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1.
J Mass Spectrom ; 55(1): e4463, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31671229

RESUMO

Noncovalent interactions between drugs and proteins play significant roles for drug metabolisms and drug discoveries. Mass spectrometry has been a commonly used method for studying noncovalent interactions. However, the harsh ionization process in electrospray ionization mass spectrometry (ESI-MS) is not conducive to the preservation of noncovalent and unstable biomolecular complexes compared with the cold spray ionization mass spectrometry (CSI-MS). A cold spray ionization providing a stable solvation-ionization at low temperature is milder than ESI, which was more suitable for studying noncovalent drug-protein complexes with exact stoichiometries. In this paper, we apply CSI-MS to explore the interactions of ginsenosides toward amyloid-ß-peptide (Aß) and clarify the therapeutic effect of ginsenosides on Alzheimer's disease (AD) at the molecular level for the first time. The interactions of ginsenosides with Aß were performed by CSI-MS and ESI-MS, respectively. The ginsenosides Rg1 bounded to Aß at the stoichiometries of 1:1 to 5:1 could be characterized by CSI-MS, while dehydration products are more readily available by ESI-MS. The binding force depends on the number of glycosyls and the type of ginsenosides. The relative binding affinities were sorted in order as follows: Rg1 ≈ Re > Rd ≈ Rg2 > Rh2, protopanaxatriol by competition experiments, which were supported by molecular docking experiment. CSI-MS is expected to be a more appropriate approach to determine the weak but specific interactions of proteins with other natural products especially polyhydroxy compounds.


Assuntos
Peptídeos beta-Amiloides/química , Ginsenosídeos/química , Simulação de Acoplamento Molecular/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Sítios de Ligação , Ligação Proteica , Sapogeninas/química , Relação Estrutura-Atividade
2.
Chem Biodivers ; 17(1): e1900516, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31725193

RESUMO

In this study, 13 panaxadiol (PD) derivatives were synthesized via reactions with aromatic compounds and amino acids. Following this, the cytotoxicity of these compounds was evaluated against four cancer cell lines (human hepatoma cells HepG-2, human lung cancer cells A549, human breast cancer cells MCF-7, and human colon cancer cells HCT-116) and one normal cell lines (human gastric epithelial cells GES-1). The results showed that the panaxadiol derivatives 3, 12, and 13 showed significant inhibition of cellular proliferation against cancer cells compared with PD, and the panaxadiol derivative 12 had the lowest IC50 value for A549 (IC50 =18.91±1.03 µm). For MCF-7 cells, most compounds exhibited good inhibition of cellular proliferation, and the panaxadiol derivative 13 showed the strongest inhibitory effect (IC50 =8.62±0.23 µm), which significantly increased the cytotoxicity of PD and was stronger than the positive control (mitomycin). For normal cells, all compounds exhibited low or no toxic effects; thus, these derivatives can be used to develop novel antiproliferative agents.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ginsenosídeos/síntese química , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
3.
Eur J Med Chem ; 185: 111729, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655431

RESUMO

Panaxatriol (PT) is a natural product derived from ginseng that possesses cardioprotective effects in isolated rat hearts. To develop more potent therapeutic agents against myocardial ischemia/reperfusion (MI/R) injury from natural products, a novel series of heterocycle ring-fused panaxatriol derivatives were designed and synthesized. In vitro results showed that approximately half of them exhibited increased cytoprotective activity compared with PT in a cardiomyocyte model of oxygen-glucose deprivation and reperfusion (OGD/R) injury. Furthermore, the in vitro activity of the representative derivative, compound 18, was also confirmed in a rat model of MI/R injury. In vivo results showed that 18 can markedly reduce myocardial infarction size, decrease circulating cardiac troponin I (cTnI) leakage, and alleviate cardiac tissue damage in the rats. Therefore, these findings provide the basis for further development of novel anti-MI/R injury agents.


Assuntos
Ginsenosídeos/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ginsenosídeos/síntese química , Ginsenosídeos/química , Masculino , Estrutura Molecular , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Troponina I/sangue
4.
Curr Top Med Chem ; 19(25): 2334-2347, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31648643

RESUMO

The dried root of ginseng (Panax ginseng C. A. Meyer or Panax quinquefolius L.) is a traditional Chinese medicine widely used to manage cancer symptoms and chemotherapy side effects in Asia. The anti-cancer efficacy of ginseng is attributed mainly to the presence of saponins, which are commonly known as ginsenosides. Ginsenosides were first identified as key active ingredients in Panax ginseng and subsequently found in Panax quinquefolius, both of the same genus. To review the recent advances on anti-cancer effects of ginsenosides against breast cancer, we conducted a literature study of scientific articles published from 2010 through 2018 to date by searching the major databases including Pubmed, SciFinder, Science Direct, Springer, Google Scholar, and CNKI. A total of 50 articles authored in either English or Chinese related to the anti-breast cancer activity of ginsenosides have been reviewed, and the in vitro, in vivo, and clinical studies on ginsenosides are summarized. This review focuses on how ginsenosides exert their anti-breast cancer activities through various mechanisms of action such as modulation of cell growth, modulation of the cell cycle, modulation of cell death, inhibition of angiogenesis, inhibition of metastasis, inhibition of multidrug resistance, and cancer immunemodulation. In summary, recent advances in the evaluation of ginsenosides as therapeutic agents against breast cancer support further pre-clinical and clinical studies to treat primary and metastatic breast tumors.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ginsenosídeos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Feminino , Ginsenosídeos/química , Ginsenosídeos/isolamento & purificação , Humanos , Panax/química , Raízes de Plantas/química
5.
Molecules ; 24(19)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561496

RESUMO

Recently Panax ginseng has been grown as a secondary crop under a pine tree canopy in New Zealand (NZ). The aim of the study is to compare the average content of ginsenosides from NZ-grown ginseng and its original native locations (China and Korea) grown ginseng. Ten batches of NZ-grown ginseng were extracted using 70% methanol and analyzed using LC-MS/MS. The average content of ginsenosides from China and Korea grown ginseng were obtained by collecting data from 30 and 17 publications featuring China and Korea grown ginseng, respectively. The average content of total ginsenosides in NZ-grown ginseng was 40.06 ± 3.21 mg/g (n = 14), which showed significantly (p < 0.05) higher concentration than that of China grown ginseng (16.48 ± 1.24 mg/g, n = 113) and Korea grown ginseng (21.05 ± 1.57 mg/g, n = 106). For the individual ginsenosides, except for the ginsenosides Rb2, Rc, and Rd, ginsenosides Rb1, Re, Rf, and Rg1 from NZ-grown ginseng were 2.22, 2.91, 1.65, and 1.27 times higher than that of ginseng grown in China, respectively. Ginsenosides Re and Rg1 in NZ-grown ginseng were also 2.14 and 1.63 times higher than ginseng grown in Korea. From the accumulation of ginsenosides, New Zealand volcanic pumice soil may be more suitable for ginseng growth than its place of origin.


Assuntos
Ginsenosídeos/análise , Ginsenosídeos/química , Panax/química , Panax/classificação , China , Geografia , Estrutura Molecular , Nova Zelândia , República da Coreia
6.
Biomed Pharmacother ; 119: 109400, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31514067

RESUMO

AIMS: Post-operative cognitive dysfunction (POCD) occurs after major surgery in elderly patients and affects the quality of patients' lives. The present study aims to explore the protective effects and possible mechanisms of compound K in old mice with POCD caused by partial hepatectomy. METHODS: Sixteen month-old mice were administered different doses of compound K from the 8th day to 14th day after partial hepatectomy. Cognitive function was subsequently measured with a Morris water-maze (MWM) test. Serum inflammatory cytokine levels were measured by magnetic bead panel; levels of cytokines in the hippocampus were analyzed using immunohistochemistry and immunoblotting. The mRNA levels of target genes were measured using real-time PCR. RESULTS: Compared with the model group, MWM scores were significantly attenuated at days 10 and 14 post-surgery in mice receiving compound K (10, 30 mg/kg) in a dose-dependent manner. Both systemic and local cytokine levels were reduced after treatment of compound K. The alterations in serum lipids were independent of the attenuation of POCD syndrome. An inhibitor of liver X receptor-α (LXRα), GGPP, reversed the effects of compound K. CONCLUSIONS: The results provide evidence for an alleviation of POCD by compound K via local inflammation inhibition in hippocampus tissue; furthermore, the data suggests the mechanism involves the LXRα pathway. The present study supports further evaluation of compound K as a potential effective modulator for POCD.


Assuntos
Envelhecimento/patologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Ginsenosídeos/uso terapêutico , Hepatectomia/efeitos adversos , Receptores X do Fígado/metabolismo , Animais , Glicemia/metabolismo , Disfunção Cognitiva/sangue , Citocinas/metabolismo , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Mediadores da Inflamação/metabolismo , Lipídeos/sangue , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos
7.
Molecules ; 24(18)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540334

RESUMO

Ginseng (Panax ginseng) has long been used as a traditional medicine for the prevention and treatment of various diseases. Generally, the harvest time and age of ginseng have been regarded as important factors determining the efficacy of ginseng. However, most studies have mainly focused on the root of ginseng, while studies on other parts of ginseng such as its berry have been relatively limited. Thus, the aim of this study iss to determine effects of harvest time on yields, phenolics/ginsenosides contents, and the antioxidant/anti-elastase activities of ethanol extracts of three- and four-year-old ginseng berry. In both three- and fourfour-year-old ginseng berry extracts, antioxidant and anti-elastase activities tended to increase as berries ripen from the first week to the last week of July. Liquid chromatography-tandem mass spectrometry analysis has revealed that contents of ginsenosides except Rg1 tend to be the highest in fourfour-year-old ginseng berries harvested in early July. These results indicate that biological activities and ginsenoside profiles of ginseng berry extracts depend on their age and harvest time in July, suggesting the importance of harvest time in the development of functional foods and medicinal products containing ginseng berry extracts. To the best of our knowledge, this is the first report on the influence of harvest time on the biological activity and ginsenoside contents of ginseng berry extracts.


Assuntos
Ginsenosídeos/química , Panax/química , Fenóis/química , Antioxidantes/química , Cromatografia Líquida , Compostos Fitoquímicos/química , Extratos Vegetais/química , Raízes de Plantas/química , Espectrometria de Massas em Tandem
8.
Arch Pharm Res ; 42(10): 862-878, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31493264

RESUMO

Ginseng is the most frequently used herbal medicine for immune system stimulation and as an adjuvant with prescribed drugs owing to its numerous pharmacologic activities. It is important to investigate the beneficial effects and interaction of ginseng with therapeutic drugs. This review comprehensively discusses drug metabolizing enzyme- and transporter-mediated ginseng-drug interaction by analyzing in vitro and clinical results with a focus on ginsenoside, a pharmacologically active marker of ginseng. Impact of ginseng therapy or ginseng combination therapy on diabetic patients and of ginseng interaction with antiplatelets and anticoagulants were evaluated based on ginseng origin and ginsenoside content. Daily administration of Korean red ginseng (0.5-3 g extract; dried ginseng > 60%) did not cause significant herb-drug interaction with drug metabolizing enzymes and transporters. Among various therapeutic drugs administered in combination with ginseng, adjuvant chemotherapy, comprising ginseng (1-3 g extract) and anticancer drugs, was effective for reducing cancer-related fatigue and improving the quality of life and emotional scores. Limited information regarding ginsenoside content in each ginseng product and plasma ginsenoside concentration among patients necessitates standardization of ginseng product and establishment of pharmacokinetic-pharmacodynamic correlation to further understand beneficial effects of ginseng-therapeutic drug interactions in future clinical studies.


Assuntos
Anticoagulantes/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Ginsenosídeos/farmacologia , Hipoglicemiantes/farmacologia , Neoplasias/tratamento farmacológico , Panax/química , Inibidores da Agregação de Plaquetas/farmacologia , Anticoagulantes/química , Antineoplásicos Fitogênicos/química , Diabetes Mellitus/tratamento farmacológico , Ginsenosídeos/química , Interações Ervas-Drogas , Humanos , Hipoglicemiantes/química , Inibidores da Agregação de Plaquetas/química
9.
Anal Chim Acta ; 1079: 237-251, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31387717

RESUMO

Panax notoginseng leaves (PNL) was considered as a potential medicinal part with abundant protopanaxdiol type ginsenosides. In this study, an integrated system was developed for simultaneously qualitative and quantitative analysis of ginsenosides in PNL using online comprehensive two-dimensional hydrophilic interaction chromatography and reversed-phase liquid chromatography coupled to a hybrid linear ion trap-Orbitrap mass spectrometry (online HILIC × RP-ESI/HRMS/MSn). The system was configured based on the combination of a XBridge amide column (150 mm × 2.1 mm, 2.5 µm) and Accucore phenyl-hexyl (50 mm × 4.6 mm, 2.6 µm) for the first and second dimensions, respectively. An additional water phase was introduced to dilute the eluent from the first dimension to decrease its elution strength in the second dimension. The online dilution, modulation interface and the second-dimension gradient program were deeply optimized to reduce possible sample loss and improve system resolution. Under the optimal conditions, a total of 226 ginsenosides were unambiguously identified or tentatively characterized by aid of high-resolution accurate mass and MSn fragment data in both negative and positive ion modes, and 93 of them were discovered as potentially new ginsenosides in PNL. Besides, the validated online HILIC × RP-LTQ-MS method was applied to determine 24 ginsenosides directly on 2D-EIC contour plots in nine batches of PNL samples. The powerful separation capability acquired by the developed online HILIC × RP system affords not only reliable structural information for identification, but also accurate quantitation. This combined system can also be used to characterize and quantify bioactive ingredients in the samples with complex matrices.


Assuntos
Ginsenosídeos/análise , Panax notoginseng/química , Folhas de Planta/química , Cromatografia Líquida/métodos , Ginsenosídeos/química , Isomerismo , Limite de Detecção , Espectrometria de Massas por Ionização por Electrospray/métodos
10.
J Agric Food Chem ; 67(36): 10245-10255, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31389238

RESUMO

Ginseng has been widely used as a functional food in the world because of its well-defined health benefits. Previous studies have confirmed that AD-1, a new ginsenoside derived from ginseng, can ameliorate thioacetamide-induced liver injury and fibrosis in mice. Simultaneously, amino acid supplementation is getting more attention as an important adjuvant therapy in the improvement of hepatopathy. The aim of this study was to conjugate AD-1 with several selected amino acids and investigate the cytotoxicity of the obtained conjugates in activated t-HSC/Cl-6 cells and normal human liver cells (LO2). Structure-activity relationships of conjugates and underlying mechanisms of the effect are also explored. The results indicated that conjugate 7c remarkably inhibited cell proliferation in activated t-HSC/Cl-6 cells (IC50 = 3.8 ± 0.4 µM) and appeared to be nontoxic to LO2. Besides, conjugate 7c had a relatively good plasma stability. Further study demonstrated that inducing S-phase arrest and activation of mitochondrial-mediated apoptosis were included in the mechanisms underlying the efficiency of conjugate 7c. These findings provided further insight into designing functional foods (ginsenoside and amino acid) for the application in prevention or improvement of liver fibrosis.


Assuntos
Aminoácidos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ginsenosídeos/farmacologia , Células Estreladas do Fígado/citologia , Aminoácidos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ginsenosídeos/química , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos
11.
Biomed Pharmacother ; 118: 108589, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31382131

RESUMO

(20R)-Dammarane-3ß, 12ß, 20, 25-tetrol (25-OH-PPD) is a ginsenoside isolated from Panax ginseng (C. A. Meyer). Previous research shows that the compound exhibits anti-cancer activities on many human cancer cell lines. In an attempt to enhance 25-OH-PPD activity, some derivatives were synthesized. Through screening of the derivative compounds for anti-cancer activity against gastric carcinoma cells, 12ß-O-(L-Chloracetyl)-dammar-20(22)-ene-3ß, 25-diol (4-XL-PPD) was selected as a strong anti-cancer agent. In this study, the anti-cancer mechanisms of 4-XL-PPD were investigated. The results showed that compound 4-XL-PPD resulted in a concentration-dependent inhibition of cells viability in gastric cancer cells, without affecting the viability of normal cell (human gastric epithelial cell line-GES-1). In BGC-803 cancer cells, 4-XL-PPD triggered apoptosis, and stimulated reactive oxygen species production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. Meantime, 4-XL-PPD effectively suppressed the migratory and invasive capabilities of BGC-803 cancer cell and inhibited the expression levels of proteins associated with migratory and invasive capabilities (MMP-2, MMP-9, E-cadherin and CD34). All the results suggest that 4-XL-PPD exhibited remarkable anticancer activity base on inducing apoptosis via generating reactive oxygen species and inhibiting migratory and invasive, which support development of 4-XL-PPD as a potential agent for cancer therapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Ginsenosídeos/química , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/patologia , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Concentração Inibidora 50 , Invasividade Neoplásica , Panax/química , Neoplasias Gástricas/metabolismo , Triterpenos/isolamento & purificação
12.
Molecules ; 24(16)2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31416121

RESUMO

As our global population ages, the treatment of neurodegenerative diseases is critical to our society. In recent years, researchers have begun to study the role of biologically active chemicals from plants and herbs to gain new inspiration and develop new therapeutic drugs. Ginseng (Panax ginseng C.A. Mey.) is a famous Chinese herbal medicine with a variety of pharmacological activities. It has been used to treat various diseases since ancient times. Extensive research over the years has shown that ginseng has potential as a neuroprotective drug, and its neuroprotective effects can be used to treat and prevent neurological damage or pathologically related diseases (such as Alzheimer's disease, Parkinson's disease, Huntington's disease, depression symptoms, and strokes). Moreover, evidence for the medicinal and health benefits of ginsenoside, its main active ingredient, in the prevention of neurodegenerative diseases is increasing, and current clinical results have not reported any serious adverse reactions to ginseng. Therefore, we briefly review the recent research and development on the beneficial effects and mechanisms of ginseng and its main active ingredient, ginsenoside, in the prevention and treatment of neurodegenerative diseases, hoping to provide some ideas for the discovery and identification of ginseng neuroprotection.


Assuntos
Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Panax/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Estudos Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Humanos , Estrutura Molecular , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Resultado do Tratamento
13.
Biomed Chromatogr ; 33(11): e4670, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31368122

RESUMO

Notoginsenoside R1 (NGR1 ), a diagnostic protopanaxatriol-type (ppt-type) saponin in Panax notoginseng, possesses potent biological activities including antithrombotic, anti-inflammatory, neuron protection and improvement of microcirculation, yet its pharmacokinetics and metabolic characterization as an individual compound remain unclear. The aim of this study was to investigate the exposure profile of NGR1 in rats after oral and intravenous administration and to explore the metabolic characterization of NGR1 . A simple and sensitive ultra-fast liquid chromatographic-tandem mass spectrometric method was developed and validated for the quantitative determination of NGR1 and its major metabolites, and for characterization of its metabolic profile in rat plasma. The blood samples were precipitated with methanol, quantified in a negative multiple reaction monitoring mode and analyzed within 6.0 min. Validation parameters (linearity, precision and accuracy, recovery and matrix effect, stability) were within acceptable ranges. After oral administration, NGR1 exhibited dose-independent exposure behaviors with t1/2 over 8.0 h and oral bioavailability of 0.25-0.29%. A total of seven metabolites were characterized, including two pairs of epimers, 20(R)-notoginsenoside R2 /20(S)-notoginsenoside R2 and 20(R)-ginsenoside Rh1 /20(S)-ginsenoside Rh1 , with the 20(R) form of saponins identified for the first time in rat plasma. Five deglycometabolites were quantitatively determined, among which 20(S)-notoginsenoside R2 , ginsenoside Rg1 , ginsenoside F1 and protopanaxatriol displayed relatively high exploration, which may partly explain the pharmacodynamic diversity of ginsenosides after oral dose.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ginsenosídeos/sangue , Ginsenosídeos/farmacocinética , Espectrometria de Massas em Tandem/métodos , Administração Intravenosa , Administração Oral , Animais , Ginsenosídeos/administração & dosagem , Ginsenosídeos/química , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray/métodos
14.
J Sci Food Agric ; 99(15): 6806-6813, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31368526

RESUMO

BACKGROUND: Enzymatic hydrolysis and high hydrostatic pressure (HHP) are common processing techniques in the extraction of active compounds from food materials. The aim of this study was to investigate the effects of enzymatic hydrolysis combined with HHP treatments on ginsenoside metabolites in red ginseng. RESULTS: The yield and changes in the levels of polyphenol and ginsenoside were measured in red ginseng treated with commercial enzymes such as Ultraflo L, Viscozyme, Cytolase PCL5, Rapidase and Econase E at atmospheric pressure (0.1 MPa), 50 MPa, and 100 MPa. ß-Glucosidase activity of Cytolase was the highest at 4258.2 mg-1 , whereas Viscozyme showed the lowest activity at 10.6 mg-1 . Pressure of 100 MPa did not affect the stability or the activity of the ß-glucosidase. Treatment of red ginseng with Cytolase and Econase at 100 MPa significantly increased the dry weight and polyphenol content of red ginseng, compared with treatments at 0.1 MPa and 50 MPa (P < 0.05). The amounts of ginsenoside and ginsenoside metabolites derived from red ginseng processed using Cytolase were higher than those derived from red ginseng treated with the other enzymes. Treatment with Cytolase also significantly increased the skin and intestinal permeability of red ginseng-derived polyphenols. CONCLUSION: Cytolase could be useful as an enzymatic treatment to enhance the yield of bioactive compounds from ginseng under HHP. In addition, ginsenoside metabolites obtained by Cytolase hydrolysis combined with HHP are functional substances with increased intestinal and skin permeability. © 2019 Society of Chemical Industry.


Assuntos
Enzimas/química , Manipulação de Alimentos/métodos , Ginsenosídeos/química , Ginsenosídeos/metabolismo , Panax/química , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Animais , Biocatálise , Hidrólise , Pressão Hidrostática , Mucosa Intestinal/metabolismo , Masculino , Panax/metabolismo , Ratos , Ratos Sprague-Dawley , Pele/metabolismo
15.
Drug Des Devel Ther ; 13: 2057-2066, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31296984

RESUMO

Background: Ginsenoside Rg3 has been reported to exert protection function on germ cells. However, the mechanisms by which Rg3 regulates apoptosis in mouse Leydig cells remain unclear. In addition, triptolide (TP) has been reported to induce infertility in male rats. Thus, this study aimed to investigate the protective effect of Rg3 against TP-induced toxicity in MLTC-1 cells. Methods: CCK-8, immunofluorescence assay, Western blotting and flow cytometry were used to detect cell proliferation and cell apoptosis, respectively. In addition, the dual luciferase reporter system assay was used to detect the interaction between miR-26a and GSK3ß in MLTC-1 cells. Results: TP significantly inhibited the proliferation of MLTC-1 cells, while the inhibitory effect of TP was reversed by Rg3. In addition, TP markedly induced apoptosis in MLTC-1 cells via increasing the expressions of Bax, active caspase 3, Cyto c and active caspase 9, and decreasing the level of Bcl-2. However, Rg3 alleviated TP-induced apoptosis of MLTC-1 cells. Moreover, the level of miR-26a was obviously downregulated by Rg3 treatment. The protective effect of Rg3 against TP-induced toxicity in MLTC-1 cells was abolished by miR-26a upregulation. Meanwhile, dual-luciferase assay showed GSK3ß was the direct target of miR-26a in MLTC-1 cells. Overexpression of miR-26a markedly decreased the level of GSK3ß. As expected, upregulation of miR-26a could abrogate the protective effects of Rg3 against TP-induced cytotoxicity via inhibiting the expression of GSK3ß. Conclusion: These results indicated that Rg3 could protect MLTC-1 against TP by downregulation of miR-26a. Therefore, Rg3 might serve as a potential agent for the treatment of male hypogonadism.


Assuntos
Antiespermatogênicos/antagonistas & inibidores , Diterpenos/antagonistas & inibidores , Regulação para Baixo/efeitos dos fármacos , Ginsenosídeos/farmacologia , Células Intersticiais do Testículo/efeitos dos fármacos , MicroRNAs/biossíntese , Fenantrenos/antagonistas & inibidores , Substâncias Protetoras/farmacologia , Animais , Antiespermatogênicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/farmacologia , Relação Dose-Resposta a Droga , Compostos de Epóxi/antagonistas & inibidores , Compostos de Epóxi/farmacologia , Ginsenosídeos/química , Masculino , Camundongos , MicroRNAs/genética , Conformação Molecular , Fenantrenos/farmacologia , Substâncias Protetoras/química , Relação Estrutura-Atividade
16.
Chem Biodivers ; 16(8): e1900188, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31298488

RESUMO

Panaxadiol is a dammarane-type ginsenoside having high ginseng content. The 3-hydroxy group of panaxadiol (PD) was modified by fatty acids and diacids. The modified panax glycol had enhanced anticancer activity. Twelve PD derivatives were evaluated and purified by chemical synthesis, column chromatography, co-synthesis, and identification. The human leukemia cells THP-1, HL-60, and human prostate cancer cell lines PC-3 were evaluated; PD derivatives were tested and evaluated in vitro by MTT assay. The results showed that the antitumor activities of some derivatives on three tumor cell lines were better than those of PD.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Ginsenosídeos/química , Panax/química , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Ginsenosídeos/síntese química , Ginsenosídeos/farmacologia , Células HL-60 , Humanos , Células PC-3 , Panax/metabolismo
17.
J Agric Food Chem ; 67(30): 8393-8401, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31291721

RESUMO

The ginsenoside 20-O-ß-glucopyranosyl-20(S)-protopanaxadiol or compound K is an essential ingredient in functional food, cosmetics, and traditional medicines. However, no study has reported the complete conversion of all protopanaxadiol (PPD)-type ginsenosides from ginseng extract into compound K using whole-cell conversion. To increase the production of compound K from ginseng extract using whole recombinant cells, the ß-glucosidase enzyme from Caldicellulosiruptor bescii was coexpressed with a chaperone expression system (pGro7), and the cells expressing the coexpression system were permeabilized with ethylenediaminetetraacetic acid. The permeabilized cells carrying the chaperone coexpression system showed a 2.6-fold increase in productivity and yield as compared with nontreated cells, and completely converted all PPD-type ginsenosides from ginseng root extract into compound K with the highest productivity among the results reported so far. Our results will contribute to the industrial biological production of compound K.


Assuntos
Proteínas de Bactérias/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Firmicutes/enzimologia , Ginsenosídeos/metabolismo , Chaperonas Moleculares/genética , Sapogeninas/metabolismo , beta-Glucosidase/genética , Proteínas de Bactérias/metabolismo , Biotransformação , Escherichia coli/química , Firmicutes/genética , Engenharia Genética , Ginsenosídeos/química , Chaperonas Moleculares/metabolismo , Panax/química , Sapogeninas/química , beta-Glucosidase/metabolismo
18.
Int J Mol Sci ; 20(14)2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31323789

RESUMO

The ginseng berry contains a variety of biologically active compounds and has a higher ginsenoside content than its roots. This study focused on the hepatoprotective activity of ginseng berry extract prepared by enzyme treatment (EGB) compared to the non-enzyme-treated ginseng berry extract (GB) and quality control of EGB. The feeding effect of EGB on alcohol-induced liver damage (AILD) was investigated by measuring the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with those of EtOH-fed mice. Furthermore, cytokine levels in the culture supernatants of EGB- or GB-treated RAW 264.7 cells were determined by enzyme-linked immunosorbent assay. The developed method was applied to the simultaneous quantification of four major ginsenosides in EGB using UPLC-QTOF/MS. Treatment with EGB at a dose of 0.5 or 1 mg/mouse significantly suppressed the AST and ALT levels in mice with AILD. Enzyme-treated ginseng berry was also found to suppress the production of inflammatory mediators like nitric oxide (NO), tumor-necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, showing higher activity than that of GB. The amount of ginsenoside Re, F5, F3, and Rd in the EGB obtained using UPLC-QTOF/MS was 45.9, 3.3, 4.0, and 6.2 mg/g, respectively. These results suggest that EGB has a potential effect on AILD, and its hepatoprotective effect provides beneficial insights into developing new candidates for the prevention and cure of AILD. Also, this study demonstrated the utility of UPLC-QTOF/MS-based major compounds for quality control (QC) of EGB.


Assuntos
Anti-Inflamatórios/uso terapêutico , Frutas/química , Fígado/efeitos dos fármacos , Panax/química , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Sobrevivência Celular/efeitos dos fármacos , Dinoprostona/sangue , Ginsenosídeos/química , Ginsenosídeos/uso terapêutico , Interleucina-6/sangue , Lipopolissacarídeos/toxicidade , Fígado/lesões , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Células RAW 264.7 , Fator de Necrose Tumoral alfa
19.
Molecules ; 24(14)2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31323835

RESUMO

We aimed to develop a sensitive method for detecting 13 ginsenosides using liquid chromatography-tandem mass spectrometry and to apply this method to pharmacokinetic studies in human following repeated oral administration of red ginseng extract. The chromatograms of Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3, Rh2, F1, compound K (CK), protopanaxadiol (PPD), and protopanaxatriol (PPT) in human plasma were well separated. The calibration curve range for 13 ginsenosides was 0.5-200 ng/mL and the lower limit of quantitation was 0.5 ng/mL for all ginsenosides. The inter- and intra-day accuracy, precision, and stability were less than 15%. Among the 13 ginsenosides tested, nine ginsenosides (Rb1, Rb2, Rc, Rd, Rg3, CK, Rh2, PPD, and PPT) were detected in the human plasma samples. The plasma concentrations of Rb1, Rb2, Rc, Rd, and Rg3 were correlated with the content in red ginseng extract; however, CK, Rh2, PPD, and PPT were detected although they are not present in red ginseng extract, suggesting the formation of these ginsenosides through the human metabolism. In conclusion, our analytical method could be effectively used to evaluate pharmacokinetic properties of ginsenosides, which would be useful for establishing the pharmacokinetic-pharmacodymic relationship of ginsenosides as well as ginsenoside metabolism in humans.


Assuntos
Ginsenosídeos/sangue , Ginsenosídeos/química , Panax/química , Extratos Vegetais/sangue , Extratos Vegetais/química , Ginsenosídeos/farmacocinética , Humanos , Redes e Vias Metabólicas , Estrutura Molecular , Extratos Vegetais/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem
20.
AAPS PharmSciTech ; 20(6): 252, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300965

RESUMO

The objective of the present study was to investigate the effect of partially hydrolyzed ginsenoside on the physicochemical properties and in vitro release of curcumin from phospholipid-based nanostructured lipid carrier (NLC). NLC formulas modified with partially hydrolyzed ginsenoside (NLC-PG) were prepared with different amounts of ginsenoside using the conventional hot-melt method. The average particle size of curcumin-loaded NLC-PG ranged from 150 to 200 nm, and polydispersity index was in the range of 0.101-0.177, indicating monodispersed particle size distribution. Optical microscopy showed no sedimentation or recrystallization of curcumin even at 10,000 µg/ml concentration as NLC-PG in distilled water, indicating significantly enhanced solubility. TEM image showed that the nanoparticles were monodispersed with a multilayered core/shell structure. X-ray diffraction and FTIR spectroscopy showed that curcumin was amorphous in the NLC-PG, and there was no interaction between curcumin and the excipients. In vitro release study using simulated gastric/intestinal fluid media revealed that the release rate (Jss) of curcumin from the NLC-PG increased as a function of the ginsenoside content in the lipid carrier. Moreover, the Jss of curcumin kept gradually increasing in the presence of lipase, whereas in the presence of viscozyme, it sharply increased until the ginsenoside content reached 9.09% and subsequently plateaued. Partially hydrolyzed ginsenoside increased the Jss of curcumin from curcumin-loaded NLC-PG and therefore may be useful for improving the bioavailability of curcumin.


Assuntos
Curcumina/química , Portadores de Fármacos/química , Ginsenosídeos/química , Lipídeos/química , Nanoestruturas/química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Curcumina/farmacocinética , Portadores de Fármacos/farmacocinética , Excipientes/química , Excipientes/farmacocinética , Ginsenosídeos/farmacocinética , Hidrólise , Lipídeos/farmacocinética , Lisofosfatidilcolinas/química , Lisofosfatidilcolinas/farmacocinética , Tamanho da Partícula , Fosfatidilcolinas/química , Fosfatidilcolinas/farmacocinética , Óleo de Soja/química , Óleo de Soja/farmacocinética , Difração de Raios X/métodos
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