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1.
Int J Mol Sci ; 25(16)2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39201671

RESUMO

Diabetic nephropathy, a leading cause of end-stage renal disease, accounts for significant morbidity and mortality. It is characterized by microinflammation in the glomeruli and myofibroblast activation in the tubulointerstitium. Salvia miltiorrhiza Bunge, a traditional Chinese medicine, is shown to possess anti-inflammatory and anti-fibrotic properties, implying its renal-protective potential. This study investigates which type of component can reduce the damage caused by diabetic nephropathy in a single setting. The ethyl acetate (EtOAc) layer was demonstrated to provoke peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ activities in renal mesangial cells by dual luciferase reporter assay. In a high glucose (HG)-cultured mesangial cell model, the EtOAc layer substantially inhibited HG-induced elevations of interleukin-1ß, transforming growth factor-ß1 (TGF-ß1), and fibronectin, whereas down-regulated PPAR-γ was restored. In addition, among the extracts of S. miltiorrhiza, the EtOAc layer effectively mitigated TGF-ß1-stimulated myofibroblast activation. The EtOAc layer also showed a potent ability to attenuate renal hypertrophy, proteinuria, and fibrotic severity by repressing diabetes-induced proinflammatory factor, extracellular matrix accumulation, and PPAR-γ reduction in the STZ-induced diabetes mouse model. Our findings, both in vitro and in vivo, indicate the potential of the EtOAc layer from S. miltiorrhiza for future drug development targeting diabetic nephropathy.


Assuntos
Acetatos , Diabetes Mellitus Experimental , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Fibrose , PPAR gama , Salvia miltiorrhiza , Salvia miltiorrhiza/química , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , PPAR gama/metabolismo , Acetatos/química , Acetatos/farmacologia , Masculino , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Fibronectinas/metabolismo , Camundongos Endogâmicos C57BL , PPAR alfa/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Glucose/metabolismo
2.
Bioorg Chem ; 141: 106843, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37696148

RESUMO

In the present study, the undescribed schitriterpenoids, kadsujanonols A-I (1-9), and eleven reported compounds (10-20) were isolated from K. japonica L. vines. Their structures of 3,4-seco-schitriterpenoids were elucidated mainly by spectroscopic analyses including 1H-, 13C-, and 2D-NMR, IR, HRESIMS spectra. The spatial configurations were determined by the single-crystal X-ray diffraction analysis of kadsujapnonol A (1), 15, 17, and 18, CD data and computational analysis. Furthermore, all isolates were evaluated for the anti-neuroinflammatory activity on LPS-stimulated NO production in BV2 microglial cells and compounds 2, 4, 5, 7, 9, 11, 13-16, and 18 exposed better or comparable suppression abilities than PDTC. Among them, kadlongilactone B (14) showed the best significant inhibiting ability (IC50 = 0.87 µg/mL) and the effect is through the attenuation of the inflammatory transcription factor p65NF-κB. Preliminary structure-activity relationship revealed that δ-lactone at the side chain and 7-member lactone at C-3/C-4, and 3,4:9,10 ring opening are important.


Assuntos
Kadsura , Kadsura/química , Relação Estrutura-Atividade , Microglia , Lactonas , Lipopolissacarídeos/farmacologia , Estrutura Molecular
3.
Chem Pharm Bull (Tokyo) ; 71(2): 183-187, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36724981

RESUMO

A formerly unpublicized briarane diterpenoid, briastecholide M (1), and its established analogue, brianodin B (2), were purified from Briareum stechei, an octocoral collected from Okinawan waters. Using spectroscopic methods, the structure of 1 was established. Functional study showed that 1 can reducing the release of inducible nitric oxide synthase (iNOS) but enhancing cyclooxygenase-2 (COX-2) protein expression.


Assuntos
Antozoários , Diterpenos , Animais , Antozoários/química , Antozoários/metabolismo , Diterpenos/farmacologia , Diterpenos/química , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/metabolismo
4.
Pharmacol Res ; 184: 106424, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36064077

RESUMO

The global COVID-19 pandemic remains a critical public health threat, as existing vaccines and drugs appear insufficient to halt the rapid transmission. During an outbreak from May to August 2021 in Taiwan, patients with severe COVID-19 were administered NRICM102, which was a traditional Chinese medicine (TCM) formula developed based on its predecessor NRICM101 approved for treating mild cases. This study aimed to explore the mechanism of NRICM102 in ameliorating severe COVID-19-related embolic and fibrotic pulmonary injury. NRICM102 was found to disrupt spike protein/ACE2 interaction, 3CL protease activity, reduce activation of neutrophils, monocytes and expression of cytokines (TNF-α, IL-1ß, IL-6, IL-8), chemokines (MCP-1, MIP-1, RANTES) and proinflammatory receptor (TLR4). NRICM102 also inhibited the spread of virus and progression to embolic and fibrotic pulmonary injury through reducing prothrombotic (vWF, PAI-1, NET) and fibrotic (c-Kit, SCF) factors, and reducing alveolar type I (AT1) and type II (AT2) cell apoptosis. NRICM102 may exhibit its protective capability via regulation of TLRs, JAK/STAT, PI3K/AKT, and NET signaling pathways. The study demonstrates the ability of NRICM102 to ameliorate severe COVID-19-related embolic and fibrotic pulmonary injury in vitro and in vivo and elucidates the underlying mechanisms.


Assuntos
Tratamento Farmacológico da COVID-19 , Lesão Pulmonar , Embolia Pulmonar , Enzima de Conversão de Angiotensina 2 , Quimiocina CCL5 , Citocinas , Fibrose , Humanos , Interleucina-6/metabolismo , Interleucina-8 , Lesão Pulmonar/tratamento farmacológico , Pandemias , Fosfatidilinositol 3-Quinases , Inibidor 1 de Ativador de Plasminogênio , Proteínas Proto-Oncogênicas c-akt , Embolia Pulmonar/tratamento farmacológico , Glicoproteína da Espícula de Coronavírus , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de von Willebrand
5.
Pharmacol Res ; 184: 106412, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36007774

RESUMO

BACKGROUND: Viral- and host-targeted traditional Chinese medicine (TCM) formulae NRICM101 and NRICM102 were administered to hospitalized patients with COVID-19 during the mid-2021 outbreak in Taiwan. We report the outcomes by measuring the risks of intubation or admission to intensive care unit (ICU) for patients requiring no oxygen support, and death for those requiring oxygen therapy. METHODS: This multicenter retrospective study retrieved data of 840 patients admitted to 9 hospitals between May 1 and July 26, 2021. After propensity score matching, 302 patients (151 received NRICM101 and 151 did not) and 246 patients (123 received NRICM102 and 123 did not) were included in the analysis to assess relative risks. RESULTS: During the 30-day observation period, no endpoint occurred in the patients receiving NRICM101 plus usual care while 14 (9.27%) in the group receiving only usual care were intubated or admitted to ICU. The numbers of deceased patients were 7 (5.69%) in the group receiving NRICM102 plus usual care and 27 (21.95%) in the usual care group. No patients receiving NRICM101 transitioned to a more severe status; NRICM102 users were 74.07% less likely to die than non-users (relative risk= 25.93%, 95% confidence interval 11.73%-57.29%). CONCLUSION: NRICM101 and NRICM102 were significantly associated with a lower risk of intubation/ICU admission or death among patients with mild-to-severe COVID-19. This study provides real-world evidence of adopting broad-spectrum oral therapeutics and shortening the gap between outbreak and effective response. It offers a new vision in our preparation for future pandemics.


Assuntos
COVID-19 , COVID-19/terapia , Humanos , Medicina Tradicional Chinesa , Pontuação de Propensão , Estudos Retrospectivos , SARS-CoV-2
6.
J Nat Prod ; 84(2): 259-267, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33459007

RESUMO

Seven new polyhydroxylated oleanane-type triterpene saponins, arenarosides A-G (1-7), together with four known compounds, were isolated from an ethanol extract of the aerial parts of the Vietnamese plant Polycarpaea arenaria. The chemical structures of the newly isolated oleanane saponins were elucidated on the basis of spectroscopic and spectrometric analysis, especially 2D NMR and HRMS. Biological evaluation revealed that 3, 4, 6, and 7 showed moderate activities against four human cancer cell lines (A549, HTC116, PC3, and RT112) with IC50 values of 6.0-9.9 µM, and 3, 4, 5, and 7 also displayed promising antiangiogenesis effects with IC50 values <5 µM in the test system used. Among the isolates, arenaroside D (4) exhibited the most potent inhibitory effects, not only in cancer cell proliferation but also in angiogenic activities. Preliminary SAR studies revealed that the presence of an acetyl group at C-22 in oleanane-type triterpene saponins increases these bioactivities.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Caryophyllaceae/química , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Inibidores da Angiogênese/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Saponinas/isolamento & purificação , Vietnã
7.
Mar Drugs ; 19(3)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669051

RESUMO

Application of LC-MS/MS-based molecular networking indicated the ethanol extract of octocoral Asterospicularia laurae is a potential source for the discovery of new xenicane derivatives. A natural product investigation of this soft coral resulted in the isolation of four new xenicane diterpenoids, asterolaurins O‒R (1‒4), together with six known compounds, xeniolide-A (5), isoxeniolide-A (6), xeniolide-B (7), 7,8-epoxyxeniolide-B (8), 7,8-oxido-isoxeniolide-A (9), and 9-hydroxyxeniolide-F (10). The structures of isolated compounds were characterized by employing spectroscopic analyses, including 2D-NMR (COSY, HMQC, HMBC, and NOESY) and high-resolution electrospray ionization mass spectrometry (HRESIMS). Asterolaurin O is the first case of brominated tricarbocyclic type floridicin in the family Xeniidae. Concerning bioactivity, the cytotoxic activity of those isolates was evaluated. As a result, compounds 1 and 2 demonstrated a selective cytotoxic effect against the MCF-7 cell line at IC50 of 14.7 and 25.1 µM, respectively.


Assuntos
Antozoários/química , Antineoplásicos/isolamento & purificação , Diterpenos/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Cromatografia Líquida , Diterpenos/química , Diterpenos/farmacologia , Humanos , Concentração Inibidora 50 , Células MCF-7 , Taiwan , Espectrometria de Massas em Tandem
8.
Molecules ; 26(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203624

RESUMO

Millettia pulchra is traditionally used for treating diseases, including joint pain, fever, anemia, and allergies. It is also a potential resource of natural flavonoid derivatives, which represents major constituents of this plant. This study aimed to isolate the major compounds from M. pulchra radix, develop and validate the HPLC-PDA method to determine their contents, and optimize its extraction. Four major flavonoid derivatives (karanjin, lanceolatin B, 2",2"-dimethylpyrano-[5″,6″:7,8]-flavone, and pongamol) were isolated using silica gel column chromatography, crystallization techniques in large amounts with high purities (>95%). A simple, accurate high-performance liquid chromatography-photodiode array (HPLC-PDA) detection method has been developed and validated with significantly statistical impacts according to International Conference on Harmonization (ICH) guidelines. The Response Surface Methodology (RSM), Artificial Neural Network (ANN) models were employed to predictive performance and optimization of the extraction process. The optimized conditions for the extraction of major flavonoids were: extraction time (twice), solvent/material ratio (9.5), and ethanol concentration (72.5%). Our research suggests an effective method, which will be helpful for quality control in the pharmaceutical development of this species.


Assuntos
Flavonoides/química , Flavonoides/isolamento & purificação , Millettia/química , Antioxidantes/química , China , Cromatografia Líquida de Alta Pressão/métodos , Etanol/química , Millettia/metabolismo , Extratos Vegetais/química , Raízes de Plantas/química , Solventes/química
9.
J Nat Prod ; 83(5): 1400-1408, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32357011

RESUMO

Seven new cucurbitane-type triterpenoids, kuguaovins A-G (1-7), and five known ones were isolated from the rattans of wild Momordica charantia. Their structures were established by spectroscopic data analyses, including 1D and 2D NMR, IR, and MS techniques. The absolute configurations of the cucurbitanes were determined from NOESY data and partially by X-ray crystallographic analysis. In pharmacological studies, compounds 1-7 and 9-12 exhibited weak anti-inflammatory effects (IC50 = 15-35 µM), based on an anti-NO production assay.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Glicosídeos/farmacologia , Momordica charantia/química , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Extratos Vegetais/química , Células RAW 264.7 , Espectrofotometria Infravermelho , Difração de Raios X
10.
Molecules ; 25(3)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32012805

RESUMO

In folk medicine, Stahlianthus thorelii Gagnep. has been used to treat diseases related to inflammation, ulcers, and cancer. There are no reports concerning the chemical components and bioactivities of S. thorelii; thus, this study aims to explore the phytochemicals, quantify the main compounds, and test the anticancer activity of isolates from S. thorelii. Dried rhizomes were extracted with 95% ethanol and, then, partitioned, fractionated, and isolated. On the basis of the result of the antiproliferative activity of the fractions, seven isolates were yielded and were identified by spectroscopic analyses. The inhibition of cancer proliferation was determined by an MTT assay and the deployed IC50 to value their efficacy. Seven compounds containing one new C-benzylated dihydrochalcone derivative, thorechalcone A (1) and 2-7 were isolated from S. thorelii. In terms of the bioactivity, compounds 1 and 3 displayed promising antiproliferative activity (WiDr, A549, and HepG2), with IC50 values <40 µM. The HPLC-UV method of quantification of two major compounds (3 and 4) was also validated. This study presented the isolations of antiproliferative potentials of new chalcone and known flavonoid derivatives from S. thorelii. The validated simple, accurate, and rapid HPLC method could be deployed for the quality control of herbal drugs.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Chalconas/isolamento & purificação , Flavonoides/isolamento & purificação , Zingiberaceae/química , Células A549 , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chalconas/química , Chalconas/farmacologia , Cromatografia Líquida de Alta Pressão , Flavonoides/química , Flavonoides/farmacologia , Células Hep G2 , Humanos , Concentração Inibidora 50 , Células MCF-7 , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
11.
Molecules ; 25(20)2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33081333

RESUMO

Eleven compounds, including nine known flavonoid glycosides (1-4, 6-8, and 10-11), one isoflavone glycoside (5), and a glansreginic acid (9), were isolated from the 80% ethanol extract of commercial Astragali Complanati Semen (ACS). All chemical structures were determined by spectroscopic analyses, including 1D and 2D NMR. Compounds 2, 4, 5, 6, 9, and 10 were isolated and identified from the title plant for the first time. Biological evaluation revealed that all the isolates showed promising anti-NO production, and 1, 2, 3, and 8 were more potent in antioxidant activity than vitamin E. The major peaks in the UPLC and HPLC profiles identified their chemical structures by comparing their retention time and UV spectra with those of the reference substances. Furthermore, nine of the eleven samples collected from North, Middle, and South regions of Taiwan possessed similar HPLC fingerprints and were identified as Astragali Complanati Semen, whereas the other two samples from southern Taiwan would be the adulterants due to the different fingerprinting patterns. In addition, an HPLC-UV method was employed to determine the content of target compound complanatuside (11) with good linear regression (R2 = 0.9998) for ACS in the Taiwanese market. Of the isolates, flavonol glycosides 1 and 3 were the major peaks in HPLC/UPLC, and showed more potent antioxidant and anti-NO production activities than that of 11, revealing that these compounds can be the available agents for the quality control of ACS.


Assuntos
Astrágalo/química , Medicamentos de Ervas Chinesas/química , Flavonoides/química , Extratos Vegetais/química , Antioxidantes/química , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Isoflavonas/química , Extratos Vegetais/farmacologia , Controle de Qualidade , Sementes/química , Taiwan
12.
Molecules ; 25(19)2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32993192

RESUMO

Dodder (Cuscuta spp.) is a parasitic weed damaging many plants and agricultural production. The native obligate parasite Cuscuta japonica Choisy (Japanese dodder) parasitizes Dimocarpus longans Lour., Ficus septica Burm. F., Ficus microcarpa L.f., Mikania micrantha H.B.K. and Melia azedarach Linn, respectively. Five Japanese dodders growing on different plants exhibit slightly different metabolites and amounts which present different pharmacological effects. Among these plants, a significant antiviral activity against influenza A virus (IAV) was found in Japanese dodder parasitizing on D. longans Lour. (CL). To further explore methanol extract components in Japanese dodder (CL), four undescribed aromatic glycosides, cuscutasides A-D (compounds 1-4) were isolated, together with twenty-six known compounds 5-30. The chemical structures of 1-4 were elucidated using a combination of spectroscopic techniques. The eighteen isolated compounds were evaluated for antiviral activity against IAV activity. Among them, 1-monopalmitin (29) displayed potent activity against influenza A virus (A/WSN/1933(H1N1)) with EC50 2.28 ± 0.04 µM and without noteworthy cytotoxicity in MDCK cells. The interrupt step of 29 on the IAV life cycle was determined. These data provide invaluable information for new applications for this otherwise harmful weed.


Assuntos
Antivirais , Cuscuta/química , Vírus da Influenza A Subtipo H1N1/crescimento & desenvolvimento , Infecções por Orthomyxoviridae , Extratos Vegetais , Sapindaceae , Animais , Antivirais/química , Antivirais/farmacologia , Cães , Células Madin Darby de Rim Canino , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia
13.
Molecules ; 24(7)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30965662

RESUMO

Six new dammarane-type saponins, gypenosides CP1-6 (16), along with 19 known compounds 7⁻25, were isolated and characterized from the aerial parts of Gynostemma pentaphyllum. Among these compounds, eight dammarane-type saponins, 2, 5, 6, 7, 11, 12, 13, and 15, exhibited the greatest antiproliferative effects against two human tumor cell lines (A549 and HepG2).


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Gynostemma/química , Saponinas/isolamento & purificação , Células A549 , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Humanos , Estrutura Molecular , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Saponinas/química , Saponinas/farmacologia , Triterpenos , Damaranos
14.
Planta Med ; 84(18): 1348-1354, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29986352

RESUMO

Phytochemical investigation of ethanol extracts from two Taiwanese collections of Vernonia cinerea resulted in the isolation of eighteen hirsutinolide-type sesquiterpenoids, including seven new ones designated as vernolides E - K (1: -7: ). All structures were determined by a combination of detailed spectroscopic analyses (NMR and MS) and comparison with reported data. In an in vitro anti-inflammatory assay, compounds 3, 7, 9, 11: , and 14: exhibited strong inhibitory activities toward NO production by LPS-induced RAW264.7 macrophages, with IC50 values of 1.18, 0.85, 0.66, 0.71 and 0.45 µM, respectively, without affecting cellular viability at 40 µM. Preliminary structure-activity relationships indicate that the ester groups at C-8 and C-13 may enhance inhibition of NO production.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Óxido Nítrico/biossíntese , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Vernonia/química , Animais , Anti-Inflamatórios não Esteroides/química , Avaliação Pré-Clínica de Medicamentos/métodos , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Células RAW 264.7 , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade
15.
Planta Med ; 81(1): 62-70, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25469855

RESUMO

Five new 5ß,19-epoxycucurbitane triterpenoids, taikugausins A-E (1-5), together with 5ß,19-epoxy-25-methoxycucurbita-6,23-diene-3ß,19-diol (6), have been isolated and characterized from the 70 % EtOH extract of the fresh fruits of Momordica charantia. The chemical structures of compounds 1-6 were elucidated on the basis of extensive spectroscopic analyses, especially 2D NMR (HMQC, HMBC, and NOESY) experiments and HRESIMS data. The relationship between NMR chemical shifts and the configuration of C-19 with an OMe group in 5ß,19-epoxycucurbitane are described. Among them, compounds 3 and 4 exhibited remarkable anti-inflammatory activities by the inhibition of nitric oxide production at the concentration of 10 µg/mL. In addition, 3 and 4 also showed moderate cytotoxicity against WiDr, Hep G2, MCF-7, and HEp-2 human tumor cell lines.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Momordica charantia/química , Animais , Anti-Inflamatórios não Esteroides/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Células Hep G2/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Saponinas/química , Saponinas/farmacologia , Triterpenos/química , Triterpenos/farmacologia
16.
Mar Drugs ; 13(9): 5796-814, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26389921

RESUMO

Two new nitrogen-containing verticillene diterpenoids, cespilamides A and B (1 and 2), three new nitrogen-containing sesquiterpenoids, cespilamides C-E (3-5), and five new norverticillene and verticillene diterpenoids, cespitaenins A-E (6-10), were isolated from the Taiwanese soft coral Cespitularia taeniata. Compound 1 possesses an unusual oxazo ring system at C-10 while compound 2 displays an unprecedented C-C bond cleavage between C-10 and C-11 with an N-ethylphenyl group at C-10. Biogenetic pathways of 1 and 2 are proposed. The absolute configuration of 1 was confirmed by Mosher's method and molecular mechanics calculations (MM2). The cytotoxicities of compounds 1-10 were evaluated against a small panel of human cancer cell lines.


Assuntos
Antozoários/química , Antozoários/metabolismo , Diterpenos/química , Sesquiterpenos/química , Animais , Diterpenos/metabolismo , Estrutura Molecular , Sesquiterpenos/metabolismo
17.
Mar Drugs ; 12(8): 4677-92, 2014 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-25153765

RESUMO

Ten new briarane diterpenoids, briaviolides A-J (1-10), together with six known briaranes, solenolides A and D, excavatolide A, briaexcavatolide I, 4ß-acetoxy-9-deacetystylatulide lactone and 9-deacetylstylatulide lactone, were isolated from the Taiwanese soft coral, Briareum violacea. Their structures were determined on the basis of spectroscopic data ((1)H- and (13)C-NMR, (1)H-(1)H COSY, HSQC, HMBC and NOESY), HR-MS and chemical methods. The absolute configuration of briaviolide A (1) was determined by X-ray crystallographic analysis. Compounds 5, 9 and derivative 11 showed moderate inhibitory activities on superoxide-anion generation and elastase release by human neutrophils in response to N-formyl-methionyl-leucyl-phenylalanine/ Cytochalasin B (fMLP/CB).


Assuntos
Antozoários/química , Diterpenos/química , Animais , Citocalasina B/metabolismo , Diterpenos/metabolismo , Diterpenos/farmacologia , Humanos , N-Formilmetionina Leucil-Fenilalanina/química , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Superóxidos/metabolismo , Taiwan
18.
Phytomedicine ; 130: 155760, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38797029

RESUMO

BACKGROUND: The Xin-yi-san herbal decoction (XYS) is commonly used to treat patients with allergic rhinitis in Taiwan. Theophylline is primarily oxidized with high affinity by human cytochrome P450 (CYP)1A2, and has a narrow therapeutic index. PURPOSE: This study aimed to investigate the inhibition of human CYP1A2-catalyzed theophylline oxidation (THO) by XYS and its adverse effects in patients. METHODS: Human CYPs were studied in recombinant enzyme systems. The influence of concurrent XYS usage in theophylline-treated patients was retrospectively analyzed. RESULTS: Among the major human hepatic and respiratory CYPs, XYS inhibitors preferentially inhibited CYP1A2 activity, which determined the elimination and side effects of theophylline. Among the herbal components of XYS decoction, Angelicae Dahuricae Radix contained potent THO inhibitors. Furanocoumarin imperatorin was abundant in XYS and Angelicae Dahuricae Radix decoctions, and non-competitively inhibited THO activity with Ki values of 77‒84 nM, higher than those (20‒52 nM) of fluvoxamine, which clinically interacted with theophylline. Compared with imperatorin, the intestinal bacterial metabolite xanthotoxol caused weaker THO inhibition. Consistent with the potency of the inhibitory effects, the docking analysis generated Gold fitness values in the order-fluvoxamine > imperatorin > xanthotoxol. During 2017‒2018, 2.6 % of 201,093 theophylline users consumed XYS. After inverse probability weighting, XYS users had a higher occurrence of undesired effects than non-XYS users; in particular, there was an approximately two-fold higher occurrence of headaches (odds ratio (OR), 2.14; 95 % confidence interval (CI), 1.99‒2.30; p < 0.001) and tachycardia (OR, 1.83; 95 % CI, 1.21‒2.77; p < 0.05). The incidence of irregular heartbeats increased (OR, 1.36; 95 % CI, 1.07‒1.72; p < 0.05) only in the theophylline users who took a high cumulative dose (≥ 24 g) of XYS. However, the mortality in theophylline users concurrently taking XYS was lower than that in non-XYS users (OR, 0.24; 95 % CI, 0.14‒0.40; p < 0.001). CONCLUSION: XYS contains human CYP1A2 inhibitors, and undesirable effects were observed in patients receiving both theophylline and XYS. Further human studies are essential to reduce mortality and to adjust the dosage of theophylline in XYS users.


Assuntos
Angelica , Inibidores do Citocromo P-450 CYP1A2 , Citocromo P-450 CYP1A2 , Medicamentos de Ervas Chinesas , Furocumarinas , Teofilina , Teofilina/farmacologia , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Citocromo P-450 CYP1A2/metabolismo , Inibidores do Citocromo P-450 CYP1A2/farmacologia , Angelica/química , Furocumarinas/farmacologia , Masculino , Interações Ervas-Drogas , Estudos Retrospectivos , Feminino , Taiwan , Pessoa de Meia-Idade , Adulto , Oxirredução , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/induzido quimicamente
19.
Heliyon ; 10(7): e28755, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586372

RESUMO

Fish mint, Houttuynia cordata Thunb. (HCT) is an edible vegetable that has also been used in traditional folk medicines. As both a medicinal herb and a dietary source, HCT has been clinically proven to be a pivotal ingredient in formulas administered to alleviate COVID-19 symptoms. With the increasing market demand for imported materials, ensuring the quality consistency of HCT becomes a significant concern. In this study, the growing time for hydroponically-cultivated HCT with seaweed extract and amino acids added (HCTW) reduced by half compared to conventional soil-cultivated HCT (HCTS). Key quantified components in HCTW, flavonoid glycosides and caffeoylquinic acid derivatives, exhibited a 143% increase over HCTS. These crucial constituents were responsible for possessing antioxidant activity (IC50 < 25 µg/mL) and anti-nitrite oxide production (IC50 < 20 µg/mL). An economically-designed hydroponic system with appropriate additives is proposed to replace HCTS with improvements of growth time, overall production yields, and bioactive qualities.

20.
Bioorg Med Chem Lett ; 23(3): 880-5, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23265871

RESUMO

Three new polyoxygenated C(18)-dibenzocyclooctadiene lignans, arisanschinins M and N (1 and 2) and schisphenin A (3), together with eight related metabolites (4-11), were isolated from the fruits of Schisandra arisanensis and Schisandra sphenanthera, respectively. The structures of 1-3 were elucidated on the basis of extensive spectroscopic and 2D NMR (HSQC, HMBC, and NOESY) analyses. The configuration of the biphenyl moiety in the octadiene ring was determined by circular dichroism (CD). Compound 1 possessed an unprecedented 3-(1-hydroxypropan-2-yl)-3-methyl-1,4-dioxo-2-one lactonide ring system attaching at C-6/C-14. Pharmacological studies revealed that compounds 3, 4, 6, 7, and 10 exhibited significant anti-hepatic fibrosis activity, while 9 and 11 showed cytotoxicity against HSC-T6 cells. The biogenetic pathway for compound 1 was also proposed.


Assuntos
Ciclo-Octanos/química , Frutas/química , Lignanas/química , Extratos Vegetais/química , Schisandra/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Ciclo-Octanos/farmacologia , Humanos , Lignanas/farmacologia , Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Extratos Vegetais/farmacologia
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