RESUMO
BACKGROUND: Sesame is a great reservoir of bioactive constituents and unique antioxidant components. It is widely used for its nutritional and medicinal value. The expanding demand for sesame seeds is putting pressure on sesame breeders to develop high-yielding varieties. A hybrid breeding strategy based on male sterility is one of the most effective ways to increase the crop yield. To date, little is known about the genes and mechanism underlying sesame male fertility. Therefore, studies are being conducted to identify and functionally characterize key candidate genes involved in sesame pollen development. Polyketide synthases (PKSs) are critical enzymes involved in the biosynthesis of sporopollenin, the primary component of pollen exine. Their in planta functions are being investigated for applications in crop breeding. RESULTS: In this study, we cloned the sesame POLYKETIDE SYNTHASE A (SiPKSA) and examined its function in male sterility. SiPKSA was specifically expressed in sesame flower buds, and its expression was significantly higher in sterile sesame anthers than in fertile anthers during the tetrad and microspore development stages. Furthermore, overexpression of SiPKSA in Arabidopsis caused male sterility in transgenic plants. Ultrastructural observation showed that the pollen grains of SiPKSA-overexpressing plants contained few cytoplasmic inclusions and exhibited an abnormal pollen wall structure, with a thicker exine layer compared to the wild type. In agreement with this, the expression of a set of sporopollenin biosynthesis-related genes and the contents of their fatty acids and phenolics were significantly altered in anthers of SiPKSA-overexpressing plants compared with wild type during anther development. CONCLUSION: These findings highlighted that overexpression of SiPKSA in Arabidopsis might cause male sterility through defective pollen wall formation. Moreover, they suggested that SiPKSA modulates vibrant pollen development via sporopollenin biosynthesis, and a defect in its regulation may induce male sterility. Therefore, genetic manipulation of SiPKSA might promote hybrid breeding in sesame and other crop species.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Sesamum , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Melhoramento Vegetal , Pólen , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Sesamum/genética , Sesamum/metabolismoRESUMO
Male gametogenesis is an important biological process critical for seed formation and successful breeding. Understanding the molecular mechanisms of male fertility might facilitate hybrid breeding and increase crop yields. Sesame anther development is largely unknown. Here, a sesame ß-ketoacyl-[acyl carrier protein] synthase I (SiKASI) was cloned and characterized as being involved in pollen and pollen wall development. Immunohistochemical analysis showed that the spatiotemporal expression of SiKASI protein was altered in sterile sesame anthers compared with fertile anthers. In addition, SiKASI overexpression in Arabidopsis caused male sterility. Cytological observations revealed defective microspore and pollen wall development in SiKASI-overexpressing plants. Aberrant lipid droplets were detected in the tapetal cells of SiKASI-overexpressing plants, and most of the microspores of transgenic plants contained few cytoplasmic inclusions, with irregular pollen wall components embedded on their surfaces. Moreover, the fatty acid metabolism and the expression of a sporopollenin biosynthesis-related gene set were altered in the anthers of SiKASI-overexpressing plants. Additionally, SiKASI interacted with an adenosine triphosphate (ATP)-binding cassette (ABC) transporter. Taken together, our findings suggested that SiKASI was crucial for fatty acid metabolism and might interact with ABCG18 for normal pollen fertility in Arabidopsis.
Assuntos
Arabidopsis , Fenômenos Biológicos , Sesamum , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase , Trifosfato de Adenosina , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Isoenzimas , Pólen/genéticaRESUMO
To investigate effects of α-asarone and ß-asarone on induced PC12 cell injury and related mechanisms. Aß toxic injury cell model was induced by Aß in PC12 cells. PC12 cells were divided into blank control group, model control group, α-asarone group (0.5, 1.0, ß-asarone group (6.3, 12.5, vasoactive intestinal peptide (VIP) group, and VIP antagonist control group. Cell survival rate was detected by CCK-8 kit; cell apoptosis rate was detected by flow cytometry. The levels of inflammatory cytokines interleukin (IL)-1, , tumor necrosis factor (TNF)-α, oxidation-related inducible nitric oxide synthase (iNOS), nitric oxide (NO), apoptosis factors caspase-3 and p53 were detected by ELISA method. The expressions of C-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) were detected by Western blotting. Compared with model control group, cell survival rates of group, ß-asarone group and VIP group increased; the cell apoptosis rate decreased; levels of apoptosis-related factors caspase-3, p53, inflammatory factors IL-1, TNF-α decreased; IL-10 level increased; levels of oxidization-related factors iNOS and NO decreased; the expression of JNK and p38MAPK protein decreased (all <0.05). After VIP antagonist intervention, the survival rate of ß-asarone group decreased; apoptosis rate increased; apoptosis related factors caspase-3, p53, inflammatory factors IL-1, TNF-α increased; IL-10 decreased; oxidation related factors iNOS and NO increased; the expression of JNK and p38MAPK protein increased (all <0.05); while there were no significant changes in these indicators of α-asarone group (all >0.05). α-asarone and ß-asarone have protective effects on PC12 cell injury induced by Aß. ß-asarone may inhibit inflammatory factors and oxidation-related factors through promoting VIP secretion, regulating JNK/MAPK pathway, and reducing PC12 cell apoptosis; however, the effect of α-asarone may be not related to VIP secretion.
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Derivados de Alilbenzenos , Anisóis , Animais , Anisóis/farmacologia , Apoptose , Células PC12 , RatosRESUMO
It has been shown that Acori tatarinowii rhizoma (ATR) extract can improve cognitive functions in Alzheimer Diseas (AD) patients or animal models. In this study, we have examined the activity of ATR in 3×Tg-AD model mice with different comprehensive behavioral tests like the Morris water maze and Y-maze test assay for behavior. Moreover, we performed LFB staining for myelin determination in the AD model mouse. By analyzing different pathways, we determined key proteins that are beneficial for ameliorating AD syndrome in the mouse. Periluminally, ATR treatment improved the learning and memory ability that was determined by comprehensive behavioral tests. Moreover, treatment reduces the p-Tau accumulation in the 3×Tg-AD mouse and the level of p-Tau accumulation was at per with the wildtype control mouse and improves the myelin lining in 3×Tg-AD mouse. In conclusion, our results indicate that ATR-treatment can improve the learning ability of AD model mice and the hyperphosphorylation of Tau protein was decreased. ATR can protect myelin lining from damage in AD syndrome.
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Doença de Alzheimer/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Bainha de Mielina/efeitos dos fármacos , Doença de Alzheimer/fisiopatologia , Animais , Modelos Animais de Doenças , Aprendizagem/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Transgênicos , Bainha de Mielina/patologia , Fosforilação , Rizoma , Proteínas tau/metabolismoRESUMO
This research assessed the gene expression patterns related to the synthesis of milk in yak, which is characterized by high fat and protein content but low yield. The yak (Bos grunniens) is one of the most crucial domestic animals in Tibetan life; however, the genetic and molecular factors underlying yak milk protein synthesis remain understudied. Yak mammary biopsies harvested during late-pregnancy (d -15) through the end of subsequent lactation (d 1, 15, 30, 60, 180, and 240) were used to evaluate gene expression via real-time quantitative PCR. The expression pattern of 41 genes encompassing multiple pathways integral to milk protein synthesis including insulin, mammalian target of rapamycin (mTOR), 5' AMP-activated protein kinase, Jak2-Stat5 signaling, and the expression of glucose and AA transporters was evaluated. Our results confirmed that most upregulated genes increased from d -15 and peaked at d 30 or 60 and then remained relatively highly expressed. Specifically, there was an increased expression of mTOR-related amino acid transporters (SLC1A5, SLC7A5, and SLC36A1), glucose transporters (SLC2A1, SLC2A3, and SLC2A8), Jak2-Stat5 pathway (ELF5), and insulin signaling pathway components (IRS1, PDPK1, and AKT1). For activation of proteins synthesis, MTOR was significantly increased only at d 1. Among inhibitors of mTOR signaling, TSC1 and PRKAA2 were significantly upregulated during lactation. The RPL23 was downregulated among ribosomal components. In conclusion, a critical role for AA and glucose transporters and insulin signaling through mTOR for regulation of yak milk protein synthesis was revealed in this study of the yak mammary gland.
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Bovinos/genética , Bovinos/metabolismo , Proteínas do Leite/biossíntese , Leite/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Feminino , Glucose/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/genética , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Lactação , Glândulas Mamárias Animais/metabolismo , Gravidez , Biossíntese de Proteínas , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , TranscriptomaRESUMO
This study was aimed to investigate the effect and mechanism of Zhenwu Tang on AVP-V2R-AQP2 pathway in NRK-52E cells in vitro. Forty eight male SD rats were randomly divided into eight groups with 6 animals in each group. Distilled water or 22.68 g·kg⻹·d⻹ Zhenwu Tang(calculated by raw drug dosage meter) was given by gavage. Blood samples were collected by cardiac punctureï¼ and the medicated serum was centrifuged from the blood by 3 000 r·min⻹. NRK-52E cells were treated with different medicated serum or dDAVP. The condition of cell proliferation was detected by RTCA. The distribution of V2R and AQP2 in cells were detected by immunofluorescence. The expression of V2Rï¼ PKA and AQP2 were detected by Western blot and AQP2 mRNA level was detected by real-time PCR. Results showed that the level of AQP2 mRNA(P<0.01) and protein expression of V2Rï¼ PKA and AQP2(P<0.05ï¼ P<0.01ï¼ P<0.05) of Z7d group which was treated with Zhenwu Tang medicated serum for 24 h were significantly higher than that of normal rat serum group. And the expression level of V2Rï¼ p-AQP2 and AQP2(P<0.01ï¼ P<0.05ï¼ P<0.01) of Z7d+dDAVP group were significantly increased comparing to normal rat serum group. The results indicate that the applying of Zhenwu Tang medicated serum could increase the expression level of V2Rï¼ PKA and AQP2 which exist in AVP-V2R-AQP2 pathway in NRK-52Eï¼ and there is synergistic effect between Zhenwu Tang medicated serum and dDAVP. So the pathway of AVP-V2R-AQP2 may be one of the mechanism for which Zhenwu Tang regulate balance of water transportation.
Assuntos
Aquaporina 2/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Receptores de Vasopressinas/metabolismo , Transdução de Sinais , Animais , Linhagem Celular , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Rim/citologia , Masculino , RNA Mensageiro , Ratos , Ratos Sprague-DawleyRESUMO
This study was aimed to investigate the protective effect and mechanism of ß-asarone on the animal model of Alzheimer's disease(AD) which was induced by intracerebroventricular injection of Aß1â42 combined cerebral ischemia. One hundred and five rats were randomly divided into seven groups including sham-operated group, AD model group, ß-asarone 10 mgâ¢kg⻹ group, ß-asarone 20 mgâ¢kg⻹ group, ß-asarone 30 mgâ¢kg⻹ group, donepezil group(0.75 mgâ¢kg⻹) and Ginkgo biloba extract group(24 mgâ¢kg⻹). Rats' learning and memory abilities, cerebric regional blood flow, pathological changes in hippocampal CA1 region, the expression level of HIF-1α and serum CAT, SOD and MDA level were detected 4 weeks later. The results showed that the application of intracerebroventricular injection of Aß1â42 joint 2-VO could lead to rats' dysfunction of learning and memory, decrease in regional cerebral blood flow. Neurons in CA1 region were arranged in disorder, and amyloid deposition was increased. The number of cerebral cortical cells expressing HIF-1α was increased as well. The level of serum CAT and SOD decreased, while level of serum MDA increased. However these symptoms were improved by 20 mgâ¢kg⻹ and 30 mgâ¢kg⻹ ß-asarone. The results indicated that ß-asarone could effectively relieve the symptoms of the AD model induced by intracerebroventricular injection of Aß1â42 combined cerebral ischemia, and the potential mechanism might be that it could attenuate damage of MDA to the body by improving the level of CAT and SOD, meanwhile the level of HIF-1α decreased as the decline of hyperoxide which might attenuate its damage to neuron, so it finally achieved alleviating Alzheimer's disease.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Anisóis/farmacologia , Derivados de Alilbenzenos , Peptídeos beta-Amiloides , Animais , Catalase/análise , Modelos Animais de Doenças , Malondialdeído/análise , Estresse Oxidativo , Fragmentos de Peptídeos , Ratos , Superóxido Dismutase/análiseRESUMO
The present study aimed to evaluate the pathogenesis of type 2 diabetes mellitus (T2DM) and the anti-diabetic effect of berberine in Zucker diabetic fatty (ZDF) rats. A urinary metabolomics analysis was performed with ultra-performance liquid chromatography/electrospray ionization synapt high-definition mass spectrometry. Pattern recognition approaches were integrated to discover differentiating metabolites. We identified 29 ions (13 in negative mode and 16 in positive mode) as 'differentiating metabolites' with this metabolomic approach. A functional pathway analysis revealed that the alterations were mainly associated with glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions and sphingolipid metabolism. These results indicated that the dysfunctions of glycometabolism and lipometabolism are involved in the pathological process of T2DM. Berberine could decrease the serum levels of glycosylated hemoglobin, total cholesterol and triglyceride and increase the secretion of insulin. The urinary metabolomics analysis showed that berberine could reduce the concentrations of citric acid, tetrahydrocortisol, ribothymidine and sphinganine to a near-normal state. These results suggested that the anti-diabetic effect of berberine occurred mainly via its regulation of glycometabolism and lipometabolism and activation of adenosine 5'-monophosphate-activated protein kinase. Our work not only provides a better understanding of the anti-diabetic effect of berberine in ZDF rats but also supplies a useful database for further study in humans and for investigating the pharmacological actions of drugs. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Berberina/química , Berberina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Metabolômica/métodos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Masculino , Ratos , Ratos ZuckerRESUMO
Type 2 diabetes mellitus (T2DM) is a high incidence metabolic disease. Glimepiride, metformin, and their combination are the most commonly used therapeutics for T2DM in the clinic, but little is known about the metabolic responses of these therapies. In this study, ultrahigh-pressure liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC/ESI-QTOF-MS)-based metabolomics was applied to detect changes in the urinary metabolomic profile of Zucker diabetic fatty (ZDF) rats in response to these treatments. Additionally, standard biochemical parameters (e.g., fasting plasma glucose, glycosylated hemoglobin, oral glucose tolerance, urinary glucose, triglyceride, total cholesterol, and insulin) and liver histopathology were monitored and observed. Six metabolites, including 3-galactosyl lactose, citric acid, sphingosine, phytosphingosine, ribothymidine, and succinoadenosine, were found significantly reverted to the normal level after these therapies. The present study is the first to present citric acid and sphinganine as the potential markers of T2DM, which could be used as indicators to observe the anti-diabetic effects of glimepiride, metformin, and their combination treatments.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Metaboloma , Metformina/farmacologia , Compostos de Sulfonilureia/farmacologia , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/urina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/urina , Quimioterapia Combinada , Metabolômica/métodos , Ratos , Ratos ZuckerRESUMO
This study was aimed to investigate the protective effect and mechanism of ß-asarone on PC12 cells injury induced byAß1â42 activated astrocytes, and provide experimental basis for ß-asarone application in the prevention and control of Alzheimer's disease (AD). Firstly, RA-h and PC12 cells were co-cultured in the special transwell chamber, and the Real time cell analysis (RTCA) system was used to real-time observe its effect on PC12 cells survival rate in the co-culture system after astrocytes injury induced by Aß1â42. The best intervention time of ß-asarone was selected according to the survival curve and parameters generated automatically. ß-asarone with different concentrations was used for intervention on astrocytes, then the changes of PC12 cells survival rate in the co-culture system were observed. Secondly, MTT assay was used to detect the effect of Aß1â42 on PC12 cells survival rate as well as the intervention effect of ß-asarone, and verify the testing results of RTCA. The levels of IL-1ß, TNF-α and BDNF in culture media of the lower chamber were detected by ELISA. The NF-κB activity and phosphorylation levels of ERK, p38 and JNK were detected by Western blot. Results showed that ß-asarone (55.5 mgâ¢L⻹) could significantly slowdown the decline of PC12 cells survival rate caused by Aß1â42-induced RA-h activation (P<0.01), significantly reduce the levels of IL-1ß, TNF-α and the phosphorylation levels of ERK, p38 and JNK in culture media of the lower chamber (P<0.01). ß-asarone(166.7 mgâ¢L⻹) could promote the release of BDNF in culture media of the lower chamber(P<0.05). These results indicated that Aß1â42 could induce RA-h activation and its release of IL-1ß, TNF-α and other inflammatory factors to aggravate the PC12 cells injury; ß-asarone could reduce the levels of IL-1ß, TNF-α, promote the release of BDNF, and inhibit the NF-κB activity as well as phosphorylation levels of ERK, p38 and JNK protein in PC12 cells.
Assuntos
Anisóis/farmacologia , Fármacos Neuroprotetores/farmacologia , Derivados de Alilbenzenos , Peptídeos beta-Amiloides , Animais , Interleucina-1beta/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Células PC12 , Fragmentos de Peptídeos , Ratos , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
INTRODUCTION: Shenqi pill (SQP) can be used to treat various kidney related diseases, but its exact mechanism of action remains unclear. We intended to analyze the role and mechanism of SQP on renal interstitial fibrosis (RIF). METHODS: After performing unilateral ureteral obstruction (UUO) surgery following the Institutional Animal Care and Use Committee guidelines, all rats were assigned into the sham group, UUO group, UUO + SQP 1.5 g/kg, UUO + SQP 3 g/kg, and UUO + SQP 6 g/kg groups. After treatment with SQP for 4 weeks, the appearance of kidney, serum creatinine (SCr), and blood urea nitrogen (BUN) levels were monitored in each group. The pathological injury, extracellular matrix (ECM), and Notch1 pathway-related protein levels were measured using H&E staining, Masson staining, immunohistochemistry, and Western blot, respectively. RESULTS: SQP could obviously ameliorate the appearance of the kidney as well as the levels of SCr and BUN in UUO rats (SCr: 67.6 ± 4.64 µM, 59.66 ± 4.96 µM, 48.76 ± 4.44 µM, 40.43 ± 3.02 µM for UUO, low, medium, and high SQP treatment groups; BUN: 9.09 ± 0.97 mM, 7.72 ± 0.61 mM, 5.42 ± 0.42 mM, 4.24 ± 0.34 mM for UUO, low, medium, and high SQP treatment groups; P < .05). SQP also effectively mitigated renal tissue injury in UUO rats (P < .05). Moreover, we uncovered that SQP significantly inhibited Collagen I, α-SMA, Collagen IV, TGF-B1, Notch1, and Jag1 protein expressions in UUO rats kidney (P < .05). CONCLUSION: Our data elucidated that SQP can alleviate RIF, and the mechanism may be related to the Notch1/Jag1 pathway. DOI: 10.52547/ijkd.7703.
Assuntos
Nitrogênio da Ureia Sanguínea , Medicamentos de Ervas Chinesas , Fibrose , Proteína Jagged-1 , Rim , Ratos Sprague-Dawley , Receptor Notch1 , Transdução de Sinais , Obstrução Ureteral , Animais , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Receptor Notch1/metabolismo , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/complicações , Obstrução Ureteral/patologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Proteína Jagged-1/metabolismo , Modelos Animais de Doenças , Nefropatias/patologia , Nefropatias/tratamento farmacológico , Nefropatias/prevenção & controle , Nefropatias/metabolismo , Creatinina/sangue , Fator de Crescimento Transformador beta1/metabolismo , Actinas/metabolismoRESUMO
INTRODUCTION: One of the most significant clinical features of chronic kidney disease is renal interstitial fibrosis (RIF). This study aimed to investigate the role and mechanism of Shenqi Pill (SQP) on RIF. METHODS: RIF model was established by conducting unilateral ureteral obstruction (UUO) surgery on rat or stimulating human kidney-2 (HK-2) cell with transforming growth factor ß1 (TGFß1). After modeling, the rats in the SQP low dose group (SQP-L), SQP middle dose group (SQP-M) and SQP high dose group (SQP-H) were treated with SQP at 1.5, 3 or 6 g/kg/d, and the cells in the TGFß1+SQP-L/M/H were treated with 2.5%, 5%, 10% SQP-containing serum. In in vivo assays, serum creatinine (SCr) and blood urea nitrogen (BUN) content were measured, kidney histopathology was evaluated., and α-smooth muscle actin (α-SMA) expression was detected by immunohistochemistry. Interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) content, inhibitor of kappa B alpha (IKBα) and P65 phosphorylation were assessed. Meanwhile, cell viability, inflammatory cytokines content, α-SMA expression, IKBα and P65 phosphorylation were detected in vitro experiment. Results. SQP exhibited reno-protective effect by decreasing SCr and BUN content, improving renal interstitial damage, blunting fibronectin (FN) and α-SMA expression in RIF rats. Similarly, after the treatment with SQP-containing serum, viability and α-SMA expression were remarkably decreased in TGFß1-stimulated HK-2 cell. Furthermore, SQP markedly down-regulated IL-1ß, IL-6, and TNF-α content, IKBα and RelA (P65) phosphorylation both in vivo and in vitro. Conclusion. SQP has a reno-protective effect against RIF in vivo and in vitro, and the effect is partly linked to nuclear factor-kappa B (NF-κB) pathway related inflammatory response, which indicates that SQP may be a candidate drug for RIF. DOI: 10.52547/ijkd.7546.
Assuntos
Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Fibrose , Rim , NF-kappa B , Animais , Humanos , Ratos , Actinas/metabolismo , Nitrogênio da Ureia Sanguínea , Linhagem Celular , Creatinina/sangue , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Fibrose/tratamento farmacológico , Fibrose/metabolismo , Fibrose/patologia , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Ratos Sprague-Dawley , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/tratamento farmacológico , Fator de Crescimento Transformador beta1/metabolismo , Obstrução Ureteral/patologia , Obstrução Ureteral/complicações , Obstrução Ureteral/tratamento farmacológicoRESUMO
Background and Aim: Previous studies of our research group have shown that Chuanxiong Renshen Decoction (CRD) has the effect of treating AD, but the exact mechanism of its effect is still not clarified. The aim of this study was to investigate the effect and mechanism of CRD on AD neuroinflammation. Materials and Methods: Morris Water Maze (MWM) tests were employed to assess the memory and learning capacity of AD mice. HE and Nissl staining were used to observe the neural cells of mice. The expression of Iba-1 and CD86 were detected by immunohistochemical staining. Utilize UHPLC-MS/MS metabolomics techniques and the KEGG to analyze the metabolic pathways of CRD against AD. Lipopolysaccharide (LPS) induced BV2 microglia cells to construct a neuroinflammatory model. The expression of Iba-1 and CD86 were detected by immunofluorescence and flow cytometry. The contents of TNF-α and IL-1ß were detected by ELISA. Western blot assay was used to detect the expression of PPARγ, p-NF-κB p65, NF-κB p65 proteins and inflammatory cytokines iNOS and COX-2 in PPARγ/NF-κB pathway with and without PPARγ inhibitor GW9662. Results: CRD ameliorated the learning and memory ability of 3×Tg-AD mice, repaired the damaged nerve cells in the hippocampus, reduced the area of Iba-1 and CD86 positive areas in both the hippocampus and cortex regions, as well as attenuated serum levels of IL-1ß and TNF-α in mice. CRD-containing serum significantly decreased the expression level of Iba-1, significantly reduced the levels of TNF-α and IL-1ß, significantly increased the protein expression of PPARγ, and significantly decreased the proteins expression of iNOS, COX-2 and p-NF-κB p65 in BV2 microglia cells. After addition of PPARγ inhibitor GW9662, the inhibitory effect of CRD-containing serum on NF-κB activation was significantly weakened. Conclusion: CRD can activate PPARγ, regulating PPARγ/NF-κB signaling pathway, inhibiting microglia over-activation and reducing AD neuroinflammation.
Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , NF-kappa B , PPAR gama , Animais , PPAR gama/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Masculino , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Transdução de Sinais/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a DrogaRESUMO
Male sterile lines are key resources for hybrid seed production and for ensuring high varietal purity. However, the genes and mechanisms underlying sesame male sterility remain largely unknown. Hence, this study identified an O-acetylserine(thiol)lyase gene SiOASTL1 and functionally characterized its roles in inducing defective anther development. Spatiotemporal expression analysis revealed that SiOASTL1 is significantly (2.7 fold) up-regulated in sterile sesame anthers at the microspore stage compared with fertile ones. Sequence and phylogenetic analyses showed that SiOASTL1 is homologous to Arabidopsis OAS-TL plastid isoforms. We thus overexpressed SiOASTL1 in Arabidopsis to unravel its regulatory roles. Cytological observation revealed that SiOASTL1 overexpression transformed transgenic plants into male sterile lines arising at the microspore development stage. SiOASTL1 overexpression decreased cysteine biosynthesis and down-regulated the expression of the sporopollenin synthesis-related genes, including AtTKPR1, AtTKPR2, AtPKSA, and AtPKSB in transgenic Arabidopsis. Consequently, the tapetum programmed cell death (PCD) was delayed, resulting in the formation of defective pollen grains with irregular walls and empty cytoplasm. Our findings prove that the induction of SiOASTL1 expression disrupts pollen development and contributes to sesame male sterility. Moreover, these results suggest that genetic manipulation of SiOASTL1 expression may facilitate the development of new hybrid varieties in sesame and other crops.
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Protection of the structural and functional integrity of the blood-brain barrier (BBB) is crucial for treating ischemic stroke (IS). Hydroxysafflor yellow A (HSYA) and quercetin (Quer), two main active components in the edible and medicinal plant Carthamus tinctorius L., have been reported to exhibit neuroprotective effects. We investigated the anti-IS and BBB-protective properties of HSYA and Quer and the underlying mechanisms. They decreased neurological deficits in middle cerebral artery occlusion (MCAO) mice, while their combination showed better effects. Importantly, HSYA and Quer ameliorated BBB permeability. Their effects on reduction of both EB leakage and infarct volume were similar, which may contribute to improved locomotor activities. Moreover, HSYA and Quer showed protective effects for hCMEC/D3 monolayer against oxygen-glucose deprivation. Src, p-Src, MMP-9, and P-gp were associated with ingredients treatments. Furthermore, molecular docking and molecular dynamics simulations revealed stable and tight binding modes of ingredients with Src and P-gp. The current study supports the potential role of HSYA, Quer, and their combination in the treatment of IS by regulating BBB integrity.
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BACKGROUND: Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. ß-Asarone, which has significant pharmacological effects on the central nervous system (CNS), was used in the prevention of cerebral ischemia in this paper. METHODS: The right middle cerebral artery occlusion model was used in the study. The effects of ß-Asarone on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Naâº-Kâº-ATPase activity and glutathione S transferase activity in a rat model were studied respectively. RESULTS: ß-Asarone significantly improved the neurological outcome after cerebral ischemia and reperfusion in terms of neurobehavioral function in rats. Meanwhile, supplementation of ß-Asarone significantly boosted the defense mechanism against cerebral ischemia via increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may help the brain recover from ischemic injury. CONCLUSIONS: These experimental results suggest that complement ß-Asarone is protective against cerebral ischemia in specific way. The administration of ß-Asarone could reduce focal cerebral ischemic/reperfusion injury. The Mechanism of ß-Asarone in protection of cerebral ischemia was via increasing antioxidants activity related to lesion pathogenesis.
Assuntos
Acorus/química , Anisóis/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Derivados de Alilbenzenos , Análise de Variância , Animais , Anisóis/química , Comportamento Animal/efeitos dos fármacos , Força da Mão , Masculino , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Ratos , Ratos WistarRESUMO
Objective: Shen Qi Wan (SQW) is the most classic prescription for the clinical therapy of chronic kidney disease in China. Nevertheless, the function of SQW in renal interstitial fibrosis (RIF) has not been clearly clarified. Our purpose was to explore the protective function of SQW on RIF. Methods: After intervention with SQW-containing serum alone at increasing concentrations (2.5, 5, and 10%) or in combination with siNotch1, the transforming growth factor-beta (TGF-ß)-induced HK-2 cell viability, extracellular matrix (ECM)-, epithelial-mesenchymal transition (EMT), and Notch1 pathway-associated protein expressions were assessed by cell counting kit-8, qRT-PCR, western blot, and immunofluorescence assays. Results: SQW-containing serum intensified the viability of TGF-ß-mediated HK-2 cells. Besides, it augmented the collagen II and E-cadherin levels, and weakened the fibronectin, α-SMA, vimentin, N-cadherin, and collagen I levels in HK-2 cells triggered by TGF-ß. Moreover, it is found that TGF-ß led to the upregulation of Notch1, Jag1, HEY1, HES1, and TGF-ß in HK-2 cells, which was partially offset by SQW-containing serum. Furthermore, cotreatment of SQW-containing serum and Notch1 knockdown further apparently alleviated the Notch1, vimentin, N-cadherin, collagen I, and fibronectin levels in HK-2 cells induced by TGF-ß. Conclusion: Collectively, these findings elucidated that SQW-containing serum attenuated RIF via restraining EMT through the repression of the Notch1 pathway.
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BACKGROUND: Shi chang pu (Acorus tatarinowii Schott) is a herbal used in the treatment of Alzheimer's disease (AD) in China. The essential oil of Shi chang pu (SCP-oil) is the main active component. However, its effects on the neuroinflammation of AD have not been well studied. PURPOSE: Neuroinflammation mediated by the NLRP3 inflammasome plays a crucial role in AD. This study was designed to evaluate the effect of SCP-oil on cognitive impairment of AppSwe/PSEN1M146V/MAPTP301L triple transgenic (3 × Tg-AD) mice model and investigate the mechanism underlying its anti-inflammation effects. METHODS: Thirty-two 3 × Tg-AD mice at 12 months and 8 wild-type B6 mice were used for this experiment. The 3 × Tg-AD mice were administered with SCP-oil or donepezil hydrochloride for 8 weeks. Morris water maze test and step-down test were used to evaluate the cognitive ability of mice. The pathological changes, neuroinflammation, and the NLRP3 inflammasome related-protein of AD mice were detected by histomorphological examination, TUNEL staining, immunofluorescence, immunohistochemistry, qRT-PCR, Elisa, and western blot assays. RESULTS: SCP-oil treatment attenuated cognitive dysfunction of 3 × Tg-AD mice. Moreover, SCP-oil also ameliorated characteristics pathological of AD, such as pathological changes damage, deposition of Aß, phosphorylation of Tau, and neuronal loss. Additionally, SCP-oil treatment alleviated the neuroinflammation and inhibited phosphorylation of IKKß, NF-κB, and NLRP3 inflammasome related-protein NLRP3, ASC, Caspase-1, cleaved-Caspase-1, and GSDMD-N in the hippocampus of 3 × Tg-AD mice. CONCLUSION: Overall, SCP-oil contributed to neuroprotection in 3 × Tg-AD mice by reduced activation of NLRP3 inflammasome by inhibiting the NF-κB signaling pathway.
Assuntos
Acorus , Doença de Alzheimer , Óleos Voláteis , Camundongos , Animais , Inflamassomos/metabolismo , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , NF-kappa B/metabolismo , Doenças Neuroinflamatórias , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Caspase 1/metabolismoRESUMO
Sesame (Sesamum indicum L.) is an ancient and globally important oil crop in the tropic and subtropic areas. Apart from being a good source of high-quality oil, sesame also represents a new source of edible leafy vegetables. However, data regarding the nutritional composition of the sesame leaves, especially their phytonutrient composition, are scarce. Previously we have developed a sesame mutant JQA with curly, wide, and thick leaves that are potentially used as a vegetable. The objective of this work was to gauge the nutrient contents in leaves of the JQA mutant by colorimetry methods. The sesame mutant JQA and its wild-type counterpart JQB were grown in the field, and leaf samples were collected at the flowering stage. Results showed that the sesame wrinkled leaves of JQA are a rich source of crude oil (5.33-6.38%), crude protein (3.14%), amino acids (> 18.6 mg/g), crude fiber (> 0.36%), cellulose or hemicellulose (> 21.4 mg/g), sugars (> 12.5 mg/g), vitamins, and flavones (> 63.2 mg/g). The wrinkled sesame leaves were high in unsaturated acid (32.0 mg/g), calcium (18.5 mg/g), potassium (16.1 mg/g), as well as vitamin B6 (24.5 mg/g), B2 (14.4 mg/g), C (1.7 mg/g) and D (1.3 mg/g) compared to other common green leafy vegetables. The fresh leaves had a mean total flavone content of 65.7 mg/g and can be consumed as fresh vegetables or preserved in a dry state. Collectively, the nutritional composition of the wrinkled leaf mutant JQA was ideal and thus had high RDIs (recommended daily intakes), suggesting that the wrinkled leaves are a rich source of nutrients and therefore suitable to be consumed as a new edible green vegetable.
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Sesamum , Sesamum/metabolismo , Verduras/genética , Folhas de Planta/genética , Folhas de Planta/metabolismo , NutrientesRESUMO
AIM: Growing evidence indicates that the glutamatergic system, especially the abnormalities of glutamate and N-methyl-D-aspartate (NMDA) receptors contribute to the pathophysiology and possibly the pathogenesis of major depressive disorders. This study is to evaluate the effect of gan mai da zao (GMDZ) decoction on glutamate and NMDA receptor in unpredictable chronic mild stress (UCMS) rats. MATERIALS AND METHODS: Sucrose preference test and open field test were used to estimate the depressive-like behaviors of UCMS rats. Glutamate levels and NMDA receptor subunits (NR1, NR2A and NR2B) in the frontal cortex and hippocampus were determined by HPLC-FLD and by western-blot respectively. RESULTS: 32 days UCMS induced depressive-like behaviors, increased glutamate concentration and decreased NMDA receptor subunits NR2A and NR2B in the frontal cortex and hippocampus of rats. However, NR1 expression remained constant in stressed rats compared with normal. The GMDZ decoction alleviated the depressive-like behavior, decreased glutamate level, and increased expression of NMDA receptor subunit NR2A and NR2B in the frontal cortex and hippocampus of stressed rats. CONCLUSIONS: These results suggest that GMDZ treatment reversed chronic unpredictable stress-induced depressive-like behaviors in UCMS rats, possibly via reducing glutamate levels and increasing the NMDA receptor subunits NR2A and NR2B in frontal cortex and hippocampus.