octodeca-(9Z,11E,15Z)-trien-oic acid (9), (6S,9R)-roseoside (10), periplanetin (11), integracin A (12), integracin B (13), 6β,19α- dihydroxyurs-3-oxours-12-en-28-oic aicd (14), ursolic acid (15), oleanic acid (16), β-sitosterol (17), and β-daucosterol (18). Conclusion This is the first report for the chemical constituents from U. lancifolia. All compounds are obtained from this plant for the first time, and compounds 9-13 are isolated from Uncaria genus for the first time. Compounds 1-8 are monoterpene indole alkaloids, which are characteristic constituents in Uncaria genus.

Research progresses in pharmacological effects of rhynchophylline and its isomers on nervous system / 药学学报

Uncaria rhynchophylla is one of the frequently used herbs in China, it is mainly used for heat-clearance, suppression of hyperactive liver, calming endogenous wind and arresting convulsion in traditional Chinese medicine (TCM). Alkaloids are the main active materials in Uncaria rhynchophylla, pharmacological studies have shown that Uncaria rhynchophylla and its alkaloids have comprehensive biological effects on the nervous system. Rhynchophylline is one of the most abundant alkaloids in Uncaria rhynchophylla. The recent studies demonstrate that rhynchophylline and its isomers (isorhynchophylline, corynoxine, corynoxine B) may be good drug candidates for treatment of Alzheimer's disease, Parkinson's disease, epilepsy, etc. Although the structures of the 4 alkaloids are very similar, they have different effects on nervous system. For example, corynoxine and corynoxine B exhibit better sedative effects than isorhynchophylline. Rhynchophylline and isorhynchophylline have been extensively studied. For development and utilization of rhynchophylline for nervous system disease, more studies are needed to unveil the structure-function relationship and the underlying mechanisms. Here, we summarizes the progresses the effects of rhynchophylline and its isomers on the nervous system.

Explore mechanism of Compound Uncaria Hypotensive Tablet for hypertension based on network pharmacology / 中国中药杂志

This paper aimed to predict the active ingredients and action targets of Compound Uncaria Hypotensive Tablet for hypertension based on network pharmacology, and discuss its possible "multi-components, multi-targets, and multi-pathways" mechanism for treatment of hypertension. The integrative pharmacological platform of traditional Chinese medicine (TCM-IP) was used to construct the component target-disease target network of Compound Uncaria Hypotensive Tablet, and the internet analysis method was used to screen the key nodes, on which the pathway enrichment analysis was carried out to explore its possible biological process in the treatment of hypertension. Target network analysis showed that, 35 predicted active ingredients of Compound Uncaria Hypotensive Tablet had a strong interaction with the prostaglandin endogenous peroxidase synthase (PTGS1, PTGS2), ATP synthetase (ATP1A1, ATP5A1, ATP5C1, ATP5B) and other 29 major proteins. Network enriched analysis showed that Compound Uncaria Hypotensive Tablet participated in the regulation of hypertension in different processes of pathology, through 15 pathways such as regulating blood pressure, G protein coupled receptor activation, adrenergic myocardial cell signal transduction and platelet activation. This study revealed the potential active compounds and possible mechanism of Compound Uncaria Hypotensive Tablet for treatment of hypertension, providing theoretical references for further systematic laboratory experiments on effective compounds and action mechanism of Compound Uncaria Hypotensive Tablet.

Decrease in Dengue virus-2 infection and reduction of cytokine/chemokine production by Uncaria guianensis in human hepatocyte cell line Huh-7

ABSTRACT BACKGROUND Dengue fever may present hemorrhages and cavitary effusions as result of exacerbated immune responses. We investigated hydro-alcoholic extracts from leaves (UGL) and bark (UGB) of the medicinal species Uncaria guinanensis with respect to antiviral effects in Dengue virus (DENV) infection and in immunological parameters associated with in vivo physiopathological features. METHODS Chemical profiles from UGB or UGL were compared in thin layer chromatography and 1H nuclear magnetic resonance using flavonoid compounds and a pentacyclic oxindole alkaloid-enriched fraction as references. DENV-2-infected hepatocytes (Huh-7) were treated with extracts. Cell viability, DENV antigens and immunological factors were detected by enzyme-linked immunosorbent assay (ELISA) or flow cytometry. FINDINGS The UGL mainly differed from UGB by selectively containing the flavonoid kaempferitrin. UGB and UGL improved hepatocyte viability. Both extracts reduced intracellular viral antigen and inhibited the secretion of viral non-structural protein (NS1), which is indicative of viral replication. Reduction in secretion of macrophage migration inhibitory factor was achieved by UGB, of interleukin-6 by UGL, and of interleukin-8 by both UGB and UGL. MAIN CONCLUSIONS The U. guianensis extracts presented, antiviral and immunomodulatory effects for DENV and possibly a hepatocyte-protective activity. Further studies may be performed to consider these products as potential candidates for the development of an herbal product for the future treatment of dengue.

Chemical constituents from leaves of Uncaria rhynchophylla / 中草药

Objective: To study the chemical constituents from the leaves of Uncaria rhynchophylla and their antioxidant activities. Methods: The compounds were isolated by various column chromatography. Their structures were identified by spectroscopic methods including 1H-NMR, 13C-NMR, MS, HR-MS, etc. The antioxidant activities were evaluated by DPPH radical scavenging assay. Results: Seventeen compounds were isolated from the leaves of U. rhynchophylla, and identified as 18, 19-hydroxy- vincosamide (1), α-tocopherol (2), α-tocospiro A (3), dihydroactinidiolide (4), ursolic acid lactone (5), 3, 4-dehydrotheaspirone (6), chakyunglupulin A (7), ursolic acid (8), protocatechuic acid (9), quercetin (10), epicatechin (11), chlorogenic acid ethyl ester (12), quercetin-3-O-robinobioside (13), rutin (14), methyl caffeate (15), strictosamide (16), and vincosamide (17). The anti-oxidative IC50 values of compounds 10, 11, and 13-15 were 7.52, 8.21, 8.14, 2.13, and 5.35 μmol/L, respectively, which were better than the positive control Vit E (IC50 value was 9.53 μmol/L). Conclusion: Compound 1 is a new compound named as vincosamide A, and compounds 2-7, 9, 12, 13, and 15 are isolated from genus Uncaria Schreber nom. cons. for the first time. Moreover, compounds 10, 11, and 13-15 have the certain prospects in the development of natural anti-oxidative agents.