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1.
J Obstet Gynaecol ; 44(1): 2303693, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38263614

RESUMEN

BACKGROUND: As women with low ovarian reserve embark on the challenging journey of in-vitro fertilisation (IVF) treatment, the choice between natural and mildly stimulated cycles becomes a pivotal consideration. It is unclear which of these two regimens is superior for women with low ovarian reserve. Our study aims to assess the impact of natural cycles on embryo quality and pregnancy outcomes in women with low ovarian reserve undergoing IVF treatment compared to mildly stimulated cycles. METHODS: This retrospective study enrolled consecutive patients with low ovarian reserve who underwent IVF/intracytoplasmic sperm injection (ICSI) at Guangdong Second Provincial General Hospital between January 2017 and April 2021. The primary outcome for pregnancy rate of 478 natural cycles and 448 mild stimulated cycles was compared. Secondary outcomes included embryo quality and oocyte retrieval time of natural cycles. RESULTS: The pregnancy rate in the natural cycle group was significantly higher than that in the mildly stimulated cycle group (51.8% vs. 40.1%, p = 0.046). Moreover, natural cycles exhibited higher rates of available embryos (84.1% vs. 78.6%, p = 0.040), high-quality embryos (61.8% vs. 53.2%, p = 0.008), and utilisation of oocytes (73% vs. 65%, p = 0.001) compared to mildly stimulated cycles. Oocyte retrievals in natural cycles were predominantly performed between 7:00 and 19:00, with 94.9% occurring during this time frame. In natural cycles with high-quality embryos, 96.4% of oocyte retrievals were also conducted between 7:00 and 19:00. CONCLUSION: Natural cycles with appropriately timed oocyte retrieval may present a valuable option for patients with low ovarian reserve.


In the realm of in-vitro fertilisation (IVF) treatment, women with low ovarian reserve often face the crucial decision of opting for natural or mildly stimulated cycles. This retrospective study, conducted between January 2017 and April 2021 at Guangdong Second Provincial General Hospital, delves into the impact of these cycles on pregnancy outcomes. Examining 478 natural cycles and 448 mildly stimulated cycles, the study reveals a notably higher pregnancy rate in the natural cycle group (51.8% vs. 40.1%). Additionally, natural cycles demonstrated higher rates of available embryos, high-quality embryos, and oocyte utilisation compared to their mildly stimulated counterparts. The findings suggest that natural cycles, with proper oocyte retrieval timing, could be a favourable choice for those with low ovarian reserve seeking IVF treatment.


Asunto(s)
Reserva Ovárica , Resultado del Embarazo , Femenino , Humanos , Masculino , Embarazo , Estudios de Cohortes , Estudios Retrospectivos , Semen , Recuperación del Oocito , Índice de Embarazo
2.
J Pineal Res ; 74(2): e12846, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36428267

RESUMEN

With the rapid change of people's lifestyle, more childbearing couples live with irregular schedules (i.e., staying up late) and suffer from decreased fertility and abortion, which can be caused by luteal phase defect (LPD). We used continuous light-exposed mice as a model to observe whether continuous light exposure may affect luteinization and luteal function. We showed that the level of progesterone in serum reduced (p < .001), the number of corpus luteum (CL) decreased (p < .01), and the expressions of luteinization-related genes (Lhcgr, Star, Ptgfr, and Runx2), clock genes (Clock and Per1), and Mt1 were downregulated (p < .05) in the ovaries of mice exposed to continuous light, suggesting that continuous light exposure induces defects in luteinization and luteal functions. Strikingly, injection of melatonin (3 mg/kg) could improve luteal functions in continuous light-exposed mice. Moreover, we found that, after 2 h of hCG injection, the level of pERK1/2 in the ovary decreased in the continuous light group, but increased in the melatonin administration group, suggesting that melatonin can improve LPD caused by continuous light exposure through activating the ERK1/2 pathway. In summary, our data demonstrate that continuous light exposure affects ovary luteinization and luteal function, which can be rescued by melatonin.


Asunto(s)
Melatonina , Ovario , Femenino , Embarazo , Ratones , Animales , Ovario/metabolismo , Ratones Endogámicos ICR , Melatonina/farmacología , Melatonina/metabolismo , Cuerpo Lúteo/metabolismo , Progesterona/metabolismo , Luteinización
3.
Biosci Biotechnol Biochem ; 87(9): 1009-1016, 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37348480

RESUMEN

Farrerol is a flavonoid found in plants with a wide range of pharmacological effects, including protection and enhancement of nerve cell function, as well as antioxidant and antibacterial properties, among others. Neurodegenerative diseases are irreversible neurological disorders resulting from the loss of neuronal cells in the brain and spinal cord. In this experiment, we investigated the neuroprotective and antioxidant effects of farrerol on glutamate-induced HT22 cells. Our results showed that farrerol inhibited reactive oxygen species expression, apoptosis, mitochondrial damage, and the activation of caspases 3 and 9 in HT22 cells induced by glutamate. Additionally, farrerol potentially regulated the Nrf2/heme oxygenase-1 (HO-1) signaling pathway, as it attenuated the nuclear translocation of Nrf2 and promoted the expression of HO-1. These findings suggest that farrerol has potential as a new therapeutic option.


Asunto(s)
Fármacos Neuroprotectores , Estrés Oxidativo , Ácido Glutámico/toxicidad , Ácido Glutámico/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Hemo-Oxigenasa 1/metabolismo , Línea Celular , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Apoptosis , Fármacos Neuroprotectores/farmacología
4.
Pak J Pharm Sci ; 36(1): 71-80, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36967499

RESUMEN

The aim of this study was to evaluate the antibacterial activity and underlying mechanism of ethanol extracts of Meconopsis quintuplinervia Regel (EMQ) against the acne-causing bacteria Propionibacterium acnes and Staphylococcus aureus. The study results indicated that EMQ was an effective antibacterial agent against P. acnes and S. aureus, with a DIZ of 14.5 and 13.2mm, MIC of 12.5 and 12.5mg/mL and MBC of 100 and 50mg/mL, respectively. EMQ induced morphological changes to bacterial cells, as determined by electron microscopy. Leakage of alkaline phosphatase and nucleic acids confirmed that EMQ compromised the membrane integrity of bacterial cells. Furthermore, protein analysis revealed that EMQ hindered total protein expression and lowered adenosine triphosphatase activity, while crystal violet staining revealed suppressed biofilm production. Bacterial adhesion analysis demonstrated that EMQ lowered the adhesive capacity of bacterial cells. The main chemical components of EMQ, identified by LC-MS, seem to have important roles in the antimicrobial effects against P. acnes and S. aureus, suggesting EMQ is a promising therapeutic for acne treatment.


Asunto(s)
Acné Vulgar , Infecciones Estafilocócicas , Humanos , Propionibacterium acnes , Staphylococcus aureus , Pruebas de Sensibilidad Microbiana , Antibacterianos/uso terapéutico , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/microbiología , Bacterias , Extractos Vegetales/química
5.
Biol Pharm Bull ; 45(12): 1847-1852, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36450537

RESUMEN

Macrophages have important roles in the progression of inflammation. Ajania purpurea Shih. is a member of the Ajania Poljakor family that grows in Tibet (China). Extracts from plants in this genus have anti-bacterial and anti-inflammatory properties. However, there are few reports on the activity and mechanism of Ajania purpurea. Here, we confirmed the anti-inflammatory effect of Ajania purpurea Shih. ethanol extract (EAPS) by examining the levels of inflammatory factors in a mouse model of peritonitis and RAW264.7 cells. The main components of EAPS detected by LC-MS analysis included piperine and chlorogenic acid. In particular, in lipopolysaccharide (LPS)-induced RAW264.7 cells, EAPS inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW264.7 cells, lowered the levels of nitric oxide (NO) and prostaglandin E2 (PGE2), as well as the release of inflammatory factors such as tumor necrosis factor-alpha (TNF-α) and pro-inflammatory cytokines such as interleukin (IL)-1ß and IL-6. In addition, Western blot analysis and immunofluorescence staining verified that EAPS inhibited the activity of the nuclear factor-kappaB (NF-κB) pathway by reducing the nuclear translocation of the p65 subunit. Furthermore, in a mouse model of peritonitis, EAPS inhibited the release of inflammatory factors, as well as the recruitment of immune cells including neutrophils and macrophages. These findings indicated that EAPS suppressed LPS-induced inflammation via inhibiting the NF-κB pathway in RAW264.7 cells and mice with peritonitis. Thus, EAPS may be a viable therapeutic method for the treatment of inflammation and related disorders.


Asunto(s)
Lipopolisacáridos , Peritonitis , Ratones , Animales , FN-kappa B , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Peritonitis/inducido químicamente , Peritonitis/tratamiento farmacológico , Dinoprostona , Modelos Animales de Enfermedad , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico
6.
Drug Chem Toxicol ; 45(6): 2535-2544, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34380357

RESUMEN

The leguminosae of Sophora moorcroftiana (Benth.) Benth.ex Baker is a drought-resistant endemic Sophora shrub species from the Qinghai-Tibet Plateau, and its seeds have hepatoprotective effects. To study the effect of S. moorcroftiana seeds on liver injury and the molecular mechanism underlying the beneficial effects, liquid chromatography-mass spectrometry was used to detect the main active components in the ethanol extract of S. moorcroftiana seeds (SM). Male mice were divided into six groups (n = 8): normal control (NC), CCl4, SM (50, 100, 200 mg/kg), and dimethyl diphenyl bicarboxylate (150 mg/kg) groups. Mice were treated as indicated (once/day, orally) for 14 days, and CCl4 (2 mL/kg) was administered intraperitoneally. The serum and liver of mice were used for biochemical assays. To explore the underlying mechanism, HepG2 cells were treated with SM, stimulated with tert-butyl hydroperoxide (t-BHP, 50 µM), and analyzed by Western blotting. The major active compounds of SM were alkaloids including 22 compounds. Serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) decreased in the SM (200 mg/kg) group. SM can activate the expression of pregnane X receptor (PXR) and downstream molecules cytochrome P4503A11 enzyme (CYP3A11), UDP glucuronosyltransferase 1 family polypeptide A 1 (UGT1A1), and inhibit the multidrug resistance protein 2 (MRP2). In addition, SM improved cell viability in t-BHP-induced HepG2 cells (64% to 83%) and decreased the activation of the mitogen-activated protein kinase (MAPK) pathway. The main compounds in SM were alkaloids. SM showed hepatoprotective effects possibly mediated by the suppression of oxidative stress through the MAPK pathway.


Asunto(s)
Alcaloides , Enfermedad Hepática Inducida por Sustancias y Drogas , Sophora , Animales , Ratones , Sophora/química , Receptor X de Pregnano , terc-Butilhidroperóxido/análisis , terc-Butilhidroperóxido/farmacología , Alanina Transaminasa/análisis , Fosfatasa Alcalina , Semillas/química , Aspartato Aminotransferasas/análisis , Extractos Vegetales/química , Alcaloides/farmacología , Hígado , Glucuronosiltransferasa , Proteínas Quinasas Activadas por Mitógenos/análisis , Proteínas Quinasas Activadas por Mitógenos/farmacología , Etanol , Citocromos/análisis , Citocromos/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control
7.
Pak J Pharm Sci ; 35(4): 1015-1021, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36008897

RESUMEN

As a popular medicinal plant traditionally used in Tibet of China, Nepeta angustifolia C. Y. Wu is mainly administered to treat apoplexia, cerebral haemorrhage, fainting and epilepsy and other symptoms, while its effect on hyperuricemia is still unclear. In the present study, we evaluated the improvement of the 70% ethanol extract of Nepeta angustifolia C. Y. Wu in fructose-induced hyperuricemic mice. The results revealed that Nepeta angustifolia C. Y. Wu significantly decreased blood glucose and blood lipid levels, as well as lowering the urinary levels of uric acid, creatinine and urea nitrogen. Meanwhile, it effectively restored the serum levels of uric acid, creatinine and urea nitrogen and inhibited serum and hepatic XOD activities and renal oxidative stress, while suppressing the secretions of TNF-α, IL-1ß and IL-6 in kidney. Nepeta angustifolia C. Y. Wu also attenuated the infiltration of inflammatory cells and reduced the production and accumulation of glycogen and collagen, while restoring the dysregulated protein expressions of renal URAT1, GLUT9, OAT1 and OAT3. In summary, our results support the idea that Nepeta angustifolia C. Y. Wu is a promising agent for treating hyperuricemia.


Asunto(s)
Medicamentos Herbarios Chinos , Hiperuricemia , Nepeta , Animales , Creatinina/metabolismo , Medicamentos Herbarios Chinos/farmacología , Etanol/farmacología , Fructosa/efectos adversos , Hiperuricemia/inducido químicamente , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/metabolismo , Riñón , Ratones , Nitrógeno/metabolismo , Urea/metabolismo , Ácido Úrico
8.
Bioorg Chem ; 114: 105066, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34134031

RESUMEN

Twenty-one eudesmane-type sesquiterpenes, including five new compounds, were isolated from the roots of Inula helenium. The structures of the new compounds (1-5) were determined by extensive spectroscopic data interpretation, single-crystal X-ray diffraction analysis and ECD calculations. Six compounds can synergistically enhance cisplatin effect against ovarian cancer cells, the structure - activity relationship for the synergistic effect of these compounds with cisplatin was revealed for the first time, which provides useful clues to develop novel sensitizers to overcome drug resistance in cancer. In addition, fifteen sesquiterpenes exhibited significant anti-inflammatory activity, which provided promising candidates for development of anti-inflammatory agent.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Inula/química , Sesquiterpenos/farmacología , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Ratones , Simulación del Acoplamiento Molecular , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Células RAW 264.7 , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Relación Estructura-Actividad
9.
J Assist Reprod Genet ; 38(6): 1373-1385, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33914207

RESUMEN

Insufficiency of oocyte activation impairs the subsequent embryo development in assisted reproductive technology (ART). Intracellular Ca2+ concentration ([Ca2+]i) oscillations switch the oocytes to resume the second meiosis and initiate embryonic development. However, the [Ca2+]i oscillation patterns in oocytes are poorly characterized. In this study, we investigated the effects of various factors, such as the oocytes age, pH, cumulus cells, in vitro or in vivo maturation, and ER stress on [Ca2+]i oscillation patterns and pronuclear formation after parthenogenetic activation of mouse oocytes. Our results showed that the oocytes released to the oviduct at 17 h post-human chorionic gonadotrophin (hCG) displayed a significantly stronger [Ca2+]i oscillation, including higher frequency, shorter cycle, and higher peak, compared with oocytes collected at earlier or later time points. [Ca2+]i oscillations in acidic conditions (pH 6.4 and 6.6) were significantly weaker than those in neutral and mildly alkaline conditions (pH from 6.8 to 7.6). In vitro-matured oocytes showed reduced frequency and peak of [Ca2+]i oscillations compared with those matured in vivo. In vitro-matured oocytes from the cumulus-oocyte complexes (COCs) showed a significantly higher frequency, shorter cycle, and higher peak compared with the denuded oocytes (DOs). Finally, endoplasmic reticulum stress (ER stress) severely affected the parameters of [Ca2+]i oscillations, including elongated cycles and lower frequency. The pronuclear (PN) rate of oocytes after parthenogenetic activation was correlated with [Ca2+]i oscillation pattern, decreasing with oocyte aging, cumulus removal, acidic pH, and increasing ER stress. These results provide fundamental but critical information for the mechanism of how these factors affect oocyte activation.


Asunto(s)
Desarrollo Embrionario/genética , Estrés del Retículo Endoplásmico/genética , Técnicas de Maduración In Vitro de los Oocitos , Oocitos/crecimiento & desarrollo , Animales , Gonadotropina Coriónica/genética , Células del Cúmulo/metabolismo , Femenino , Meiosis/genética , Ratones , Partenogénesis/genética , Embarazo
10.
J Asian Nat Prod Res ; 23(1): 20-25, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31793831

RESUMEN

Two new guaiane sesquiterpenes, 7-(1-hydroxyethyl)-4-methyl-1-azulenecarboxaldehyde (1) and 7-isopropenyl-4-methyl-1-azulenecarboxylic acid (2), together with 5 known sesquiterpenes, were isolated from the fruiting bodies of Lactarius deliciosus. All structures were elucidated based on extensive spectroscopic methods, including 1 D and 2 D-NMR spectroscopy and high resolution mass spectrometry.


Asunto(s)
Basidiomycota , Sesquiterpenos , Cuerpos Fructíferos de los Hongos , Estructura Molecular , Sesquiterpenos de Guayano
11.
Pharm Biol ; 58(1): 1061-1068, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33161828

RESUMEN

CONTEXT: Ganoderma lucidum (Leyss. ex Fr.) Karst. (Polyporaceae) triterpenoids (GLTs), the main components and bioactive metabolites of G. lucidum, have antitumour activity. OBJECTIVE: We investigated the effects of GLTs in lung cancer tumour-bearing nude mice and their potential mechanism. MATERIALS AND METHODS: Forty BALB/c nude mice were randomly divided into four groups: saline control, GLT (1 g/kg/day), gefitinib (GEF, 15 mg/kg/day), and GLT (1 g/kg/day) + GEF (15 mg/kg/day) for 14 days. Cell viability was conducted using the Cell Counting Kit-8 assay. The tumour volume, inhibition rate, histopathological, microvessel density (MVD), mRNAs, and proteins were determined. RESULTS: GLTs inhibited the cell viability of A549 cells with an IC50 value of 14.38 ± 0.29 mg/L, while the IC50 value of GEF was 10.26 ± 0.47 µmol/L. The tumour inhibition rate in the GLT + GEF group (51.54%) was significantly decreased relative to the saline control… group (p < 0.05). The MVD in the GLT + GEF group (2.9 ± 0.7) was significantly decreased than that in the saline control group (12.8 ± 1.4, p < 0.05). The angiostatin, endostatin, and Bax protein expression in the GLT, GEF, and GLT + GEF groups were significantly increased compared to those in the saline control group, while the VEGFR2 and Bcl-2 protein expression were decreased. DISCUSSION AND CONCLUSIONS: Our study provided evidence that GLT and GEF combination therapy may be a promising candidate for the treatment of lung cancer and as an experimental basis for clinical treatment.


Asunto(s)
Neoplasias Pulmonares/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Reishi/química , Triterpenos/farmacología , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Neoplasias Pulmonares/irrigación sanguínea , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neovascularización Patológica/patología , Triterpenos/aislamiento & purificación
12.
J Oleo Sci ; 73(3): 359-370, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38433000

RESUMEN

Neuronal cell death and dysfunction of the central nervous system can be caused by oxidative stress, which is associated with the development of neurodegenerative diseases. Sophocarpine, an alkaloid compound derived from Sophora moorcroftiana (Benth.) Baker seeds, has a wide range of medicinal value. This study sought to determine how sophocarpine exerts neuroprotective effects by inhibited oxidative stress and apoptosis in mouse hippocampus neuronal (HT22) cells. 20mM glutamate-induced HT22 cells were used to develop an in vitro model of oxidative stress damage. The Cell Counting Kit-8 (CCK-8) assay was used to assess cell viability. According to the instructions on the kits to detect reactive oxygen species (ROS) levels and oxidative stress indicators. HT22 cells were examined using immunofluorescence and Western Blotting to detect Nuclear Factor Erythroid 2-related Factor 2 (Nrf2) expression. The expression of proteins and messenger RNA (mRNA) for heme oxygenase-1 (HO-1) was examined by Western Blotting and Quantitative real time polymerase chain reaction (qRT-PCR). Mitochondrial membrane potential (MMP) and Cell apoptosis were used by 5, 5', 6, 6'-Tetrachloro-1, 1', 3, 3'-tetraethyl-imidacarbocyanine iodide (JC- 1) kit and Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick-End Labeling (TUNEL) apoptosis assay kit, respectively. Finally, the expression of pro-apoptotic proteins was detected by Western Blotting. The result demonstrated that sophocarpine (1.25 µM-10 µM) can significantly inhibit glutamate-induced cytotoxicity and ROS generation, improve the activity of antioxidant enzymes. Sophocarpine increased the expression of HO-1 protein and mRNA and the nuclear translocation of Nrf2 to play a cytoprotective role; however, cells were transfected with small interfering RNA targeting HO-1 (si-HO-1) reversed the above effects of sophocarpine. In addition, sophocarpine significantly inhibited glutamate induced mitochondrial depolarization and further inhibited cell apoptosis by reducing the expression level of caspase-related proteins.


Asunto(s)
Alcaloides , Matrinas , Fármacos Neuroprotectores , Animales , Ratones , Alcaloides/farmacología , Ácido Glutámico/toxicidad , Fármacos Neuroprotectores/farmacología , Factor 2 Relacionado con NF-E2 , Especies Reactivas de Oxígeno , ARN Mensajero/genética , Humanos
13.
J Med Food ; 25(12): 1112-1125, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36445749

RESUMEN

Diabetic patients are more prone to developing nonalcoholic fatty liver disease (NAFLD) compared with healthy people. As a plant homologous to both medicine and food, Malus toringoides (Rehd.) Hughes has been used as an intervention for both NAFLD and diabetes. However, the effect and mechanism of M. toringoides on NAFLD on type 2 diabetes mellitus (T2DM) is unclear. The current investigation was designed to evaluate the ameliorative effects and mechanism of M. toringoides ethanol extract (CBTM-E375) on T2DM, and to identify the compounds in these extracts. The effects of CBTM-E375 on T2DM were verified using a high-fat diet-/streptozotocin-induced diabetic rat and free fatty acid (0.5 mM)-induced human hepatocellular carcinoma cell (HepG2) models. The components of CBTM-E375 were identified by high performance liquid chromatography-mass spectrometry/mass spectrometry. Our results demonstrate that CBTM-E375 ameliorated lipid accumulation (total cholesterol, triglyceride), oxidative stress (superoxide dismutase, catalase, malondialdehyde, glutathione peroxidase), and inflammation (tumor necrosis factor-α [TNF-α], interleukin [IL]-1ß, IL-6, C-reactive protein [CRP]) in vivo and in vitro, these effects were associated with a CBTM-E375-mediated downregulation of SREBP-1c (sterol regulatory element binding protein 1c) and the NF-κB (nuclear factor κB) signaling pathway. A total of 20 chemical compounds were identified in CBTM-E375, including phlorizin, isoquercitrin, chlorogenic acid, quercetin, naringenin, and trigonelline, which have been reported to have positive effects on diabetes or on NAFLD.


Asunto(s)
Diabetes Mellitus Tipo 2 , Malus , Enfermedad del Hígado Graso no Alcohólico , Humanos , Ratas , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Malus/metabolismo , Regulación hacia Abajo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Hígado/metabolismo , Metabolismo de los Lípidos
14.
Artículo en Inglés | MEDLINE | ID: mdl-36310615

RESUMEN

Malus toringoides (Rehd.) Hughes (Rosaceae) is used as a traditional folk medicine in the Tibet autonomous region of China to treat hypertension, hyperglycemia, and hyperlipidemia. However, few modern pharmacological data on the use of this plant against diabetic syndrome are available. In this study, we examined the vascular protection provided by a 70% ethanol extract of M. toringoides (EMT) in human umbilical vein endothelial cells (HUVECs) grown in high-glucose medium and in a high-fat diet/streptozotocin-induced rat diabetes model. EMT significantly suppressed the expression of cell adhesion molecules in both HUVECs and diabetic rats. EMT also inhibited activation of the CX3CL1/CX3CR1 axis and the nuclear factor kappa B (NF-κB) signaling pathway in vivo and in vitro. The results provide a significant information on the vasoprotective properties of M. toringoides that may contribute to the development and application of related herbal medicines.

15.
Gene ; 769: 145227, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33059025

RESUMEN

After fertilization, parental chromosomes decondense and form pronuclei. During these processes, germ cell genomes merge and give rise to the zygotic genome. Multiple pronuclei (MPN) formation is usually caused by polyspermic fertilization or oocyte-derived meiotic failure, and account for 15-18% of cytogenetically abnormal cases among spontaneous abortions. However, pathogenic gene mutations responsible for human MPN formation still need to be identified. Tubulin ß eight class VIII (TUBB8) is the major ß-tubulin isotype that assembles the human oocyte spindle. In this study, we identified 3 novel heterozygous missense mutations (c.524 T > C [p.V175A], c.10_12delins CTT [p.I4L], and c.1045 G > A [p.V349I]) in TUBB8 that were associated with a new phenotype: MPN in zygotes after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). These mutations were found in 3 independent female patients with infertility, and had experienced 2-3 failed IVF/ICSI attempts due to zygotic developmental arrest. These sites are evolutionarily conserved in primate TUBB8 genes as well as in other human ß-tubulin isotypes, suggesting that they have important biochemical functions. This finding reveals previously unreported phenotypes caused by TUBB8 mutations and will be helpful for future genetic counseling of infertile patients with MPN.


Asunto(s)
Mutación , Tubulina (Proteína)/genética , Cigoto/metabolismo , Adulto , Núcleo Celular/genética , Femenino , Fertilización , Humanos , Infertilidad Femenina/genética , Fenotipo , Embarazo
16.
J Ethnopharmacol ; 255: 112771, 2020 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-32201300

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: As an important medicinal material constituting a variety of traditional Chinese medicine prescriptions, Nepeta angustifolia C. Y. Wu was used as a folk medicine to treat various vascular-related diseases including apoplexia, and cerebral haemorrhage in Tibet, China. Our previous studies have shown that this plant had a significant protective effect on vascular dysfunction of the intracerebral haemorrhage and diabetic rats. In present study, we aimed to investigate the protective effects and underlying mechanisms of Nepeta angustifolia on diabetic nephropathy (DN), a microvascular complication. AIM OF THE STUDY: This study is aim to evaluate the protective effect of ethanol extracts of N. angustifolia (NA) on DN, and explore mechanism of action to provide basis for its pharmacological action against DN. MATERIALS AND METHODS: High-fat diet and low-dose streptozotocin administration (HFD/STZ) induced diabetic rats were randomly divided into 5 groups (n = 8): the diabetic model group, metformin group, and three dose groups of NA (60 mg/kg, 120 mg/kg, 240 mg/kg). After administration of NA for 8 weeks, the blood, urine and renal tissue were collected for subsequent experiments. Biochemical markers (urine protein, Cr, BUN), oxidative stress makers (SOD, GSH-px and MDA) and pro-inflammatory mediators (TNF-α, IL-1ß, IL-6 and MCP-1) were evaluated by commercial kit and ELISA, respectively. The effect of NA on DN was further confirmed by evaluation of renal histopathology by using the H&E, PAS and Masson staining. The H2O2-induced HBZY-1 cells (rat glomerular mesangial cells) were also been used to evaluate the renal protective effect of NA (50 µg/mL, 100 µg/mL, 200 µg/mL). The oxidative stress makers were detected by commercial kit. The levels of apoptosis and related proteins (caspase 3, 9) were detected by TUNEL assay and western blot analysis, respectively. The depolarization of mitochondrial membrane potential was detected by JC-1 staining assay. RESULTS: The administration of NA is helpful to maintain near normal body weight, blood glucose, urine volume, urine protein, kidney index and serum levels of Cr and BUN. NA treatment significantly improve renal dysfunction by the down-regulation of renal oxidative stress and pro-inflammatory mediators in HFD/STZ induced diabetic rats. In vitro experiments, NA has a significant cellular protective effect in H2O2-induced HBZY-1 cells, as well as the regulation in increases of SOD level and the decreases of ROS and MDA levels. Furthermore, NA treatment can significantly inhibit H2O2 induced mesangial cells apoptosis by the increasing mitochondrial potential and suppressing caspases-madiated signaling pathway. CONCLUSIONS: NA has obvious improvement on renal dysfunction in HFD/STZ induced diabetic rats. NA can protect mesangial cells by inhibiting oxidative stress induced apoptosis, which may be related to its regulation of mitochondrial-caspase apoptosis pathway.


Asunto(s)
Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Células Mesangiales/efectos de los fármacos , Nepeta , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Antioxidantes/aislamiento & purificación , Línea Celular , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Dieta Alta en Grasa , Mediadores de Inflamación/metabolismo , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Células Mesangiales/metabolismo , Células Mesangiales/patología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Nepeta/química , Extractos Vegetales/aislamiento & purificación , Ratas Sprague-Dawley , Estreptozocina
17.
Food Chem ; 313: 126092, 2020 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-31923866

RESUMEN

Trigonella foenum-graecum L. (fenugreek) is used as a leafy vegetable and spice in China and North African countries. However, the biochemical components of its aerial parts were rarely explored. In this study, the bioactivities of the various extract fractions from the aerial parts of this edible plant were assessed, the ethyl acetate extract fraction exhibited strong antioxidant and anti-inflammatory effects. Through bioassay-guided isolation, one new pterocarpan (1), as well as twelve known pterocarpans (2-13) were obtained, nine of them (5-13) were first reported in the fenugreek, four pterocarpans (9, 11-13) had strong antioxidant activity, eleven pterocarpans (1-3, 5-12) possessed obvious anti-inflammatory activity. This study indicates that pterocarpans are main bioactive components of this edible plant. Apart from its nutritional value as food, the aerial parts of this plant can also be further explored as functional foods or antioxidants in food industry.


Asunto(s)
Pterocarpanos/química , Trigonella/química , Animales , Antiinflamatorios/química , Antioxidantes/química , Conformación Molecular , Componentes Aéreos de las Plantas/química , Componentes Aéreos de las Plantas/metabolismo , Pterocarpanos/metabolismo
18.
Cell Cycle ; 18(21): 2893-2901, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31496367

RESUMEN

Rab GTPases have multiple regulatory functions in intracellular vesicle transport. In recent years, there has been an increasing interest in the roles of Rab proteins in mammalian oocytes. In this paper, we show the specific distribution pattern of Rab24 during mouse oocyte meiosis. Furthermore, we find that Rab24 depletion results in the failure of maturational progression in mouse oocytes. Notably, the frequency of meiotic apparatus abnormality is significantly increased in Rab24-depleted oocytes relative to controls. In addition, lagging chromosomes are readily observed in anaphase/telophase oocytes with Rab24 knockdown. In support of this, the depletion of Rab24 disturbs the kinetochore-microtubule attachments in oocytes, and contributes to the production of aneuploid eggs. Taken together, the results of this study identify Rab24 as a novel factor in the modulation of meiotic apparatus assembly and meiotic progression during mouse oocyte maturation.


Asunto(s)
Segregación Cromosómica/fisiología , Meiosis/fisiología , Oocitos/crecimiento & desarrollo , Proteínas de Unión al GTP rab/genética , Proteínas de Unión al GTP rab/metabolismo , Animales , Femenino , Cinetocoros/metabolismo , Ratones , Ratones Endogámicos ICR , Oocitos/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/genética , Huso Acromático/metabolismo
19.
J Ethnopharmacol ; 231: 187-196, 2019 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-30419276

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional folk medicine Nepeta angustifolia C. Y. Wu (NA) reportedly possesses various biological activities, such as anti-inflammatory, analgesic, antihypoxia, and antifatigue effects. In this study, we evaluated the anti-vascular inflammation effects of N. angustifolia extract in human umbilical vein endothelial cells (HUVECs) induced by high glucose (HG) as well as the underlying mechanisms and verified its activity in diabetic rats. MATERIALS AND METHODS: HUVECs were exposed to 25 mM glucose to induce endothelial dysfunction. Adhesion molecule expression and reactive oxygen species (ROS) were assayed. IκB and IκB phosphorylation, nuclear factor-κB (NF-κB), HO-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) were examined by Western blot. Nuclear localisation of Nrf2 was also examined using immunofluorescence. The in vivo study of NA was tested in diabetic rats in which the thoracic aorta and serum were collected to observe aorta histological change, and evaluate endothelial function and vascular inflammation. RESULTS: The results revealed that HG can significantly promote the generation of ROS, the expression of cell adhesion molecules (CAMs), and the phosphorylation and degradation of IκB and NF-κB activation in HUVECs. These HG-induced phenomena were suppressed by NA-induced heme oxygenase (HO)- 1 expression in a dose- and time-dependent manner by activating Nrf2. The HO-1 inhibitor tin protoporphyrin also dramatically reversed the NA-induced inhibition of CAM expression and the reduction in ROS production. Furthermore, NA also elicited anti-vascular dysfunction effects in diabetic rats, where endothelial function was improved and vascular inflammation was alleviated. CONCLUSION: All these findings indicated that NA attenuated high glucose-induced vascular dysfunction in vitro and in vivo.


Asunto(s)
Antiinflamatorios/farmacología , Diabetes Mellitus Experimental/metabolismo , Hemo-Oxigenasa 1/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Nepeta , Extractos Vegetales/farmacología , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/patología , Moléculas de Adhesión Celular/metabolismo , Células Cultivadas , Diabetes Mellitus Experimental/patología , Glucosa , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Proteínas I-kappa B/metabolismo , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo
20.
J Med Food ; 21(7): 726-733, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29620952

RESUMEN

Epimedium brevicornu Maxim has been used as a traditional herbal drug in China. In this study, the anti-inflammatory effects of E. brevicornu Maxim ethanol extract (EBME) were investigated in RAW264.7 macrophages and mice challenged with lipopolysaccharide (LPS). Results showed that EBME attenuated inflammation by decreasing the production of several proinflammatory mediators, such as nitric oxide (NO), prostaglandin (PG) E2, inducible nitric oxide synthase, and cyclooxygenase-2, in LPS-stimulated RAW264.7 macrophages. EBME increased the expression of heme oxygenase-1 (HO-1) and promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2. The inhibitory effects of EBME on LPS-stimulated NO and PGE2 expression were partially reversed by HO-1 inhibitor. EBME also elicited an anti-inflammatory effect by inhibiting the production of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 in LPS-induced peritonitis. Therefore, EBME exhibited anti-inflammatory effects in vitro and in vivo.


Asunto(s)
Antiinflamatorios/administración & dosificación , Epimedium/química , Peritonitis/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Animales , Antiinflamatorios/análisis , Antiinflamatorios/aislamiento & purificación , Dinoprostona/inmunología , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/inmunología , Humanos , Interleucina-6/genética , Interleucina-6/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Ratones , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/inmunología , Óxido Nítrico/inmunología , Peritonitis/genética , Peritonitis/inmunología , Extractos Vegetales/análisis , Extractos Vegetales/aislamiento & purificación , Células RAW 264.7
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