RESUMEN
Sjögren's syndrome (SS) is an autoimmune disorder characterized by oral dryness that is primarily attributed to tumor necrosis factor alpha (TNF-α)-mediated reduction in saliva production. In traditional Chinese medicine, goji berries are recognized for their hydrating effect and are considered suitable to address oral dryness associated with Yin deficiency. In the present study, we used goji berry juice (GBJ) to investigate the potential preventive effect of goji berries on oral dryness caused by SS. Pretreatment of human salivary gland cells with GBJ effectively prevented the decrease in aquaporin-5 (AQP-5) mRNA and protein levels induced by TNF-α. GBJ also inhibited histone H4 deacetylation and suppressed the generation of intracellular reactive oxygen species (ROS). Furthermore, GBJ pretreatment reserved mitochondrial membrane potential and suppressed the upregulation of Bax and caspase-3, indicating that GBJ exerted an antiapoptotic effect. These findings suggest that GBJ provides protection against TNF-α in human salivary gland cells and prevents the reduction of AQP-5 expression on the cell membrane. Altogether, these results highlight the potential role of GBJ in preventing oral dryness caused by SS.
Asunto(s)
Lycium , Síndrome de Sjögren , Xerostomía , Humanos , Factor de Necrosis Tumoral alfa/metabolismo , Lycium/metabolismo , Glándulas Salivales/metabolismo , Glándulas Salivales/patología , Xerostomía/inducido químicamente , Xerostomía/prevención & control , Xerostomía/complicaciones , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/metabolismo , Síndrome de Sjögren/patología , Acuaporina 5/genéticaRESUMEN
Amyloid ß (Aß) is thought to be involved in the pathogenesis of Alzheimer's disease (AD). Aß aggregation in the brain is considered the cause of AD. Therefore, inhibiting Aß aggregation and degrading existing Aß aggregates is a promising approach for the treatment and prevention of the disease. In searching for inhibitors of Aß42 aggregation, we found that meroterpenoids isolated from Sargassum macrocarpum possess potent inhibitory activities. Therefore, we searched for active compounds from this brown alga and isolated 16 meroterpenoids, which contain three new compounds. The structures of these new compounds were elucidated using two-dimensional nuclear magnetic resonance techniques. Thioflavin-T assay and transmission electron microscopy were used to reveal the inhibitory activity of these compounds against Aß42 aggregation. All the isolated meroterpenoids were found to be active, and compounds with a hydroquinone structure tended to have stronger activity than those with a quinone structure.
Asunto(s)
Enfermedad de Alzheimer , Sargassum , Terpenos , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/antagonistas & inhibidores , Sargassum/química , Terpenos/química , Terpenos/farmacologíaRESUMEN
Zamamiphidins B (1) and C (2), two new manzamine-related alkaloids with an unprecedented fused diazahexacyclic ring system, were isolated from an Amphimedon sp. marine sponge collected in Okinawa. The structures of zamamiphidins B (1) and C (2) including the relative configurations were elucidated on the basis of spectroscopic data.
Asunto(s)
Alcaloides , Poríferos , Alcaloides/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Animales , Línea Celular Tumoral , Estructura Molecular , Poríferos/químicaRESUMEN
Two new guaianolide sesquiterpenes, lanicepines A (1) and B (2), possessing unusual amino acid-derived substituents at C-13, were isolated from the flowering aerial parts of Saussurea laniceps, a traditional herbal medicine also known as "snow lotus". The structures of 1 and 2 were elucidated based on spectroscopic analysis including applications of the modified Mosher's method and Marfey's method as well as ECD calculations. Lanicepine A (1) contains a dihydropyridinone moiety with a carbamoyl and a hydroxymethyl group. This substituent was considered to consist of asparagine and a C4 unit. In contrast, lanicepine B (2) has a substituent that seems to be derived from l-proline and a C4 unit. Lanicepines A (1) and B (2) and two related known sesquiterpenes isolated from the same plant material, 11ß,13-dihydrodesacylcynaropicrin (3) and 11ß,13-dihydrodesacylcynaropicrin 8-O-ß-d-glucoside (4), demonstrated inhibitory activity against IL-1ß production from LPS-stimulated microglial cells.
Asunto(s)
Saussurea , Sesquiterpenos , Aminoácidos/análisis , Estructura Molecular , Componentes Aéreos de las Plantas/química , Saussurea/química , Sesquiterpenos/química , Sesquiterpenos de Guayano/químicaRESUMEN
Two new polyacetylene glycosides, kamiohnoyneosides A and B, were isolated from the flowers of edible Chrysanthemum "Kamiohno", along with a known polyacetylene glycoside and two known monoterpene glycosides. The structures of new compounds were elucidated on the basis of spectroscopic data. Kamiohnoyneoside A and three known compounds moderately inhibited formation of Nε-(carboxymethyl)lysine, one of the representative advanced glycation endproducts.
Asunto(s)
Chrysanthemum/química , Flores/química , Glicósidos/química , Polímero Poliacetilénico/químicaRESUMEN
The production and accumulation of advanced glycation end products (AGEs) have been implicated in diabetes and diabetic complication. This study was conducted as a search for an AGE inhibitor from brown alga, Sargassum macrocarpum. Separation and purification were performed using AGEs inhibitory activity as an index, yielding isolation of 11 meroterpenoids, of which 3 were new compounds: macrocarquinoids A (1), B (6), and C (9). Their structures were elucidated using NMR spectral analysis with 2D techniques. All tested compounds showed AGEs inhibitory activity. Particularly, macrocarquinoid C (9) possessed the strongest activity (IC50: 1.0 mM) of isolated compounds. This activity was stronger than that of aminoguanidine (positive control).
Asunto(s)
Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Sargassum/química , Terpenos/uso terapéutico , Estructura Molecular , Terpenos/farmacologíaRESUMEN
The manzamine alkaloids are absolutely one of the most fascinating marine natural products. The representative manzamine alkaloids, manzamines A-C, were isolated from a marine sponge Haliclona sp. collected off Cape Manzamo, Okinawa, Japan. The manzamine alkaloids are a unique class of alkaloids possessing a characteristic heterocyclic system, and exhibit a diverse range of bioactivities including cytotoxicity, antimicrobial activity, antimalarial activity, antiviral and antiinflammatory activities, antiinsecticidal activity, and proteasome inhibitory activity. About 100 manzamine alkaloids have been isolated from more than 16 species of marine sponges belonging to 5 families. The unusual ring systems, an intriguing suggested biogenetic pathway, and promising biological activities of manzamine alkaloids have attracted great interest as challenging targets for the total synthesis. This review is the continuation of the previous review published in volume 60 of The Alkaloids and covers isolation, structure elucidation, biosynthesis and biogenesis, chemical synthesis, and biological activity of manzamine alkaloids reported from 2003 to 2018.
Asunto(s)
Alcaloides/farmacología , Antiinfecciosos/farmacología , Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Alcaloides/química , Alcaloides/metabolismo , Animales , Antiinfecciosos/química , Antiinfecciosos/metabolismo , Antiinflamatorios/química , Antiinflamatorios/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Carbazoles/química , Carbazoles/metabolismo , Carbazoles/farmacología , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/metabolismo , Alcaloides Indólicos/farmacología , Estructura MolecularRESUMEN
Two new bromotyrosine alkaloids, ma'edamines C and D, were isolated from an Okinawan marine sponge Suberea sp. The structures of ma'edamines C and D were elucidated on the basis of spectroscopic data. Ma'edamines C and D were the first natural products possessing a unique tetrasubstituted pyridinium moiety such as N-alkyl-3,5-diethyl-2-propylpyridinium and N-alkyl-3,5-diethyl-4-propylpyridinium, respectively. Ma'edamines C and D exhibited moderate cytotoxicity against murine leukemia cell line L1210 in vitro.
Asunto(s)
Alcaloides/química , Poríferos/química , Tirosina/análogos & derivados , Animales , Tirosina/químicaRESUMEN
Two new bromotyrosine alkaloids, ceratinadins E (1) and F (2), were isolated from an Okinawan marine sponge Pseudoceratina sp. as well as a known bromotyrosine alkaloid, psammaplysin F (3). The gross structures of 1 and 2 were elucidated on the basis of spectroscopic data. The absolute configurations of 1 and 2 were assigned by comparison of the NMR and ECD data with those of a known related bromotyrosine alkaloid, psammaplysin A (4). Ceratinadins E (1) and F (2) are new bromotyrosine alkaloids possessing an 8,10-dibromo-9-methoxy-1,6-dioxa-2-azaspiro[4.6]undeca-2,7,9-trien-4-ol unit with two or three 11-N-methylmoloka'iamine units connected by carbonyl groups, respectively. Ceratinadin E (1) exhibited antimalarial activities against a drug-resistant and a drug-sensitive strains of Plasmodium falciparum (K1 and FCR3 strains, respectively).
Asunto(s)
Alcaloides/farmacología , Antimaláricos/farmacología , Plasmodium falciparum/efectos de los fármacos , Poríferos , Tirosina/análogos & derivados , Alcaloides/química , Alcaloides/aislamiento & purificación , Animales , Antimaláricos/química , Antimaláricos/aislamiento & purificación , Dicroismo Circular , Espectroscopía de Resonancia Magnética , Estructura Molecular , Compuestos de Espiro/química , Compuestos de Espiro/aislamiento & purificación , Compuestos de Espiro/farmacología , Tirosina/química , Tirosina/aislamiento & purificación , Tirosina/farmacologíaRESUMEN
The investigation of the Vietnamese marine sponge Spongia sp. led to the isolation of three new sesquiterpene phenols, langconols A-C (1-3), and one new sesquiterpene hydroxyquinone, langcoquinone C (4), together with two known meroterpenoids (5 and 6). Their structures were determined on the basis of spectroscopic analyses and comparisons with published data. Furthermore, the antibacterial assays of the isolates 1-6 suggested that 4 and 6 had significant antibacterial activities against Bacillus subtilis and Staphylococcus aureus, with MICs ranging from 6.25 to 25.0µM, while 1 and 3 possessed significant antibacterial activities against B. subtilis with MICs of 12.5 and 25.0µM, respectively. In contrast, cytotoxic assays of the isolated compounds 1-6, as well as compounds 7-15 previously isolated from this sponge, indicated that 1 and the previously reported anti-B. subtilis and anti-S. aureus sesquiterpene phenol 9 lacked cytotoxic activities against three human cancer cell lines (A549, lung cancer; MCF7, breast cancer; HeLa, cervix cancer) and a human normal cell line (WI-38 fibroblast).
Asunto(s)
Antibacterianos/química , Poríferos/química , Sesquiterpenos/química , Células A549 , Animales , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Bacillus subtilis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células HeLa , Humanos , Células MCF-7 , Espectroscopía de Resonancia Magnética , Conformación Molecular , Poríferos/metabolismo , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Staphylococcus aureus/efectos de los fármacosRESUMEN
A new manzamine alkaloid, zamamidine D (1), was isolated from an Okinawan Amphimedon sp. marine sponge. The structure of zamamidine D (1) including the relative configuration was elucidated on the basis of spectroscopic data. Zamamidine D (1) is the first manzamine alkaloid possessing a 2,2'-methylenebistryptamine unit as the aromatic moiety instead of a ß-carboline unit. Zamamidine D (1) showed antimicrobial activity against several bacteria and fungi.
Asunto(s)
Alcaloides/aislamiento & purificación , Carbolinas/aislamiento & purificación , Poríferos/química , Alcaloides/química , Alcaloides/farmacología , Animales , Carbazoles/química , Carbolinas/química , Carbolinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Japón , Biología Marina , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Three new acylated triterpene saponins, acernikoenosides A-C (1-3), were isolated from the stem bark of Acer nikoense, together with a known sterol glucoside. Their structures were elucidated on the basis of extensive spectroscopic analyses. This study provided the first example of triterpene saponins isolated from this plant. The anti-genotoxic activity of 1, 3 and 4 against ultraviolet irradiation was evaluated by comet assay.
Asunto(s)
Aceraceae/química , Antimutagênicos/farmacología , Corteza de la Planta/química , Tallos de la Planta/química , Saponinas/farmacología , Triterpenos/farmacología , Acilación , Antimutagênicos/química , Antimutagênicos/aislamiento & purificación , Células Cultivadas , Humanos , Estructura Molecular , Saponinas/química , Saponinas/aislamiento & purificación , Triterpenos/química , Triterpenos/aislamiento & purificación , Rayos UltravioletaRESUMEN
Twenty new neo-clerodane type diterpenoids, scutefolides G1-S (1-20), were isolated from the 70 % aqueous acetone extract of the aerial parts of Scutellaria coleifolia. Their structures were elucidated by extensive spectroscopic analyses. The absolute configurations of 1, 2, 7, 8, 14 and 15 were determined by means of the CD exciton chirality method. Compounds 1, 2, 5, 7, 8, 12, 14, 15, 18 and 19 were evaluated for their cytotoxic activities against four human cancer cell lines, and anti-bacterial activities against methicillin-resistant Staphylococcus aureus.
Asunto(s)
Diterpenos de Tipo Clerodano/aislamiento & purificación , Extractos Vegetales/química , Scutellaria/química , Acilación , Línea Celular Tumoral , Diterpenos de Tipo Clerodano/química , Diterpenos de Tipo Clerodano/farmacología , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Estructura Molecular , Neoplasias , Componentes Aéreos de las Plantas/química , Extractos Vegetales/farmacologíaRESUMEN
Coleifolides A and B (1 and 2), two new sesterterpenoids with a ß-methyl-α,ß-unsaturated-γ-lactone moiety, were isolated from the aerial parts of Scutellaria coleifolia H.Lév. (Lamiaceae), together with three known compounds. Their structures were elucidated by NMR and MS examinations. Coleifolides A and B were concluded to be partially racemic compounds by the HPLC analysis using a chiral column or introduction of chiral derivatizing agents. The absolute configuration of the major isomer was determined by analyses of the CD spectrum as well as NMR data of (R)- and (S)-2-NMA derivatives. Coleifolides A and B are structurally similar to manoalide derivatives, previously isolated from marine sponges, and appear to be the first examples of this type of compounds being isolated from higher plants.
Asunto(s)
Lactonas/análisis , Componentes Aéreos de las Plantas/química , Scutellaria/química , Sesterterpenos/análisis , Cromatografía Líquida de Alta Presión , Lactonas/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Conformación Molecular , Extractos Vegetales/química , Sesterterpenos/aislamiento & purificaciónRESUMEN
Scutefolides A1 and A2, two acylated neo-clerodanes with a 19,18-γ-lactone, scutefolides B1, B2 and C, three 19-nor-neo-clerodanes, together with scutefolides D, E1, E2 and F, four neo-clerodanes, were isolated from the EtOAc-soluble fraction of the aerial parts of Scutellaria coleifolia. Their structures were established on the basis of spectroscopic analysis. The absolute configurations of four of these compounds were elucidated by the CD exciton chirality method. Cytotoxic activities of scutefolides D-F against four cancer cell lines (KB, A549, HeLa, and MCF7) were also evaluated, but they were inactive.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Diterpenos de Tipo Clerodano/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Scutellaria/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Diterpenos de Tipo Clerodano/química , Diterpenos de Tipo Clerodano/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Células HT29 , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Componentes Aéreos de las Plantas/químicaRESUMEN
INTRODUCTION: According to published information, it has not been determined whether the inhalation of cigarette smoke can induce chromosome aberrations and/or point mutations in mice, though cigarette smoke is clearly carcinogenic to mice. We tested clastogenicity of inhaled cigarette smoke in mouse by a micronucleus test using peripheral erythrocytes. Since it is important to determine the in vivo anti-genotoxic effect against inhaled cigarette smoke to reduce the risk of tobacco carcinogenesis, we also tested in vivo anti-gnotoxic effect against inhaled cigarette smoke of a Connarus extract whose in vitro anti-genotoxic effect was shown. RESULTS: Male ICR mice were exposed for 1 min to a 6-fold dilution of the smoke once a day for up to 14 consecutive days. Although the frequencies of reticulocytes with micronucleus (MNRETs) and erythrocytes with micronuclei (MN erythrocytes) did not increase within 72 h after a single inhalation of cigarette smoke, the frequency of MN erythrocytes increased significantly upon inhalation for 7 and 14 days. When the Connarus extract was fed to mice at >23.7 ppm during the inhalation period of 14 days, frequency of MN erythrocytes was significantly lower than that at 0 ppm. In vitro antioxidant activity of Connarus extract was almost same to that of vitamin C. The antioxidant activity of the Connarus extract might play an important role in its anti-genotoxic effect against cigarette smoke in vivo, like vitamins C. CONCLUSIONS: Consecutive inhalation of cigarette smoke is clastogenic to mouse bone marrow as shown by the increased frequency of MN erythrocytes. Also, it was shown the possibility that the Connarus extract reduces the risk of tobacco carcinogenesis.
RESUMEN
Four new triterpenoids, indicalilacols A-D (1-4), were isolated from the MeOH extract of the fruits of Azadirachta indica, including a new 19(10â9ß)abeo-tirucallane derivative, two new tirucallane-type triterpenoids, and a new euphane-type triterpenoid, along with three known tirucallane-type triterpenoids. Their structures were elucidated on the basis of spectroscopic analyses. The absolute configuration of 2 was elucidated by the chemical conversion of 2 into 21-oxo-melianodiol 24,25-acetonide. Compounds 2, 6-8 exhibited moderate cytotoxicity against three human cancer cell lines, including multidrug-resistant (MDR) cancer cells (KB-C2). Although compound 5 was not cytotoxic against any of the tested cancer cell lines, 5 showed cytotoxicity against KB-C2 cells in the presence of 2.5 µM colchicine, suggesting that 5 might have an MDR-reversal effect.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Azadirachta/química , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias , Extractos Vegetales/química , Triterpenos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Línea Celular Tumoral , Frutas/química , Humanos , Estructura Molecular , Neoplasias/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Triterpenos/química , Triterpenos/farmacología , Triterpenos/uso terapéuticoRESUMEN
Secoiridoid glucosides, including two conjugates with a phenolic and two conjugates with a nicotinic acid derivative (3 and 4), together with seven known secoiridoid derivatives, were isolated from flower buds of Lonicera japonica. The structures were elucidated by spectroscopic analyses. Anti-influenza activities of six isolated compounds were also evaluated by plaque assay and neuraminidase inhibitory assay.
Asunto(s)
Glucósidos Iridoides/aislamiento & purificación , Lonicera/química , Ácidos Nicotínicos/aislamiento & purificación , Fenoles/aislamiento & purificación , Antivirales/farmacología , Flores/química , Virus de la Influenza A/efectos de los fármacos , Glucósidos Iridoides/química , Glucósidos Iridoides/farmacología , Estructura Molecular , Neuraminidasa/antagonistas & inhibidores , Ácidos Nicotínicos/química , Fenoles/química , Fenoles/farmacologíaRESUMEN
Rigenolide A (1), a new secoiridoid glucoside with a cyclobutane skeleton and three new acylated secoiridoid glucosides, 2'-(2,3-dihydroxybenzoyl)-gentiopicroside (2), 2'-(2,3-dihydroxybenzoyl)-swertiamarin (3), 3'-(2,3-dihydroxybenzoyl)-sweroside (4), along with two noriridoids (7 and 8) and two known secoiridoid glucosides (5 and 6), were isolated from Gentiana rigescens Franch. The structures of new compounds were elucidated by extensive spectroscopic analyses. The isolated compounds were evaluated for DPPH free-radical scavenging activity.
Asunto(s)
Gentiana/química , Glucósidos Iridoides/aislamiento & purificación , Extractos Vegetales/química , Acilación , Compuestos de Bifenilo/metabolismo , Glucósidos Iridoides/química , Glucósidos Iridoides/farmacología , Estructura Molecular , Picratos/metabolismo , Extractos Vegetales/farmacología , Pironas/química , Pironas/aislamiento & purificación , Pironas/farmacologíaRESUMEN
Seven new sesquiterpene lactone glycosides (1-7) were isolated from the H2O-soluble fraction from the MeOH extract of the roots of Ferula varia. Their structures were elucidated by extensive spectroscopic analyses. The absolute configurations of compounds 1 and 2 were determined by modified Mosher's method.