ABSTRACT
Four undescribed compounds (two 1,5-anhydro-d-glucitol derivatives and two galloyl derivatives) and fourteen known compounds were isolated and structurally identified from leaves of Acer ginnala Maxim. (Amur maple). Structures and absolute configurations of the four undescribed compounds were determined using extensive analysis of NMR spectroscopic, HRESI-MS, modified Mosher ester method, and comparison with spectroscopic data of known compounds. Bioactivity evaluation revealed that the isolated 1,5-anhydro-d-glucitol derivative, galloylated flavonol rhamnosides, and galloylated flavanols had inhibitory effects on both protein tyrosine phosphatase-1B (PTP1B, IC50 values ranging of 3.46-12.65 µM) and α-glucosidase (IC50 values ranging of 0.88-6.06 µM) in comparison with a positive control for PTP1B (ursolic acid, IC50 = 5.10 µM) or α-glucosidase (acarbose, IC50 = 141.62 µM). A combination of enzyme kinetic analysis and molecular docking provided additional evidence in favor of their inhibitory activities and mechanism. These data demonstrate that A. ginnala Maxim. together with its constituents are promising sources of potent candidates for developing novel anti-diabetic medications.
Subject(s)
Acer , Enzyme Inhibitors , Enzyme Inhibitors/chemistry , alpha-Glucosidases/metabolism , Acer/chemistry , Acer/metabolism , Flavonoids/metabolism , Sorbitol/chemistry , Sorbitol/pharmacology , Molecular Docking Simulation , Kinetics , Plant Leaves/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Protein Tyrosine Phosphatase, Non-Receptor Type 1ABSTRACT
Allantoin is an abundant component of yams and has been known as a skin protectant due to its pharmacological activities. In previous methods for allantoin determination using high-performance liquid chromatography (HPLC), the separation was unsatisfactory. We herein developed a 1H quantitative nuclear magnetic resonance (qNMR) method for quantification of allantoin in the flesh and peel of yams. The method was carried out based on the relative ratio of signals integration of allantoin to a certain amount of the internal standard dimethyl sulfone (DMSO2) and validated in terms of specificity, linearity (range 62.5-2000 µg/ml), sensitivity (limit of detection (LOD) and quantification (LOQ) 4.63 and 14.03 µg/ml, respectively), precision (RSD% 0.02-0.26), and recovery (86.35-92.11%). The method was then applied for the evaluation of allantoin in flesh and peel extracts of four different yams cultivated in Korea.
Subject(s)
Dioscorea , Dioscorea/chemistry , Proton Magnetic Resonance Spectroscopy/methods , Allantoin/analysis , Allantoin/pharmacology , Magnetic Resonance Spectroscopy , Limit of Detection , Chromatography, High Pressure Liquid/methodsABSTRACT
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a profound negative impact on patients' quality of life. Four known secondary fungal metabolites were found in the chemical study of the Antarctic fungus Pleosporales sp. SF-7343, including 14-methoxyalternate C (1), 5'-methoxy-6-methyl-biphenyl-3,4,3'-triol (2), 3,8,10-trihydroxy-4-methoxy-6-methylbenzocoumarin (3), and alternariol monomethyl ether (4). Additionally, we identified the skin anti-inflammatory composition from the SF-7343 strain. Interleukin-8 and -6 Screening results showed that compound 1 inhibited IL-8 and IL-6 in tumor necrosis factor-α/interferon-γ stimulated HaCaT cells. Compound 1 showed inhibitory effects on MDC and RANTES. It also downregulated the expression of intercellular adhesion molecule-1 (ICAM-1) and upregulated the expression of involucrin. The results of the mechanistic study showed that compound 1 inhibited the nuclear translocation of nuclear factor-kappa B p65 and STAT3. In conclusion, this study demonstrates the potential of the Antarctic fungal strain SF-7343 as a bioactive resource to inhibit skin inflammation, such as AD.
Subject(s)
Dermatitis, Atopic , NF-kappa B , Humans , NF-kappa B/metabolism , Quality of Life , Cytokines/metabolism , Keratinocytes/metabolism , Anti-Inflammatory Agents/therapeutic use , Tumor Necrosis Factor-alpha/metabolism , Dermatitis, Atopic/metabolism , Janus Kinase 2/metabolism , STAT3 Transcription Factor/metabolismABSTRACT
Phenanthrenes are bioactive phenolic compounds found in genus Dioscorea, in which they are distributed more in peel than in flesh. Recent studies on phenanthrenes from Dioscorea sp. peels have revealed the potential for valuable biomaterials. Herein, an analytical method using high-performance liquid chromatography (HPLC) for quantitation of bioactive phenanthrenes was developed and validated. The calibration curves were obtained using the phenanthrenes (1-3) previously isolated from Dioscorea batatas concentrations in the range of 0.625-20.00 µg/ml with a satisfactory coefficient of determination (R2) of 0.999. The limit of detection (LOD) and the limit of quantification (LOQ) values of the isolated phenanthrenes ranged from 0.78-0.89 and 2.38-2.71 µg/ml, respectively. The intraday and interday precision ranged from 0.25-7.58%. The recoveries of the isolated phenanthrenes were from 95 to 100% at concentrations of 1.25, 2.5, and 5.0 µg/ml. Additionally, phenanthrenes (1-3) were found in all investigated peel extracts. Hence, the developed method was encouraging for the quantitative analysis of phenanthrenes in genus Dioscorea.
Subject(s)
Dioscorea , Phenanthrenes , Chromatography, High Pressure Liquid , Phenols , Plant ExtractsABSTRACT
Microglia play a significant role in immune defense and tissue repair in the central nervous system (CNS). Microglial activation and the resulting neuroinflammation play a key role in the pathogenesis of neurodegenerative disorders. Recently, inflammation reduction strategies in neurodegenerative diseases have attracted increasing attention. Herein, we discovered and evaluated the anti-neuroinflammatory potential of compounds from the Antarctic fungi strain Aspergillus sp. SF-7402 in lipopolysaccharide (LPS)-stimulated BV2 cells. Four metabolites were isolated from the fungi through chemical investigations, namely, 5-methoxysterigmatocystin (1), sterigmatocystin (2), aversin (3), and 6,8-O-dimethylversicolorin A (4). Their chemical structures were elucidated by extensive spectroscopic analysis and HR-ESI-MS, as well as by comparison with those reported in literature. Anti-neuroinflammatory effects of the isolated metabolites were evaluated by measuring the production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in LPS-activated microglia at non-cytotoxic concentrations. Sterigmatocystins (1 and 2) displayed significant effects on NO production and mild effects on TNF-α and IL-6 expression inhibition. The molecular mechanisms underlying this activity were investigated using Western blot analysis. Sterigmatocystin treatment inhibited NO production via downregulation of inducible nitric oxide synthase (iNOS) expression in LPS-stimulated BV2 cells. Additionally, sterigmatocystins reduced nuclear translocation of NF-κB. These results suggest that sterigmatocystins present in the fungal strain Aspergillus sp. are promising candidates for the treatment of neuroinflammatory diseases.
Subject(s)
Microglia , NF-kappa B , Antarctic Regions , Anti-Inflammatory Agents/chemistry , Aspergillus/metabolism , Interleukin-6/metabolism , Lipopolysaccharides/metabolism , Lipopolysaccharides/pharmacology , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Signal Transduction , Sterigmatocystin/metabolism , Sterigmatocystin/pharmacology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Chemical investigation of the Antarctic fungi Pleosporales sp. SF-7343 revealed four known secondary fungal metabolites: alternate C (1), altenusin (2), alternariol (3), and altenuene (4). The compound structures were identified primarily by NMR and MS analyses. Atopic dermatitis, an inflammatory disease, is driven by the abnormal activation of T helper (Th) 2 cells and barrier dysfunction. We attempted to identify the anti-inflammatory components of SF-7343. Initial screening showed that compounds 1 and 3 inhibited the secretion of interleukin-8 and -6 in tumor necrosis factor-α/interferon-γ-treated HaCaT cells, and these compounds also showed inhibitory effects on CCL5 and CCL22. Compounds 1 and 3 also downregulated the protein expression levels of intercellular adhesion molecule-1 and upregulated the expression of filaggrin and involcurin. The mechanism study results showed that compounds 1 and 3 inhibited nuclear translocation of nuclear factor-kappa B p65 and the phosphorylation of STAT1 and STAT3. Compound 1, but not compound 3, significantly promoted the expression of heme oxygenase (HO)-1. The effects of compound 1 were partly reversed by co-treatment with a HO-1 inhibitor, tin protoporphyrin IX. Taken together, this study demonstrates the potential value of Antarctic fungal strain SF-7343 isolates as a bioresource for bioactive compounds to prevent skin inflammation.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Ascomycota/chemistry , Biological Products/pharmacology , Keratinocytes/drug effects , Antarctic Regions , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Biological Products/chemistry , Biological Products/isolation & purification , Cell Survival/drug effects , Cells, Cultured , Filaggrin Proteins , Gene Expression , Heme Oxygenase-1/metabolism , Humans , Intercellular Adhesion Molecule-1 , Interferon-gamma/metabolism , Keratinocytes/metabolism , Molecular Structure , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The bitter melon, Momordica charantia L., was once an important food and medicinal herb. Various studies have focused on the potential treatment of stomach disease with M. charantia and on its anti-diabetic properties. However, very little is known about the specific compounds responsible for its anti-inflammatory activities. In addition, the in vitro inhibitory effect of M. charantia on pro-inflammatory cytokine production by lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) has not been reported. Phytochemical investigation of M. charantia fruit led to the isolation of 15 compounds (1-15). Their chemical structures were elucidated spectroscopically (one- and two-dimensional nuclear magnetic resonance) and with electrospray ionization mass spectrometry. The anti-inflammatory effects of the isolated compounds were evaluated by measuring the production of the pro-inflammatory cytokines interleukin IL-6, IL-12 p40, and tumor necrosis factor α (TNF-α) in LPS-stimulated BMDCs. The cucurbitanes were potent inhibitors of the cytokines TNF-α, IL-6, and IL-12 p40, indicating promising anti-inflammatory effects. Based on these studies and in silico simulations, we determined that the ligand likely docked in the receptors. These results suggest that cucurbitanes from M. charantia are potential candidates for treating inflammatory diseases.
Subject(s)
Bone Marrow Cells/drug effects , Dendritic Cells/drug effects , Fruit/chemistry , Momordica charantia/chemistry , Triterpenes/pharmacology , Animals , Cells, Cultured , Cytokines/metabolism , Mice , Mice, Inbred C57BLABSTRACT
In this study, chemical investigation of methanol extract of the air-dried fruits of Luffa cylindrica led to the identification of a new δ-valerolactone (1), along with sixteen known compounds (2-17). Their chemical structures including the absolute configuration were elucidated by extensive spectroscopic analysis and electronic circular dichroism analysis, as well as by comparison with those reported in the literature. For the first time in literature, we have examined the binding potential of the isolated compounds to highly conserved protein, Mpro of SARS-CoV-2 using the molecular docking technique. We found that the isolated saponins (14-17) bind to the substrate-binding pocket of SARS-CoV-2 Mpro with docking energy scores of -7.13, -7.29, -7.47, and -7.54 kcal.mol-1, respectively, along with binding abilities equivalent to an already claimed N3 protease inhibitor (-7.51 kcal.mol-1).
Subject(s)
Antiviral Agents/metabolism , Coronavirus 3C Proteases/metabolism , Cysteine Proteinase Inhibitors/metabolism , Luffa/chemistry , SARS-CoV-2/drug effects , Saponins/metabolism , Antiviral Agents/chemistry , Antiviral Agents/isolation & purification , Catalytic Domain , Coronavirus 3C Proteases/chemistry , Cysteine Proteinase Inhibitors/chemistry , Cysteine Proteinase Inhibitors/isolation & purification , Fruit/chemistry , Molecular Docking Simulation , Protein Binding , Saponins/chemistry , Saponins/isolation & purificationABSTRACT
Three new sesquilignans, zijusesquilignans A-C (1-3), together with fifteen known compounds (4-18), were isolated from fruits of Ziziphus jujuba var. inermis Rehder (Rhamnaceae). Their chemical structures were established using spectroscopic analyses including 1D- and 2D-NMR, HR-EIMS, and ECD spectra. These compounds were assessed for their inhibitory effects on nitric oxide (NO) production. Of these compounds, 1-3 and 17 displayed inhibitory effects on NO production, with IC50 values ranging from 18.1 to 66.4⯵M. Pretreatment with 1 and 17 significantly suppressed LPS-induced expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein in cells. Moreover, compounds 1-3, 7, 9, and 17 exhibited cytotoxic activities against three human tumor cell lines, with IC50 values ranging from 8.4 to 44.9⯵M.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Fruit/chemistry , Lignans/pharmacology , Ziziphus/chemistry , Animals , Anti-Inflammatory Agents/isolation & purification , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Cyclooxygenase 2/metabolism , Humans , Lignans/isolation & purification , Mice , Molecular Structure , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , RAW 264.7 Cells , Republic of KoreaABSTRACT
The author would like to include conflict of interest statement of the online published article. The correct conflict of interest statement should read as.
ABSTRACT
Five new compounds, 9,3'-dimethoxyhierochin A (1), 6-oxo-trans-neocnidilide (2), (±)-(3E)-trans-6-hydroxy-7-methoxydihydroligustilide (3), (±)-cnidiumin (4), and 6-(1-oxopentyl)-salicylic acid methyl ester (5), together with twenty known compounds (6-25), were isolated from the rhizome of Cnidium officinale. The chemical structures of new compounds were established by NMR spectroscopic techniques, mass spectrometry, Mosher's method, and CD spectrum. Their anti-inflammatory activities were evaluated against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW 264.7 cells. Compounds 7, 13, and 14 showed inhibitory effects with IC50 values of 5.1, 24.5, and 27.8 µM, respectively. In addition, compounds 7, 13, and 14 reduced LPS-induced inducible nitric oxide synthase (iNOS) expression and cyclooxygenase-2 (COX-2) protein in a concentration-dependent manner.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cnidium/chemistry , Lipopolysaccharides/antagonists & inhibitors , Macrophages/drug effects , Nitric Oxide/antagonists & inhibitors , Rhizome/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Cell Survival/drug effects , Cells, Cultured , Cyclooxygenase 2/metabolism , Dose-Response Relationship, Drug , Lipopolysaccharides/pharmacology , Macrophages/metabolism , Mice , Molecular Structure , Nitric Oxide/biosynthesis , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/biosynthesis , RAW 264.7 Cells , Structure-Activity RelationshipABSTRACT
Five new lactones, litsenolide F1 (1), lisealactone H1 (10), lisealactone H2 (11), akolactone D (13), and akolactone E (14), along with thirteen known compounds were isolated from the pericarps of Litsea japonica (Thunb.) Jussieu. Their chemical structures were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR, HRMS, and chemical methods. The isolated compounds were evaluated for their inhibitory effects on NO production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Among them, 2-alkylidene-3-hydroxy-4-methylbutanolide derivatives (compounds 1-9) exhibited the most potent activity, with IC50 values in the range of 2.9-12.8⯵M. In additon, compounds 1, 3, 4, and 6 showed inhibition of iNOS and COX-2 expression in concentration-dependent manner. Compound 3 suppresses mRNA expression of iNOS, COX-2, IL-6, and TNF-α in LPS-stimulated RAW264.7 cells. Based on these evidence, the isolated lactones from L. japonica could be promissing candidates for the development of new anti-inflammatory agents.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Fruit/chemistry , Lactones/pharmacology , Litsea/chemistry , Nitric Oxide/antagonists & inhibitors , Plant Extracts/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Cyclooxygenase 2/metabolism , Cytokines/antagonists & inhibitors , Cytokines/biosynthesis , Dose-Response Relationship, Drug , Lactones/chemistry , Lactones/isolation & purification , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/metabolism , Plant Extracts/chemistry , Plant Extracts/isolation & purification , RAW 264.7 Cells , Structure-Activity RelationshipABSTRACT
Coptis chinensis has been used as a medicinal herb in traditional oriental medicine. In this study, chemical investigation of a water extract of C. chinensis identified two new quaternary protoberberines (1, 2), a new tricyclic amide (3), together with five known compounds. Their chemical structures were elucidated by analysis with 1D and 2D NMR and high-resolution mass spectroscopy, as well as by comparison with those reported in the literature. Compounds 4, 5, and 7 showed potent inhibition against acetylcholinesterase (AChE) with IC50 values of 1.1, 5.6, and 12.9⯵M, respectively. Compounds 2 and 4 showed inhibition of butyrylcholinesterase (BChE) with IC50 values of 11.5 and 27.8⯵M, respectively. The kinetic activities were investigated to find out the type of enzyme inhibition involved. The types of AChE inhibition shown by compounds 5 and 7 were noncompetitive; BChE inhibition by compound 2 was also noncompetitive.
Subject(s)
Acetylcholinesterase/metabolism , Berberine Alkaloids/pharmacology , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/pharmacology , Coptis/chemistry , Rhizome/chemistry , Amides/chemistry , Amides/isolation & purification , Amides/pharmacology , Animals , Berberine Alkaloids/chemistry , Berberine Alkaloids/isolation & purification , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/isolation & purification , Dose-Response Relationship, Drug , Electrophorus , Horses , Kinetics , Molecular Structure , Structure-Activity RelationshipABSTRACT
Two new benzofurans, 2-(3,4-dimethoxyphenyl)-5-(1,3-dihydroxypropyl)-7-methoxybenzofuran (1) and 2-(3,4-methylenedioxyphenyl)-5-(3-hydroxymethyletoxy-1-hydroxypropyl)-7-methoxybenzofuran (2), a new triterpene, 3ß, 6ß, 21ß-trihydroxyolean-12-ene (3), and eleven known compounds were isolated from the stem bark of Styrax obassia. The structures of the isolated compounds were established by extensive spectroscopic analyses, including 1D and 2D NMR and HRMS. Their anti-inflammatory activities were evaluated against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages. Compound 1 was shown to reduce LPS-induced iNOS expression in a dose-dependent manner. In addition, pretreating cells with 1 significantly suppressed their LPS-induced expression of COX-2 protein.