ABSTRACT
Four ethanol fractionated crude extracts (EFCEs [A-D]) purified from the leaves of Cinnamomum macrostemon Hayata were screened for antioxidative effects and mitochondrial function in HaCaT cells. The higher cell viability indicated that EFCE C was mildly toxic. Under the treatment of 50 ng/mL EFCE C, the hydrogen peroxide (H2O2)-induced cytosolic and mitochondrial reactive oxygen species levels were reduced as well as the H2O2-impaired cell viability, mitochondrial membrane potential (MMP), ATP production, and mitochondrial mass. The conversion of globular mitochondria to tubular mitochondria is coincident with EFCE C-restored mitochondrial function. The mitophagy activator rapamycin showed similar effects to EFCE C in recovering the H2O2-impaired cell viability, MMP, ATP production, mitochondrial mass, and also mitophagic proteins such as PINK1, Parkin, LC3 II, and biogenesis protein PGC-1α. We thereby propose the application of EFCE C in the prevention of oxidative stress in skin cells.
Subject(s)
Cell Survival , Cinnamomum , Hydrogen Peroxide , Keratinocytes , Membrane Potential, Mitochondrial , Mitochondria , Mitophagy , Oxidative Stress , Plant Extracts , Reactive Oxygen Species , Humans , Mitophagy/drug effects , Keratinocytes/drug effects , Keratinocytes/metabolism , Keratinocytes/cytology , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Membrane Potential, Mitochondrial/drug effects , Reactive Oxygen Species/metabolism , Hydrogen Peroxide/metabolism , Cell Survival/drug effects , Cinnamomum/chemistry , Mitochondria/drug effects , Mitochondria/metabolism , Adenosine Triphosphate/metabolism , Plant Leaves/chemistry , Antioxidants/pharmacology , Ubiquitin-Protein Ligases/metabolism , Sirolimus/pharmacology , HaCaT Cells , Protein Kinases/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/geneticsABSTRACT
The cultivation of one actinobacteria strain, Herbidospora yilanensis, was isolated from sediment samples collected from Yilan County City in Taiwan, resulting in the isolation of five previously undescribed compounds: herbidosporayilanensins A-E (1-5), and four compounds isolated from nature for the first time: herbidosporayilanensins F-I (6-9). Their structures were elucidated by spectroscopic analyses, including 1D- and 2D-NMR experiments with those of known analogues, and on the basis of HR-EI-MS mass spectrometry, their antimycobacterial activities were also evaluated.
Subject(s)
Actinobacteria/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Actinobacteria/isolation & purification , Anti-Bacterial Agents/pharmacology , Antitubercular Agents/chemistry , Antitubercular Agents/metabolism , Antitubercular Agents/pharmacology , Geologic Sediments/microbiology , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Structure , Mycobacterium tuberculosis/drug effects , Soil Microbiology , TaiwanABSTRACT
Phytochemical investigation and chromatographic separation of extracts from one new actinobacteria strain Amycolatopsis taiwanensis that was isolated from soil of Yilan township, in the north of Taiwan, led to the isolation of nine new compounds, amycolataiwanensins A-I (1-9, resp.), and one new natural product, namely amycolataiwanensin J (10). The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic-data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Of the isolates, 3, 5, 7 and 8 exhibited potent anti-NO production activity, with IC50 values of 17.52, 12.31, 17.81 and 13.32 µM, respectively, compared to that of quercetin, an iNOS inhibitor with an IC50 value of 35.94 µM. This is the first report on indole metabolite from the genus Amycolatopsis.
Subject(s)
Anti-Inflammatory Agents/chemistry , Biological Products/chemistry , Lipopolysaccharides/adverse effects , Amycolatopsis/chemistry , Amycolatopsis/isolation & purification , Animals , Anti-Inflammatory Agents/pharmacology , Biological Products/isolation & purification , Biological Products/pharmacology , Inhibitory Concentration 50 , Mice , Molecular Structure , Nitric Oxide/metabolism , RAW 264.7 Cells , Secondary Metabolism , Soil Microbiology , TaiwanABSTRACT
Phytochemical investigation and chromatographic separation of extracts from the actinobacteria strain Saccharomonospora piscinae that was isolated from dried fishpond sediment of Kouhu township, in the south of Taiwan, led to the isolation of three new compounds, saccharpiscinols A-C (1-3, respectively), and three new natural products, namely (2S)-5,7,3',4'-tetrahydroxy-6,8-dimethylflavanone (4), methyl-4-hydroxy-2-methoxy-6-methylbenzoate (5), and (±)-7-acetyl-4,8-dihydroxy-6-methyl-1-tetralone (6). Compounds 4-6 were reported before as synthesized products, herein, they are reported from nature for the first time. The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Saccharpiscinol A showed inhibitory activities against LPS-induced NO production.
Subject(s)
Actinobacteria/chemistry , Anti-Inflammatory Agents/pharmacology , Flavonoids/pharmacology , Animals , Anti-Inflammatory Agents/chemistry , Cell Survival/drug effects , Chromatography, High Pressure Liquid , Complex Mixtures , Flavonoids/chemistry , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Mice , Nitric Oxide/biosynthesis , RAW 264.7 CellsABSTRACT
Cultivation of the actinobacteria strain Isoptericola chiayiensis, a mangrove-derived actinobacteria that was isolated from a mangrove soil collected in Chiayi County, resulted in the isolation of one new 2-furanone derivative, isopterfuranoneâ (1), one new sesquiterpenoid, isopterchiayioneâ (2), one new benzenoid derivative, isopterinoidâ (3), five new flavonoids, chiayiflavans A-Eâ (4-8), and 4 metabolites isolated for the first time from nature source, methyl 3-(4-methyl-2,5-dioxopyrrolidin-3-yl)propanoate (9), 3-ethyl-4-methylpyrrolidine-2,5-dioneâ (10), chiayiensolâ (11) and chiayiensic acidâ (12). Their structures were determined through in-depth spectroscopic and mass-spectrometric analyses. Most of the isolates showed potent inhibitory effects on NO production in LPS-stimulated RAW 264.7 murine macrophages cells with IC50 values ranging from 9.36 to 40.02â µM. Of these isolates, 4 and 5 showed NO inhibitory activity with IC50 values of 17.14 and 9.36â µM, stronger than the positive control quercetin (IC50 =36.95â µM). This is the first report on flavan metabolites from the genus Isoptericola.
Subject(s)
Actinobacteria/chemistry , Flavonoids/chemistry , Sesquiterpenes/chemistry , Actinobacteria/metabolism , Animals , Cell Survival/drug effects , Flavonoids/isolation & purification , Flavonoids/pharmacology , Lipopolysaccharides/pharmacology , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Magnetic Resonance Spectroscopy , Mice , Molecular Conformation , Nitric Oxide/metabolism , RAW 264.7 Cells , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , Soil MicrobiologyABSTRACT
BACKGROUND: Avicequinone-B (Naphtho[2,3-b]furan-4,9-dione) is a furanonaphthoquinone derivative. It is a hydrophobic compound with poor aqueous solubility, which may restrict its potential pharmaceutical and biomedical applications. PURPOSE: We synthesized different liposomal formulations of Avicequinone-B, and measured their particle size, aqueous solubility, and physicochemical properties. In addition, we investigated the anticancer activity of liposomal Avicequinone-B in human cutaneous squamous cell carcinoma (SCC) cells. METHODS: Liposomal Avicequinone-B formulations were synthesized using the thin-film hydration method. Drug yield, encapsulation efficiency and aqueous solubility were determined by high performance liquid chromatography. Particle size and polydispersity index were measured by submicron particle size analyzer, and ultrastructural morphology was visualized by transmission electron microscopy. Thermal transitions were determined by differential scanning calorimetry. Anti-skin cancer activity was determined in HSC-1 cells (human cutaneous SCC cell line) using the MTS cytotoxicity assay, apoptosis was assessed by caspase-3/7 activity assay, mitochondrial membrane potential was determined by JC-10 assay, and signal transduction pathways were evaluated by Western blot analysis. RESULTS: Liposomal Avicequinone-B formulations showed adequate yield and high encapsulation efficiency. These liposomal formulations produced small, uniformly sized nanoparticles, and greatly increased the aqueous solubility of Avicequinone-B. Differential scanning calorimetry showed loss of thermal phase transitions. In addition, liposomal Avicequinone-B showed significant cytotoxic effect on HSC-1 cells, through reduction of mitochondrial membrane potential, increased cytosolic cytochrome-c level, increased cleaved caspase 8 level, and induction of apoptosis. This was mediated through activation of ERK, p38 and JNK signaling pathways. CONCLUSION: Liposomal Avicequinone-B demonstrated improved aqueous solubility and physicochemical characteristics, and induced apoptosis in cutaneous SCC cells. Therefore, liposomal Avicequinone-B may have potential uses as a topical anti-skin cancer drug formulation in the future.
Subject(s)
Apoptosis/drug effects , Benzoquinones/chemistry , Carcinoma, Squamous Cell/drug therapy , Drug Compounding , Liposomes/chemistry , Skin Neoplasms/drug therapy , Benzoquinones/pharmacology , Calorimetry, Differential Scanning , Caspase 8/drug effects , Caspase 8/metabolism , Cell Line, Tumor , Humans , Nanoparticles/chemistry , Particle Size , Solubility , Water/chemistrySubject(s)
Acne Conglobata/complications , Acquired Hyperostosis Syndrome/diagnosis , Acquired Hyperostosis Syndrome/drug therapy , Etanercept/administration & dosage , Isotretinoin/administration & dosage , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Arthralgia/drug therapy , Chest Pain/drug therapy , Drug Therapy, Combination , Humans , Male , TaiwanABSTRACT
Cultivation of the fungal strain Annulohypoxylon ilanense, an endophytic fungus isolated from the wood of medicinal plant Cinnamomum species, resulted in the isolation of one new furanoid derivative, ilanefuranone (1), one new pyrrole alkaloid, ilanepyrrolal (2), and one new biarylpropanoid derivative, ilanenoid (3), together with 22 known compounds, of which one α-tetralone analog, (-)-(4R)-3,4-dihydro-4,6-dihydroxynaphthalen-1(2H)-one (4) was isolated for the first time from a natural source. The structures were elucidated on the basis of physicochemical evidence, in-depth NMR spectroscopic analysis, and high-resolution mass spectrometry, and the antimycobacterial activities were also evaluated.
Subject(s)
Antitubercular Agents/chemistry , Cinnamomum/microbiology , Furans/chemistry , Guaiacol/analogs & derivatives , Pyrroles/chemistry , Saccharomycetales/chemistry , Alkaloids/chemistry , Alkaloids/isolation & purification , Alkaloids/pharmacology , Antitubercular Agents/isolation & purification , Antitubercular Agents/pharmacology , Furans/isolation & purification , Furans/pharmacology , Guaiacol/chemistry , Guaiacol/isolation & purification , Guaiacol/pharmacology , Magnetic Resonance Spectroscopy , Mass Spectrometry , Microbial Sensitivity Tests , Molecular Conformation , Mycobacterium tuberculosis/drug effects , Plants, Medicinal/microbiology , Pyrroles/isolation & purification , Pyrroles/pharmacology , Saccharomycetales/isolation & purification , Tetralones/chemistry , Tetralones/isolation & purification , Tetralones/pharmacologyABSTRACT
An investigation on the secondary metabolites from the BuOH extract of the fermentation broth of the thermotolerant polyester-degrading actinomycete Actinomadura miaoliensis BCRC 16873 was carried out. One previously undescribed α-pyrone (=pyran-2-one) derivative, designated as miaolienone (1), and a new butanolide, miaolinolide (2), together with 13 known compounds, 3-15, were obtained. Their structures were established on the basis of extensive 1D- and 2D-NMR analyses in combination with HR-MS experiments. In addition, the isolated compounds 1-15 were evaluated for the inhibitory effects of the isolates on the production of tumor necrosis factor (TNF-α) induced by lipopolysaccharide (LPS). Among the isolates, 1 and 2 significantly inhibited TNF-α production in U937 cells in vitro, and the IC(50) values were 0.59 and 0.76 µM, respectively. Compounds 3-5 displayed moderate inhibitory activities on LPS-induced TNF-α production.