RESUMEN
Piper longum L.(PL) is considered one of the most important species traditionally used for treating various ailments and has indicated the presence of alkaloids, flavonoids, and steroids. In this study, we isolated the chemical compounds of PLleaves,andmeasuredNO, IL-6, iNOS, as well as COX-2 protein levels. In addition, molecular docking analysis were used to further understand anti-inflammation effect of the compounds. We identified one new alkaloid named piperlongumine A (1) with ten known compounds (2-11). The new compound (1) and two other alkaloids 2E)-3-(4-hydroxy-3-methoxyphenyl)-1-(pyrrol-1-yl)propanone (7) and piperchabamide A (8) significantlyreduced NO production in LPS-stimulated RAW 264.7 cells with the IC50 values of 0.97 ± 0.05 mM, 0.91 ± 0.07mM, 1.63 ± 0.14 mM, respectively. Moreover, at concentration of 2 mM, compound 1 inhibited approximately 98 ± 0.64 % of IL-6 secretion, and decreased iNOS and COX-2 protein level by about 96 and 19 folds compared to LPS treatment alone, respectively. Furthermore, compounds 1, 7, and 8 were predicted to bind and inhibit IL-6, TNF-a, and iNOS, with compound 1 showing the highest binding energy of -7.09 kcal/mol. This study provides new insights for potential anti-inflammatory drug design and warrants further investigation.
RESUMEN
Olean-12-en-27-oic acids possess a variety of pharmacological effects. However, their effects and underlying mechanisms on osteoclastogenesis remain unclear. This study aimed to investigate the anti-osteoclastogenic effects of five olean-12-en-27-oic acid derivatives including 3α,23-isopropylidenedioxyolean-12-en-27-oic acid (AR-1), 3-oxoolean-12-en-27-oic acid (AR-2), 3α-hydroxyolean-12-en-27-oic acid (AR-3), 23-hydroxy-3-oxoolean-12-en-27-oic acid (AR-4), and aceriphyllic acid A (AR-5). Among the five olean-12-en-27-oic acid derivatives, 3-hydroxyolean-12-en-27-oic acid derivatives, AR-3 and AR-5, significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced mature osteoclast formation by reducing the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, F-actin ring formation, and mineral resorption activity. AR-3 and AR-5 decreased RANKL-induced expression levels of osteoclast-specific marker genes such as c-Src, TRAP, and cathepsin K (CtsK) as well as c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). Mice treated with either AR-3 or AR-5 showed significant protection of the mice from lipopolysaccharide (LPS)-induced bone destruction and osteoclast formation. In particular, AR-5 suppressed RANKL-induced phosphorylation of JNK and ERK mitogen-activated protein kinases (MAPKs). The results suggest that AR-3 and AR-5 attenuate osteoclast formation in vitro and in vivo by suppressing RANKL-mediated MAPKs and NFATc1 signaling pathways and could potentially be lead compounds for the prevention or treatment of osteolytic bone diseases.
Asunto(s)
Resorción Ósea , Lipopolisacáridos/toxicidad , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ácido Oleanólico/análogos & derivados , Osteoclastos , Ligando RANK/metabolismo , Animales , Resorción Ósea/inducido químicamente , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismo , Resorción Ósea/patología , Ratones , Ratones Endogámicos ICR , Ácido Oleanólico/farmacología , Osteoclastos/metabolismo , Osteoclastos/patología , Células RAW 264.7RESUMEN
In the ongoing research to find new diabetes constituents from the genus Wedelia, the chemical constituent of Wedelia trilobata leaves, a Vietnamese medicinal plant species used to treat type 2 diabetes mellitus, was selected for detailed investigation. From a methanolic extract, two new ent-kaurane diterpenoids, wedtrilosides A and B (1 and 2), along with five known metabolites (3-7), were isolated from W. trilobata. The chemical structures of (1-7) were assigned via spectroscopic techniques (IR, 1D, 2D NMR and HR-QTOF-MS data) and chemical methods. The isolates were evaluated for α-amylase and α-glucosidase inhibitory activities compared to the clinical drug acarbose. Among them, compounds 4, 6, and 7 showed the most potent against α-glucosidase enzyme with IC50 values of 27.54⯱â¯1.12, 173.78⯱â¯2.37, and 190.40⯱â¯2.01⯵g/mL. While moderate inhibitory effect against α-amylase was observed with compounds 6 and 7 (with IC50â¯=â¯181.97⯱â¯2.62 and 52.08⯱â¯0.56⯵g/mL, respectively). The results suggested that the antidiabetic properties from the leaves of W. trilobata are not simply a result of each isolated compound, but are due to other factors such as the accessibility of polyphenolic groups to α-amylase and α-glucosidase activities.
Asunto(s)
Diterpenos/química , Inhibidores de Glicósido Hidrolasas/química , Glicósidos/química , Hojas de la Planta/química , Wedelia/química , alfa-Amilasas/antagonistas & inhibidores , Diterpenos/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Glicósidos/aislamiento & purificación , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Plantas Medicinales/químicaRESUMEN
This paper evaluated the inhibitory effect of 3-O-[ß-d-glucopyranosyl-(1â4)-ß-d-glucuronopyranosyl] oleanolic acid 28-O-ß-d-glucopyranosyl ester (PFS), a major saponin isolated from Polyscias fruticosa leaves, on α-amylase and α-glucosidase, and its potential for reducing the postprandial blood glucose level in mice. In enzyme inhibition assays, PFS strongly inhibited porcine pancreas α-amylase and yeast α-glucosidase. Using the Lineweaver-Burk equation, we found that PFS inhibited porcine pancreas α-amylase in a mixed noncompetitive mode, and yeast α-glucosidase via noncompetitive inhibition. In the sucrose tolerance test, PFS at 100 mg/kg body weight significantly decreased the postprandial blood glucose level in mice fed a high-sucrose diet. These findings suggest that P. fruticosa leaves and their major saponin PFS can be used to prevent and treat diabetes and its complications.
Asunto(s)
Araliaceae/química , Hipoglucemiantes/farmacología , Hojas de la Planta/química , Saponinas/farmacología , Animales , Araliaceae/clasificación , Femenino , Hipoglucemiantes/aislamiento & purificación , Masculino , Ratones , Ratones Endogámicos BALB C , Saponinas/aislamiento & purificaciónRESUMEN
Seven anthraquinones including two new compounds namely capillasterquinones A and B (1 and 2) and one new butenolide namely capillasterolide (8) were isolated and structurally elucidated from the crinoid Capillaster multiradiatus. The inhibitory effect of compounds 1-8 on lipopolysaccharide (LPS)-induced nitric oxide (NO) production as well as inhibition of 1 on expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) proteins in RAW264.7 cells were also evaluated. As the obtained results, capillasterquinone A (1) showed strong NO production inhibitory activity with an IC50 of 5.89±0.11 µM. In addition, compound 1 reduced the LPS-induced iNOS and COX-2 expressions in a dose-dependent manner.
Asunto(s)
4-Butirolactona/análogos & derivados , Antraquinonas/farmacología , Equinodermos/química , Inhibidores Enzimáticos/farmacología , 4-Butirolactona/química , 4-Butirolactona/aislamiento & purificación , 4-Butirolactona/farmacología , Animales , Antraquinonas/química , Antraquinonas/aislamiento & purificación , Ciclooxigenasa 2/metabolismo , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Ratones , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/metabolismo , Células RAW 264.7 , Relación Estructura-ActividadRESUMEN
Using various chromatographic separation techniques, ten flavonoid glycosides, including six new compounds namely barringosides A-F (1-6), were isolated from a methanol extract of the Barringtonia acutangula leaves. The structure elucidation was confirmed by spectroscopic analyses, including 1D and 2D NMR, and HR ESI MS. Their inhibitory effects on LPS-induced NO production in RAW264.7 cells were also evaluated. Among the isolated compounds, quercetin 3-O-ß-d-(6-p-hydroxybenzoyl)galactopyranoside (9) showed significant effect with an IC50 of 20.00±1.68µM. This is the first report of these flavonoid glycosides from Barringtonia genus and their inhibition on LPS-induced NO production in RAW264.7 cells was reported here for the first time.
Asunto(s)
Barringtonia/química , Flavonoides/farmacología , Glicósidos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Óxido Nítrico/antagonistas & inhibidores , Animales , Relación Dosis-Respuesta a Droga , Flavonoides/química , Flavonoides/aislamiento & purificación , Glicósidos/química , Glicósidos/aislamiento & purificación , Lipopolisacáridos/farmacología , Ratones , Estructura Molecular , Óxido Nítrico/biosíntesis , Células RAW 264.7 , Relación Estructura-ActividadRESUMEN
Two new triterpene saponins, camelliosides I and J (1 and 2), two new megastigmane glycosides, camellistigosides A and B (3 and 4), and two known megastigmane glycosides, icariside B1 (5) and (6S,9R)-roseoside (6), were isolated from a methanol extract of the Camellia bugiamapensis leaves using various chromatographic separation techniques. Their structures were elucidated based on spectroscopic analyses, including HR ESI MS, CD, 1D and 2D NMR. Their inhibitory effects on LPS-induced NO production in RAW264.7 cells were evaluated. This is the first report of the chemical constituents and biological activity of C. bugiamapensis.
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Camellia/química , Ciclohexanonas/farmacología , Glucósidos/farmacología , Norisoprenoides/farmacología , Saponinas/farmacología , Triterpenos/farmacología , Animales , Ciclohexanonas/química , Ciclohexanonas/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Glucósidos/química , Glucósidos/aislamiento & purificación , Humanos , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Ratones , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Norisoprenoides/química , Norisoprenoides/aislamiento & purificación , Células RAW 264.7 , Saponinas/química , Saponinas/aislamiento & purificación , Relación Estructura-Actividad , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
A phytochemical fractionation of a methanol extract of Ophiopogon japonicus tubers led to the isolation of a new homoisoflavanone, homoisopogon A (1), and three new homoisoflavanes, homoisopogon B-D (2-4). Their chemical structures were elucidated by mass, NMR, and circular dichroism (CD) spectroscopic methods. Homoisopogon A (1) exhibited potent cytotoxicity against human lung adenocarcinoma LU-1, human epidermoid carcinoma KB, and human melanoma SK-Mel-2 cancer cells with IC50 values ranging from 0.51 to 0.66 µM.
Asunto(s)
Ensayos de Selección de Medicamentos Antitumorales , Isoflavonas/aislamiento & purificación , Isoflavonas/farmacología , Ophiopogon/química , Extractos Vegetales/química , Tubérculos de la Planta/química , Línea Celular Tumoral , Humanos , Isoflavonas/química , Estructura Molecular , Extractos Vegetales/farmacologíaRESUMEN
Twelve steroids, including five new compounds 1-5, were isolated and structurally elucidated from a methanol extract of the Vietnamese soft coral Sinularia conferta. Their cytotoxic effects against three human cancer cell lines, lung carcinoma (A-549), cervical adenocarcinoma (HeLa), and pancreatic epithelioid carcinoma (PANC-1), were evaluated using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assays. Among isolated compounds, 10 exhibited potent cytotoxic effects on all three tested cell lines with IC50 values of 3.64±0.18, 19.34±0.42, and 1.78±0.69 µM, respectively.
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Antozoos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Esteroides/aislamiento & purificación , Esteroides/farmacología , Animales , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Conformación Molecular , Esteroides/química , Relación Estructura-ActividadRESUMEN
Two new pyrrole oligoglycosides, plancipyrrosides A and B (1 and 2), were isolated from methanol extract of the Vietnamese starfish Acanthaster planci using various chromatographic procedures. Their structures were elucidated by spectroscopic methods including one and two dimensional (1D- and 2D)-NMR and Fourier transform ion cyclotron resonance (FT-ICR)-MS. The finding of 1 and 2 represents the third case of pyrrole oligoglycosides obtaining reported to date. Moreover, plancipyrroside B (2) exhibits a potent inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells with IC50 of 5.94±0.34 µM, whereas plancipyrroside A (1) shows this inhibitory activity with IC50 of 16.61±1.85 µM.
Asunto(s)
Glicósidos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Óxido Nítrico/biosíntesis , Pirroles/farmacología , Estrellas de Mar/química , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Glicósidos/química , Glicósidos/aislamiento & purificación , Macrófagos/metabolismo , Ratones , Conformación Molecular , Pirroles/química , Pirroles/aislamiento & purificaciónRESUMEN
BACKGROUND: This study evaluated the cytotoxic activity of extracts from Caesalpinia sappan heartwood against multiple cancer cell lines using an MTT cell viability assay. The cell death though induction of apoptosis was as indicated by DNA fragmentation and caspase-3 enzyme activation. RESULTS: A methanol extract from C. sappan (MECS) showed cytotoxic activity against several of the cancer cell lines. The most potent activity exhibited by the MECS was against HeLa cells with an IC50 value of 26.5 ± 3.2 µg/mL. Treatment of HeLa cells with various MECS concentrations resulted in growth inhibition and induction of apoptosis, as indicated by DNA fragmentation and caspase-3 enzyme activation. CONCLUSION: This study is the first report of the anticancer properties of the heartwood of C. sappan native to Vietnam. Our findings demonstrate that C. sappan heartwood may have beneficial applications in the field of anticancer drug discovery.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis , Caesalpinia/química , Extractos Vegetales/farmacología , Haz Vascular de Plantas/metabolismo , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular , Citotoxinas/farmacología , Fragmentación del ADN , Ensayos de Selección de Medicamentos Antitumorales/métodos , Activación Enzimática/efectos de los fármacos , Femenino , Formazáns , Inhibidores de Crecimiento/farmacología , Células HeLa , Humanos , Indicadores y Reactivos , Concentración 50 Inhibidora , Metanol , Ratones Endogámicos C57BL , Sales de Tetrazolio , VietnamRESUMEN
Using DFT calculations, the structural and electronic properties of the ZZ7 p-PdSe2 nanoribbons (ZZ7) with the four kinds of vacancy defects, including ZZ7-VPd, ZZ7-VSe, ZZ7-VPd+Se, and ZZ7-V2Se are studied, in which their stability, diverse geometries, and altered electronic properties are determined through the formation energies, optimal structural parameters, electronic band structures, and DOSs. Specifically, the formation energies of all studied systems show significant negative values around -3.9 eV, evidencing their good thermal stability. The geometries of four defective structures exhibit different diversification, whereas only the ZZ7-V2Se structure possesses the highly enhanced feature, identified as the most effective substrate for the acetone and acetonitrile adsorption. On the electronic behaviors, the ZZ7 band structure displays the nonmagnetic metallic characteristics that become the ferromagnetic half-metallic band structures for the ZZ7-VPd and ZZ7-VSe and the ferromagnetic semi-metallic band structures for the ZZ7-VPd+Se and ZZ7-V2Se. For adsorption of the acetone and acetonitrile on the ZZ7-V2Se structure, the energetic stability, adsorption sites, adsorption distances, charge transfers, and electronic characteristics of the adsorbed systems are determined by the adsorption energies, optimal adsorption sites, adsorption distances, Mulliken populations, and DOSs. The adsorption energies of the acetone- and acetonitrile-adsorbed ZZ7-V2Se systems display significant values at -1.2 eV and -0.86 eV at the preferable sites of 8 and 11, respectively, indicating their great adsorption ability. The adsorption mechanism of the acetone- and acetonitrile-adsorbed systems belongs to the physisorption owing to absence of chemical bonds, in which the bond lengths of the ZZ7-V2Se substrate show a very small deviation. Under the acetone and acetonitrile adsorptions, the ferromagnetic semi-metallic DOSs of the ZZ7-V2Se become the ferromagnetic half-metallic DOSs for the ZZ7-V2Se-acetone-8 and the ferromagnetic semiconducting DOSs for the ZZ7-V2Se-acetonitrile-11. Our systematic results can provide a complete understanding of the acetone- and acetonitrile adsorptions on the potential ZZ7-V2Se structure, which is very useful for nanosensor application.
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Two new phenolic compounds, caesalpiniaphenols G-H (1 and 2), were isolated from Vietnamese Caesalpinia sappan heartwood. The chemical structures were established mainly by extensive spectroscopic studies and chemical evidence. Compounds 1 and 2 showed potent inhibitory activity against HL-60 cancer cell lines with respective IC50 values of 16.7 and 22.5 µg/mL. Treating HL-60 cells with various concentrations of 1 resulted in growth inhibition and the induction of apoptosis.
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Caesalpinia/química , Citotoxinas/farmacología , Fenoles/farmacología , Extractos Vegetales/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Humanos , Concentración 50 Inhibidora , VietnamRESUMEN
The use of non-invasive approaches for monitoring therapy processes in cancer patients at late stages is truly needed. In this work, we aim to develop an electrochemical interface based on polydopamine combined with gold nanoparticles and reduced graphene oxide for impedimetric detection of lung cancer cells. Gold nanoparticles (around 75 nm) were dispersed onto reduced graphene oxide material pre-electrodeposited onto disposable fluorine doped tin oxide electrodes. The coordination between gold and carbonaceous material has somehow improved the mechanical stability of this electrochemical interface. Polydopamine was later introduced onto modified electrodes via self-polymerization of dopamine in an alkaline solution. The result has demonstrated the good adhesion and biocompatibility of polydopamine towards A-549 lung cancer cells. The presence of the two conductive materials (gold nanoparticles and reduced graphene oxide) has led to a six-times decrease in charge transfer resistance of polydopamine film. Finally, the as-prepared electrochemical interface was employed for impedimetric detection of A-549 cells. The detection limit was estimated to be only 2 cells per mL. These findings have proved the possibilities to use advanced electrochemical interfaces for point-of-care applications.
RESUMEN
One-dimensional (1D) novel pentagonal materials have gained significant attention as a new class of materials with unique properties that could influence future technologies. In this report, we studied the structural, electronic, and transport properties of 1D pentagonal PdSe2 nanotubes (p-PdSe2 NTs). The stability and electronic properties of p-PdSe2 NTs with different tube sizes and under uniaxial strain were investigated using density functional theory (DFT). The studied structures showed an indirect-to-direct bandgap transition with slight variation in the bandgap as the tube diameter increased. Specifically, (5 × 5) p-PdSe2 NT, (6 × 6) p-PdSe2 NT, (7 × 7) p-PdSe2 NT, and (8 × 8) p-PdSe2 NT are indirect bandgap semiconductors, while (9 × 9) p-PdSe2 NT exhibits a direct bandgap. In addition, under low uniaxial strain, the surveyed structures were stable and maintained the pentagonal ring structure. The structures were fragmented under tensile strain of 24%, and compression of -18% for sample (5 × 5) and -20% for sample (9 × 9). The electronic band structure and bandgap were strongly affected by uniaxial strain. The evolution of the bandgap vs. the strain was linear. The bandgap of p-PdSe2 NT experienced an indirect-direct-indirect or a direct-indirect-direct transition when axial strain was applied. A deformability effect in the current modulation was observed when the bias voltage ranged from about 1.4 to 2.0 V or from -1.2 to -2.0 V. Calculation of the field effect I-V characteristic showed that the on/off ratio was large with bias potentials from 1.5 to 2.0 V. This ratio increased when the inside of the nanotube contained a dielectric. The results of this investigation provide a better understanding of p-PdSe2 NTs, and open up potential applications in next-generation electronic devices and electromechanical sensors.
RESUMEN
Prostate cancer (PCa) remains the most diagnosed non-skin cancer amongst the American male population. Treatment for localized prostate cancer consists of androgen deprivation therapies (ADTs), which typically inhibit androgen production and the androgen receptor (AR). Though initially effective, a subset of patients will develop resistance to ADTs and the tumors will transition to castration-resistant prostate cancer (CRPC). Second generation hormonal therapies such as abiraterone acetate and enzalutamide are typically given to men with CRPC. However, these treatments are not curative and typically prolong survival only by a few months. Several resistance mechanisms contribute to this lack of efficacy such as the emergence of AR mutations, AR amplification, lineage plasticity, AR splice variants (AR-Vs) and increased kinase signaling. Having identified SRC kinase as a key tyrosine kinase enriched in CRPC patient tumors from our previous work, we evaluated whether inhibition of SRC kinase synergizes with enzalutamide or chemotherapy in several prostate cancer cell lines expressing variable AR isoforms. We observed robust synergy between the SRC kinase inhibitor, saracatinib, and enzalutamide, in the AR-FL+/AR-V+ CRPC cell lines, LNCaP95 and 22Rv1. We also observed that saracatinib significantly decreases AR Y534 phosphorylation, a key SRC kinase substrate residue, on AR-FL and AR-Vs, along with the AR regulome, supporting key mechanisms of synergy with enzalutamide. Lastly, we also found that the saracatinib-enzalutamide combination reduced DNA replication compared to the saracatinib-docetaxel combination, resulting in marked increased apoptosis. By elucidating this combination strategy, we provide pre-clinical data that suggests combining SRC kinase inhibitors with enzalutamide in select patients that express both AR-FL and AR-Vs.
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Four new N-phenethylbenzamide derivatives, named piperbetamides A-D (1-4), and six allylbenzene derivatives (5-10) were isolated from the stems of Piper betle L. Their structures were determined by HR-ESI-MS and NMR spectroscopic methods. Compounds 1-10 were evaluated for their inhibitory effects on the growth of nine microorganisms including five Gram-negative (Escherichia coli, Salmonella enterica serovar Typhimurium, Shigella flexneri, Pseudomonas aeruginosa, and Extended-spectrum beta-lactam resistant Klebsiella pneumoniae), three Gram-positive (Listeria monocytogenes, Methicilin-resistant Staphylococcus aureus, Vancomycin-resistant Enterococcus faecalis), and one yeast (Candida albicans) strains. Compounds 1, 3, 4, 6 and 10 exhibited potential antimicrobial activity against S. flexneri, L. monocytogenes, methicillin-resistant S. aureus and vancomycin-resistant E. faecalis with minimum inhibitory concentration (MIC) values in the range of 16-32 µg/mL.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Piper betle , Antibacterianos/química , Vancomicina/farmacologíaRESUMEN
Top-of-the-basilar artery occlusion frequently causes infarction of the midbrain, thalamus, and portions of the temporal and occipital lobes as the vascular supply of these regions comes from the posterior communicating and posterior cerebral arterial tributaries of the basilar artery. Clinical signs include an array of visual, oculomotor, and behavioral abnormalities, usually without prominent motor dysfunction, which makes diagnosis challenging for those inexperienced with these sign. We describe a 59-year-old male presenting with acute ischemic stroke due to top-of-the-basilar artery occlusion. Despite attempting several paraclinical examinations relating the sudden coma with Glasgow Coma Scale of 6 points, the neuroimaging detected the large vessel occlusion that was difficult to recognize. After confirming top-of-the-basilar artery occlusion, the recanalization was realized immediately. The patient was discharged with good clinical recovery.
RESUMEN
BACKGROUND: Elevated activity of osteoclasts (OCs) is linked to osteolytic bone diseases, such as osteoporosis and rheumatoid arthritis. Developing natural anti-osteoclastogenic compounds with greater efficacy and fewer adverse effects is crucial for preventing or treating osteolytic bone diseases. N-triterpene cycloartane saponins (NTCSs) are rarely found in nature, and their inhibitory effects on OC differentiation in vitro and in vivo have not yet been explored. PURPOSE: This study was aimed to investigate the effect of mussaendoside O, an NTCS isolated from Mussaenda pubescens, on RANKL-induced OC differentiation and its underlying mechanism in vitro, and lipopolysaccharide (LPS)-induced bone resorption in a mouse model. METHODS: The content of mussaendoside O in methanol extract of M. pubescens was determined by HPLC. The inhibitory effects of mussaendoside O on RANKL-induced OC formation were assessed using TRAP staining, western blotting, immunofluorescence staining, and real-time qPCR. Meanwhile, the effects of mussaendoside O on LPS-induced inflammatory responses were assessed using a Griess reagent and qPCR. The effects of mussaendoside O on LPS-induced bone resorption in a mouse model were evaluated using micro-CT and immunohistochemical staining. RESULTS: Mussaendoside O inhibited RANKL-induced TRAP-positive multinucleated OC formation in a concentration-dependent manner without affecting cell viability. However, mussaendoside O did not inhibit LPS-induced mRNA expression of COX-2, iNOS, and TNF-α. Mice orally administrated with mussaendoside O exhibited significant protection from LPS-induced bone resorption and OC formation. At the molecular level, mussaendoside O suppressed RANKL-activated phosphorylation of p38 MAPK and JNK, as well as c-Fos expression. In addition, mussaendoside O suppressed RANKL-induced NFATc1 activation and the expression of its target genes, including OSCAR, DC-STAMP, CtsK, and TRAP. CONCLUSION: Mussaendoside O attenuates OC differentiation in vitro and LPS-induced bone resorption in a mouse model by inhibiting the RANKL-activated c-Fos/NFATc1 signaling pathways. Therefore, mussaendoside O may be a valuable lead compound for preventing or treating of osteolytic bone diseases.