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ETHNOPHARMACOLOGICAL RELEVANCE: "Snow-white waterlily" (Nymphaea candida) dried flower possesses various efficacy in Uighur medicine such as reducing fever and nourishing the liver, anti-inflammatory and cough relieving, moistening the throat and quenching thirst. AIM OF THE STUDY: Polyphenols are characteristic component of N. candida as well as its quality markers, and the purpose of this study was to conduct investigations into anti-inflammatory, antitussive, antipyretic, and analgesic activities of the polyphenol-enriched fraction from N. candida (NCTP) in order to validate the traditional efficacy of this plant. MATERIALS AND METHODS: The polyphenols in NCTP were analyzed by HPLC, and an acute oral toxicity study was conducted for NCTP. The anti-inflammatory activities of NCTP were evaluated using xylene induced ear edema, capillary permeability, cotton pellet granuloma, and carrageenan-induced rat paw edema, of which multiple biochemical indices were measured in carrageenan-induced rat paw edema such as prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2),5-lipoxygenase (5-LOX), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities; the analgesic activities were investigated using acetic acid writhing, hot plate test, and formalin test; the anti-tussive and antipyretic effects were tested by ammonia induced cough in mice and yeast-induced fever respectively. RESULTS: NCTP with LD50 of 5222 mg/kg was low toxicity and safety. NCTP (200 mg/kg) could significantly reduce ear swelling and capillary permeability by 30.63% and 31.37%, respectively. NCTP revealed 15.76% inhibiting activities in cotton pellet granuloma in mice at a dosage of 200 mg/kg. Furthermore, NCTP (50, 100, and 200 mg/kg) substantially decreased carrageenin-induced paw edema in rats between 1 and 5 h, and NCTP could decrease PGE2, 5-LOX, COX-2 levels as well as IL-6, IL-1ß, TNF-α activities compared with the control group; NCTP could decrease MDA contents in carrageenin-induced rise, and increase SOD and GSH activities. Furthermore, the dose-dependent inhibition effect of NCTP on pain was revealed in the hot plate experiment. In addition to reducing the amount of writhes brought on by acetic acid, NCTP (50, 100, and 200 mg/kg) significantly inhibited pain latency against both stages of the formalin test. Moreover, NCTP (50, 100, 200 mg/kg) showed the better antitussive activities in mice in a dose-dependent manner. In the yeast-induced pyrexia test, dosages of 50, 100, and 200 mg/kg resulted in a statistically significant drop in rectal temperature. CONCLUSION: The experimental results proved the analgesic, anti-inflammatory, anti-tussive and antipyretic activities of the polyphenol-enriched fraction from N. candida, and supported the traditional use of this plant as well.
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Antipiréticos , Antitusígenos , Nymphaea , Ratas , Ratones , Animales , Antipiréticos/farmacología , Antipiréticos/uso terapéutico , Antipiréticos/química , Carragenina , Antitusígenos/uso terapéutico , Polifenoles/farmacología , Polifenoles/uso terapéutico , Factor de Necrosis Tumoral alfa , Saccharomyces cerevisiae , Interleucina-6 , Ciclooxigenasa 2 , Dinoprostona , Extractos Vegetales/uso terapéutico , Extractos Vegetales/toxicidad , Antiinflamatorios/efectos adversos , Analgésicos/farmacología , Analgésicos/uso terapéutico , Analgésicos/química , Dolor/tratamiento farmacológico , Antiinflamatorios no Esteroideos/uso terapéutico , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/patología , Acetatos , Tos/tratamiento farmacológico , Granuloma/tratamiento farmacológico , Superóxido DismutasaRESUMEN
This study aimed to investigate the hypoglycaemic and hypolipidemic activities of total flavonoids from Nymphaea candida (NCTF). The result showed that NCTF could significantly ameliorate various indicators such as FBG, OGTT, TC, TG, LDL-C, and HDL-C in ALX-induced diabetic mice compared with the model group. Meanwhile, in the therapeutical effect study of NCTF on high-fat and high-sugar diets combined with STZ-induced T2DM mice, all parameters including RBG, INS, and INSR related to diabetes were significantly improved by NCTF as well as the serum ALT, AST, ALP, CR, MDA, and IL-6 activities. NCTF could significantly increase the expression levels of SOD and PPAR-γ in T2DM. Pathological observation showed that NCTF could improve the damage to pancreatic and liver tissues in T2DM mice. In conclusion, NCTF has better hypoglycaemic and hypolipidemic effects, and its mechanism may be related to its antioxidant, PPAR-γ regulation, and inhibiting inflammatory cytokine expression.
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In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.
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Artritis Reumatoide , Periploca , Ratas , Animales , Cisteína , Citidina Difosfato Colina , Farmacología en Red , Fosforilcolina , Metabolómica , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores , Glicerofosfolípidos , Metionina , Purinas , Cromatografía Líquida de Alta PresiónRESUMEN
Mitochondria-targeted photodynamic therapy (PDT) has recently been recognized as a promising strategy for effective cancer treatment. In this work, a mitochondria-targeted near-infrared (NIR) aggregation-induced emission (AIE)-active phosphorescent Ir(III) complex (Ir1) is reported with highly favourable mitochondria-targeted bioimaging and cancer PDT properties. Complex Ir1 has strong absorption in the visible light region (â¼500 nm) and can effectively produce singlet oxygen (1O2) under green light (525 nm) irradiation. It preferentially accumulates in the mitochondria of human breast cancer MDA-MB-231 cells as revealed by colocalization analysis. Complex Ir1 displays high phototoxicity toward human breast cancer MDA-MB-231 cells and mouse breast cancer 4T1 cells. Complex Ir1 induces reactive oxygen species (ROS) production, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in MDA-MB-231 cells upon photoirradiation, leading to apoptotic cell death. The favorable PDT performance of Ir1in vivo has been further demonstrated in tumour-bearing mice. Together, the results suggest that Ir1 is a promising photosensitizer for mitochondria-targeted imaging and cancer phototherapy.
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Neoplasias de la Mama , Fotoquimioterapia , Ratones , Humanos , Animales , Femenino , Iridio/farmacología , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Mitocondrias , Línea Celular TumoralRESUMEN
The hypoimmunogenicity of tumors is one of the main bottlenecks of cancer immunotherapy. Enhancing tumor immunogenicity can improve the efficacy of tumor immunotherapy by increasing antigen exposure and presentation, and establishing an inflammatory microenvironment. Here, a multifunctional antigen trapping nanoparticle with indocyanine green (ICG), aluminum hydroxide (Al(OH)3) and oxaliplatin (OXA) (PPIAO) has been developed for tumor photoacoustic/ultrasound dual-modality imaging and therapy. The combination of photothermal/photodynamic therapy and chemotherapy induced tumor antigen exposure and release through immunogenic death of tumor cells. A timely capture and storage of antigens by aluminum hydroxide enabled dendritic cells to recognize and present those antigens spatiotemporally. In an ovarian tumor model, the photoacoustic-mediated PPIAO NPs combination therapy achieved a transition from "cold tumor" to "hot tumor" that promoted more CD8+ T lymphocytes activation in vivo and intratumoral infiltration, and successfully inhibited the growth of primary and metastatic tumors. An in situ tumor vaccine effect was produced from the treated tumor tissue, assisting mice against the recurrence of tumor cells. This study provided a simple and effective personalized tumor vaccine strategy for better treatment of metastatic and recurrent tumors. The developed multifunctional tumor antigen trapping nanoparticles may be a promising nanoplatform for integrating multimodal imaging monitoring, tumor treatment, and tumor vaccine immunotherapy.
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Vacunas contra el Cáncer , Nanopartículas , Neoplasias Ováricas , Humanos , Femenino , Ratones , Animales , Fototerapia/métodos , Nanopartículas/uso terapéutico , Hidróxido de Aluminio , Línea Celular Tumoral , Verde de Indocianina , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/tratamiento farmacológico , Inmunoterapia , Antígenos de Neoplasias , Microambiente TumoralRESUMEN
Previous studies have reported that recombinant tumor necrosis factor (TNF)-α has powerful antiviral activity but severe systematic side effects. Jasminin is a common bioactive component found in Chinese herbal medicine beverage "Jasmine Tea". Here, we report that jasminin-induced endogenous TNF-α showed antiviral activity in vitro. The underlying TNF-α-inducing action of jasminin was also investigated in RAW264.7 cells. The level of endogenous TNF-α stimulated by jasminin was first analyzed by an enzyme-linked immunosorbent assay (ELISA) from the cell culture supernatant of RAW264.7 cells. The supernatants were then collected to investigate the potential antiviral effect against herpes simplex virus 1 (HSV-1). The antiviral effects of jasminin alone or its supernatants were evaluated by a plaque reduction assay. The potential activation of the PI3K-Akt pathway, three main mitogen-activated protein kinases (MAPKs), and nuclear factor (NF)-κB signaling pathways that induce TNF-α production were also investigated. Jasminin induces TNF-α protein expression in RAW264.7 cells without additional stimuli 10-fold more than the control. No significant up-expression of type I, II, and III interferons; interleukins 2 and 10; nor TNF-ß were observed by the jasminin stimuli. The supernatants, containing jasminin-induced-TNF-α, showed antiviral activity against HSV-1. The jasminin-stimulated cells caused the simultaneous activation of the Akt, MAPKs, and NF-κB signal pathways. Furthermore, the pretreatment of the cells with the Akt, MAPKs, and NF-κB inhibitors effectively suppressed jasminin-induced TNF-α production. Our research provides evidence that endogenous TNF-α can be used as a strategy to encounter viral infections. Additionally, the Akt, MAPKs, and NF-κB signaling pathways are involved in the TNF-α synthesis that induced by jasminin.
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Fosfatidilinositol 3-Quinasas , Factor de Necrosis Tumoral alfa , Antivirales/farmacología , Lipopolisacáridos/farmacología , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Oleandrigenin-3-O-ß-D-diginoside (a derivative of odoroside A), isolated and purified by our group, has seldom been explored for its pharmacological activity. This study aimed at clarifying the mechanisms towards the leukaemia-suppressive role of odoroside A (compound #1) and its derivative, oleandrigenin-3-O-ß-D-diginoside (compound #2) isolated from Nerium oleander. Viability and nuclear morphology change were assessed by CCK-8 assay and fluorescence microscope, respectively. Then, the cell apoptosis and autophagy induced by the compounds were detected by flow cytometry and Western blot. Xenograft model of nude mice was also applied to measure the leukaemia-suppressive effects of compound #2 in vivo. The result displayed that compound #1 and compound #2 inhibited the proliferation of HL60 and K562 cells and stronger effects were found in HL60 than K562 cells. Both of the compounds induced a dose-dependent apoptosis and autophagy in HL60 cells, where compound #2 was more potent than compound #1. Compound #2 also demonstrated a time-dependent apoptosis and autophagy in HL60 cells. Furthermore, ROS generation and JNK phosphorylation occurred in a dose-dependent manner in the cells treated with compound #2. Mitochondria also played critical role, proved by the decrease of Bcl-2, the release of cyto c to cytosol and the activation of caspase-3 and caspase-9. Moreover, the antitumour effects of compound #2 were validated in the nude mouse xenograft model in vivo. Odoroside A and its derivative inhibited the growth of leukaemia by inducing apoptosis and autophagy through the activation of ROS/JNK pathway. These results suggest that the compounds can serve as potential antitumour agents against leukaemia, especially acute myeloid leukaemia (AML).
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Antineoplásicos Fitogénicos/farmacología , Cardenólidos/farmacología , Leucemia/tratamiento farmacológico , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Cardenólidos/administración & dosificación , Cardenólidos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células HL-60 , Humanos , Células K562 , Leucemia/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nerium/química , Especies Reactivas de Oxígeno/metabolismo , Factores de Tiempo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Nigella glandulifera Freyn et Sint. (N. glandulifera) seeds are widely used in traditional Uyghur medicine for a variety of immuno-inflammatory diseases. The total saponins from N. glandulifera seeds (TSNGS) have been shown to have analgesic, antioxidant, and anti-inflammatory effects that can alleviate joint pain and swelling. AIM OF THE STUDY: Rheumatoid arthritis (RA) is a chronic and progressive, debilitating autoimmune disease for which current treatments are not sufficiently effective and result in unsatisfactory side effects. This study aimed to mechanistically investigate the therapeutic effects of TSNGS on RA. MATERIALS AND METHODS: Qualitative analysis of TSNGS was performed using ultra-high-performance liquid chromatography-Q-Orbitrap-high-resolution mass spectrometry. Rats with collagen-induced arthritis (CIA), IL-1ß-induced HFLS-RAs, and VEGF-induced HUVECs were analyzed to determine the efficacy and mechanism of TSNGS on RA. RESULTS: Twenty-one compounds were identified in TSNGS. TSNGS (10, 50, or 250 mg/kg) reduced the severity of arthritis, indicated by a lower arthritis score, reduced paw swelling, and body weight in rats with CIA. TSNGS ameliorated histopathological changes involving inflammatory infiltration, bone degeneration, and angiogenesis in knee and ankle joints. TSNGS improved the immuno-inflammatory response by restoring the levels of the cytokines IFN-γ, TNF-α, IL-1ß, IL-6, IL-17A, IL-4, and IL-10, and increasing the number of CD4+CD25+ Tregs in the peripheral circulation and Foxp3 levels in knee joints in rats with CIA. Furthermore, TSNGS increased the OPG/RANKL ratio and downregulated p-p65 in serum and joint synovia. Inhibition of angiogenesis by TSNGS was associated with recovery of the angiogenesis-related Ang/Tie-2 signaling pathway. CONCLUSIONS: It was established that TSNGS provides a therapeutic effect on RA by alleviating synovitis, bone degeneration, and angiogenesis via the OPG/RANKL/NF-κB and Ang/Tie-2 pathways and may be used for the treatment of RA.
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Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Nigella/química , Saponinas/farmacología , Angiopoyetinas/metabolismo , Animales , Antirreumáticos/administración & dosificación , Antirreumáticos/aislamiento & purificación , Antirreumáticos/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Masculino , FN-kappa B/metabolismo , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Ratas , Ratas Wistar , Receptor TIE-2/metabolismo , Saponinas/administración & dosificación , Saponinas/aislamiento & purificación , SemillasRESUMEN
The purpose of this study was to investigate the effect of sodium butyrate on slaughter performance, serum indexes and the intestinal barrier in rabbits. Six hundred healthy weaned rabbits were randomly divided into three groups (5 replicates per group, 40 rabbits per replicate): control (fed a basal diet), sodium butyrate (fed a basal diet containing 0.5% sodium butyrate) and antibiotic (fed a basal diet containing 0.004% antibiotic). The trial lasted 35 days, including 7 days of pretesting and 28 days of formal testing. The results showed that dietary sodium butyrate supplementation increased the full-bore weight, the half-bore weight and the half-bore rate of rabbits. Meanwhile, the content of aspartate aminotransferase (AST) in serum was increased in rabbits fed the sodium butyrate diet. According to the intestinal barrier, after adding sodium butyrate to feed, the tight junction function of the rabbit intestine is enhanced, and the intestinal microbial composition is also improved. To sum up, after sodium butyrate was added to feed instead of antibiotics, slaughter performance was significantly enhanced, serum indexes were improved, and intestinal barrier function was also enhanced. Therefore, sodium butyrate can be added to feed as an additive and can replace antibiotics.
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Alimentación Animal , Suplementos Dietéticos , Alimentación Animal/análisis , Animales , Ácido Butírico , Dieta/veterinaria , Intestinos , ConejosRESUMEN
The purpose of this study was to investigate the effects on growth of Lysine (Lys) supplementation in a low protein diet. We also investigated the gene or protein expression related to skeletal muscle development and intestinal amino acid transporters, and determined the major signalling associated with Lys-regulating skeletal muscle development. 1000 healthy, weights averaging 938.6 ± 6.54 g weaned rabbits were randomly divided into five groups (five replicates in each group and 40 rabbits in each replicate). These groups consisted of the normal protein group (NP group, consuming a diet containing 16.27% protein), the low protein group (LP group, 14.15%-14.19% protein) and the LP group with an addition of 0.15%, 0.3% or 0.45% Lys. The trial included 7 d of pre-feeding and 28 d of exposure to the treatment. Compared with NP diet and LP diet, LP+0.3% Lys group improved growth performance (p < 0.05), full-bore weight and half-bore weight of rabbits (p < 0.05). The LP+0.3% Lys group also resulted in a decrease in the excretion of faecal nitrogen and urinary nitrogen (FN; UN; p < 0.05), and an increase in nitrogen utilisation rate (NUR; p < 0.05). LP diet increased the mRNA expression of MSTN and WWP1, and decreased the mRNA expression of IGF1 (p < 0.05). LP diet decreased the protein expression of P-P70S6K1, P-4EBP1 and P-S6 (p < 0.05). LP+0.3% Lys group attenuated the effects of LP diet on the expression of MSTN, WWP1, IGF1, P-P70S6K1, P-4EBP1 and P-S6 (p < 0.05). LP+0.3% Lys group resulted in an increase in mRNA expression of MyoD and protein expression of P-mTOR relative to the NP and LP groups (p < 0.05). In summary, the addition of Lys to a LP diet provides a theoretical basis for the popularisation and application of Lys in rabbit production.
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Dieta con Restricción de Proteínas , Lisina , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Dieta con Restricción de Proteínas/veterinaria , Suplementos Dietéticos , Lisina/farmacología , Desarrollo de Músculos , Músculo Esquelético/metabolismo , Nitrógeno/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ConejosRESUMEN
Rheumatoid arthritis (RA) is a widespread inflammatory disease whose clinical manifestations are joint swelling, pain, and disability, affecting approximately 1% of individuals worldwide. Conventional anti-RA drugs currently used in clinic have severe side effects. The present study is aimed at investigating the antiarthritic effects of total saponins from Nigella glandulifera seeds (TSNGS) in rats with adjuvant-induced rheumatoid arthritis (AIA). Arthritis score, paw swelling, and body weight were monitored throughout the period of TSNGS treatment. The histopathological features and levels of cytokines, including IFN-γ, TNF-α, IL-1ß, IL-4, IL-6, IL-10, and IL-17A, and OPG/RANKL signaling, were measured to determine the amelioration by TSNGS and its potential mechanisms on the inflammatory response and bone erosion. The differentiation of regulatory T cells (Tregs) in serum was assessed by flow cytometry. The results demonstrate that TSNGS at 10 mg/kg, 50 mg/kg, and 250 mg/kg inhibited AIA-induced clinical score, paw swelling, and histological changes. TSNGS reduced the immune-inflammatory reaction by restoring the secretion and expression of inflammatory cytokines and elevating the proportion of CD4+ CD25+ Tregs, accompanied by an increase in transcription factor Foxp3 levels. TSNGS also displayed bone protection by upregulation of the OPG/RANKL pathway. Collectively, TSNGS inhibited arthritis in AIA rats and so represents a potential novel treatment for RA.
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Antiinflamatorios/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Inflamación/prevención & control , Osteogénesis/efectos de los fármacos , Saponinas/administración & dosificación , Animales , Artritis Experimental/complicaciones , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Artritis Experimental/patología , Artritis Reumatoide/complicaciones , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Regulación hacia Abajo , Femenino , Inflamación/etiología , Masculino , Nigella , Extractos Vegetales/administración & dosificación , Ratas Wistar , Saponinas/aislamiento & purificaciónRESUMEN
This experiment was conducted to investigate the effects of zinc oxide/zeolite on growth performance, serum biochemistry, intestinal morphology, and microflora of weaned piglets. Two hundred and fifty-six weaned piglets (Duroc × Landrace × Large) at 21 days of age were randomly assigned to 2 groups with 8 replicates and 16 piglets in each pen. The diets of high dose of zinc oxide group (HD-ZnO) supplemented with 1500 mg/kg zinc as zinc oxide, but the diet of experimental group supplemented with 500 mg/kg zinc as zinc oxide that supported on zeolite (SR-ZnO). The experiment was conducted for 2 weeks after weanling. The results showed replacement of high-dosed zinc oxide by SR-ZnO had no significant effects on growth performance and intestinal morphology. However, the dietary supplementation of SR-ZnO reduced the diarrhea rate (P < 0.05), increased the activity of serum alkaline phosphatase (ALP) (P < 0.01), and tended to reduce zinc release in stomach (P = 0.06) and increase serum total protein (TP) (P = 0.07). Although there were no significant effects in ileal microflora on α diversity, the abundance of Campylobacters was found significantly decreased (P < 0.05), whereas the abundance of Clostridium was increased (P < 0.05) after lower-dosed SR-ZnO replacement. It is revealed that replacement of HD-ZnO (1500 mg/kg) by SR-ZnO (500 mg/kg) in creep feed could improve the zinc bioavailability, regulate the intestinal flora, and alleviate the postweaning diarrhea in weaned piglets. Accordingly, the application of SR-ZnO would reduce the zinc in feed and therefore benefits for the ecological environment.
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Microbioma Gastrointestinal , Zeolitas , Óxido de Zinc , Animales , Diarrea/prevención & control , Diarrea/veterinaria , Suplementos Dietéticos , Porcinos , Destete , Zeolitas/farmacología , Óxido de Zinc/farmacologíaRESUMEN
Crocins, a series of hydrophilic carotenoids that are either mono- or di-glycosyl polyene esters of crocetin extracted from dried saffron stigma or fruits of gardenia, are attracting much attention due to their wide range of pharmacological effects. In our previous study, GJ-4, a mixture of crocin analogues, was obtained and derived from gardenia fruits. Mainly 18 crocin analogues were identified from GJ-4 and found to exhibit neuroprotective effects in in vitro and in vivo models. In this present study, we continue to investigate the therapeutic effects of GJ-4 on learning and memory impairments in a 2VO-induced VaD model, and the potential mechanism. In addition, the metabolic profiles and pharmacokinetic properties of GJ-4 were determined using liquid chromatography-electrospray ionization-mass spectrometry after single and multiple oral doses. All these findings presented here will serve as a solid basis to develop GJ-4 as a new therapeutic agent for dementia.
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Carotenoides/farmacocinética , Demencia/tratamiento farmacológico , Frutas/química , Gardenia/química , Nootrópicos/farmacocinética , Animales , Conducta Animal/efectos de los fármacos , Demencia/inducido químicamente , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos ICR , FitoterapiaRESUMEN
BACKGROUND: Apocynum venetum leaves are used as a kind of phytomedicine and the main ingredient in some traditional Chinese medicine products for the relief of colitis. To understand the bioactive constituents of A. venetum L., we did a phytochemistry study and investigated anti-Inflammatory effects of compounds and explored the underlying mechanisms. METHODS: We isolated compounds from ethanol extract of A. venetum L. leaf and detected the most effective compound by NO inhibition assay. We investigated anti-Inflammatory effects on dextran sulfate sodium (DSS)-induced colitis mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The disease activity index was determined by scores of body weight loss, diarrhea and rectal bleeding; histological damage was analyzed by H&E staining; macrophages change in the colon were analyzed by immunohistochemistry (IHC); myeloperoxidase activity was measured by myeloperoxidase assay kits; levels of proinflammatory cytokines were determined by qPCR and ELISA; protein production such as COX-2, iNOS, STAT3 and ERK1/2 were determined by western blotting. RESULTS: We isolated uvaol from ethanol extract of A. venetum L. leaf and found uvaol has excellent potential of inhibiting NO production. We further found uvaol could attenuate disease activity index (DAI), colon shortening, colon injury, and colonic myeloperoxidase activity in DSS-induced colitis mice. Moreover, uvaol significantly reduces mRNA expression and production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, and MCP-1) and infiltration of macrophages in colonic tissues of colitis mice. Studies on LPS challenged murine macrophage RAW246.7 cells also revealed that uvaol reduces mRNA expression and production of pro-inflammatory cytokines and mediators. Mechanically, uvaol inhibits the pro-inflammatory ERK/STAT3 axis in both inflamed colonic tissues and macrophages. CONCLUSIONS: A. venetum leaf contains uvaol and uvaol has potent anti-inflammatory effects on DSS-induced experimental colitis and LPS-stimulated RAW264.7 macrophage cells. These results suggest uvaol is a prospective anti-inflammatory agent for colonic inflammation.
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The purpose of this study was to investigate the effect of iodine supplementation during pregnancy on thyroid function and also its effect on postpartum depression in an iodine-sufficient area. Healthy pregnant women were divided into three groups: group A (vitamin iodine-150) receiving vitamin containing 150 µg iodine, group B (vitamin iodine-0) receiving vitamin without iodine, and group C (no vitamin) receiving no vitamin. General information was collected by questionnaire and thyroid function was determined in the third trimester of pregnancy. Depression was assessed 1 month postpartum by the Edinburgh postnatal depression scale (EPDS). The results showed that there was no significant difference in thyroid-stimulating hormone (TSH) level among the three groups (P > 0.05). FT4 concentration was significantly lower in group A (n = 234: 10.68 pmol/L) than in group B (n = 220: 11.47 pmol/L) and group C (n = 195: 11.64 pmol/L) (P < 0.05), However, it was still within the normal range. EPDS scores obtained from group B (3.50) and group C (3.00) were similar but markedly lower than group A (5.00) (P < 0.05). Despite the difference in the EPDS score, the prevalence of postpartum depression was not significantly different among the three groups. In conclusion, 150 µg/day iodine supplementation for pregnant women in areas with adequate iodine had little effect on thyroid function in the third trimester, and serum FT4 level could not be increased. Iodine supplementation during pregnancy also had no significant effect on postpartum depression.
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Depresión Posparto , Yodo , Depresión Posparto/tratamiento farmacológico , Depresión Posparto/epidemiología , Depresión Posparto/prevención & control , Suplementos Dietéticos , Femenino , Humanos , Embarazo , Pruebas de Función de la Tiroides , Glándula Tiroides , Tirotropina , Tiroxina , VitaminasRESUMEN
We examined the effects of shading photosynthetic characteristics, yield, and tolerance to low light in two potato varieties (Jizhangshu 12 and Jizhangshu 8) at four growth stages (seedling, seedling/budding, budding/early flowering and flowering/harvest). There were three shading treatments (0(CK), 20% and 50%). The results showed that at both 20% and 50% shading rates, the SPAD value (a measure of leaf cellular chlorophyll content) of the two varieties decreased significantly at the seedling stage compared with CK treatment. No significant change in the SPAD value occurred at the seedling/budding stage or the budding/early-flowering stage. However, the SPAD value increased marginally after shading at the initial flowering stage. Under the 50% shading regime, the SPAD values of both varieties followed the same trend as the 20% regime. The range of changes at different growth stages remained similar. The only exception was that shading at the beginning of flowering increased SPAD value. Shading had little effect on leaf stomatal conductance (gs) at each developmental stage. There was no significant difference between all treatments and the control, except that the gsvalue of Jizhangshu 8 decreased significantly (43.9%) compared with the control under 50% shading at the beginning of flowering. After the shading treatment, the intercellular CO2 concentration (Ci) of leaves showed an upward trend. 50% shading at the seedling and seedling/budding stages could significantly increase Ci, but not at other stages. The net photosynthetic rate (Pn) of the four periods were all decreased after 15 d of shading. The Pn reduction of the two varieties, 50% shading, was greater than 20% shading. The decline range of Pn of Jizhangshu 12 was less than that of Jizhangshu 8 at all stages, except for that at the seedling stage. The yield of shading treatments decreased in all four stages, with the decrease rate of 50% shading treatment being greater than that of the 20% shading treatment. 'Jizhangshu 12'was not tolerant to low light at the seedling stage but performed better than 'Jizhangshu 8' at other stages. The comprehensive analysis of two test varieties implied that varieties with strong tolerance to low light experienced a smaller boost in intercellular CO2 concentration and a smaller drop in net photosynthetic rate, stomatal conductance, and yield post-shading.
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Solanum tuberosum , Clorofila , Fotosíntesis , Hojas de la Planta , PlantonesRESUMEN
Gastric cancer stem cell (GCSC) is implicated in gastric cancer relapse, metastasis and drug resistance. However, the key molecule(s) involved in GCSC survival and the targeting drugs are poorly understood. We discovered increased secreted clusterin (S-Clu) protein expression during the sphere-forming growth of GCSC via mass spectrometry. Overexpression of clusterin was detected in 69/90 (77%) of primary GC tissues and significantly associated with T stage, lymph node metastasis and TNM stage. Depletion of clusterin (Clu, the full-length intracellular clusterin) led to the declustering of GCSC tumorspheres and apoptosis of GCSC. Subsequently, we found clusterin was in complex with heat shock protein 90 beta (HSP90) and involved in regulating the cellular level of HSP90 client proteins. Furthermore, by screening a collection of drugs/inhibitors, we found that verteporfin (VP), a phototherapy drug, blocked clusterin gene expression, decreased the HSP90 client proteins and caused cell death of GCSC. VP treatment is more effective in eradicating GCSCs than in killing GC cells. Both clusterin silencing or VP treatment deterred tumor growth in human GCSC xenografts. These findings collectively suggest that GC patients can promptly benefit from clusterin-targeted therapy as well as VP treatment in combination with or subsequent to conventional chemotherapy for reducing mortality of GC.
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Clusterina/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Verteporfina/farmacología , Verteporfina/uso terapéutico , Animales , Western Blotting , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Inmunoprecipitación , Espectrometría de Masas , Ratones , Ratones Endogámicos BALB C , Unión Proteica/efectos de los fármacos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To observe the curative effect of needling stimulation of the back segment (10 spots below the spinous processes from T 3 to T 12)of the Governor Vessel in the treatment of gastroesophageal reflux disease(GERD)accompanied with somnipathy. METHODS: A total of 58 patients of GERD accompanied with somnipathy were randomly divided into acupuncture group (nï¼28) and medication group (nï¼30)according to random number table method. For patients of the acupuncture group, the spots below the spinous processes from T 3 to T 12, including acupoints Shenzhu (GV 12), Shendao (GV 11), Lingtai (GV 10), Zhiyang (GV 9), Jinsuo (GV 8), Zhongshu (GV 7) and non-acupoints (T 4, T 8, T 12) were punctured with filiform needles, once every other day for 8 weeks. Patients of the medication group were ordered to take Omeprazole capsules (20 mg/time), twice a day for 8 weeks. The therapeutic effect was assessed by "Reflux Diagnostic Questionnaire" (RDQï¼scores of symptoms of heartburn, retrosternal pain, acid regurgitation and food regurgitation, 0ï¼40 points), GERD symptom scale (scores of symptoms of the digestive system, five-sense organs, cardiovascular system, etc., 0ï¼84 points) and Pittsburgh Sleep Quality Index (PSQI, scores of sleep quality, fall asleep time, sleep duration, sleep efficiency, etc., 0ï¼21 points), respectively. RESULTS: After the treatment, RDQ score, GERD symptom scale score and PSQI score were significantly decreased in both acupuncture and medication groups compared with their own pre-treatment(P<0.01), and the decreased scores of RDQ, GERD scale and PSQI were significantly lower in the acupuncture group than in the medication group (P<0.01). The cured plus markedly effective rates for RDQ in the two groups were 43.3% (13/30) and 71.4% (20/28), respectively, and the effective rates of the medication and acupuncture groups were 56.7% (17/30) and 89.3% (25/28) for GERD scale, and 60.0% (18/30) and 92.9% (26/28) for PSQI, respectively. The cured plus markedly effective rate for RDQ, and the effective rates for GERD scale and PSQI were signi-ficantly higher in the acupuncture group than in the medication group respectively (P<0.05ï¼P<0.01)ï¼. CONCLUSION: Acupuncture stimulation of acupoints of Governor Vessel at the back segment is effective in improving symptoms of GERD patients with somnipathy.
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Reflujo Gastroesofágico , Puntos de Acupuntura , Reflujo Gastroesofágico/terapia , Humanos , Resultado del TratamientoRESUMEN
The leaves of Juniperus sabina (Cupressaceae) are used in traditional Uygur medicine for the treatment of rheumatism and arthritic pain. This study aimed to investigate the analgesic and anti-inflammatory effects of total flavonoids from leaves of Juniperus sabina (JSTF) on rodents. The anti-inflammatory activity was investigated using the carrageenan, egg albumin, or histamine-induced rat paw edema as well as xylene-induced ear edema, capillary permeability, and cotton pellet granuloma while the antinociceptive activity was evaluated using the mouse writhing, formalin, and hot-plate tests. JSTF (125, 250, 500 mg/kg) significantly inhibited xylene-induced ear edema in mice (inhibition ratio as 16.22%, 40.67%, and 51.78%, respectively) and also significantly ameliorated acetic acid increased vascular permeability in mice (inhibition ratio as 11.63%, 32.56%, and 53.49%, respectively). JSTF (250 and 500 mg/kg) gave significant reduction of carrageenin-induced paw oedema at the interval of 1 h and 5 h. Administration of JSTF (500 mg/kg) caused a significant anti-inflammatory effect against oedema induced by egg albumin or histamine at the interval of 0.5 h and 4 h, and both which induced the paw oedema were also inhibited by JSTF (250 mg/kg) at a point in 1, 2, or 3 h after the inflammation. Furthermore, JSTF (125, 250, and 500 mg/kg) produced time-course increase in pain threshold in hot-plate test also. JSTF produced concentration-dependent inhibition on cyclooxygenase-2 (COX-2) or 5-lipoxygenase (5-LO) activities in vitro, and their IC50 values were 31.92 and 129.26 µg/mL, respectively. Moreover, JSTF significantly caused a significant dose-dependent inhibition on acetic acid induced writhing response in mice (inhibition ratio as 23.27%, 36.91%, and 50.76%, respectively). JSTF also significantly ameliorated formalin-induced pain in mice in the late phase on dose-dependent way. These results confirms the clinical use of J. sabina for treatment of rheumatoid arthritis in ethnomedicine, and its effective mechanism will be further studied in the future.
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Six new cardenolides (1-6), including three 14-hydroxylated cardenolides and three 14-carbonylated cardenolides were isolated from the dried aerial parts of Nerium oleander Linn in addition to twenty-seven known compounds (7-33). Their structures were elucidated on the basis of extensive spectroscopic evidences and single-crystal X-ray diffraction analysis. Compounds 1, 4, 7-10 and 13 exhibited significant cytotoxicity against four colon cancer cell lines (HCT116, HT29, SW620, RKO), one gastric cancer cell line (GT) and one cervical cancer cell line (HeLa) in vitro.