RESUMEN
The Ziziphus genus, belonging to the Rhamnaceae family, holds significant economic, nutritional, and medicinal value. However, much remains to be discovered about its diversity and physical characteristics. Factors such as growth, resilience to changes, disease resistance, and unique features contribute to the quality of Ziziphus species. This study aims to investigate the genomes of 200 genotypes from five Ziziphus species: Ziziphus jujuba (Zj), Ziziphus nummularia (Zm), Ziziphus oxyphylla (Zx), Ziziphus mauritiana (Zm), and the cultivated variety Ziziphus jujube var. jujube, collected from Pakistan and China. Our goal is to identify single nucleotide polymorphisms (SNPs) associated with eight different traits and understand the genetic diversity within the selected Ziziphus species and their genotypes. Using high-quality SNPs obtained through genotype-by-sequencing (GBS), we conducted population structure, phylogenetic, and principal coordinates analyses, identifying a total of 10,945 clean SNPs. These genotypes were categorized into two groups, A and B. Natural Ziziphus variants in Pakistan, specifically Z. jujuba and Z. nummularia, exhibited high levels of genetic diversity and polymorphic information content (PIC) of 0.46 and 0.41, respectively, compared to other species. Furthermore, we identified 15 influential candidate genes that play crucial roles in regulating agronomic traits, such as fruit width and diameter, leaf width, plant height, and stem diameter within this group. This study provides valuable insights that can be utilized in Ziziphus breeding efforts.
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Genotipo , Polimorfismo de Nucleótido Simple , Ziziphus , Ziziphus/genética , Ziziphus/fisiología , Polimorfismo de Nucleótido Simple/genética , Filogenia , Pakistán , Fenotipo , Genoma de Planta/genética , ChinaRESUMEN
Background and Objectives: Rivaroxaban is a direct-acting anticoagulant used to prevent stroke in patients with atrial fibrillation. Rivaroxaban is a substrate for P-glycoprotein, which is encoded by the ABCB1 gene. Rivaroxaban is also metabolized by the CYP3A5 gene. Therefore, the current study is carried out to study the effects of polymorphisms in the ABCB1 and CYP3A5 genes, which may affect the plasma levels of rivaroxaban, with subsequent clinical outcomes (bleeding events) associated with the therapy. Materials and Methods: The study was conducted on 66 naive patients with atrial fibrillation treated with rivaroxaban. Blood samples of rivaroxaban were taken at 3 h and after 1 month following the administration of the drug to measure plasma levels. The blood level of rivaroxaban was measured with an HPLC-UV detector. Sanger sequencing was used to find polymorphisms in the targeted genes. Coagulation parameters were measured at 3 h and after 1 month of administration of rivaroxaban. Frequencies of bleeding events were recorded throughout the one-month course of drug therapy. Results: The heterozygous and homozygous mutant genotypes of ABCB1 (rs2032582, rs1045642, rs1128503, and rs4148738) and CYP3A5 (rs776746) showed lower plasma concentrations as compared to the wild-type genotype. ABCB1 (rs2032582, rs1045642, rs1128503, and rs4148738) and CYP3A5 (rs776746) gene polymorphisms had a statistically significant impact on the plasma concentration of rivaroxaban among the heterozygous and homozygous mutant genotypes compared to the wild-type genotype. The heterozygous variant of ABCB1 and homozygous variant of CYP3A5 suffered more events of bleeding. Conclusions: It was concluded that ABCB1 (rs2032582, rs1045642, rs1128503, and rs4148738) and CYP3A5 (rs776746) gene polymorphisms had a significant impact on the plasma levels of rivaroxaban in patients treated for atrial fibrillation on day three as well as after one month of the therapy. The lowest plasma levels were observed in patients with a homozygous variant of ABCB1 (rs2032582, rs1045642, or rs4148738) along with the CYP3A5*1/*3 allele. The heterozygous variant of ABCB1 SNPs and homozygous variant of CYP3A5 SNPs suffered more events of bleeding.
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Subfamilia B de Transportador de Casetes de Unión a ATP , Fibrilación Atrial , Citocromo P-450 CYP3A , Hemorragia , Rivaroxabán , Humanos , Rivaroxabán/uso terapéutico , Rivaroxabán/farmacocinética , Rivaroxabán/efectos adversos , Rivaroxabán/sangre , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/genética , Fibrilación Atrial/complicaciones , Masculino , Femenino , Hemorragia/inducido químicamente , Persona de Mediana Edad , Anciano , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Estudios Longitudinales , Citocromo P-450 CYP3A/genética , Relación Normalizada Internacional , Estudios de Seguimiento , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/farmacocinética , Inhibidores del Factor Xa/sangre , Genotipo , Polimorfismo Genético , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/farmacocinéticaRESUMEN
Peanut (Arachis hypogaea L.) is an important food and feed crop worldwide and is affected by various biotic and abiotic stresses. The cellular ATP levels decrease significantly during stress as ATP molecules move to extracellular spaces, resulting in increased ROS production and cell apoptosis. Apyrases (APYs) are the nucleoside phosphatase (NPTs) superfamily members and play an important role in regulating cellular ATP levels under stress. We identified 17 APY homologs in A. hypogaea (AhAPYs), and their phylogenetic relationships, conserved motifs, putative miRNAs targeting different AhAPYs, cis-regulatory elements, etc., were studied in detail. The transcriptome expression data were used to observe the expression patterns in different tissues and under stress conditions. We found that the AhAPY2-1 gene showed abundant expression in the pericarp. As the pericarp is a key defense organ against environmental stress and promoters are the key elements regulating gene expression, we functionally characterized the AhAPY2-1 promoter for its possible use in future breeding programs. The functional characterization of AhAPY2-1P in transgenic Arabidopsis plants showed that it effectively regulated GUS gene expression in the pericarp. GUS expression was also detected in flowers of transgenic Arabidopsis plants. Overall, these results strongly suggest that APYs are an important future research subject for peanut and other crops, and AhPAY2-1P can be used to drive the resistance-related genes in a pericarp-specific manner to enhance the defensive abilities of the pericarp.
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Arabidopsis , Fabaceae , Arachis/genética , Apirasa/genética , Filogenia , Arabidopsis/genética , Fitomejoramiento , Fabaceae/genética , Plantas Modificadas Genéticamente , Adenosina Trifosfato , Regulación de la Expresión Génica de las PlantasRESUMEN
Background and Objectives: We have recently reported that Fluvastatin, Atorvastatin, Simvastatin and Rosuvastatin have calcium channel antagonistic activities using rabbits' intestinal preparations. The current study is focused on the effects of Pitavastatin and Lovastatin for possible inhibition of vascular L-Type calcium channels, which may have vasorelaxant effect(s). Combined effects of Pitavastatin and Lovastatin in the presence of Amlodipine were also tested for vasorelaxation. Materials and Methods: Possible relaxing effects of Pitavastatin and Lovastatin on 80 mM Potassium chloride (KCL)-induced contractions and on 1 µM norepinephrine (N.E)-induced contractions were studied in isolated rabbit's aortic strips preparations. Relaxing effects on 80 mM KCL-induced vascular contractions were further verified by constructing Calcium Concentration Response Curves (CCRCs), in the absence and presence of three different concentrations of Pitavastatin and Lovastatin using CCRCs as negative control. Verapamil was used as a standard drug that has L-Type calcium channel binding activity. In other series of experiments, we studied drug interaction(s) among Pitavastatin, Lovastatin, and amlodipine. Results: The results of this study imply that Lovastatin is more potent than Pitavastatin for having comparatively lower EC50 (7.44 × 10-5 ± 0.16 M) in intact and (4.55 × 10-5 ± 0.10 M) in denuded aortae for KCL-induced contractions. Lovastatin amplitudes in intact and denuded aortae for KCL-induced contractions were, respectively, 24% and 35.5%; whereas amplitudes for Pitavastatin in intact and denuded aortae for KCL-induced contractions were 34% and 40%, respectively. A left shift in the EC50 values for the statins was seen when we added amlodipine in EC50 (Log Ca++ M). Right shift for CCRCs state that Pitavastatin and Lovastatin have calcium channel antagonistic effects. Lovastatin in test concentration (6.74 × 10-7 M) produced a right shift in relatively lower EC50 (-2.5 ± 0.10) Log Ca++ M as compared to Pitavastatin, which further confirms that lovastatin is relatively more potent. The right shift in EC50 resembles the right shift of Verapamil. Additive effect of Pitavastatin and Lovastatin was noted in presence of amlodipine (p < 0.05). Conclusions: KCL (80 mM)-induced vascular contractions were relaxed by Pitavastatin and Lovastatin via inhibitory effects on L-Type voltage-gated calcium channels. Lovastatin and Pitavastatin also relaxed Norepinephrine (1 µM)-induced contractions giving an insight for involvement of dual mode of action of Pitavastatin and Lovastatin.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Vasodilatadores , Animales , Conejos , Amlodipino/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lovastatina/farmacología , Lovastatina/uso terapéutico , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/metabolismo , Verapamilo/farmacología , Norepinefrina/farmacologíaRESUMEN
Background and Objectives: We have recently reported that stains have calcium channel blocking activity in isolated jejunal preparations. In this study, we examined the effects of atorvastatin and fluvastatin on blood vessels for a possible vasorelaxant effect. We also studied the possible additional vasorelaxant effect of atorvastatin and fluvastatin, in the presence of amlodipine, to quantify its effects on the systolic blood pressure of experimental animals. Materials and Methods: Atorvastatin and fluvastatin were tested in isolated rabbits' aortic strip preparations using 80mM Potassium Chloride (KCl) induced contractions and 1 micro molar Norepinephrine (NE) induced contractions. A positive relaxing effect on 80 mM KCl induced contractions were further confirmed in the absence and presence of atorvastatin and fluvastatin by constructing calcium concentration response curves (CCRCs) while using verapamil as a standard calcium channel blocker. In another series of experiments, hypertension was induced in Wistar rats and different test concentrations of atorvastatin and fluvastatin were administered in their respective EC50 values to the test animals. A fall in their systolic blood pressure was noted using amlodipine as a standard vasorelaxant drug. Results: The results show that fluvastatin is more potent than amlodipine as it relaxed NE induced contractions where the amplitude reached 10% of its control in denuded aortae. Atorvastatin relaxed KCL induced contractions with an amplitude reaching 34.4% of control response as compared to the amlodipine response, i.e., 39.1%. A right shift in the EC50 (Log Ca++ M) of Calcium Concentration Response Curves (CCRCs) implies that statins have calcium channel blocking activity. A right shift in the EC50 of fluvastatin with relatively less EC50 value (-2.8 Log Ca++ M) in the presence of test concentration (1.2 × 10-7 M) of fluvastatin implies that fluvastatin is more potent than atorvastatin. The shift in EC50 resembles the shift of Verapamil, a standard calcium channel blocker (-1.41 Log Ca++ M). Conclusions: Atorvastatin and fluvastatin relax the aortic strip preparations predominantly through the inhibition of voltage gated calcium channels in high molar KCL induced contractions. These statins also inhibit the effects of NE induced contractions. The study also confirms that atorvastatin and fluvastatin potentiate blood pressure lowering effects in hypertensive rats.
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Bloqueadores de los Canales de Calcio , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Ratas , Conejos , Animales , Bloqueadores de los Canales de Calcio/farmacología , Bloqueadores de los Canales de Calcio/uso terapéutico , Atorvastatina/farmacología , Atorvastatina/uso terapéutico , Fluvastatina/farmacología , Fluvastatina/uso terapéutico , Vasodilatadores/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Amlodipino/farmacología , Amlodipino/uso terapéutico , Calcio , Presión Sanguínea , Ratas Wistar , Verapamilo/farmacología , Canales de Calcio/farmacología , Cloruro de Potasio/farmacologíaRESUMEN
This study is carried out to assess the effects of rosuvastatin and simvastatin on blood vessels for possible vasorelaxant effect. The study is also translating the possible vasorelaxant effect in Wistar rats for a subsequent fall in systolic blood pressure. It is evident from the EC50, that rosuvastatin is more effective on relaxing N.E induced contractions, while simvastatin is more effective on relaxing KCL induced contractions. Simvastatin is equipotent when compared to effects of amlodipine on KCl induced contractions in denuded aortae. Simvastatin produced significant right shift in test concentration 1.1× 10-6M with its respective EC50 -1.85logCa++M as compared to its respective control EC50 -3logCa++M. Rosuvastatin also produced significant right shift in the EC50. In conclusion, it is stated that rosuvastatin and simvastatin relax the aortic strips preparations through inhibition of voltage gated calcium channels and inhibition of N.E induced contractions. Rosuvastatin and simvastatin have additive effects when used in the presence of a standard vaso-relaxant drug like amlodipine, which further confirms its additive effect on decreasing the systolic blood pressure of hypertensive rats (P<0.05).
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Amlodipino , Antihipertensivos , Animales , Ratas , Ratas Wistar , Antihipertensivos/farmacología , Amlodipino/farmacología , Rosuvastatina Cálcica/farmacología , Simvastatina/farmacología , Vasodilatación , Vasodilatadores/farmacologíaRESUMEN
Alzheimer's disease is an emerging health disorder associated with cognitive decline and memory loss. In this study, six curcumin analogs (1a−1f) were synthesized and screened for in vitro cholinesterase inhibitory potential. On the basis of promising results, they were further investigated for in vivo analysis using elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) behavioral models. The binding mode of the synthesized compounds with the active sites of cholinesterases, and the involvement of the cholinergic system in brain hippocampus was determined. The synthesized curcumin analog 1d (p < 0.001, n = 6), and 1c (p < 0.01, n = 6) showed promising results by decreasing retention time in EPM, significantly increasing % SAP in Y-maze, while significantly (p < 0.001) enhancing the % discrimination index (DI) and the time exploring the novel objects in NORT mice behavioral models. A molecular docking study using MOE software was used for validation of the inhibition of cholinesterase(s). It has been indicated from the current research work that the synthesized curcumin analogs enhanced memory functions in mice models and could be used as valuable therapeutic molecules against neurodegenerative disorders. To determine their exact mechanism of action, further studies are suggested.
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Curcumina , Escopolamina , Acetilcolinesterasa/metabolismo , Amnesia/inducido químicamente , Amnesia/tratamiento farmacológico , Animales , Colinérgicos , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/uso terapéutico , Colinesterasas , Modelos Animales de Enfermedad , Aprendizaje por Laberinto , Ratones , Simulación del Acoplamiento Molecular , Escopolamina/efectos adversosRESUMEN
Polyploidization has played a major role in plant evolution and can alter plant morphology, phenology, and ecology within only one or a few generations. Ziziphus species are economically as well as nutritionally important fruit-yielding trees. Identification of genotypes with unique traits or those with higher ploidy levels or a broader genetic base could lead to further improvements within the species. The current study has assessed the ploidy levels in the Ziziphus species (Ziziphus jujuba Mill. and Ziziphus nummularia (Burm. f. Wight & Arn) with phenotypic traits, flow cytometry, and chromosomal count as well as with SSRs markers. Morphological traits were inferred to be the most important drivers of trait variations among the investigated genotypes. The total sugar, total cAMPs, titratable acid, and chlorophyll (a, b, and total) were also significantly different in contrast with diploid plants, which showed that tetraploid Ziziphus had the potential to increase nutritional contents. Out of twenty (20), five (5) Z. jujuba genotypes (ZJL-9, ZJL-12, ZJL-17, ZJL-18, and ZJL-19) were found tetraploid 2n = 4x = 48, with genome size ranging from 965.9 to1238.8 Mb that was significantly higher than the tetraploid Z. jujuba Mill. variety Dongzao. Similarly, Z. nummularia ZNL-07 to ZNL-15 have found tetraploid 2n = 4x = 72 with genomic sizes ranging from 1152.2 to 1746.8 Mb respectively. Simple sequence repeats (SSRs) marker was applied to assess the genetic relationship within Ziziphus genotypes. To the best of our understanding, this is the first report on the identification of naturalized random tetraploids within the Pakistani Ziziphus species. This study provides important insights into the genomic architecture of Ziziphus species with implications for classification, conservation, and improvements of Ziziphus germplasm resources.
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The current study intended to isolate, characterize and identify biocontrol bacteria possessing broad-spectrum antifungal activity from the phyllosphere of different crops including maize, wheat and potato and to assess their growth-promoting activity. In this study 14/113 biocontrol bacteria showed antifungal activity. Bacterial isolates M11 and M33 from maize out of 113 were re-selected on the basis of their strong (more than 50%) broad spectrum antifungal activity after their assessment against four economically important phytopathogenic fungi including Alternaria alternata, Rhizoctonia solani, Fusarium oxysporum and Fusarium verticillioides. The isolates were further assessed for plant growth promoting traits, i.e., indole-3-acetic acid production, phosphate solubilization, production of cellulase, microbial volatile compounds, hydrogen cyanide and siderophores. All fourteen isolates showed positive results for the production of indole-3-acetic acid hormone and cellulase enzyme, 10 isolates were positive for hydrogen cyanide production; siderophores production was observed in 7 isolates while 5 isolates showed ability to solubilize inorganic phosphate. Microbial volatile compounds were only synthesized by M11 and M33, which were identified as Bacillus amyloliquefaciens and Bacillus subtilis respectively by 16S rRNA gene sequencing. The survival study revealed that biocontrol bacteria B. amyloliquefaciens and B. subtilis have the ability to survive in cost effective molasses containing carrier material up to a three-month period.
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Celulasas , Sideróforos , Antifúngicos , Bacillus subtilis , Hongos , Hormonas , Cianuro de Hidrógeno , Fosfatos , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , ARN Ribosómico 16S/genética , Microbiología del Suelo , Zea mays/microbiologíaRESUMEN
Napier grass (Pennisetum purpureum) is well-known due to its high biomass production. The epiphytic microbiota was prepared from Napier, alfalfa, and red clover grass and served as an inoculum. The chopped sterilized Napier grass was inoculated with reconstituted epiphytic microbiota, and treatments were designed as: distilled water (N0); Napier grass epiphytic microbiota (NP); alfalfa epiphytic microbiota (AL); and red clover epiphytic microbiota (RC). The results reveal that the reconstituted epiphytic microbiota bacteria efficiently adapted in Napier grass silage, improved fermentation, and produced lactic acid. The alfalfa-grass inoculum rapidly dropped pH and enhanced the lactic acid (LA) and the ratio of lactic acid-to-acetic acid (LA/AA) during the entire ensiling process. However, red clover attains high lactic acid, while Napier grass produces high acetic acid-type fermentation at terminal silage. After day 60 of ensiling, Lactobacillus proportion was higher in AL (85.45%), and RC (59.44%), inocula as compared with NP (36.41%), inoculum. The NP inoculum terminal silage was diverse than AL and RC inocula and dominated by Enterobacter (16.32%) and Enterobacteriaceae (10.16%) and also significantly (p < 0.05) higher in acetic acid. The present study concluded that AL and RC epiphytic microbiota successfully develop and more efficient than Napier grass microbiota. It is suggested that abundant microbiota isolate from alfala and red clover and develop more economical and efficient inocula for quality fermentation of Napier grass silage in practice.
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Microbiota , Pennisetum , Fermentación , Secuenciación de Nucleótidos de Alto Rendimiento , Ensilaje , TecnologíaRESUMEN
Datura metel has been recommended in several human disorders including a remedy for liver toxicity. The current study was designed to evaluate the hepatoprotective effect of methanolic extract of D. metel in animal model. Acute toxicity of methanolic crude extract of Datura metel (MEDM) was studied in animals in various doses 500-2000 mg/kg. Mice of either sex were divided into groups (n=6). One group received normal saline intraperitonially as negative control, while other gentamicin 100mg/kg for 8 days as positive control. 3rd group received 50mg/kg silymarin as standard, 4th group received 100mg/kg of MEDM, 5th group received 200mg/kg MEDM while 6th group received 300mg/kg MEDM and gentamicin 100mg/kg for 8 days. The blood samples were collected on 9th day and the animals were then dissected and the liver of all the animals were isolated. MEDM was found safe in acute toxicity test at various doses up to 2000 mg/kg. The levels of serum glutamic pyruvic transaminase and alkaline phosphatase were elevated significantly with gentamicin treatment which significantly down-regulated by MEDM (100, 200 and 300 mg/kg) in a dose dependent manner.. The histological examination showed that the MEDM has markedly treated the inflammatory infiltrate, fatty changes and congested blood vessels which were induced by gentamicin. The findings of our study thus proved the absolute of MEDM in acute toxicity test; followed by significant hepatoprotective effect in gentamicin induced hepatotoxic mice.
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Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Datura metel/química , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Alanina Transaminasa/sangre , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/sangre , Fosfatasa Alcalina/metabolismo , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Evaluación Preclínica de Medicamentos , Femenino , Gentamicinas , Hígado/metabolismo , Hígado/patología , Masculino , Metanol/química , Ratones , Fitoterapia/métodos , Extractos Vegetales/química , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Pruebas de Toxicidad Aguda/métodosRESUMEN
Forty-seven million people are living with memory-related disorders worldwide. Phytomedicines are gaining extensive interest in the treatment of these ailments. Memory-enhancing (acute and chronic) potentials of commercial grade extracts of Bacopa monnieri (200 mg/kg, po), Ginkgo biloba (150 mg/kg, po), and Lavandula angustifolia (200 mg/kg, po) and their mixture (B. monnieri 100 mg/kg, G. biloba 75 mg/kg, and L. angustifolia 100 mg/kg, po) were compared for their synergistic/additive effects on the Morris water maze (MWM) test and elevated plus maze (EPM) test in scopolamine-induced amnesia in mice. Escape latency and accumulative path length were significantly reduced both in acute (up to day 6) and chronic trials (days 8-14) in B. monnieri-, G. biloba-, and L. angustifolia-treated animals and their mixtures (n = 8, p < .05) in MWM. Furthermore, in probe trials (acute on day 7 and chronic on day 15), the number of crossing-overs at platform position and time spent in platform quadrant were significantly increased, while transfer latency in EPM was decreased in treated animals as compared to the saline group (n = 8, p < .05). The mixture showed synergistic effects on memory enhancement as compared to each extract individually in mice. Further studies may be carried out on the active compounds of B. monnieri at the cellular and molecular levels.
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Moxifloxacin and gemifloxacin were tested on isolated rabbits' jejunal preparations as little is known about its effects on gastrointestinal tissues. Moxifloxacin and gemifloxacin were tested in concentrations 0.01-10µg/mL for possible effect(s) on isolated rabbits' jejunal preparations. The drugs were applied on spontaneous, on low K+ (20mM)-induced contractions and on high K+ (80mM)-induced contractions. Response was plotted as % of its respective controls. EC50 for Moxifloxacin and Gemifloxacin on spontaneous (without Glibenclamide) contractions are 2.83±0.5µg/mL and 1.11±0.2µg/mL, respectively. Moxifloxacin and Gemifloxacin relaxed the low K+ (20mM) -induced contractions, which were inhibited in presence of Glibenclamide (3µM). Our result indicates that the relaxant activity of Moxifloxacin and Gemifloxacin is mediated possibly through activation of ATP-sensitive potassium channels (KATP). The relaxant effect of Moxifloxacin and Gemifloxacin is predominantly mediated by activation of ATP-Sensitive potassium channels (KATP), which could be cause of one of relaxing mechanisms.
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Gemifloxacina/farmacología , Canales KATP/efectos de los fármacos , Moxifloxacino/farmacología , Parasimpatolíticos/farmacología , Animales , Bioensayo , Femenino , Gliburida/farmacología , Yeyuno/efectos de los fármacos , Masculino , Contracción Muscular/efectos de los fármacos , Relajantes Musculares Centrales/farmacología , Relajación Muscular/efectos de los fármacos , ConejosRESUMEN
Chenopodium ambrosioides is abundantly available in Malakand region. As constituents and concentrations of essential oils vary based on its geographical location, we carried our current study to extract and evaluate its possible relaxant activity in rabbits' jejunum and anti-leishmanial activity against promastigotes of Leishmania tropica. The essential oil was obtained from aerial fresh parts through steam distillation followed by GC/MS analysis. Antispasmodic activity was performed on spontaneous and KCl induced contractions. Curves for calcium concentration response (CCRCs) were prepared with and without different concentrations of essential oils and verapamil - a standard calcium channel blocker as per our reported procedures. GC/MS analysis indicated that the essential oil contains 4-carene (56.59%) and o-cymene (41.46%), the two most abundant compounds previously reported from this species. The LD50 value for acute toxicity is 279.66±2.2mg/kg. The essential oil have significant antileishmanial activity with LC50 of Log10 (1.83±0.0026) ×10-6mg/ml, potent relaxant activity on rabbits' jejunal preparations with respective EC50 = 1.46±0.15mg/ml for spontaneous activity. For KCl (80mM) induced contractions, EC50=0.26±0.02mg/ml. In CCRCs, the oil produced a right shift as exhibited by verapamil. More, its relaxant activity, which is mediated through calcium channel blocking mechanism, proves a rationale for its traditional use in gut spasm.
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Antiprotozoarios/farmacología , Chenopodium ambrosioides , Yeyuno/efectos de los fármacos , Leishmania tropica/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Aceites Volátiles/farmacología , Parasimpatolíticos/farmacología , Animales , Cromatografía de Gases y Espectrometría de Masas , Aceites Volátiles/química , Aceites de Plantas/química , Aceites de Plantas/farmacología , ConejosRESUMEN
KEY MESSAGE: Two novel resistant QTLs mapped and candidate genes identified for Aspergillus flavus resistance in cultivated peanut using SLAF-seq. Aflatoxin contamination in peanuts caused by Aspergillus flavus is a serious food safety issue for human health around the world. Host plant resistance to fungal infection and reduction in aflatoxin are crucial for mitigating this problem. Identification of the resistance-linked markers can be used in marker-assisted breeding for varietal development. Here we report construction of two high-density genetic linkage maps with 1975 SNP loci and 5022 SNP loci, respectively. Two consistent quantitative trait loci (QTL) were identified as qRAF-3-1 and qRAF-14-1, which located on chromosomes A03 and B04, respectively. QTL qRAF-3-1 was mapped within 1.67 cM and had more than 19% phenotypic variance explained (PVE), while qRAF-14-1 was located within 1.34 cM with 5.15% PVE. While comparing with the reference genome, the mapped QTLs, qRAF-3-1 and qRAF-14-1, were located within a physical distance of 1.44 Megabase pair (Mbp) and 2.22 Mbp, harboring 67 and 137 genes, respectively. Among the identified candidate genes, six genes with the same function were found within both QTLs regions. In addition, putative disease resistance RPP13-like protein 1 (RPP13), lipoxygenase (Lox), WRKY transcription factor (WRKY) and cytochrome P450 71B34 genes were also identified. Using microarray analysis, genes responded to A. flavus infection included coding for RPP13, pentatricopeptide repeat-containing-like protein, and Lox which may be possible candidate genes for resistance to A. flavus. The QTLs and candidate genes will further facilitate marker development and validation of genes for deployment in the molecular breeding programs against A. flavus in peanuts.
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Arachis/genética , Aspergillus flavus/patogenicidad , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Polimorfismo de Nucleótido Simple , Aflatoxinas/química , Arachis/microbiología , Mapeo Cromosómico , Biología Computacional , Ligamiento Genético , Marcadores Genéticos , Genotipo , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Enfermedades de las Plantas/microbiología , Sitios de Carácter CuantitativoRESUMEN
Datura metel is traditionally used as a remedy for renal toxicity. However, the nephroprotection has not been scientifically validated yet. To evaluate the nephroprotective like effect of methanolic extract of D. metel in gentamicin induced mice model, mice of either sex were divided into groups. One group received normal saline as negative control. The 2nd group received gentamicin 100mg/kg for 8 days as positive control, 3rd group received 50mg/kg silymarin as standard, while the reaming groups received 100, 200 and 300 mg/kg of MEDM and gentamicin 100mg/kg, for 8 days. The blood and urine samples were collected on 9th day, animals were then dissected and whole kidneys were removed and preserved in formalin for later histological examinations. The level of serum creatinine, blood urea nitrogen, urine creatinine and urine urea were significantly (P<0.05) elevated and the renal MDA level was also elevated significantly (P<0.05) by gentamicin in mice. After the treatment of test animals with MEDM, the elevated level of serum and urine biomarkers by gentamicin were reversed by MEDM. The nephroprotective effect was found in dose dependent manner. As the MEDM significantly protected the nephrotoxicity via its antioxidant effect. The findings of our study thus proved the scientific background for the nephroprotective effect of MEDM.
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Datura metel/química , Gentamicinas/efectos adversos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Extractos Vegetales/uso terapéutico , Sustancias Protectoras/uso terapéutico , Animales , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Creatinina/orina , Modelos Animales de Enfermedad , Femenino , Riñón/efectos de los fármacos , Riñón/patología , Enfermedades Renales/sangre , Enfermedades Renales/orina , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Fitoquímicos/análisis , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Urea/orinaRESUMEN
Ziziphus nummularia is an important source of valuable phytoconstituents, which are widely used in traditional medicine system of Indo-Pak sub-continent. In this study we investigated the distribution of phenolic compounds in the fruit pericarps of six different genotypes (ZNP01-06) of Z. nummularia growing in the unexplored hilly areas of Pakistan. The methanolic extracts of these genotypes were screened for total phenolic content (TPC), total flavonoid content (TFC), antioxidant, and cholinesterase inhibitory potentials. The observed biological potentials were explained in terms of the outcome of molecular docking and HPLC analyses. Among them, genotype ZNP02 displayed high TPC (88.50 ± 1.23 µg/mL) and showed potent scavenging activity against DPPH (67.03 ± 1.04 µg/mL) and ABTS (65.3 ± 1.74 µg/mL) in comparison to ascorbic acid (68.7 ± 0.47 µg/mL). Moreover, genotypes ZNP01, ZNP02, and ZNP04 displayed potent inhibition against acetyl and butyryl cholinesterases (AChE and BChE) with IC50 values of 21.2, 20.5, and 23.7 µg/mL (AChE) and 22.7, 24.4, and 33.1 µg/mL (BChE), respectively. Furthermore, the individual compounds in the most potent species ZNP01 responsible for potent enzyme inhibition (identified through HPLC-UV analysis), were computed via docking simulation software to the enzyme structures. Among these compounds rutin exhibited significant binding affinity with value of -9.20 kcal/mol. The differences amongst the phytochemical compositions of the selected genotypes highlighted the genotypic variations in them. Based on our results it was concluded that the selected plant can be used as remedy of oxidative stress and neurodegenerative diseases. However, further studies are needed to isolate responsible compounds and test the observed potential in vivo, along with toxicological evaluations in animal models.
Asunto(s)
Acetilcolinesterasa , Inhibidores de la Colinesterasa/química , Frutas , Genotipo , Simulación del Acoplamiento Molecular , Ziziphus , Acetilcolinesterasa/química , Cromatografía Líquida de Alta Presión , Evaluación Preclínica de Medicamentos , Frutas/química , Frutas/genética , Proteínas Ligadas a GPI/antagonistas & inhibidores , Proteínas Ligadas a GPI/química , Humanos , Espectrofotometría Ultravioleta , Ziziphus/química , Ziziphus/genéticaRESUMEN
The current work is documented to investigate the actions of azithromycin on intestinal smooth muscles as there are reports of gastrointestinal upsets with use of azithromycin. Azithromycin was tested on rabbit's jejunal and rat's ileal preparations in test concentrations (µM) of 0.01, 0.03, 0.1, 0.3, 1, 3, 5, 10 and 15µM. After mounting the tissues in organ bath containing Tyrode's solution, spasmogenic activity of azithromycin was observed. To explore its possible mechanisms, response of azithromycin was noted in the presence of 0.3µM atropine, 3µM loratadine, 0.3µM ondansetron, 10µM metoclopramide, 0.3µM verapamil, 1µM propranolol, 3µM amiodarone and combination of 0.3µM each atropine, ondansetron, verapamil and propranolol (AOVP). Mean % Emax for azithromycin was 67.6±1.6 and 54.0±2.1 (% of ACh max) for rabbit's jejunal and rat's ileal preparations, respectively. The Mean % Emax for azithromycin in the presence of various antagonists for rabbit's jejunal and rat's ileal preparations was as: 2.4±0.1 and 11.4±1.3 with atropine; 67.9±2.0 and 50.7±1.9 with loratadine; 27.5±0.5 and 34.0±2.9 with ondansetron; 88.4±1.2 and 79.1±3.8 with metoclopramide; 13.6±1.2 and 22.3±2.5 with verapamil; 10.2±2.1 and 15.6±1.4 with propranolol; 68.4±1.3 and 58.0±3.4 with amiodarone. Results reveal that the spasmogenic response of azithromycin is mainly mediated through muscarinic receptors. However, we found involvement of mixed pathway including serotonergic receptors, voltage gated calcium channels and voltage gated sodium channels.
Asunto(s)
Azitromicina/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Íleon/efectos de los fármacos , Yeyuno/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Animales , Canales de Calcio/metabolismo , Femenino , Íleon/metabolismo , Técnicas In Vitro , Yeyuno/metabolismo , Masculino , Músculo Liso/metabolismo , Conejos , Ratas , Receptores Muscarínicos/metabolismo , Receptores de Serotonina/metabolismo , Canales de Sodio Activados por Voltaje/metabolismoRESUMEN
The current work is an attempt to know that in which fraction(s) the relaxant constituents of Rosa moschata concentrate. Crude methanolic extract of Rosa moschata was prepared as per our reported procedure. Sub fractions of methanol extract were extracted with different solvents in increasing order of polarity i.e. n-hexane > chloroform > ethyl acetate > n-butanol > residual aqueous fractions. Different concentrations (0.01, 0.03, 0.1, 0.3, 1, 3, 5 and 10 mg/ml) of the fractions were tested on spontaneous contractions and KCl induced contractions on rabbits' jejunal preparations. Calcium Concentration Response Curves (CCRCs) in the presence and absence of the test fractions using verapamil were constructed to understand its mechanisms. EtOA fraction was more relaxant with EC50 values 0.812±0.149 mg/ml on spontaneous and 2.01±0.08 mg/ml on KCl induced contractions. we also found right shift in its EC50 values expressed as log [Ca++]M values. In presence of 0.3 mg/ml EtOA fraction, its EC50 value was -2.22±0.035 vs control EC50 -2.71±0.21. For n-BuOH fraction, EC50 value was -1.82±0.00 vs control with EC50 -2.28±0.049 at concentration of 0.3 mg/ml. Ethyl acetate fraction of Rosa moschata was more potent and is therefore can be a target for activity guided isolation of calcium channel antagonists.
Asunto(s)
Frutas/química , Extractos Vegetales/farmacología , Rosa/química , Animales , Bloqueadores de los Canales de Calcio/farmacología , Femenino , Yeyuno/efectos de los fármacos , Masculino , Contracción Muscular/efectos de los fármacos , Extractos Vegetales/química , Conejos , Solventes/química , Verapamilo/farmacologíaRESUMEN
Three substituted flavone derivatives have been synthesized from substituted O-hydroxy acetophenones and 4-trifluoromethyl benzaldehyde in good yield. These compounds were characterized by NMR spectroscopy and single crystal X-ray Diffraction. Compound F1 and F3 were re-crystallized from their concentrated solutions in chloroform ethyl acetate mixture while F2 was re-crystallized in ethyl acetate n-hexane mixture. Compound F1 and F3 are monoclinic (space group P21/c) with lattice parameters: [a, b, c (A) / ß (°)] = 13.332 (2), 15.616 (2) / 6.2898 (8) and 13.9716 (15), 7.1868 (7), 13.6912 (14) / 91.113(6) respectively. Compound F2 is Triclinic (space group P-1) and has lattice parameters: [a, b, c (Å) / α, ß, γ (°)] = 6.5002 (6), 8.3801 (9), 13.5989 (14) / 89.348(5), 85.141(4), 84.521(5). Antioxidant, antibacterial and cytotoxic profile was investigated. The compounds showed moderate to less activity on 1,1-diphenyl-2-picryl-hydrazyl (DPPH), Hydrogen peroxide (H/2/O/2) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) models of radical scavenging activity while promising antibacterial potentials were recorded. Furthermore, these molecules can also be used as potential candidates for new antitumor agents.