RESUMO
Four biflavonoid glycosides, balsamisides A-D (1-4), and nine known compounds (5-13) were obtained from the white petals of Impatiens balsamina. The 2D structures of the purified phytochemicals were established using conventional NMR techniques in addition to the new long-range HSQMBC NMR experiment. Acid hydrolysis followed by experimental and quantum-mechanics-based ECD data analysis permitted full configurational assignment of the purified metabolites. Compounds 1-13 were assessed for their potential to impede the generation of nitric oxide in lipopolysaccharide-stimulated BV2 cells. They were also investigated for potential neuroprotective activity using C6 cells and cytotoxicity against some human tumor cell lines, but were inactive (IC50 > 10 µM) against all the cell lines.
Assuntos
Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Biflavonoides/isolamento & purificação , Biflavonoides/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Impatiens/química , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Algoritmos , Animais , Anti-Inflamatórios não Esteroides/química , Biflavonoides/química , Glicosídeos/química , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Fármacos Neuroprotetores/química , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , República da CoreiaRESUMO
The purpose of this study was to evaluate the wound-healing effects of a novel benzalkonium chloride (BC)-loaded hydrocolloid wound dressing (HCD). A BC-loaded HCD was prepared with various constituents using a hot melting method, and its mechanical properties and antimicrobial activities were assessed. The in vivo wound healings of the BC-loaded HCD in various would models were evaluated in rats compared with a commercial wound dressing, Duoderm™. This BC-loaded HCD gave better skin adhesion, swelling, mechanical strength, and flexibility compared with the commercial wound dressing. It showed excellent antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. In addition, as compared with the commercial wound dressing, it showed more improved wound healings and tissue restoration effect on the excision, infection, and abrasion wounds in rats. Thus, this novel BC-loaded HCD would be an excellent alternative to the commercial wound dressing for treatment of various wounds.
Assuntos
Anti-Infecciosos Locais/administração & dosagem , Curativos Hidrocoloides , Compostos de Benzalcônio/administração & dosagem , Cicatrização/efeitos dos fármacos , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
In a continuing search for bioactive constituents from Dioscoreaceae medicinal plants, two new cyclic diarylheptanoids, diosniponol A (1) and B (2), together with 10 known compounds (3-12) were isolated from the rhizomes of Dioscorea nipponica. The structures of these new compounds were determined by spectroscopic analyses, including extensive two-dimensional nuclear magnetic resonance, high-resolution mass spectrometry, and optical rotation. All isolated compounds 1-12 were evaluated for their effects on nitric oxide (NO) production in murine microglia cell line BV-2. Compounds 8 and 11 showed potent inhibitory activities on NO production (IC50 13.36 and 14.36 µM, respectively) without cell toxicity in lipopolysaccharide-activated BV-2 cells.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Diarileptanoides/farmacologia , Dioscorea/química , Óxido Nítrico/antagonistas & inibidores , Rizoma/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Linhagem Celular , Diarileptanoides/química , Diarileptanoides/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico/biossínteseRESUMO
Pharbinilic acid (1), the first naturally occurring allogibberic acid, was isolated from ethanol extracts of morning glory (Pharbitis nil) seeds. Its absolute configuration was determined by NOESY NMR and ECD experiments. Compound 1 showed weak cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cells and weakly inhibited nitric oxide production in lipopolysaccharide-activated BV-2 microglia cells.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Ipomoea nil/química , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico/biossíntese , República da Coreia , Sementes/químicaRESUMO
A phytochemical investigation on the essential oil of Thuja orientalis resulted in the isolation and identification of three new sesquiterpenes, 3α-methoxy-4α-epoxythujopsane (1), Δ³,¹5-4ß-epoxythujopsene (2), and Δ³,4-thujopsen-2,15-diol (3), together with eight known sesquiterpenoids (4-11). The structures of these new compounds were elucidated based on spectroscopic data analyses including extensive 2D-NMR data and HR-ESIMS. The full assignments of ¹H and ¹³C NMR chemical shifts for thujopsadiene (4) were obtained by 2D-NMR for the first time. All compounds (1-11) showed antiproliferative activities against the SK-OV-3 and SK-MEL-2 cell lines with IC50 values of 5.85-28.64 µM. In addition, compounds 1, 3, 4, 7, 8, and 9 significantly inhibited nitric oxide production in lipopolysaccharide-activated BV-2 cells with IC50 values of 3.93-17.85 µM without cell toxicity.
Assuntos
Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Óxido Nítrico/biossíntese , Óleos Voláteis/uso terapêutico , Fitoterapia , Sesquiterpenos/uso terapêutico , Thuja/química , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Lipopolissacarídeos , Estrutura Molecular , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologiaRESUMO
The rhizome of Dioscorea japonica is a food and medicinal source known as 'San Yak' in Korea. Two new furostanol saponins, coreajaponins A (1) and B (2), together with 10 known compounds (3-12) were isolated from the rhizomes of D. japonica. Their structures were determined by spectroscopic methods, including 1D and 2D NMR techniques, HRMS, and chemical methods. Nerve growth factor (NGF), a crucial factor for neuronal survival and differentiation, can potentially improve neurodegenerative diseases and diabetic polyneuropathy. We evaluated the effects of isolates (1-12) on NGF induction in a C6 rat glioma cell line. Coreajaponin B (2) upregulated NGF content without significant cell toxicity, as did 6, 8, 9, and 11.
Assuntos
Dioscorea/química , Fator de Crescimento Neural/biossíntese , Rizoma/química , Saponinas/isolamento & purificação , Sequência de Carboidratos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Neurônios/citologia , Neurônios/efeitos dos fármacos , Saponinas/química , Saponinas/farmacologiaRESUMO
Two new tetrahydroprotoberberine-aporphine dimeric alkaloids, corydaturtschines A (1) and B (2), and a new aporphine derivative, ethyl glausuccinate (3), together with 13 known protoberberine (4-16) and nine known aporphine alkaloids (17-25), were isolated from the tubers of Corydalis turtschaninovii. The structures of these new compounds were determined through spectral analyses, including extensive 2D-NMR data. The absolute configurations of the compounds were clarified by CD spectroscopic studies. The isolated compounds were tested for their cytotoxicity against four human cancer cell lines in vitro using a sulforhodamine B bioassay.
Assuntos
Antineoplásicos Fitogênicos/química , Alcaloides de Berberina/química , Corydalis/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Aporfinas/química , Aporfinas/isolamento & purificação , Aporfinas/farmacologia , Alcaloides de Berberina/isolamento & purificação , Alcaloides de Berberina/farmacologia , Linhagem Celular Tumoral , Humanos , Ressonância Magnética Nuclear Biomolecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Tubérculos/químicaRESUMO
Two new phenolic amides, pharnilatins A (1) and B (2), were isolated from the seeds of Pharbitis nil. These new compounds possess a p-coumaroyl unit with a structurally unique side chain, (2S,3S)-2,3-dihydroxyputrescine. The chemical structures and absolute stereochemistries of the new compounds were determined on the basis of spectroscopic analyses including 1D- and 2D-NMR experiments and chemical reactions. Compounds 1 and 2 exhibited cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 human tumor cells. However, none of the compounds inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated microglia cells.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Ipomoea nil/química , Amidas/química , Amidas/isolamento & purificação , Amidas/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular , Linhagem Celular Tumoral , Ácidos Cumáricos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias/tratamento farmacológico , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Sementes/químicaRESUMO
Onychomycosis is a prevailing disease caused by fungal infection of nails that mostly affects athletes and the elderly. Ciclopirox is approved by the US Food and Drug Administration for the topical treatment of onychomycosis. However, the desired penetration of ciclopirox into the nail bed has not been achieved via topical application for efficient treatment. Therefore, the main aim of this study was to enhance ciclopirox permeation and retention in nail by the development of a new nail lacquer formulation. We screened the effects of different solvents, alkalizing agents, and permeation enhancers on the permeation of bovine hooves by ciclopirox and its retention in human nail clippings. The results suggest that isopropyl alcohol, potassium hydroxide, and urea as the solvent, alkalizing agent, and permeation enhancer, respectively, improved the permeation of the ciclopirox nail lacquer formulation the most with high flux rates. Comparison of the final formulation and marketed product revealed enhanced retention of ciclopirox from our developed formulation in human nail clippings. Therefore, our newly developed nail lacquer may be a potentially effective formulation for the treatment of onychomycosis in humans.
Assuntos
Antifúngicos/metabolismo , Casco e Garras/metabolismo , Laca , Unhas/metabolismo , Piridonas/metabolismo , Administração Tópica , Animais , Antifúngicos/administração & dosagem , Bovinos , Ciclopirox , Casco e Garras/efeitos dos fármacos , Humanos , Unhas/efeitos dos fármacos , Onicomicose/tratamento farmacológico , Onicomicose/metabolismo , Permeabilidade/efeitos dos fármacos , Piridonas/administração & dosagemRESUMO
Nerve growth factor (NGF)-induced neuronal regeneration has emerged as a strategy to treat neuronal degeneration-associated disorders. However, direct NGF administration is limited by the occurrence of adverse effects at high doses of NGF. Therefore, development of a therapeutic strategy to promote the NGF trophic effect is required. In view of the lack of understanding of the mechanism for potentiating the NGF effect, this study investigated molecular targets of DA-9801, a well-standardized Dioscorea rhizome extract, which has a promoting effect on NGF. An increase in intracellular calcium ion level was induced by DA-9801, and chelation of extracellular calcium ions with ethylene-bis(oxyethylenenitrilo)tetraacetic acid (EGTA) suppressed the potentiating effect of DA-9801 on NGF-induced neurite outgrowth. In addition, EGTA treatment reduced the DA-9801-induced phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), the major mediators of neurite outgrowth. To find which calcium ion-permeable channel contributes to the calcium ion influx induced by DA-9801, we treated PC12 cells with various inhibitors of calcium ion-permeable channels. NF449, a P2X1 receptor selective antagonist, significantly abolished the potentiating effect of DA-9801 on NGF-induced neurite outgrowth and abrogated the DA-9801-induced ERK1/2 phosphorylation. In addition, transfection with siRNA of P2X1 receptor significantly reduced the DA-9801-enhanced neurite outgrowth. In conclusion, calcium ion influx through P2X1 receptor mediated the promoting effect of DA-9801 on NGF-induced neurite outgrowth via ERK1/2 phosphorylation.
Assuntos
Fator de Crescimento Neural/metabolismo , Neuritos/efeitos dos fármacos , Crescimento Neuronal/efeitos dos fármacos , Preparações de Plantas/farmacologia , Purinérgicos/farmacologia , Receptores Purinérgicos P2X1/metabolismo , Animais , Cálcio/metabolismo , Quelantes de Cálcio/farmacologia , Cátions Bivalentes/metabolismo , Ácido Egtázico/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neuritos/fisiologia , Crescimento Neuronal/fisiologia , Fármacos Neuroprotetores/farmacologia , Células PC12 , Fosforilação/efeitos dos fármacos , RNA Interferente Pequeno , Ratos , Receptores Purinérgicos P2X1/genéticaRESUMO
The objective of this study was to evaluate the healing effects of a chitosan-based, film-forming gel containing tyrothricin (TYR) in various rat wound models, including burn, abrasion, incision, and excision models. After solidification, the chitosan film layer successfully covered and protected a variety of wounds. Wound size was measured at predetermined timepoints after wound induction, and the effects of the film-forming gel were compared with negative (no treatment) and positive control groups (commercially available sodium fusidate ointment and TYR gel). In burn, abrasion and excision wound models, the film-forming gel enabled significantly better healing from 1 to 6 days after wound induction, compared with the negative control. Importantly, the film-forming gel also enabled significantly better healing compared with the positive control treatments. In the incision wound model, the breaking strength of wound strips from the group treated with the film-forming gel was significantly increased compared with both the negative and positive control groups. Histological studies revealed advanced granulation tissue formation and epithelialization in wounds treated with the film-forming gel. We hypothesize that the superior healing effects of the film-forming gel are due to wound occlusion, conferred by the chitosan film. Our data suggest that this film-forming gel may be useful in treating various wounds, including burn, abrasion, incision and excision wounds.
Assuntos
Antibacterianos/uso terapêutico , Quitosana/química , Portadores de Fármacos/química , Tirotricina/uso terapêutico , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/tratamento farmacológico , Animais , Antibacterianos/administração & dosagem , Modelos Animais de Doenças , Feminino , Géis , Estrutura Molecular , Ratos Sprague-Dawley , Tirotricina/administração & dosagemRESUMO
Streptococcus mutans is frequently associated with dental caries. Bacterial fermentation of food debris generates an acidic environment on the tooth surface, ultimately resulting in tooth deterioration. Therefore, various mouthwashes have been used to reduce and prevent Streptococcus mutans. The aim of this study was to evaluate the antimicrobial activities of 4 commercial mouthwashes and those of 10% and 20% ethanol solutions (formula A, B, C, D, E and F) against Streptococcus mutans using biofilm and planktonic methods. The range of reduction in the viable cell count of Streptococcus mutans as estimated by the biofilm and planktonic methods was 0.05-5.51 log (P ≤ 0.01) and 1.23-7.51 log (P ≤ 0.001) compared with the negative control, respectively, indicating that the planktonic method had a stronger antibacterial effect against S. mutans. Among the tested formulations, formula A (Garglin regular® mouthwash) was the most effective against Streptococcus mutans (P ≤ 0.001).
Assuntos
Anti-Infecciosos/farmacologia , Antissépticos Bucais/farmacologia , Streptococcus mutans/fisiologia , Biofilmes/efeitos dos fármacos , Testes de Sensibilidade Microbiana , República da Coreia , Streptococcus mutans/efeitos dos fármacosRESUMO
To develop a novel sodium alginate based Centella asiatica (CA)-loaded hydrocolloid wound dressing (HCD) providing excellent mechanical properties and improved wound healing, numerous CA-loaded HCDs were prepared with various ingredients using the hot melting method. The effect of sodium alginate, styrene-isoprene-styrene copolymer (SIS) and petroleum hydrocarbon resin (PHR) on the mechanical properties of CA-loaded HCDs was investigated. The effect of disintegrants on swelling and drug release was assessed. Moreover, the in vivo wound healing potentials of the selected CA-loaded HCD in various wound models such as abrasion, excision and infection were evaluated in comparison with the commercial product. Polyisobutylene and SIS hardly affected the mechanical properties, but PHR improved the tensile strength and elongation at break. Disintegrants such as croscarmellose sodium, sodium starch glycolate and crospovidone improved the swelling ratio of the CA-loaded HCD. Furthermore, the CA-loaded HCD without croscarmellose sodium poorly released the drug, but that with 2% croscarmellose sodium showed about 27% drug release in 24h. In particular, the CA-loaded HCD composed of CA/polyisobutylene/SIS/PHR/liquid paraffin/sodium alginate/croscarmellose sodium at the weight ratio of 1/8/25/25/12/27/2 furnished excellent mechanical properties and drug release. As compared with the commercial product, it offered improved healing effects in excision, infection and abrasion type wounds in rats. Thus, this novel CA-loaded HCD could be a potential candidate for the treatment of various wounds.
Assuntos
Centella/química , Coloides/química , Coloides/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Cicatrização/efeitos dos fármacos , Alginatos/química , Animais , Bandagens , Carboximetilcelulose Sódica/química , Reagentes de Ligações Cruzadas/química , Excipientes/química , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Hidrocarbonetos/química , Masculino , Petróleo , Extratos Vegetais , Polienos/química , Polímeros/química , Poliestirenos/química , Povidona/química , Ratos , Ratos Sprague-Dawley , Resistência à Tração , Terpenos/químicaRESUMO
The purpose of this research was to assess the acylation reactions of peptides, salmon calcitonin (sCT), human parathyroid hormone 1-34 (hPTH1-34) and leuprolide, in poly(lactic-co-glycolic acid) (PLGA) microspheres. Capillary electrophoresis (CE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used for determining and monitoring peptide acylation and quantitating acylation products in the degrading PLGA microspheres. In the degrading PLGA microspheres of sCT and hPTH1-34, the acylation products were observed and determined to be adducts with glycolic acid units from degradable PLGA polymer by MALDI-TOF MS. In the microsphere of leuprolide, however, the acylation product was not observed even after 28 days of incubation at the release medium, which represents the different stabilities among peptides according to the primary structure. As the leuprolide contains tyrosine and serine having hydroxyl group of nucleophilic amino acids, the acylation reaction of peptide is shown to be mainly due to the primary amino groups of N-terminus or lysine residue. The complementary use of CE and MALDI-TOF MS will be useful for searching the counter measures as well as determining the peptide acylation in the manufactured formulations on the market.
Assuntos
Ácido Láctico/química , Hormônios Peptídicos/química , Ácido Poliglicólico/química , Polímeros/química , Acilação , Sequência de Aminoácidos , Animais , Calcitonina/química , Portadores de Fármacos/química , Eletroforese Capilar , Glicolatos/química , Humanos , Leuprolida/química , Lisina/química , Microesferas , Dados de Sequência Molecular , Hormônio Paratireóideo/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Salmão , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study.
RESUMO
In the search for antitumor compounds from Korean natural resources, activity-guided fractionation and purification processes were used on seeds of morning glory (Pharbitis nil). Air-dried P. nil seeds were extracted with ethanol and separated into n-hexane, chloroform, ethyl acetate, and n-butanol. Four new lignans, pharbilignans A-D (1-4) were isolated from the most active ethyl acetate fraction of the ethanol extract. Their structures were characterized on the basis of spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance (NMR) techniques, high resolution mass spectrometry (HRMS), and circular dichroism (CD) spectroscopy. The cytotoxic activities of the isolates (1-4) were evaluated by determining their inhibitory effects on four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15) using a sulforhodamine B (SRB) bioassay. Pharbilignan C (3) showed potent cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines with IC50 values of 1.42, 0.16, 0.20, and 0.14 µM, respectively. On the basis of the expanded understanding that inflammation is a crucial cause in tumor progress, we also evaluated anti-inflammatory activity of the isolates (1-4). Pharbilignan C (3) strongly inhibited nitric oxide (NO) production in the lipopolysaccharide (LPS)-activated BV-2 microglia cell line with an IC50 value of 12.8 µM.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ipomoea nil/química , Lignanas/farmacologia , Sementes/química , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Extratos Vegetais/química , República da CoreiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea nipponica (Dioscoreaceae) have been used as traditional medicines for diabetes, inflammatory and neurodegenerative diseases in Korea. The aim of the study was to isolate the bioactive components from the rhizomes of Dioscorea nipponica and to evaluate their anti-neuroinfalmmatory and neuroprotective activities. MATERIAL AND METHODS: The phytochemical investigation of 50% EtOH extract of Dioscorea nipponica using successive column chromatography over silica gel, Sephadex LH-20, and preparative high performance liquid chromatography (HPLC) resulted in the isolation and identification of 17 phenolic derivatives, including four new phenolic compounds (1-4). The structural elucidation of these compounds was based on spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy techniques, mass spectrometry, and optical rotation. All isolated compounds were evaluated for their effects on nerve growth factor (NGF) secretion in a C6 rat glioma cell line and nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV2 cells. The neurite outgrowth of compound 16 was further evaluated by using mouse neuroblastoma N2a cell lines. RESULTS: Three new stilbene derivatives, diosniponol C (1), D (2) and diosniposide A (3) and one new phenanthrene glycoside, diosniposide B (4), together with 13 known compounds were isolated from the rhizomes of Dioscorea nipponica. Of the tested compounds (1-17), phenanthrene, 3,7-dihydroxy-2,4,6-trimethoxy-phenanthrene (16) was the most potent NGF inducer, with 162.35±16.18% stimulation, and strongly reduced NO levels with an IC50 value of 19.56 µM in BV2 microglial cells. Also, it significantly increased neurite outgrowth in N2a cells. CONCLUSIONS: This study supports the ethnopharmacological use of Dioscorea nipponica rhizomes as traditional medicine.
Assuntos
Anti-Inflamatórios/farmacologia , Dioscorea/química , Fármacos Neuroprotetores/farmacologia , Fenóis/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Glioma/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Concentração Inibidora 50 , Lipopolissacarídeos/administração & dosagem , Medicina Tradicional Coreana , Camundongos , Fator de Crescimento Neural/metabolismo , Neuritos/efeitos dos fármacos , Neuritos/metabolismo , Neuroblastoma/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/isolamento & purificação , Óxido Nítrico/metabolismo , Fenóis/administração & dosagem , Fenóis/isolamento & purificação , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Ratos , RizomaRESUMO
In this study, we evaluated the effects of silicone-based gel on the healing of hypertrophic scars in the rabbit ear model. After 4-week application of silicone-based gel containing allantoin, dexpanthenol and heparin (Noscarna™) to scars in a rabbit ear model of hypertrophic scarring, significant improvements in hypertrophic scar healing and a great loss of skin pigment were observed compared to the non-treated control, base or silicone control-treated scars. Furthermore, histological analysis of Noscarna™-treated scars revealed a significant reduction in scar elevation index (SEI), anterior skin and epithelial thicknesses, inflammatory cells, vessels, collagen disorganization and fibroblasts compared to all control hypertrophic scars. Furthermore, Noscarna™ showed more favorable effects on hypertrophic scars than a commercial product, Contractubex®. Therefore, these results clearly demonstrated that the newly developed silicone-based gel, Noscarna™, could be a promising formulation as an effective therapeutic agent for hypertrophic scars.
Assuntos
Alantoína/farmacologia , Cicatriz Hipertrófica/tratamento farmacológico , Heparina/farmacologia , Ácido Pantotênico/análogos & derivados , Alantoína/administração & dosagem , Animais , Cicatriz Hipertrófica/patologia , Modelos Animais de Doenças , Combinação de Medicamentos , Feminino , Heparina/administração & dosagem , Ácido Pantotênico/administração & dosagem , Ácido Pantotênico/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Coelhos , Géis de Silicone/química , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Pigmentação da Pele/efeitos dos fármacosRESUMO
Diabetic neuropathy has multiple aspects of pathophysiology including metabolic derangements and alterations of microvessel with hyperglycemia. Currently, there is no effective long-term treatment based on the pathologic mechanisms. Nerve regeneration with nerve growth factor (NGF) has been on clinical trials as a treatment option. This article reviews an action of a herbal medicine, DA 9801, whose mechanism of action is related to NGF in treating diabetic neuropathy.
Assuntos
Neuropatias Diabéticas/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Preparações de Plantas/uso terapêutico , Animais , Neuropatias Diabéticas/fisiopatologia , Dioscorea/química , Drogas em Investigação/isolamento & purificação , Drogas em Investigação/farmacologia , Drogas em Investigação/uso terapêutico , Humanos , Fator de Crescimento Neural/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Extratos Vegetais/farmacologia , Preparações de Plantas/isolamento & purificação , Preparações de Plantas/farmacologiaRESUMO
Edible yams are tropical crops that serve as important staple foods in many parts of the world. The rhizome of Dioscorea japonica , well-known as "Japanese yam", is a food and medicinal source known as "San Yak" in Korea. Bioassay-guided fractionation and chemical investigation of the extract of this yam resulted in the identification of two new withanolides, named dioscorolide A (1) and dioscorolide B (2). The structures of these new compounds were determined by spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR) techniques, high-resolution mass spectrometry (HRMS), and chemical methods. The cytotoxic activities of the isolates (1 and 2) were evaluated by determining their inhibitory effects on four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15) and a human normal cell line (HUVEC) using a sulforhodamine B (SRB) bioassay. Compounds 1 and 2 showed cytotoxicity against tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15) with IC(50) values ranging from 6.3 to 26.9 µM and exhibited lower activity against the normal cell line (HUVEC) with IC(50) values ranging from 27.1 to 28.8 µM, suggesting selective toxicity among tumor and normal cells.