RESUMEN
Centipeda minima (CMX) has been widely investigated using network pharmacology and clinical studies for its effects on hair growth via the JAK/STAT signaling pathway. Human hair follicle papilla cells exhibit hair regrowth through the expression of Wnt signaling-related proteins. However, the mechanism of action of CMX in animals has not been elucidated fully. This study examined the effect of induced hair loss and its side-effects on the skin, and observed the mechanism of action of an alcoholic extract of CMX (DN106212) on C57BL/6 mice. Our results showed that DN106212 was more effective in promoting hair growth than dimethyl sulfoxide in the negative control and tofacitinib (TF) in the positive control when mice were treated with DN106212 for 16 days. We confirmed that DN106212 promotes the formation of mature hair follicles through hematoxylin and eosin staining. We also found that the expression of vascular endothelial growth factor (Vegfa), insulin-like growth factor 1 (Igf1), and transforming growth factor beta 1 (Tgfb1) is related to hair growth using PCR. DN106212-treated mice had significantly higher expression of Vegfa and Igf1 than TF-treated ones, and inhibiting the expression of Tgfb1 had similar effects as TF treatment. In conclusion, we propose that DN106212 increases the expression of hair growth factors, promotes the development of hair follicles, and promotes hair growth. Although additional experiments are needed, DN106212 may serve as an experimental basis for research on natural hair growth-promoting agents.
RESUMEN
Feature-based molecular networking analysis suggested the presence of naphthol tetramers in Daldinia childae 047219, the same species but a different strain from one used previously for the discovery of naphthol trimers promoting adiponectin synthesis. The new tetramers were composed of 5-methoxy-4-naphthol, each of which was connected to one another in various positions. Targeted isolation afforded six previously unreported naphthol tetramers (1-6) together with 13 known polyketides (7-19) including naphthol monomers, dimers, and trimers. Structures of the isolated compounds were established by using NMR and mass spectroscopic analysis. Nodulisporin A (13), nodulisporin B (14), and 1,1',3',3â³-ternaphthalene-5,5',5â³-trimethoxy-4,4',4â³-triol (16) demonstrated anti-inflammatory activities against NO production, but the new compounds were less active.
Asunto(s)
Ascomicetos , Xylariales , Naftoles , Espectrometría de Masas en TándemRESUMEN
Actinidia polygama has been used as a traditional medicine for treating various diseases. In the present study, 13 compounds, including three new monoterpenoids (1-3), were isolated from the leaves of A. polygama to investigate the bioactive constituents of the plant. The structures were characterized by analyzing spectroscopic and chiroptical data. These compounds were preliminarily screened for their ability to increase insulin secretion levels after glucose stimulation. Of these, 3-O-coumaroylmaslinic acid (4) and jacoumaric acid (5) showed activity. In further biological studies, these compounds exhibited increased glucose-stimulated insulin secretion (GSIS) activity without cytotoxicity in rat INS-1 pancreatic ß-cells as well as α-glucosidase inhibitory activity. Furthermore, both compounds increased insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), pancreatic and duodenal homeobox-1 (PDX-1), and peroxisome proliferator-activated receptor-γ (PPAR-γ) expression. Hence, these compounds may be developed as potential antidiabetic agents.
Asunto(s)
Actinidia , alfa-Glucosidasas , Ratas , Animales , Secreción de Insulina , alfa-Glucosidasas/metabolismo , Actinidia/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Glucosa/metabolismo , Insulina/metabolismoRESUMEN
Xinghamide A (1), a new nonapeptide, was discovered in Streptomyces xinghaiensis isolated from a halophyte, Suaeda maritima (L.) Dumort. Based on high-resolution mass and NMR spectroscopic data, the planar structure of 1 was established, and, in particular, the sequence of nine amino acids was determined with ROESY and HMBC NMR spectra. The absolute configurations of the α-carbon of each amino acid residue were determined with 1-fluoro-2,4-dinitrophenyl-l-and -d-leucine amide (Marfey's reagents) and 2,3,4,6-tetra-O-acetyl-ß-d-glucopyranosyl isothiocyanate, followed by LC-MS analysis. The anti-inflammatory activity of xinghamide A (1) was evaluated by inhibitory abilities against the nitric oxide (NO) secretion and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.
Asunto(s)
Aminoácidos , Streptomyces , Aminoácidos/química , Streptomyces/metabolismo , Espectroscopía de Resonancia Magnética , Cromatografía LiquidaRESUMEN
Previously, we isolated six heterocyclic compounds (1-6) from the fruits of mulberry trees (Morus alba L.) and determined that loliolide affords rat pancreatic islet ß-cell (INS-1) protection against streptozotocininduced cytotoxicity. In the present study, we further investigated the effect of the six heterocyclic compounds (1-6) on glucose-stimulated insulin secretion (GSIS) in INS-1 cells. Among them, (R)5hydroxypyrrolidin2one(1) and indole (6) increased GSIS without inducing cytotoxicity. Additionally, compounds 1 and 6 enhanced the phosphorylation of total insulin receptor substrate-2, phosphatidylinositol 3-kinase, and Akt, and activated pancreatic and duodenal homeobox-1, which play a crucial role in ß-cell functions related to insulin secretion. Collectively, these findings indicate that (R)5hydroxypyrrolidin2one(1) and indole (6), isolated from M. alba fruits, may be beneficial in managing type 2 diabetes.
Asunto(s)
Glucosa/antagonistas & inhibidores , Compuestos Heterocíclicos/farmacología , Hipoglucemiantes/farmacología , Secreción de Insulina/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Glucosa/farmacología , Compuestos Heterocíclicos/química , Hipoglucemiantes/química , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Estructura Molecular , Ratas , Relación Estructura-ActividadRESUMEN
Flowers of Prunus persica (L.) Batsch (Rosaceae), known as peach blossoms, have been reported to exert anti-obesity effects by improving hepatic lipid metabolism in obese mice. However, little is known regarding the anti-adipogenic effects of the phenolic compounds isolated from P. persica flowers. This study investigated the inhibitory effects of compounds extracted from P. persica flowers (PPF) on adipogenesis in 3T3-L1 murine preadipocytes using adipogenic differentiation assays. Additionally, we compared the anti-adipogenic effects of the phenolic compounds isolated from PPF, such as prunasin amide (1), amygdalin amide (2), prunasin acid (3), mandelamide (4), methyl caffeate (5), ferulic acid (6), chlorogenic acid (7), benzyl α-l-xylpyranosyl-(1 â 6)-ß-d-glucopyranoside (8), prunin (9), naringenin (10), nicotiflorin (11), astragalin (12), afzelin (13), and uridine (14), on adipogenesis in 3T3-L1 murine preadipocytes. PPF and compounds 4-7 and 10 significantly inhibited adipogenesis. Among them, mandelamide (4) exhibited the maximum inhibitory activity with an IC50 of 36.04 ± 1.82 µM. Additionally, mandelamide downregulated the expression of key adipogenic markers, such as extracellular signal-regulated kinase, c-Jun-N-terminal kinase, P38, CCAAT/enhancer-binding protein α, CCAAT/enhancer-binding protein ß, peroxisome proliferator activated receptor γ, and glucocorticoid receptor. These results indicate that mandelamide is an active ingredient of PPF possessing anti-obesity properties.
Asunto(s)
Adipogénesis/efectos de los fármacos , Flores/química , Ácidos Mandélicos/farmacología , Fenoles/farmacología , Fitoquímicos/farmacología , Prunus persica/química , Células 3T3-L1 , Animales , Fármacos Antiobesidad/farmacología , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Diferenciación Celular/efectos de los fármacos , Gotas Lipídicas/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , PPAR gamma/metabolismoRESUMEN
Tacrolimus (FK506), a calcineurin inhibitor, is an effective immunosuppressive agent mainly used to lower the risk of organ rejection after allogeneic organ transplant. However, FK506-associated adverse effects, such as nephrotoxicity, may limit its therapeutic use. In this study, we confirmed that epigallocatechin-3-gallate (EGCG), sanguiin H-6, and gallic acid increased cell survival following FK506-induced cytotoxicity in renal epithelial LLC-PK1. Among these compounds, gallic acid exerted the strongest protective effect, further confirmed in the FK506-induced nephrotoxicity rat model. Additionally, we identified supporting evidence for the nephroprotective function of gallic acid using molecular docking and bioavailability investigations.
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Ácido Gálico/farmacología , Riñón/efectos de los fármacos , Células LLC-PK1/efectos de los fármacos , Sustancias Protectoras/farmacología , Syzygium/química , Tacrolimus/antagonistas & inhibidores , Animales , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ácido Gálico/química , Masculino , Estructura Molecular , Sustancias Protectoras/química , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , Porcinos , Tacrolimus/farmacologíaRESUMEN
We aimed to compare the estrogenic activities of compounds isolated from Moutan Cortex Radicis (MRC, Paeonia suffruticosa Andrews) and identify their potential use in hormone replacement therapy. We quantified seven marker components (gallic acid, oxypaeoniflorin, paeoniflorin, ethyl gallate, benzoic acid, benzoylpaeoniflorin, and paeonol) in MRC using a high-performance liquid chromatography simultaneous analysis assay. To investigate the estrogenic activity of MRC and the seven marker components, an E-screen assay was conducted using the estrogen receptor (ER)-positive MCF-7 human breast cancer cell line. Among them, ethyl gallate caused cell proliferation in a concentration-dependent manner at concentrations above 25 µM and was clearly suppressed by combination treatment with the ER antagonist ICI 182,780. Therefore, ethyl gallate may be a compound of MRC that can increase the estrogenic effect in ER-positive MCF-7 cells.
Asunto(s)
Estrona/química , Ácido Gálico/análogos & derivados , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/metabolismo , Estrógenos , Ácido Gálico/química , Ácido Gálico/farmacología , Glucósidos/química , Terapia de Reemplazo de Hormonas , Humanos , Monoterpenos/química , Paeonia/química , Paeonia/metabolismo , Unión Proteica , Relación Estructura-ActividadRESUMEN
Fourteen azaphilone-type polyketides (1-14), including nine new ones (1-6 and 8-10), were isolated from cultures of Vitex rotundifolia-associated Penicillium sp. JVF17, and their structures were determined by spectroscopic analysis together with computational methods and chemical reactions. Neuroprotective effects of the isolated compounds were evaluated against glutamate-induced neurotoxicity. Treatment with compounds 3, 6, 7, and 11-14 increased cell viabilities of hippocampal neuronal cells damaged by glutamate, with compound 12 being the most potent. Compound 12 markedly decreased intracellular Ca2+ and nuclear condensation levels. Mechanistically, molecular markers of apoptosis induced by treatment with glutamate, i.e., phosphorylation of MAPKs and elevated Bax/Bcl-2 expression ratio, were significantly lowered by compound 12. The azaphilones with an isoquinoline core structure were more active than those with pyranoquinones, but N-substitution decreased the activity. This study, including the structure-activity relationship, indicates that the azaphilone scaffold is a promising lead toward the development of novel neuroprotective agents.
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Benzopiranos/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Penicillium/química , Pigmentos Biológicos/farmacología , Policétidos/farmacología , Animales , Apoptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Hipocampo/citología , Ratones , Proteínas Quinasas Activadas por Mitógenos , Estructura Molecular , Proteínas Proto-Oncogénicas c-bcl-2 , República de Corea , Relación Estructura-Actividad , Vitex/microbiología , Proteína X Asociada a bcl-2RESUMEN
Eight new naphtho[1,2-c]furan derivatives (1-8) along with six known analogues (9-14) were isolated from culture medium of the basidiomycete Basidioradulum radula. The structures of these compounds were identified using spectroscopic analysis, and their absolute configurations were resolved using X-ray diffraction, ECD, and VCD. Compounds 7 and 14 inhibited the cell viability of human prostate cancer DU-145 cells with IC50 values of 7.54 ± 0.03 µM and 5.04 ± 0.03 µM, respectively. At 8 µM, compounds 7 and 14 increased the percentage of apoptotic cells and upregulated the protein expression related to the apoptosis caspase pathways in DU-145 cells. Furthermore, the hallmarks of cells undergoing apoptosis, such as chromatin condensation, were also observed at this concentration. However, compound 7 and 14 showed no effect on the proliferation of splenocytes isolated from cyclophosphamide-induce immunosuppressed mice.
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Antineoplásicos/farmacología , Basidiomycota/química , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ciclofosfamida , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Bazo/efectos de los fármacos , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
Menopause, caused by decreases in estrogen production, results in symptoms such as facial flushing, vaginal atrophy, and osteoporosis. Although hormone replacement therapy is utilized to treat menopausal symptoms, it is associated with a risk of breast cancer development. We aimed to evaluate the estrogenic activities of Spartina anglica (SA) and its compounds and identify potential candidates for the treatment of estrogen reduction without the risk of breast cancer. We evaluated the estrogenic and anti-proliferative effects of extracts of SA and its compounds in MCF-7 breast cancer cells. We performed an uterotrophic assay using an immature female rat model. Among extracts of SA, belowground part (SA-bg-E50) had potent estrogenic activity. In the immature female rat model, the administration of SA-bg-E50 increased uterine weight compared with that in the normal group. Among the compounds isolated from SA, 1,3-di-O-trans-feruloyl-(-)-quinic acid (1) had significant estrogenic activity and induced phosphorylation at serine residues of estrogen receptor (ER)α. All extracts and compounds from SA did not increase MCF-7 cell proliferation. Compound 1 is expected to act as an ERα ligand and have estrogenic effects, without side effects, such as breast cancer development.
Asunto(s)
Fitoestrógenos/farmacología , Extractos Vegetales/farmacología , Poaceae/metabolismo , Útero/efectos de los fármacos , Animales , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Receptor alfa de Estrógeno/agonistas , Receptor alfa de Estrógeno/metabolismo , Femenino , Humanos , Ligandos , Células MCF-7 , Estructura Molecular , Tamaño de los Órganos , Fitoestrógenos/aislamiento & purificación , Fitoestrógenos/toxicidad , Componentes Aéreos de las Plantas/metabolismo , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Raíces de Plantas/metabolismo , Poaceae/crecimiento & desarrollo , Ratas Sprague-Dawley , Relación Estructura-Actividad , Útero/crecimiento & desarrollo , Útero/metabolismoRESUMEN
The epithelial-mesenchymal transition (EMT) of cancer cells is a crucial process in cancer cell metastasis. An Aquimarina sp. MC085 extract was found to inhibit A549 human lung cancer cell invasion, and caprolactin C (1), a new natural product, α-amino-ε-caprolactam linked to 3-methyl butanoic acid, was purified through bioactivity-guided isolation of the extract. Furthermore, its enantiomeric compound, ent-caprolactin C (2), was synthesized. Both 1 and 2 inhibited the invasion and γ-irradiation-induced migration of A549 cells. In transforming growth factor-ß (TGF-ß)-treated A549 cells, 2 inhibited the phosphorylation of Smad2/3 and suppressed the EMT cell marker proteins (N-cadherin, ß-catenin, and vimentin), as well as the related messenger ribonucleic acid expression (N-cadherin, matrix metalloproteinase-9, Snail, and vimentin), while compound 1 did not suppress Smad2/3 phosphorylation and the expression of EMT cell markers. Therefore, compound 2 could be a potential candidate for antimetastatic agent development, because it suppresses TGF-ß-induced EMT.
Asunto(s)
Antineoplásicos/farmacología , Caproatos/farmacología , Flavobacteriaceae/química , Lactonas/farmacología , Células A549 , Animales , Organismos Acuáticos , Línea Celular Tumoral/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
The fruits of the mulberry tree (Morus alba L.), known as white mulberry, have been consumed in various forms, including tea, beverages, and desserts, worldwide. As part of an ongoing study to discover bioactive compounds from M. alba fruits, the anti-inflammatory effect of compounds from M. alba were evaluated in lipopolysaccharide (LPS)-stimulated mouse RAW 264.7 macrophages. Phytochemical analysis of the ethanol extract of the M. alba fruits led to the isolation of 22 compounds. Among the isolated compounds, to the best of our knowledge, compounds 1, 3, 5, 7, 11, 12, and 14-22 were identified from M. alba fruits for the first time in this study. Inhibitory effects of 22 compounds on the production of the nitric oxide (NO) known as a proinflammatory mediator in LPS-stimulated RAW 264.7 macrophages were evaluated using NO assays. Western blot analysis was performed to evaluate the anti-inflammatory effects of cyclo(L-Pro-L-Val) (5). We evaluated whether the anti-inflammatory effects of cyclo(L-Pro-L-Val) (5) following LPS stimulation in RAW 264.7 macrophages occurred because of phosphorylation of IκB kinase alpha (IKKα), IκB kinase beta (IKKß), inhibitor of kappa B alpha (IκBα), nuclear factor kappa B (NF-κB) and activations of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Cyclo(L-Pro-L-Val) (5) significantly suppressed phosphorylations of IKKα, IKKß, IκBα, and NF-κB and activations of iNOS and COX-2 in a concentration-dependent manner. Taken together, these results indicate that cyclo(L-Pro-L-Val) (5) can be considered a potential therapeutic agent for the treatment of inflammation-associated disorders.
Asunto(s)
Antiinflamatorios/farmacología , Dipéptidos/farmacología , Frutas/química , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Morus/química , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Macrófagos/metabolismo , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/metabolismo , Células RAW 264.7 , Transducción de Señal/efectos de los fármacosRESUMEN
Oxidative stress leads to protein degeneration or mitochondrial dysfunction, causing neuronal cell death. Glutamate is a neurotransmitter that nerve cells use to send signals. However, the excess accumulation of glutamate can cause excitotoxicity in the central nervous system. In this study, we deciphered the molecular mechanism of catechin-mediated neuroprotective effect on glutamate-induced oxidative stress in mouse hippocampal neuronal HT22 cells. Cellular antioxidant activity was determined using the 1,1-diphenyl-picryl hydrazyl (DPPH) assay and 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) staining. Furthermore, the levels of intracellular calcium (Ca2+) as well as nuclear condensation and protein expression related to neuronal damage were assessed. All five catechins (epigallocatechin gallate, gallocatechin gallate (GCG), gallocatechin, epicatechin gallate, and epicatechin) showed strong antioxidant effects. Among them, GCG exhibited the highest neuroprotective effect against glutamate excitotoxicity and was used for further mechanistic studies. The glutamate-induced increase in intracellular Ca2+ was reduced after GCG treatment. Moreover, GCG reduced nuclear condensation and the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinases (JNK) involved in cell death. The neuroprotective effect of GCG against glutamate-induced oxidative stress in HT22 cells was attributed to the reduction in intracellular free radicals and Ca2+ influx and also the inhibition of phosphorylation of ERK and JNK. Furthermore, the antioxidant effect of GCG was found to be likely due to the inhibition of phosphorylation of ERK and JNK that led to the effective suppression of neurocytotoxicity caused by glutamate in HT22 cells.
Asunto(s)
Antioxidantes/farmacología , Catequina/análogos & derivados , Ácido Glutámico/toxicidad , Hipocampo/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Catequina/farmacología , Células Cultivadas , Hipocampo/metabolismo , Hipocampo/patología , Ratones , FosforilaciónRESUMEN
Catalpa pod has been used in traditional medicine for the treatment of diabetes mellitus in South America. Studies on the constituents of Catalpa species have shown that it is rich in iridoids. In the present study, three previously undescribed compounds (2-4), including two secoiridoid derivatives along with twelve known compounds, were isolated from the fruits of Catalpa bignonioides Walt. In addition, fully assigned 13C-NMR of 5,6-dihydroxy-7,4'-dimethoxyflavone-6-O-sophoroside (1) is reported for the first time in the present study. The structures of compounds were determined on the basis of extensive spectroscopic methods, including UV, IR, 1D, and 2D NMR, mass spectroscopy, and CD spectroscopic data. All the isolated compounds were evaluated for α-glucosidase inhibitory activity. Among the tested compounds, compounds 2, 3, and 9 exhibited significant inhibitory activity against α-glucosidase enzyme assay. Meanwhile, the effect of compounds 2, 3, and 9 on glucose-stimulated insulin secretion (GSIS) was measured using pancreatic ß-cells. Compounds 2, 3, and 9 exhibited non-cytotoxicity-stimulated insulin secretion in INS-1 cells. The expression levels of proteins associated with ß-cell function and insulin secretion such as phosphorylation of total insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, activated pancreatic duodenal homeobox-1 (PDX-1), and peroxisome proliferator-activated receptor-γ (PPAR-γ) were increased in INS-1 cells after treatment with compounds 2, 3, and 9. The findings of the present study could provide a scientific warrant for their application as a potential antidiabetic agent.
Asunto(s)
Bignoniaceae/química , Frutas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Secreción de Insulina/efectos de los fármacos , alfa-Glucosidasas/metabolismo , Animales , Línea Celular , Glucosa/farmacología , Inhibidores de Glicósido Hidrolasas/análisis , Inhibidores de Glicósido Hidrolasas/química , Espectroscopía de Resonancia Magnética , PPAR gamma/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación/efectos de los fármacos , Ratas , alfa-Glucosidasas/químicaRESUMEN
The aim of our study was to investigate the effect of three lignans (schisandrol A, schisandrol B, and schisandrin C) on insulin secretion in rat INS-1 pancreatic ß-cells and glucose uptake in mouse C2C12 skeletal muscle cells. Schisandrol A and schisandrin C enhanced insulin secretion in response to high glucose levels with no toxic effects on INS-1 cells. The effect of schisandrin C was superior to that of gliclazide (positive control), a drug commonly used to treat type 2 diabetes (T2D). In addition, western blot analysis showed that the expression of associated proteins, including peroxisome proliferator-activated receptor γ (PPARγ), pancreatic and duodenal homeobox 1 (PDX-1), phosphatidylinositol 3-kinase (PI3K), Akt, and insulin receptor substrate-2 (IRS-2), was increased in INS-1 cells after treatment with schisandrin C. In addition, insulin secretion effect of schisandrin C were enhanced by the Bay K 8644 (L-type Ca2+ channel agonist) and glibenclamide (K+ channel blocker), were abolished by the nifedipine (L-type Ca2+ channel blocker) and diazoxide (K+ channel activator). Moreover, schisandrin C enhanced glucose uptake with no toxic effects on C2C12 cells. Western blot analysis showed that the expression of associated proteins, including insulin receptor substrate-1 (IRS-1), AMP-activated protein kinase (AMPK), PI3K, Akt, glucose transporter type 4 (GLUT-4), was increased in C2C12 cells after treatment with schisandrin C. Schisandrin C may improve hyperglycemia by enhancing insulin secretion in pancreatic ß-cells and improving glucose uptake into skeletal muscle cells. Our findings may provide evidence that schisandrin C may be beneficial in devising novel anti-T2D strategies.
Asunto(s)
Glucosa/metabolismo , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Insulina/biosíntesis , Lignanos/farmacología , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Compuestos Policíclicos/farmacología , Adenosina Trifosfato/biosíntesis , Biomarcadores , Canales de Calcio/genética , Canales de Calcio/metabolismo , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Línea Celular , Ciclooctanos/química , Ciclooctanos/farmacología , Expresión Génica , Lignanos/química , Compuestos Policíclicos/química , Canales de Potasio/genética , Canales de Potasio/metabolismoRESUMEN
Armillariella tabescens (Scop.) Sing., a mushroom of the family Tricholomataceae, has been used in traditional oriental medicine to treat cholecystitis, improve bile secretion, and regulate bile-duct pressure. The present study evaluated the estrogen-like effects of A. tabescens using a cell-proliferation assay in an estrogen-receptor-positive breast cancer cell line (MCF-7). We found that the methanol extract of A. tabescens fruiting bodies promoted cell proliferation in MCF-7 cells. Using bioassay-guided fractionation of the methanol extract and chemical investigation, we isolated and identified four steroids and four fatty acids from the active fraction. All eight compounds were evaluated by E-screen assay for their estrogen-like effects in MCF-7 cells. Among the tested isolates, only (3ß,5α,22E)-ergost-22-en-3-ol promoted cell proliferation in MCF-7 cells; this effect was mitigated by the ER antagonist, ICI 182,780. The mechanism underlying the estrogen-like effect of (3ß,5α,22E)-ergost-22-en-3-ol was evaluated using Western blot analysis to detect the expression of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), Akt, and estrogen receptor α (ERα). We found that (3ß,5α,22E)-ergost-22-en-3-ol induced an increase in phosphorylation of ERK, PI3K, Akt, and ERα. Together, these experimental results suggest that (3ß,5α,22E)-ergost-22-en-3-ol is responsible for the estrogen-like effects of A. tabescens and may potentially aid control of estrogenic activity in menopause.
Asunto(s)
Receptor alfa de Estrógeno/metabolismo , Estrona/farmacología , Transducción de Señal/efectos de los fármacos , Agaricales/química , Productos Biológicos/química , Productos Biológicos/farmacología , Biomarcadores , Proliferación Celular/efectos de los fármacos , Estrona/análogos & derivados , Estrona/aislamiento & purificación , Estrona/uso terapéutico , Femenino , Hongos/química , Terapia de Reemplazo de Hormonas , Humanos , Células MCF-7 , Modelos Biológicos , Estructura MolecularRESUMEN
Guggulsterone is a bioactive plant sterol naturally found in migratory plants. It exists in various forms, and its active compounds include the isomers cis-guggulsterone (E-GS) and trans-guggulsterone (Z-GS). In this study, the anti-inflammatory effects of these two isomeric pregnadienedione steroids were investigated against lipopolysaccharide-induced inflammatory reaction in RAW264.7 mouse macrophages. Our results showed that both guggulsterones inhibited the production of NO in macrophages treated with lipopolysaccharide, with IC50 values ranging from 3.0 to 6.7 µM. E-GS exerted higher efficacy than Z-GS, and its anti-inflammatory effects was mediated through inhibition of iNOS and COX-2 expression.
Asunto(s)
Antiinflamatorios/farmacología , Inhibidores de la Ciclooxigenasa 2/farmacología , Macrófagos/efectos de los fármacos , Óxido Nítrico/antagonistas & inhibidores , Pregnenodionas/farmacología , Animales , Antiinflamatorios/síntesis química , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/síntesis química , Regulación hacia Abajo/efectos de los fármacos , Escherichia coli/química , Lipopolisacáridos/farmacología , Ratones , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Pregnenodionas/síntesis química , Células RAW 264.7 , EstereoisomerismoRESUMEN
Calvatia nipponica is an extremely rare mushroom with a limited number of studies on its chemical components and biological activities published. Here we report the isolation of a novel sterol, calvatianone (1), possessing a 6/5/6/5-fused ring system with a contracted tetrahydrofuran B-ring, and four known steroids (2-5) from the fruiting bodies of C. nipponica. The structure of calvatianone including its absolute configuration was determined by NMR spectroscopic analyses, HR-ESIMS, gauge-including atomic orbital NMR chemical shift calculations, and ECD calculations. Ergosterol peroxide (3) and cyathisterol (4) suppressed the cell viability increase induced by 17ß-estradiol in MCF-7 breast cancer cell lines, suggesting a possible approach for these compounds to serve as ERα antagonists.
Asunto(s)
Agaricales/química , Cuerpos Fructíferos de los Hongos/química , Esteroles/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Dicroismo Circular , Estradiol , Antagonistas de Estrógenos/farmacología , Receptor alfa de Estrógeno/antagonistas & inhibidores , Femenino , Humanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Espectrometría de Masa por Ionización de Electrospray , Esteroides/químicaRESUMEN
The absolute configuration and corrected NMR assignment of 17-hydroxycyclooctatin isolated from Streptomyces sp. M56 recovered from a nest of South African Macrotermes natalensis termites are reported. 17-Hydroxycyclooctatin is a unique tricyclic diterpene (C20) consisting of a fused 5-8-5 ring system, and in this study, its structure was unambiguously determined by a combination of HR-ESIMS and 1D and 2D NMR spectroscopic experiments to produce corrected NMR assignments. The absolute configuration of 17-hydroxycyclooctatin is reported for the first time in the current study using chemical reactions and quantum chemical ECD calculations. The corrected NMR assignments were verified using a gauge-including atomic orbital NMR chemical shifts calculation, followed by DP4 probability. To understand the pharmacological properties of 17-hydroxycyclooctatin, a network pharmacological approach and molecular docking analyses were used, which also predicted its effects on human breast cancer cell lines. Cytotoxicity and antiestrogenic activity of 17-hydroxycyclooctatin were determined, and it was found this compound may be an ERα antagonist.