ABSTRACT
Food-derived angiotensin-converting enzyme-inhibitory (ACE-I) peptides have attracted extensive attention. Herein, the ACE-I peptides from Scomber japonicus muscle hydrolysates were screened, and their mechanisms of action and inhibition stability were explored. The quantitative structure-activity relationship (QSAR) model based on 5z-scale metrics was developed to rapidly screen for ACE-I peptides. Two novel potential ACE-I peptides (LTPFT, PLITT) were predicted through this model coupled with in silico screening, of which PLITT had the highest activity (IC50: 48.73 ± 7.59 µM). PLITT inhibited ACE activity with a mixture of non-competitive and competitive mechanisms, and this inhibition mainly contributed to the hydrogen bonding based on molecular docking study. PLITT is stable under high temperatures, pH, glucose, and NaCl. The zinc ions (Zn2+) and copper ions (Cu2+) enhanced ACE-I activity. The study suggests that the QSAR model is effective in rapidly screening for ACE-I inhibitors, and PLITT can be supplemented in foods to lower blood pressure.
Subject(s)
Protein Hydrolysates , Quantitative Structure-Activity Relationship , Molecular Docking Simulation , Protein Hydrolysates/pharmacology , Protein Hydrolysates/chemistry , Peptides/pharmacology , Peptides/chemistry , Muscles/metabolism , Ions , Angiotensins , Peptidyl-Dipeptidase A/metabolismABSTRACT
In this study, Colla corii asini (CCA) was fractionated into three fractions with different molecular weights using ultracentrifugation equipment. Components with a molecular weight of >10 kDa in F1 accounted for 81.90%, whereas that in F2 and F3 was 15.63% and 0.94%, respectively. The immunomodulatory activity of CCA fractions was investigated using RAW264.7 cell model and their antioxidant abilities were evaluated by 2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) and ferric-reducing antioxidant power (FRAP) assay. The results indicated that RAW264.7 cells treated with F1 released the highest level of nitric oxide, reactive oxygen species, interleukin-6, and tumor necrosis factor-α. The ABTS and FRAP value of F1 were 65.81% and 29.33 µM TE/L, respectively, which were 22.53%, 128.44% and 43.72%, 132.16% higher than that of F2 and F3, respectively. These results suggested that components with a molecular weight of >10 kDa in CCA had stronger immunomodulatory and antioxidant ability, which would help develop the health food based on CCA. PRACTICAL APPLICATIONS: Colla corii asini (CCA) is a famous protein-based traditional Chinese medicine and nutritional supplement. During the processing of CCA, the molecular weight (MW) of CCA collagen components changed dynamically due to the protein aggregation, degradation, and the Maillard reaction. Some studies have shown that the MW distribution of CCA was not uniform. However, the MW range of CCA components which has strong antioxidant and immunomodulatory activity is still not clear, and few studies have reported the mechanism of CCA's immunomodulatory activity and active ingredients. Therefore, it is important to figure out the characteristics of CCA components with stronger immunomodulatory and antioxidant ability, such as the MW distribution and chemical composition of CCA fractions. And this study will be great for the processing of CCA products which has better biological functions.
Subject(s)
Antioxidants , Gelatin , Antioxidants/pharmacology , Gelatin/chemistry , Collagen/chemistryABSTRACT
In order to promote the extraction of biological calcium from fish bone, ultrasonication was used to process micrometer-scale fish bone particles (MFPs) and investigate the mechanism of action in relation to bone structure. With ultrasonication treatment (300 W, 60°C, 2 h), the content of calcium release increased by 25.6%. Calcium release reached 94.0% of total calcium after 24-h treatment. The surface of the MFPs was significantly damaged by ultrasound-induced cavitation, resulting in holes and separation of the layered structure. X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) analysis demonstrated that the crystalline structure of hydroxyapatite was disrupted, the triple helical structure of mineralized collagen fibrils (MCFs) was loosened, and hydrogen bonding in collagen decreased, facilitating the release of hydroxyapatite crystals. Thus, ultrasonication may be a practical alternative to nanomilling for industrial processing of waste fish bones to produce soluble calcium as an ingredient in calcium supplements and supplemented foods.
ABSTRACT
We aimed to evaluate the anti-fatigue effects of the oyster polypeptide (OP) fraction and its regulatory effect on the gut microbiota in mice. Our exhaustive swimming experiment showed that the swimming time of the low-, middle- and high-dose groups of the OP fraction was increased by 1.82, 2.18 and 2.44 times compared with the control group, respectively. Besides, the liver glycogen levels of the three groups were increased by 19.3%, 42.02% and 65.07%, while the lactate levels were decreased by 18.85%, 21.18% and 28.74%, respectively. Moreover, administration of the OP fraction upregulated the expressions of PEPCK and AMPK, but downregulated the TNF-α expression. Correlation analysis between the gut microbiota and fatigue-related biochemical indicators showed that Faecalibacterium, Desulfovibri and Intestinibacter were negatively correlated with the swimming time, blood lactate, blood urea nitrogen, liver glycogen and muscle glycogen, while Yaniella and Romboutsia were positively correlated. Therefore, the OP fraction had anti-fatigue effects, and could regulate the abundance of gut microbiota and maintain its balance.
Subject(s)
Fatigue , Gastrointestinal Microbiome/drug effects , Ostreidae/chemistry , Peptides/pharmacology , Animals , Blood Urea Nitrogen , Body Weight/drug effects , Fatigue/genetics , Fatigue/metabolism , Fatigue/microbiology , Fatigue/pathology , Gene Expression , Glutathione Peroxidase/blood , Glycogen/metabolism , Lactic Acid/blood , Liver/cytology , Liver/drug effects , Liver Glycogen/metabolism , Male , Mice , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Peptides/chemistry , Physical Exertion , Superoxide Dismutase/blood , SwimmingABSTRACT
In this study, the encapsulation mechanism of oxyresveratrol and ß-cyclodextrin (ß-CD) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) was studied. As this research shows, oxyresveratrol and two cyclodextrins (CDs) were able to form inclusion complexes in a 1:1 stoichiometry. However, the interaction with HP-ß-CD was more efficient, showing up as higher encapsulation constant (KF) (35,864.72 ± 3415.89 M-1). The KF values exhibited a strong dependence on temperature and pH, which decreased as they increased. From the thermodynamic parameters (ΔH°, ΔS°, and ΔG°) of the oxyresveratrol loaded ß-CD (oxyresveratrol-ß-CD) and HP-ß-CD (oxyresveratrol-HP-ß-CD), it could be seen that the complexation process was spontaneous and exothermic, and the main driving forces between oxyrsveratrol and CDs were hydrogen bonding and van der waals force. Besides, molecular docking combined with ¹H-NMR were used to explain the most possible mode of interactions between oxyresveratrol and CDs.
Subject(s)
2-Hydroxypropyl-beta-cyclodextrin/chemistry , Plant Extracts/chemistry , Stilbenes/chemistry , beta-Cyclodextrins/chemistry , Capsules , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Molecular Docking Simulation , Spectrometry, Fluorescence , Temperature , ThermodynamicsABSTRACT
Artocarpus heterophyllus is an evergreen tree distributed in tropical regions, and its fruit (jackfruit) is well-known as the world's largest tree-borne fruit. Although A. heterophyllus has been widely used in folk medicines against inflammation, its potential in cancer chemoprevention remains unclear. Herein we identified artocarpin from A. heterophyllus as a promising colorectal cancer chemopreventive agent by targeting Akt kinase. Phenotypically, artocarpin exhibited selective cytotoxicity against human colon cancer cells. Artocarpin impaired the anchorage-independent growth capability, suppressed colon cancer cell growth, and induced a G1 phase cell cycle arrest which was followed by apoptotic as well as autophagic cell death. Mechanistic studies revealed that artocarpin directly targeted Akt 1 and 2 kinase activity evidenced by in vitro kinase assay, ex vivo binding assay as well as Akt downstream cellular signal transduction. Importantly, oral administration of artocarpin attenuated colitis-associated colorectal tumorigenesis in mice. Taken together, artocarpin, a bioactive component of A. heterophyllus, might merit investigation as a potential colorectal cancer chemopreventive agent.
Subject(s)
Artocarpus/chemistry , Colorectal Neoplasms/prevention & control , Mannose-Binding Lectins/administration & dosage , Phytochemicals/administration & dosage , Plant Extracts/administration & dosage , Plant Lectins/administration & dosage , Animals , Cell Proliferation/drug effects , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/physiopathology , G1 Phase Cell Cycle Checkpoints/drug effects , Humans , Male , Mice , Mice, Inbred BALB C , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
Flavonoids are an important type of natural tyrosinase inhibitor, but their inhibitory activity and mechanism against tyrosinase are very different because of their different structures. In this study, the inhibitory activity and mechanism differences between norartocarpetin and luteolin for tyrosinase were investigated by a combination of kinetic studies and computational simulations. The kinetic analysis showed that norartocarpetin reversibly inhibited tyrosinase in a competitive manner, whereas luteolin caused reversible noncompetitive inhibition. Both norartocarpetin and luteolin showed a single type of quenching and a static-type quenching mechanism. A computational simulation indicated that the hydroxyl groups of the B ring of norartocarpetin interacted with tyrosinase residues Asn81 and His85 in the active pocket, while the hydroxyl groups of the B ring of luteolin bound residues Asn81 and Cys83. HPLC and UPLC-MS/MS further confirmed that luteolin acted as a substrate or a suicide inhibitor, yet norartocarpetin acted as an inhibitor.
Subject(s)
Enzyme Inhibitors/pharmacokinetics , Flavonoids/pharmacokinetics , Luteolin/pharmacokinetics , Molecular Docking Simulation/methods , Monophenol Monooxygenase/antagonists & inhibitors , Artocarpus/enzymology , Computer Simulation , Dose-Response Relationship, Drug , Flavonoids/chemistry , Kinetics , Luteolin/chemistry , Monophenol Monooxygenase/metabolism , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Protein Structure, Secondary , Tandem Mass Spectrometry/methodsABSTRACT
The purpose of this study is to prepare an oxyresveratrol (Oxy) microemulsion (ME) with improved Oxy's solubility and stability and to investigate its antibrowning effects on fresh-cut lotus root slices. The formula of OxyME consisted of ethyl butyrate, Tween 80, PEG400, and water with w/w of 4%, 10.67%, 5.33%, and 80%, respectively. Encapsulating Oxy into OxyME greatly increased its solubility and stability compared with that of in water. Strong antibrowning effects were observed on fresh-cut lotus root slices treated with OxyME, even better than 4-hexylresorcinol. The addition of ascorbic acid (VC) into OxyME greatly improved the Oxy stability in long-term storage and antibrowning effects on fresh-cut lotus root slices. However, the simultaneous addition of calcium chloride and VC did not obviously improve the antibrowning effects compared with the addition of VC alone. These results indicated that Oxy+VCME may be suitable as an antibrowning agent for fresh-cut vegetables.
Subject(s)
Ascorbic Acid/administration & dosage , Lotus/drug effects , Plant Extracts/administration & dosage , Plant Roots/drug effects , Stilbenes/administration & dosage , Drug Delivery Systems , Emulsions , Isomerism , Solubility , VegetablesABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Morus australis, one of the major Morus species growing in East Asia, is rich in phenolic compounds. The extract of M. australis has been used as skin whitening components for a long period. The action mechanisms of its principal constituents are still unclear. This study aims to evaluate the skin lightening effects of phenolic compounds extracted from the root of M. australis in different melanocyte systems and artificial skin models. MATERIALS AND METHODS: The depigmenting effect of resorcinol type polyphenols (RTPs) from the root extract of M. australis was evaluated in murine b16 and melan-a cell lines using a combined sulforhodamine B assay. Tyrosinase activity and the expression of melanogenesis proteins were evaluated for the mechanism study. The artificial skin model is used as a replacement of the animal test. RESULTS: Only Kuwanon O and Sanggenon T were found to have significant depigmenting effects in both murine b16 and melan-a cell lines. Their depigmenting mechanisms are slightly different in the two cell systems. In b16 cells, Kuwanon O and Sanggenon T, together with the other two RTPs, induced post-transcriptional degradations of MITF without suppressing its mRNA expression, leading to significant decreases of TRP-1 and TRP-2 production. While in melan-a cells, the levels of tyrosinase families were suppressed via MITF downregulation at both transcription and translation level by RTPs, with Kuwanon O inducing the greatest suppression. Further evaluations in artificial skin model demonstrated the outstanding depigmenting effects of Kuwanon O and Sanggenon T. CONCLUSIONS: Kuwanon O and Sanggenon T from M.australis root extract are two potential skin whitening ingredients. To screen resorcinol flavonone derivatives with an isoprenyl group in the Diels-Alder substituent might be an option for the search of potent hypopigmenting agents from plants.
Subject(s)
Flavanones/pharmacology , Melanins/metabolism , Melanocytes/drug effects , Melanoma, Experimental/metabolism , Morus/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Resorcinols/pharmacology , Skin Lightening Preparations/pharmacology , Skin Pigmentation/drug effects , Animals , Cell Line, Tumor , Dose-Response Relationship, Drug , Flavanones/isolation & purification , Flavonoids , Humans , Melanocytes/metabolism , Melanocytes/pathology , Melanoma, Experimental/genetics , Melanoma, Experimental/pathology , Mice , Microphthalmia-Associated Transcription Factor/genetics , Microphthalmia-Associated Transcription Factor/metabolism , Monophenol Monooxygenase/metabolism , Phytotherapy , Plant Extracts/isolation & purification , Plants, Medicinal , Resorcinols/isolation & purification , Skin Lightening Preparations/isolation & purification , Skin, ArtificialABSTRACT
SCOPE: Quercetin, a flavonoid, widely distributed in edible fruits and vegetables, was reported to effectively inhibit 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) formation in a food model (roast beef patties) with itself being converted into a novel compound 8-C-(E-phenylethenyl)quercetin (8-CEPQ). Here we investigated whether 8-CEPQ could be formed in a real food system, and tested its anticancer activity in human colon cancer cell lines. METHODS AND RESULTS: LC-MS was applied for the determination of 8-CEPQ formation in onion/beef soup. Anticancer activity of 8-CEPQ was evaluated by using cell viability assay and flow cytometry. Results showed that 8-CEPQ suppressed proliferation and caused G2 phase arrest in colon cancer cells. Based on immunofluorescent staining assay, western blot assay, and RNA knockdown data, we found that 8-CEPQ did not cause apoptotic cell death. Instead, it induced autophagic cell death. Moreover, treatment with 8-CEPQ induced phosphorylation of extracellular signal-regulated kinase (ERK). Inhibition of ERK phosphorylation by the mitogen-activated protein kinase kinase (MEK)/ERK inhibitor U0126 attenuated 8-CEPQ-induced autophagy and reversed 8-CEPQ-mediated cell growth inhibition. CONCLUSION: Our results demonstrate that 8-CEPQ, a novel quercetin derivative, could be formed in onion/beef soup. 8-CEPQ inhibited colon cancer cell growth by inducing autophagic cell death through ERK activation.
Subject(s)
Antineoplastic Agents/pharmacology , Cooking , Onions , Quercetin/analogs & derivatives , Quercetin/chemistry , Red Meat , Autophagy/drug effects , Cell Cycle Checkpoints/drug effects , Cell Death/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Enzyme Activation , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Quercetin/pharmacologyABSTRACT
Chalcones and their derivatives have attracted great interests in recent years for their comprehensive biological activities. In this study, 2,4,2',4'-tetrahydroxychalcone and its two derivatives, 1,3,5-tris-(2,4-dihydroxy-phenyl)pentane-1,5-dione (new compound) and 7,2',4'-trihydroxyflavanone, were synthesized through one-pot green procedure catalyzed by boric acid in polyethylene glycol 400. Their structures were identified by ESI-MS and NMR spectral. Tyrosinase inhibitory activity and antibrowning test results showed that compounds 1-3 exhibited strong tyrosinase inhibitory activities and significant antibrowning effects on the fresh-cut lotus root slices at room temperature in 48 h. Among them, 0.01% 1,3,5-tris-(2,4-dihydroxy-phenyl)pentane-1,5-dione combined with 0.5% VC showed the best antibrowning ability. In brief, this study offers a protocol for one-pot green synthesis of high efficiency tyrosinase inhibitors which may be suitable as antibrowning agents for fresh-cut vegetables. More important, this study developed a new type of 1,5-dione derivative which may serve as new lead structures for novel tyrosinase inhibitors discovery.
Subject(s)
Chalcones/chemistry , Enzyme Inhibitors/chemistry , Lotus/chemistry , Monophenol Monooxygenase/chemistry , Plant Extracts/chemistry , Enzyme Inhibitors/chemical synthesis , Food Preservation , Green Chemistry Technology , Molecular Structure , Vegetables/chemistry , Vegetables/drug effectsABSTRACT
Recently correlation studies between dietary advanced glycation end products (AGEs) and the progression of chronic diseases have attracted much attention. To explore the impact of dietary AGEs on the health risk of people consuming a high-fat diet (HFD), male Sprague-Dawley rats were used as the research subject. Under HFD, free N(ε)-(carboxymethyl)lysine (CML, a major AGE, 60 mg/kg body weight/day) was administered by gavage for 12 consecutive weeks. The results indicated that protein-bound CML accumulation in the kidney, heart, lung, pancreas, and muscle significantly increased to 178 ± 36, 161 ± 2, 106 ± 11, 39 ± 8, and 141 ± 20 µg/g dry matter, respectively, compared to HFD control levels of 86 ± 9, 127 ± 10, 89 ± 6, 23 ± 2, and 95 ± 3 µg/g dry matter, whereas no statistical increase was found in the liver and spleen. An increase of the protein-bound CML might be due to free CML binding to proteins in tissues by covalent bonds. Moreover, the rats' serum low-density lipoprotein cholesterol concentration, fasting blood glucose levels, and energy expenditure also increased obviously. These findings indicated that long-term intake of high-dose free CML might be a health risk factor for rats with HFD. This could provide valuable information for further study on the possible effects of long-term consumption of CML-rich fatty foods on human health, involving the progression of chronic disease.
Subject(s)
Diet, High-Fat/adverse effects , Lysine/analogs & derivatives , Animals , Blood Glucose/analysis , Energy Metabolism , Glycation End Products, Advanced/adverse effects , Lipoproteins, LDL/blood , Lysine/administration & dosage , Lysine/adverse effects , Lysine/metabolism , Male , Protein Binding , Rats , Rats, Sprague-Dawley , Risk FactorsABSTRACT
Norartocarpetin is a flavone widely distributed in Moraceae plants with strong tyrosinase inhibitory activity. However, its poor solubility in aqueous systems and in food grade solvents (oils) limits its extensive applications. The aim of this study was to improve the solubility of norartocarpetin by developing an oil-in-water (o/w) microemulsion with food grade components. A microemulsion was developed and characterized, and its chemical and physical stabilities were also evaluated within 8 weeks. Using the construction of pseudoternary phase diagrams, the optimized formulation of 2% w/w of ethyl oleate, 12% w/w of Tween 80, 6% w/w of polyethylene glycol 400, and 80% w/w of water was obtained, with a maximum solubility of norartocarpetin up to 1.73 ± 0.21 mg/mL, at least a 1000-fold increase in solubility. The microemulsion base and norartocarpetin-loaded microemulsion were demonstrated to be stable after accelerated and long-term conditions (8 weeks). The norartocarpetin microemulsion still showed strong tyrosinase inhibitory activity and antibrowning effect on fresh-cut apple slices. These combined results indicated that norartocarpetin microemulsion may be suitable as an antibrowning agent for fresh-cut fruits.
Subject(s)
Enzyme Inhibitors/chemistry , Flavones/chemistry , Monophenol Monooxygenase/antagonists & inhibitors , Moraceae/chemistry , Plant Extracts/chemistry , Color , Emulsions/chemistry , Enzyme Inhibitors/isolation & purification , Flavones/isolation & purification , Monophenol Monooxygenase/analysis , Plant Extracts/isolation & purification , SolubilityABSTRACT
Artocarpus heterophyllus is an evergreen fruit tree cultivated in many tropical regions. Previous studies have shown that some of its compositions exhibited potential tyrosinase inhibition activities. This study indentified 8 new phenolic compounds, artoheterophyllins E-J (1-6), 4-geranyl-2',3,4',5-tetrahydroxy-cis-stilbene (7), and 5-methoxymorican M (8) and 2 new natural compounds (9 and 10), 2,3-dihydro-5,7-dihydroxy-2-(2-hydroxy-4-methoxyphenyl)-4H-benzopyran-4-one and 6-[(1S,2S)-1,2-dihydroxy-3-methylbutyl]-2-(2,4-dihydroxyphenyl)-5-hydroxy-7-methoxy-3-(3-methyl-2-buten-1-yl)-4H-1-benzopyran-4-one, together with 23 known compounds (11-33), from the ethanol extract of the wood of A. heterophyllus. The structures of the eight new compounds (1-8) and two new natural compounds were established by extensive 1D- and 2D-NMR experiments. The anticancer effects of the isolated compounds were examined in MCF-7, H460, and SMMC-7721 human cancer cell lines by MTT assay. Compounds 5, 11, 12, and 30 significantly reduced the cell viabilities of these cell lines. Especially, compounds 11 and 30 resulted in more potent cytotoxicity than the positive control, 5-fluorouracil (5-Fu), in SMMC-7721 cell line, with IC50 values of 15.85 and 12.06 µM, whereas compound 30 exhibited more potent cytotoxicity than 5-Fu in NCI-H460 cell line, with an IC50 value of 5.19 µM. In addition, this study suggests that compounds 11 and 30 from the wood of A. heterophyllus have anticancer potential via MAPK pathways.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Artocarpus/chemistry , Cell Proliferation/drug effects , Phenols/chemistry , Apoptosis/drug effects , Caspases/genetics , Caspases/metabolism , Cell Line, Tumor , Fruit/chemistry , Humans , Inhibitory Concentration 50 , MCF-7 Cells , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Extracts/chemistryABSTRACT
The twigs of Cudrania tricuspidata were found to show strong tyrosinase inhibitory activity, and further detailed component analysis resulted in the isolation of a new flavanol glucoside, (2S,3S)-2,3-trans-dihydromorin-7-O-ß-d-glucoside (1), plus twenty-seven known compounds (2-28). Their structures were elucidated on the basis of ESI-MS and NMR spectral data. Among the isolated compounds, trans-dihydromorin (8), oxyresveratrol (9), and steppogenin (12) were found to exhibit significant tyrosinase inhibition activities. Moreover, the structure-activity relationship of these isolated compounds was also discussed.
Subject(s)
Enzyme Inhibitors/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Moraceae/chemistry , Enzyme Inhibitors/chemistry , Molecular Structure , Structure-Activity RelationshipABSTRACT
The phytochemical profiles of Morus australis roots, stems and twigs were firstly compared by HPLC analysis. It was found that Morus australis stem extract mainly contained one known tyrosinase inhibitor, oxyresveratrol, while its root and twig extract might contain some unknown potential tyrosinase inhibitors. The root extract of Morus australis was further investigated in this study. One new compound, austraone A, together with 21 known compounds, was isolated and their structures were identified by interpretation of MS and NMR data. In the tyrosinase inhibitory testing, some of them, such as oxyresveratrol, moracenin D, sanggenon T, and kuwanon O, exhibited stronger tyrosinase inhibitory activities than that of kojic acid. These results suggested the Morus australis root extract as a good source of natural tyrosinase inhibitors with a great potential to be used in foods as anti-browning agents and in cosmetics as skin-whitening agents.
Subject(s)
Enzyme Inhibitors/pharmacology , Heterocyclic Compounds, 4 or More Rings/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Morus/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Stilbenes/pharmacology , Agaricales/enzymology , Benzofurans/chemistry , Benzofurans/isolation & purification , Benzofurans/pharmacology , Chromatography, High Pressure Liquid , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Molecular Structure , Phenols/chemistry , Phenols/isolation & purification , Phenols/pharmacology , Plant Extracts/chemistry , Plant Stems/chemistry , Pyrones/pharmacology , Resveratrol , Stilbenes/chemistry , Stilbenes/isolation & purificationABSTRACT
The phytochemcal profiles of Cudrania cochinchinensis leaf, twig, stem and root were compared by HPLC analysis. It was found that C. cochinchinensis stem extract contained some unknown natural products with potential tyrosinase inhibitory activities. Therefore, the chemical constitutes in extract (95% ethanol) of C. cochinchinensis stem were further investigated in this study. A new racemic mixture, (±)2,3-cis-dihydromorin, and fifteen known phenolic compounds, dihydrokaempferol 7-O-ß-d-qlucopyranoside, skimmin, quercetin-7-O-ß-d-glucoside, 2,3-dihydroquercetin 7-O-ß-d-glucoside, kaempferol-7-O-ß-glucopyranoside, quercetin-3,7-di-O-ß-d-glucoside, morin-7-O-ß-d-glucoside, 1,3,5,8-tetrahydroxyxanthen-9-one, 2,3-trans-dihydromorin, aromadendrin, oxyresveratrol, genistin, protocatechuic acid, kaempferol 3,7-di-O-ß-glucopyranoside, and naringenin were isolated. Spectral techniques (MS, (1)H NMR and (13)C NMR) were utilized for their structural identification and their inhibitory activities on mushroom tyrosinase were also evaluated. The results showed that tyrosinase inhibitory activities of (±)2,3-cis-dihydromorin (IC(50) = 31.1 µM), 2,3-trans-dihydromorin (IC(50) = 21.1 µM), and oxyresveratrol (IC(50) = 2.33 µM), were more potent than that of kojic acid (IC(50) = 50.8 µM), a well-known tyrosinase inhibitor, indicating that Cudrania cochinchinensis stem will be a great potential agent for the development of effective natural tyrosinase inhibitors.
Subject(s)
Enzyme Inhibitors/pharmacology , Monophenol Monooxygenase/metabolism , Moraceae/chemistry , Phenols/pharmacology , Plant Roots/chemistry , Plant Stems/chemistry , Agaricales/enzymology , Chromatography, High Pressure Liquid/methods , Flavonoids/chemistry , Flavonoids/isolation & purification , Hydroxybenzoates/chemistry , Hydroxybenzoates/isolation & purification , Isoflavones/chemistry , Isoflavones/isolation & purification , Magnetic Resonance Imaging , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Quercetin/analogs & derivatives , Quercetin/analysis , Quercetin/metabolism , Stilbenes/chemistry , Stilbenes/isolation & purificationABSTRACT
The phytochemical profiles of Morus nigra roots and twigs were compared by HPLC with those of the old and young twigs of Morus alba which are known to contain oxyresveratrol and mulberroside A as major components. It was found that M. nigra root extract contains some unknown natural products with potential tyrosinase inhibitory activity. The extract (95% ethanol) of the roots of M. nigra was further investigated in this study. One new compound, 5'-geranyl-5,7,2',4'-tetrahydroxyflavone, and twenty-eight known phenolic compounds were isolated. Their structures were identified by mass spectrometry and NMR spectroscopy. Nine compounds, 5'-geranyl-5,7,2',4'-tetrahydroxyflavone, steppogenin-7-O-beta-D-glucoside, 2,4,2',4'-tetrahydroxychalcone, moracin N, kuwanon H, mulberrofuran G, morachalcone A, oxyresveratrol-3'-O-beta-D-glucopyranoside and oxyresveratrol-2-O-beta-D-glucopyranoside, showed better tyrosinase inhibitory activities than kojic acid. It was noteworthy that the IC(50) values of 2,4,2',4'-tetrahydroxychalcone and morachalcone A were 757-fold and 328-fold lower than that of kojic acid, respectively, suggesting a great potential for their development as effective natural tyrosinase inhibitors.
Subject(s)
Enzyme Inhibitors/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Morus/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Structure-Activity RelationshipABSTRACT
An HPLC method was developed and validated to compare the chemical profiles and tyrosinase inhibitors in the woods, twigs, roots, and leaves of Artocarpus heterophyllus . Five active tyrosinase inhibitors including dihydromorin, steppogenin, norartocarpetin, artocarpanone, and artocarpesin were used as marker compounds in this HPLC method. It was discovered that the chemical profiles of A. heterophyllus twigs and woods are quite different. Systematic chromatographic methods were further applied to purify the chemicals in the twigs of A. heterophyllus. Four new phenolic compounds, including one isoprenylated 2-arylbenzofuran derivative, artoheterophyllin A (1), and three isoprenylated flavonoids, artoheterophyllin B (2), artoheterophyllin C (3), and artoheterophyllin D (4), together with 16 known compounds, were isolated from the ethanol extract of the twigs of A. heterophyllus. The structures of compounds 1-4 were elucidated by spectroscopic analysis. However, the four new compounds did not show significant inhibitory activities against mushroom tyrosinase compared to kojic acid. It was found that similar compounds, such as norartocarpetin and artocarpesin in the twigs and woods of A. heterophyllus, contributed to their tyrosinase inhibitory activity.
Subject(s)
Artocarpus/chemistry , Monophenol Monooxygenase/antagonists & inhibitors , Peptides/chemistry , Plant Extracts/chemistry , Agaricales/enzymology , Fungal Proteins/antagonists & inhibitors , Plant Bark/chemistry , Plant Roots/chemistryABSTRACT
AIM OF THE STUDY: Fissistigma oldhamii (Hemsl.) Merr, a traditional Chinese herb medicine, is used for treating rheumatoid arthritis in China. In our previous study, an effective compound, 7'-(3',4'-dihydroxyphenyl)-N-[(4-methoxyphenyl) ethyl] propenamide (Z23), from this herb has showed potent immunosuppressive effects both in vitro and in vivo. However, its anti-inflammatory effect and mechanism is still need to explore. MATERIALS AND METHODS: We examined the in vitro effects of Z23 on the production of nitric oxide (NO), prostaglandin E2 (PGE2) and cytokines by lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. RESULTS: Z23 significantly decreased the production of PGE2, NO, tumour necrosis factor alpha (TNFalpha) and IL6 production. Inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX2) gene expression were also significantly reduced. CONCLUSIONS: These results demonstrated that Z23 exerted an anti-inflammatory effect through modulating the synthesis of several mediators and cytokines involved in the inflammatory process. This study provided evidence to understand the therapeutic effects of Fissistigma oldhamii (Hemsl.) Merr and indicated that Z23 has the potential for treatment of various inflammatory diseases where the overproduction of NO, PGE2 and inflammatory cytokines has been shown to play a role, e.g. rheumatoid arthritis.