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Bioassay-guided fractionation of P. quinquefolium and P. ginseng root extracts afforded six compounds. Among these, two bioactive compounds ginsenoside Re (1) and (20S)-ginsenoside Rg2 (5) exhibiting significant relaxation in rabbit corpus cavernosum with EC50 values of 95.1 and 114.7 µM, respectively. In addition, the phytochemical composition of the water extract of the roots of P. quinquefolium was investigated, and thirty-one compounds were characterized, including four undescribed compounds panajaponol B (18) and panaxjapynes D-F (21-23). Moreover, the spectral characteristics and biosynthetic pathway of Panax triterpene saponins were discussed according to our results and some previous reports.
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OBJECTIVE: Previously, we have successfully purified and synthesized viscolin, an agent derived from Viscum coloratum extract, which has shown significant potential in the treatment of stroke. Our study aimed to evaluate the neuroprotective effects of viscolin. METHODS: We first assessed the cytotoxicity of viscolin on primary neuronal cultures and determined its antioxidant and radical scavenging properties. Subsequently, we identified the optimal dose-response of viscolin in protecting against glutamate-induced neurotoxicity. RESULTS: Our results demonstrated that viscolin at a concentration of 10 µM effectively reduced neuronal cell death up to 6 hours after glutamate-induced neurotoxicity. Additionally, we investigated the therapeutic window of opportunity and the potential of viscolin in preventing necrotic and apoptotic damage in cultured neurons exposed to oxygen glucose deprivation-induced neurotoxicity. Our findings showed that viscolin treatment significantly reduced DNA breakage, prevented the release of cytochrome c from mitochondria to cytosol, increased the expression of anti-apoptotic protein Bcl-2, decreased the expression of pro-apoptotic protein Bax, and reduced the number of TUNEL-positive cells. Additionally, our in vivo investigation demonstrated a reduction in brain infarction following middle cerebral artery occlusion. CONCLUSION: Viscolin has potential utility as a therapeutic agent in the treatment of stroke.
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In posterior spine surgery, retractors exert pressure on paraspinal muscles, elevating intramuscular pressure and compromising blood flow, potentially causing muscle injury during ischemia-reperfusion. Ginkgo biloba extract (EGb 761), known for its antioxidant and free radical scavenging properties and its role in treating cerebrovascular diseases, is investigated for its protective effects against muscle ischemia-reperfusion injury in vitro and in vivo. Animals were randomly divided into the control group, receiving normal saline, and experimental groups, receiving varying doses of EGb761 (25/50/100/200 mg/kg). A 2-h hind limb tourniquet-induced ischemia was followed by reperfusion. Blood samples collected pre-ischemia and 24 h post-reperfusion, along with muscle tissue samples after 24 h, demonstrated that EGb761 at 1000 µg/mL effectively inhibited IL-6 and TNF-α secretion in RAW 264.7 cells without cytotoxicity. EGb761 significantly reduced nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and increased glutathione (GSH) levels compared to the control after 24 h. Muscle tissue sections revealed more severe damage in the control group, indicating EGb761's potential in mitigating inflammatory responses and oxidative stress during ischemia-reperfusion injury, effectively protecting against muscle damage.
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Anti-Inflamatórios , Antioxidantes , Ginkgo biloba , Membro Posterior , Músculo Esquelético , Extratos Vegetais , Traumatismo por Reperfusão , Animais , Ginkgo biloba/química , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Extratos Vegetais/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/irrigação sanguínea , Camundongos , Membro Posterior/irrigação sanguínea , Masculino , Ratos , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Interleucina-6/metabolismo , Ratos Sprague-Dawley , Extrato de GinkgoRESUMO
A previous 1H-NMR method allowed the quantification of ephedrine alkaloids; however, there were some disadvantages. The cyclized derivatives resulted from the impurities of diethyl ether were identified and benzene was selected as the better extraction solvent. The locations of ephedrine alkaloids were confirmed with 2D NMR. Therefore, a specific 1H-NMR method has been modified for the quantification of ephedrine alkaloids. Accordingly, twenty Ephedrae Herba samples could be classified into three classes: (I) E. sinica-like species; (II) E. intermedia-like species; (III) others (lower alkaloid contents). The results indicated that ephedrine and pseudoephedrine are the major alkaloids in Ephedra plants, but the concentrations vary greatly determined by the plant species and the collection locations.
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Alcaloides , Ephedra , Efedrina , Espectroscopia de Prótons por Ressonância Magnética , Pseudoefedrina , Efedrina/análise , Pseudoefedrina/análise , Ephedra/química , Alcaloides/análise , Espectroscopia de Prótons por Ressonância Magnética/métodosRESUMO
OBJECTIVE: Ribonuclease P RNA component H1 (RPPH1) is a long non-coding RNA (lncRNA) associated with cancer progression. Higher RPPH1 expression in breast and cervical cancer samples than that in normal tissues were observed through the lncRNASNP2 database; therefore, silencing RPPH1 expression might be a potential strategy for cancer treatments, even though RPPH1 is also an RNA subunit of ribonuclease P involved in processing transfer RNA (tRNA) precursors and the effect of RPPH1 knockdown is not yet fully understood. METHODS: Differentially expressed genes (DEGs) were identified through RNA sequencing in each shRNA-transfected RPPH1 knockdown MDA-MB-231, RPPH1 knockdown HeLa cell, and respective control cells, then the gene ontology enrichment analysis was performed by IPA and MetaCore database according to these DEGs, with further in vitro experiments validating the effect of RPPH1 silencing in MDA-MB-231 and HeLa cells. RESULTS: Hundreds of down-regulated DEGs were identified in RPPH1 knockdown MDA-MB-231 and HeLa cells while bioinformatics analysis revealed that these genes were involved in pathways related to immune response and cancerogenesis. Compared to mock- and vector-transfected cells, the production of mature tRNAs, cell proliferation and migration capacity were inhibited in RPPH1-silenced HeLa and MDA-MB-231 cells. Additionally, RPPH1 knockdown promoted G1 cell cycle arrest mainly through the down-regulation of cyclin D1, although glycolytic pathways were only affected in RPPH1 knockdown HeLa cells but not MDA-MB-231 cells. CONCLUSION: This study demonstrated that knockdown RPPH1 affected tRNA production, cell proliferation and metabolism. Our findings might provide insight into the role of RPPH1 in tumor development.
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Multidrug resistance (MDR) is a multifactorial issue in cancer treatment. Drug efflux transporters, particularly P-glycoprotein (P-gp), are major contributors to such resistance. In the present study, we evaluated the P-gp-inhibiting and MDR-reversing effects of two compounds, namely rhein, an anthraquinone, and diacerein, the acetylated prodrug of rhein. ABCB1/Flp-In-293 was used as a model for investigating the related molecular mechanisms, and the multi-drug-resistant cancer cell line KB/VIN was used as a platform for evaluating the reversal of MDR0. The results indicated that at a concentration of 2.5 µM, both diacerein and rhein significantly inhibited P-gp efflux function. They also downregulated P-gp expression by interacting with the signal transducer and activator of transcription 3. Further investigation of the inhibitory mechanism of these compounds revealed that both stimulated P-gp ATPase activity dose dependently and engaged in the noncompetitive inhibition of rhodamine 123 efflux. Furthermore, rhein was revealed to be a potent reverser of MDR in cancer, and the combination of 30 µM rhein and 1000 nM vincristine exerted a strong synergistic effect, achieving a high combination index (CI) of 0.092. Diacerein demonstrated potential applications as a selective cytotoxic agent against multi-drug-resistant cancer cells at a concentration of > 18.92 µM and as a mild MDR reverser at doses of < 10 µM. In conclusion, diacerein and rhein are potential candidates for P-gp inhibition and MDR reversal in cancer cells.
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Neoplasias , Pró-Fármacos , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antraquinonas/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Pró-Fármacos/farmacologia , Fator de Transcrição STAT3/metabolismoRESUMO
OBJECTIVES: Lithium has numerous neuroplastic and neuroprotective effects in patients with stroke. Here, we evaluated whether delayed and short-term lithium treatment reduces brain infarction volume and improves electrophysiological and neurobehavioral outcomes following long-term recovery after cerebral ischemia and the possible contributions of lithium-mediated mechanisms of neuroplasticity. METHODS: Male Sprague Dawley rats were subjected to right middle cerebral artery occlusion for 90 min, followed by 28 days of recovery. Lithium chloride (1 mEq/kg) or vehicle was administered via intraperitoneal infusion once per day at 24 h after reperfusion onset. Neurobehavioral outcomes and somatosensory evoked potentials (SSEPs) were examined before and 28 days after ischemia-reperfusion. Brain infarction was assessed using Nissl staining. Primary cortical neuron cultures were exposed to oxygen-glucose deprivation (OGD) and treated with 2 or 20 µM lithium for 24 or 48 h; subsequent brain-derived neurotrophic factor (BDNF), growth-associated protein-43 (GAP-43), postsynaptic density-95 (PSD-95), and synaptosomal-associated protein-25 (SNAP-25) levels were analyzed using western blotting. RESULTS: Compared to controls, lithium significantly reduced infarction volume in the ischemic brain and improved electrophysiological and neurobehavioral outcomes at 28 days post-insult. In cultured cortical neurons, BDNF, GAP-43, and PSD-95 expression were enhanced by 24- and 48-h treatment with lithium after OGD. CONCLUSION: Lithium upregulates BDNF, GAP-43, and PSD-95, which partly accounts for its improvement of neuroplasticity and provision of long-term neuroprotection in the ischemic brain.Abbreviations: BDNF: brain-derived neurotrophic factor; ECM: extracellular matrix; EDTA: ethylenediaminetetraacetic acid; GAP-43: growth-associated protein-43; GSK-3ß: glycogen synthase kinase-3ß; HBSS: Hank's balanced salt solution; LCBF: local cortical blood perfusion; LDF: laser-Doppler flowmetry; MCAO: middle cerebral artery occlusion; MMP: matrix metalloproteinase; NMDA: N-methyl-D-aspartate; NMDAR: N-methyl-D-aspartate receptor; OCT: optimal cutting temperature compound; OGD: oxygen-glucose deprivation; PSD-95: postsynaptic density-95; SDS: sodium dodecyl sulfate; SNAP-25: synaptosomal-associated protein-25; SSEP: somatosensory evoked potential.
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Isquemia Encefálica , Proteína 4 Homóloga a Disks-Large , Proteína GAP-43 , Lítio , Fármacos Neuroprotetores , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Ácido Edético , Proteína GAP-43/metabolismo , Glucose , Glicogênio Sintase Quinase 3 beta/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Lítio/farmacologia , Cloreto de Lítio/farmacologia , Masculino , N-Metilaspartato , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Oxigênio , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Dodecilsulfato de SódioRESUMO
Seven new anthraquinones with rare 2-isopropyldihydrofuran (1-3) and 2,2-dimethylpyrano (4-7) moieties together with thirty-four known compounds were isolated from the extracts of whole Hedyotis diffusa plants. Their structures were elucidated and established by various spectroscopic and spectrometric analytical methods. Among these isolates, selected compounds were examined for their anti-inflammatory activity. The results showed that rare substituted anthraquinones displayed potent inhibitory activity with IC50 values ranging from 0.15 ± 0.01 to 5.52 ± 1.59 µM on the N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release cellular models. Meanwhile, the proposed drug target of the active anthraquinone was studied by computer modeling. The binding affinity between the anti-inflammatory anthraquinone and elastase was evaluated by molecular docking. These results provided the scientific insight into the medicinal values of Hedyotis diffusa and vision of development as lead compounds.
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OBJECTIVES: Lithium exerts a broad neuroprotective effect on the brain. This study examined whether lithium exerts therapeutic effects on stroke by restoring neural connections at the ischemic core of cortices post brain insult. METHODS: We treated rats with lithium or vehicle (saline) every 24 h for the first 72 h, starting at the beginning of reperfusion after inducing middle cerebral artery occlusion (MCAO) in rats. Somatosensory evoked potential (SSEP) recording and behavioral testing were employed to evaluate the beneficial effects of lithium treatment. To examine the effects of lithium-induced neuroplasticity, we evaluated the dendritic morphology in cortex pyramidal cells and the primary neuronal cell culture that underwent brain insults and oxygen and glucose deprivation (OGD), respectively. RESULTS: The results demonstrated that rats subjected to MCAO had prolonged N1 latency and a decreased N1/P1 amplitude at the ipsilateral cortex. Four doses of lithium reduced the brain infarction volume and enhanced the SSEP amplitude. The results of neurobehavioral tests demonstrated that lithium treatment improved sensory function, as demonstrated by improved 28-point clinical scale scores. In vitro study results showed that lithium treatment increased the dendritic lengths and branches of cultured neurons and reversed the suppressive effects of OGD. The in vivo study results indicated that lithium treatment increased cortical spine density in various layers and resulted in the development of the dendritic structure in the contralateral hemisphere. CONCLUSION: Our study confirmed that neuroplasticity in cortical neurons is crucial for lithium-induced brain function 50 recovery after brain ischemia.
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Córtex Cerebral/efeitos dos fármacos , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Infarto da Artéria Cerebral Média/complicações , AVC Isquêmico/complicações , Compostos de Lítio/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Células Piramidais/efeitos dos fármacos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Células Cultivadas , Modelos Animais de Doenças , Compostos de Lítio/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , RatosRESUMO
It is reported that various fungi have been used for medicine and edible foods. The tropical Trametes genus is popular and well-known in Vietnam for its health effects and bioactivities. In this study, the fruiting bodies of the edible fungi T. cubensis and T. suaveolens were collected in Vietnam. The preliminary bioactivity screening data indicated that the methanol extracts of the fruiting bodies of T. cubensis and T. suaveolens displayed significant inhibition of superoxide anion generation and elastase release in human neutrophils. Therefore, the isolation and characterization were performed on these two species by a combination of chromatographic methods and spectrometric analysis. In total, twenty-four compounds were identified, and among these (1-3) were characterized by 1D-, 2D-NMR, and HRMS analytical data. In addition, the anti-inflammatory potentials of some purified compounds were examined by the cellular model for the inhibition of superoxide anion generation and elastase release in human neutrophils. Among the isolated compounds, (5,14), and (19) displayed significant anti-inflammatory potential. As the results suggest, the extracts and isolated compounds from T. cubensis and T. suaveolens are potential candidates for the further development of new anti-inflammatory lead drugs or natural healthy foods.
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Anti-Inflamatórios/análise , Carpóforos/química , Polyporaceae/química , Anti-Inflamatórios/farmacologia , Linhagem Celular , Humanos , Modelos Moleculares , Neutrófilos/efeitos dos fármacos , Neutrófilos/enzimologia , Neutrófilos/metabolismo , Elastase Pancreática/antagonistas & inibidores , Elastase Pancreática/metabolismo , Superóxidos/antagonistas & inibidores , Superóxidos/metabolismo , VietnãRESUMO
Cancer multi-drug resistance (MDR) caused by P-glycoprotein (P-gp) efflux is a critical unresolved clinical concern. The present study analyzed the effect of cinnamophilin on P-gp inhibition and MDR reversion. The effect of cinnamophilin on P-gp was investigated through drug efflux assay, ATPase assay, MDR1 shift assay, and molecular docking. The cancer MDR-reversing ability and mechanisms were analyzed through cytotoxicity and combination index (CI), cell cycle, and apoptosis experiments. P-gp efflux function was significantly inhibited by cinnamophilin without influencing the drug's expression or conformation. Cinnamophilin uncompetitively inhibited the efflux of doxorubicin and rhodamine 123 and exhibited a distinct binding behavior compared with verapamil, the P-gp standard inhibitor. The half maximal inhibitory concentration of cinnamophilin for doxorubicin and rhodamine 123 efflux was 12.47 and 11.59 µM, respectively. In regard to P-gp energy consumption, verapamil-stimulated ATPase activity was further enhanced by cinnamophilin at concentrations of 0.1, 1, 10, and 20 µM. In terms of MDR reversion, cinnamophilin demonstrated synergistic cytotoxic effects when combined with docetaxel, vincristine, or paclitaxel. The CI was < 0.7 in all experimental combination treatments. The present study showed that cinnamophilin possesses P-gp-modulating effects and cancer MDR resensitizing ability.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adenosina Trifosfatases/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Guaiacol/análogos & derivados , Lignanas/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Antibióticos Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sítios de Ligação/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina/farmacocinética , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Sinergismo Farmacológico , Guaiacol/farmacologia , Humanos , Simulação de Acoplamento Molecular , Rodamina 123 , Verapamil/farmacocinéticaRESUMO
Multidrug resistance (MDR), for which the mechanisms are not yet fully clear, is one of the major obstacles to cancer treatment. In recent years, signal transducer and activator of transcription 3 (STAT3) were found to be one of the important MDR mechanism pathways. Based on the previous research, zhankuic acid A, B, and C were found to have collateral sensitivity effects on MDR cancer cells, and MDR inhibitory activity of zhankuic acid methyl ester was found to be better than that of its acid. Therefore, we executed a systematic examination of the structure-activity relationship of zhankuic acid methyl ester derivatives to collateral sensitivity in MDR cancer cells. The results showed that compound 12 is the best in terms of chemoreversal activity, where the reversal fold was 692, and the IC50 value of paclitaxel combined with 10 µM compound 12 treatment was 1.69 nM in MDR KBvin cells. Among all the derivatives, methyl ester compounds were found to be better than their acids, and a detailed discussion of the structure-activity relationships of all of the derivatives is provided in this work. In addition, compounds 8, 12, and 26 were shown to influence the activation of STAT3 in KBvin cells, accounting for part of their chemoreversal effects. Our results may provide a new combined therapy with paclitaxel to treat multidrug-resistant cancers and provide a new therapy option for patients.
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BACKGROUND AND PURPOSE: Neutrophil overactivation is crucial in the pathogenesis of acute lung injury (ALI). Bletinib (3,3'-dihydroxy-2',6'-bis(p-hydroxybenzyl)-5-methoxybibenzyl), a natural bibenzyl, extracted from the Bletilla plant, exhibits anti-inflammatory, antibacterial, and antimitotic effects. In this study, we evaluated the therapeutic effects of bletinib in human neutrophilic inflammation and LPS-mediated ALI in mice. EXPERIMENTAL APPROACH: In human neutrophils activated with the formyl peptide (fMLP), we assessed integrin expression, superoxide anion production, degranulation, neutrophil extracellular trap (NET) formation, and adhesion through flow cytometry, spectrophotometry, and immunofluorescence microscopy. Immunoblotting was used to measure phosphorylation of Src family kinases (SFKs) and downstream proteins. Finally, a LPS-induced ALI model in male BALB/c mice was used to investigate the potential therapeutic effects of bletinib treatment. KEY RESULTS: In activated human neutrophils, bletinib reduced degranulation, respiratory burst, NET formation, adhesion, migration, and integrin expression; suppressed the enzymic activity of SFKs, including Src, Lyn, Fgr, and Hck; and inhibited the phosphorylation of SFKs as well as Vav and Bruton's tyrosine kinase (Btk). In mice with ALI, the pulmonary sections demonstrated considerable amelioration of prominent inflammatory changes, such as haemorrhage, pulmonary oedema, and neutrophil infiltration, after bletinib treatment. CONCLUSION AND IMPLICATIONS: Bletinib regulates neutrophilic inflammation by inhibiting the SFK-Btk-Vav pathway. Bletinib ameliorates LPS-induced ALI in mice. Further biochemical optimisation of bletinib may be a promising strategy for the development of novel therapeutic agents for inflammatory diseases.
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Lesão Pulmonar Aguda , Quinases da Família src , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Quinases da Família src/metabolismoRESUMO
Drug resistance of cancer cells stands for the major problem of the treatment failure for chemotherapy or target therapy. Overexpression of efflux pumps leading to multidrug resistance (MDR) is still an important issue needed to be solved. In the present study, Taiwanofungus salmoneus was selected as the topic and eleven undescribed constituents including four naphthoquinones salmonones A-D (1-4) and seven triterpenoids salmoneatins A-G (5-11), along with one chromanone (12) and two benzenoids (13 and 14) reported from the natural sources for the first time, as well as twenty-one known compounds were characterized. The structures of undescribed compounds were established by the spectroscopic and spectrometric analyses. In addition, the plausible biosynthetic mechanism of purified naphthoquinones was proposed and these compounds may be the excellent chemotaxonomic markers. Moreover, the isolates were evaluated for their P-gp inhibitory effects and the results showed that most of the examined compounds were effective. Among the tested compounds, 5, 10, 2,3-dimethoxy-5-(2',5'-dimethoxy-3',4'-methylenedioxyphenyl)-7-methyl-[1,4]naphthoquinone, zhankuic acid A methyl ester, and camphoratin F can reverse the resistance of paclitaxel or vincristine with the reversal folds in the range of 51093.3 and 259.5. These experimental data would initiate the possible development of Taiwanofungus salmoneus for the cancer therapy in the future.
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Antineoplásicos/farmacologia , Carpóforos/química , Naftoquinonas/farmacologia , Polyporales/química , Triterpenos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Naftoquinonas/química , Naftoquinonas/isolamento & purificação , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificação , Células Tumorais CultivadasRESUMO
A highly specific and sensitive proton nuclear magnetic resonance (1H-NMR) method has been developed for the quantification of ephedrine alkaloid derivatives in Ephedra herbal commercial prescriptions. At the region of δ 4.0 to 5.0 ppm in the 1H NMR spectrum, the characteristic signals are separated well from each other, and six analogues in total, methylephedrine (ME), ephedrine (EP), norephedrine (NE), norpseudoephedrine (NP), pseudoephedrine (PE), and methylpseudoephedrine (MP) could be identified. The quantities of these compounds are calculated by the relative ratio of the integral values of the target peak for each compound to the known concentrations of the internal standard anthracene. The present method allows for a rapid and simple quantification of ephedrine alkaloid derivatives in Ephedra-related commercial prescriptions without any preliminary purification steps and standard compounds, and accordingly it can be a powerful tool to verify different Ephedra species. In comparison to conventional chromatographic methods, the advantages of this method include the fact that no standard compounds are required, the quantification can be directly performed on the crude extracts, a better selectivity for various ephedrine alkaloid derivatives, and the fact that a very significant time-gain may be achieved.
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Alcaloides/análise , Ephedra/química , Efedrina/análogos & derivados , Efedrina/análise , Ephedra/classificação , Estudos de Viabilidade , Humanos , Limite de Detecção , Espectroscopia de Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/estatística & dados numéricos , Medicina Tradicional Chinesa , Fenilpropanolamina/análise , Preparações de Plantas/química , Pseudoefedrina/análise , Especificidade da EspécieRESUMO
BACKGROUND: Temozolomide (TMZ) has been widely used to treat glioblastoma multiforme (GBM). However, many mechanisms are known to quickly adapt GBM cells to chemotherapy with TMZ, leading to drug resistance and expansion of tumor cell populations. METHODS: We subjected human glioblastoma cell lines and an animal model of glioblastoma xenografts with TMZ-based adjuvant treatments to evaluate the synergistic effect of cinnamophilin (CINN), a free radical scavenger. RESULTS: Our results showed that the combined treatment of CINN and TMZ potentiated the anticancer effect and apoptotic cell death in glioma cell lines and enhanced antitumor action in glioma xenografts. TMZ induced reactive oxygen species (ROS) burst and elevated G2 arrest in glioma cells. The CINN-suppressed ROS burst in TMZ-treated glioma cells might be associated with increased apoptosis, as indicated by the upregulation of TUNEL-positive glioma cells. CINN-pretreated glioma cells exhibited increased cyclin B expression and reduced phosphorylation of Cdk1, suggesting reduced G2 arrest in the combined treatment group. Moreover, CINN lowered the protein level of LC3, a hallmark of autophagy, in TMZ-treated cells. CONCLUSIONS: These findings suggest that CINN may restore TMZ toxicity in glioma cancer by suppressing the ROS/G2 arrest pathway.
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An investigation is performed into the efficiency of the Streptomyces griseus HUT 6037 enzyme immobilized in three different mesoporous silicas, namely mesoporous silica film, mesocellular foam, and rod-like SBA-15. It is shown that for all three supports, the pH value changes the surface charge and charge density and hence determines the maximum loading capacity of the enzyme. The products of the enzyme hydrolytic reaction are analyzed by 1H-NMR. The results show that among the three silica supports, the mesoporous silica film (with a channel length in the range of 60-100 nm) maximizes the accessibility of the immobilized enzyme. The loading capacity of the enzyme is up to 95% at pH 7 and the activity of the immobilized enzyme is maintained for more than 15 days when using a silica film support. The order of the activity of the enzyme immobilized in different mesoporous silica supports is: mesoporous silica film > mesocellular foam > rod-like SBA-15. Furthermore, the immobilized enzyme can be easily separated from the reaction solution via simple filtration or centrifugation methods and re-used for hydrolytic reaction as required.
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A new dimeric quaternary protoberberine alkaloid, bispalmatrubine (1), and thirteen known compounds (2-14) were purified from the tubers of Tinospora dentata. Their structures were determined by spectroscopic and spectrometric analytical methods. Among the isolates, eight compounds were examined for their in vitro anti-inflammatory potential and several tested alkaloids displayed moderate inhibitory effects of N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release.
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Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Tinospora/química , Alcaloides/química , Alcaloides/farmacologia , Alcaloides de Berberina/química , Citocalasina B/farmacologia , Humanos , Estrutura Molecular , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Tubérculos/química , Plantas Medicinais/química , Superóxidos/metabolismoRESUMO
Twelve undescribed lanostane-type triterpenes, and twenty-two known triterpenes were isolated and identified from a medicinal bracket fungus Fomitopsis pinicola (Sw.) P. Karst. The structures of these compounds were determined by spectroscopic and spectrometric analyses. The antiinflammatory potential of thirty-two triterpene compounds was evaluated using neutrophils as an assay model, and pinicolasin J was the most potent inhibitor of superoxide anion generation and elastase release, with IC50 values of 1.81 ± 0.44 and 2.50 ± 0.64 µM, respectively. This study provides scientific insight into the nutritional supplement value and medicinal development of Fomitopsis pinicola.
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Anti-Inflamatórios/farmacologia , Coriolaceae/química , Inibidores Enzimáticos/farmacologia , Carpóforos/química , Elastase Pancreática/antagonistas & inibidores , Triterpenos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Estrutura Molecular , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
This study investigates the application of the paramagnetic shift reagent tris(dipivaloylmethanato)-europium(III) in NMR spectral studies of permethoxyacridone alkaloids (1-3) and pyranoacridone alkaloids (4-6). The induced chemical shifts (∆δ) of all protons were observed for the same molecule, and were compared to deduce the positions resulting from the distance nearby the Eu(dpm)3. Assignment of the H-2, H-4 and H-8 of polysubstituted acridones could be distinguished based on the least-squares method of lanthanide-induced shifts plotted against the mole ratios of Eu(dpm)3 to the substrate. The developed method is not only potentially useful for determining the planar structures of polysubstituted compounds, such as acridones, anthraquinones, xanthones, flavonoids, and phenanthrenes, but also applicable for their stereochemistry.