Modulation of cyclophosphamide-induced immunosuppression and intestinal flora in broiler by deep eutectic solvent extracted polysaccharides of Acanthopanax senticosus.

Introduction: The aim of this experiment was to investigate the modulation effect of Acanthopanax senticosus polysaccharide (ASPS-PD) extracted with deep eutectic solvent on cyclophosphamide-induced immunosuppression in broilers and its modulation of the gut microbiota of broilers. Methods: The 108 one-day-old broilers were divided into six groups, including the control group, the Cyclophosphamide (CY) model group, the ASPS-PD control group, the ASPA-PD high and low dose groups and the Astragalus polysaccharide group. Body weight, feed intake, feed conversion ratio, and immune organ index of broilers at 7, 14, and 21 days were determined; IL-2, IFN-γ, and lgG1 levels were determined by enzyme-linked immunosorbent assay (ELISA); Broiler caeca feces were analyzed by amplification and 16S rRNA sequencing. Results: The results showed that ASPS-PD can restore growth performance, increase immune organ index and improve serum cytokine levels of IL-2 and IFN-γ and immunoglobulin lgG1 levels in CY-treated broilers. The analysis of cecum flora showed that ASPS-PD can promote the proliferation of beneficial bacteria and reduce the number of harmful bacteria, regulating intestinal flora. Discussion: Therefore, ASPA-PD may be a potential novel immunomodulator to ameliorate CY-induced immunosuppression and intestinal flora dysregulation in broiler.

Covalent Organic Framework-Based Materials for Advanced Lithium Metal Batteries.

Lithium metal batteries (LMBs), with high energy densities, are strong contenders for the next generation of energy storage systems. Nevertheless, the unregulated growth of lithium dendrites and the unstable solid electrolyte interphase (SEI) significantly hamper their cycling efficiency and raise serious safety concerns, rendering LMBs unfeasible for real-world implementation. Covalent organic frameworks (COFs) and their derivatives have emerged as multifunctional materials with significant potential for addressing the inherent problems of the anode electrode of the lithium metal. This potential stems from their abundant metal-affine functional groups, internal channels, and widely tunable architecture. The original COFs, their derivatives, and COF-based composites can effectively guide the uniform deposition of lithium ions by enhancing conductivity, transport efficiency, and mechanical strength, thereby mitigating the issue of lithium dendrite growth. This review provides a comprehensive analysis of COF-based and derived materials employed for mitigating the challenges posed by lithium dendrites in LMB. Additionally, we present prospects and recommendations for the design and engineering of materials and architectures that can render LMBs feasible for practical applications.

Prebiotic characteristics of degraded polysaccharides from Acanthopanax senticosus polysaccharide on broilers gut microbiota based on in vitro digestion and fecal fermentation.

This study aimed to evaluate the effect of low molecular weight Acanthopanax polysaccharides on simulated digestion, probiotics, and intestinal flora of broilers in vitro. The experiments were carried out by H2O2-Vc degradation of Acanthopanax polysaccharides, in vitro simulated digestion to evaluate the digestive performance of polysaccharides with different molecular weights, in vitro probiotic evaluation of the probiotic effect of polysaccharides on lactobacilli and bifidobacteria, in vitro anaerobic fermentation and high-throughput sequencing of 16S rRNA genes to study the impact of Acanthopanax polysaccharides on the intestinal flora of broilers, and the effect of Acanthopanax polysaccharides on the short-chain fatty acids of intestines were determined by GC-MS method. The results showed that the molecular weight of Acanthopanax polysaccharide (ASPS) was 9,543 Da, and the molecular weights of polysaccharides ASPS-1 and ASPS-2 were reduced to 4,288 Da and 3,822 Da after degradation, and the particle sizes, PDIs, and viscosities were also significantly decreased. ASPS-1 has anti-digestive properties and better in vitro probiotic properties. The addition of ASPS-1 regulates the structure of intestinal microorganisms by regulating fecalibacterium to produce short-chain fatty acids, promoting the colonization of beneficial bacteria such as fecalibacterium, paraprevotella and diminishing the prevalence of detrimental bacteria such as Fusobacteria. Interestingly the ASPS-1 group found higher levels of Paraprevotella, which degraded trypsin in the gut, reducing inflammation, acted as a gut protector, and was influential in increasing the levels of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and total SCFAs in the fermented feces. Therefore, the degraded ASPS-1 can better regulate the structure of intestinal flora and promote the production of SCFAs, creating possibilities for its use as a potential prebiotic, which is conducive to the intestinal health of poultry.

Preparation, Characterization, and Bioactivities of Polysaccharide-Nano-Selenium and Selenized Polysaccharides from Acanthopanax senticosus.

Acanthopanax senticosus polysaccharide-nano-selenium (ASPS-SENPS) and A. selenopanax selenized polysaccharides (Se-ASPS) were synthesized, and their characterization and biological properties were compared. The acid extraction method was used to extract the polysaccharides of A. selenopanax, followed by decolorization using the hydrogen peroxide method and deproteinization based on the Sevage method, and the purification of A. senticosus polysaccharides (ASPS) was carried out using the cellulose DEAE-52 ion column layer analysis method. An A. senticosus polysaccharide-nano-selenium complex was synthesized by a chemical reduction method using ASPS as dispersants. The selenization of polysaccharides from A. selenopanax was carried out using the HNO3-Na2SeO3 method. The chemical compositions, scanning electron microscopy images, infrared spectra, and antioxidant properties of ASPS-SENPS and Se-ASPS were studied, and they were also subjected to thermogravimetric analysis. The results indicated that the optimal conditions for the synthesis of ASPS-SENPS include the following: when ASPS accounts for 10%, the ratio of ascorbic acid and sodium selenium should be 4:1, the response time should be 4 h, and the reaction temperature should be 50 °C. The most favorable conditions for the synthesis of Se-ASPS were as follows: m (Na2SeO3):m (ASPS) = 4:5, response temperature = 50 °C, and response time = 11.0 h. In the in vitro antioxidant assay, when the mass concentration of Se-ASPS and ASPS-SENPS was 5 mg/mL, the removal rates for DPPH free radicals were 88.44 ± 2.83% and 98.89 ± 3.57%, respectively, and the removal rates for ABTS free radicals were 90.11 ± 3.43% and 98.99 ± 1.73%, respectively, stronger than those for ASPS. The current study compares the physiological and bioactivity effects of ASPS-SENPS and Se-ASPS, providing a basis for future studies on polysaccharides.

Eco-Friendly and Efficient Extraction of Polysaccharides from Acanthopanax senticosus by Ultrasound-Assisted Deep Eutectic Solvent.

A green extraction method was developed using deep eutectic solvent extraction for the polysaccharide from Acanthopanax senticosus (A. senticosus). Among the eight types of DES prepared, the DES with a ratio of 1:4 L-malic acid to L-proline was found to be a suitable extraction solvent based on the extraction efficiency. The extraction parameters were optimized by Plackett-Burman and response surface methodology (RSM). The best extraction conditions were found for L-malic acid. Under the conditions of an L-malic acid/L-proline ratio of 1:4, ultrasonic power of 240 W, material-liquid ratio of 31.068 g/mL, water content of 32.364%, extraction time of 129.119 min, and extraction temperature of 60 °C, the extraction rate of A. senticosus polysaccharides was 35.452 ± 0.388 mg-g-1. This rate was higher than that of polysaccharides obtained by hot water extraction (13.652 ± 0.09 mg-g-1). The experimental results were best fitted by the quasi-secondary kinetic model when compared to two other kinetic models. Electron microscopic observations showed that DESs were more destructive to plant cells. The polysaccharide extracted from DESs had more monosaccharide components, a lower molecular weight, a higher antioxidant capacity, and superior anti-glycation activity compared to polysaccharides extracted from water (ASPS-PW). This study demonstrates the effectiveness of DESs in obtaining polysaccharides from A. senticosus.

Observation and manipulation of quantum interference in a superconducting Kerr parametric oscillator.

Quantum tunneling is the phenomenon that makes superconducting circuits "quantum". Recently, there has been a renewed interest in using quantum tunneling in phase space of a Kerr parametric oscillator as a resource for quantum information processing. Here, we report a direct observation of quantum interference induced by such tunneling and its dynamics in a planar superconducting circuit through Wigner tomography. We experimentally elucidate all essential properties of this quantum interference, such as mapping from Fock states to cat states, a temporal oscillation due to the pump detuning, as well as its characteristic Rabi oscillations and Ramsey fringes. Finally, we perform gate operations as manipulations of the observed quantum interference. Our findings lay the groundwork for further studies on quantum properties of superconducting Kerr parametric oscillators and their use in quantum information technologies.

Covalent Organic Frameworks: Their Composites and Derivatives for Rechargeable Metal-Ion Batteries.

Covalent organic frameworks (COFs) have attracted considerable interest in the field of rechargeable batteries owing to their three-dimensional (3D) varied pore sizes, inerratic porous structures, abundant redox-active sites, and customizable structure-adjustable frameworks. In the context of metal-ion batteries, these materials play a vital role in electrode materials, effectively addressing critical issues such as low ionic conductivity, limited specific capacity, and unstable structural integrity. However, the electrochemical characteristics of the developed COFs still fall short of practical battery requirements due to inherent issues such as low electronic conductivity, the tradeoff between capacity and redox potential, and unfavorable micromorphology. This review provides a comprehensive overview of the recent advancements in the application of COFs, COF-based composites, and their derivatives in rechargeable metal-ion batteries, including lithium-ion, lithium-sulfur, sodium-ion, sodium-sulfur, potassium-ion, zinc-ion, and other multivalent metal-ion batteries. The operational mechanisms of COFs, COF-based composites, and their derivatives in rechargeable batteries are elucidated, along with the strategies implemented to enhance the electrochemical properties and broaden the range of their applications.

Study on Extraction and Purification of Acanthopanax senticosus Polyphenols by an Ionic Liquid-Assisted Aqueous Two-Phase System.

This study aimed to extract and purify polyphenols from Acanthopanax senticosus. A new green method was developed, in which ionic liquids (ILs) were used as aqueous two-phase (ATP) adjuvants to extract the polyphenols from A. senticosus. An ionic liquid-assisted aqueous two-phase system (IL-ATPS) was established. The purification of the polyphenols from the extraction fluid by AB-8 macroporous resin was conducted, and the kinetic mechanisms were studied. The reuse of ionic liquids was executed. The results showed that an [OMIM]Br-assisted ethanol/NaH2PO4 system (IL-ATPS) was the best extraction solvent. In this study, the following optimal extraction conditions were determined: 32 wt.% ethanol, 25 wt.% NaH2PO4, 9 wt.% additional ionic liquid, a solid-liquid ratio of 1:40 g/mL, an extraction temperature of 50 °C, a pH of 4.0, an extraction time of 50 min, and an extraction rate of the polyphenols at 15.90 mg/g. The optimum adsorption parameters of the macroporous resin AB-8 were as follows: a flow rate of 3.5 BV·h-1, a sample volume of 40 mL, an elution flow rate of 3.5 BV·h-1, an eluent volume of 80 mL, and an eluant that was constituted by an 85% volume fraction of ethanol. The decolorization effect of 4% activated carbon was better than the other amounts; in addition, a decolorization rate of 76.81% and an ionic liquid recovery rate of 81.12% were found to be the most optimal. Compared with the traditional extraction methods, IL-ATPS has the advantages of requiring simple operation, saving time, and high efficiency. In addition, it can be used for the extraction of the polyphenolic compounds.

Optimization of Enzyme-Assisted Aqueous Extraction of Polysaccharide from Acanthopanax senticosus and Comparison of Physicochemical Properties and Bioactivities of Polysaccharides with Different Molecular Weights.

To obtain the optimal process for the enzyme-assisted aqueous extraction of polysaccharides from Acanthopanax senticosus, and study the physicochemical properties of polysaccharides of different molecular weights, the extraction of Acanthopanax polysaccharides was optimized using the BBD response surface test. The polysaccharides with different molecular weights were obtained by ethanol-graded precipitation at 40%, 60%, and 80%, which were presented as ASPS40, ASPS60, and ASPS80. The polysaccharides were analyzed by HPGPC, ion chromatography, FT-IR, UV, SEM, TGA, XRD, Congo red, and I2-KI tests. The antioxidant assay was used to evaluate their antioxidant properties in vitro. The findings demonstrated that the recovery rate of Acanthopanax polysaccharide was 10.53 ± 0.682%, which is about 2.5 times greater compared to the conventional method of hot water extraction. Based on FT-IR, TGA, polysaccharides with different molecular weights did not differ in their structure or thermal stability. The XRD suggests that the internal structure of ASPSs is amorphous. Congo red and I2-KI showed that all three polysaccharides had triple helix structures with longer branched chains and more side chains. Furthermore, the antioxidant results showed the antioxidant activity of polysaccharides is not only related to the molecular weight size but also can be related to its composition and structure. These studies developed a green, and scalable method to produce polysaccharides from Acanthopanax senticosus and evaluated the properties of Acanthopanax polysaccharides of different molecular weights.

Research Progress and Molecular Mechanisms of Endothelial Cells Inflammation in Vascular-Related Diseases.

Endothelial cells (ECs) are widely distributed inside the vascular network, forming a vital barrier between the bloodstream and the walls of blood vessels. These versatile cells serve myriad functions, including the regulation of vascular tension and the management of hemostasis and thrombosis. Inflammation constitutes a cascade of biological responses incited by biological, chemical, or physical stimuli. While inflammation is inherently a protective mechanism, dysregulated inflammation can precipitate a host of vascular pathologies. ECs play a critical role in the genesis and progression of vascular inflammation, which has been implicated in the etiology of numerous vascular disorders, such as atherosclerosis, cardiovascular diseases, respiratory diseases, diabetes mellitus, and sepsis. Upon activation, ECs secrete potent inflammatory mediators that elicit both innate and adaptive immune reactions, culminating in inflammation. To date, no comprehensive and nuanced account of the research progress concerning ECs and inflammation in vascular-related maladies exists. Consequently, this review endeavors to synthesize the contributions of ECs to inflammatory processes, delineate the molecular signaling pathways involved in regulation, and categorize and consolidate the various models and treatment strategies for vascular-related diseases. It is our aspiration that this review furnishes cogent experimental evidence supporting the established link between endothelial inflammation and vascular-related pathologies, offers a theoretical foundation for clinical investigations, and imparts valuable insights for the development of therapeutic agents targeting these diseases.

Pharmacokinetic studies of hyperoside-2-hydroxypropyl-ß-cyclodextrin inclusion complex and ameliorated DSS-induced colitis in mice.

An inclusion complex formation with cyclodextrin is a promising method to improve the bioavailability of water-insoluble drugs. The pharmacokinetic characteristics of Hyperoside-2-hydroxypropyl-ß-cyclodextrin inclusion complex in rats were evaluated. Compared with Hyperoside, the results showed that maximum plasma concentration and AUC0-t indexes of Hyperoside inclusion complex in rat plasma were increased, the value of half-life time was prolonged, and the value of apparent clearance was decreased, which proved that Hyperoside complexed with 2-hydroxypropyl-ß-cyclodextrin could improve its bioavailability and increase its blood concentration. Secondly, the therapeutic effect of Hyperoside before and after complexing was further compared through the dextran sodium sulfate-induced colitis in mice. The experimental results showed that under the same dose, the Hyperoside inclusion complex had a better therapeutic effect, which could significantly increase the body weight of mice, improve the disease activity index, alleviate colon shortening, improve pathological colon changes, and have a better protective effect on colitis mice. According to 16S rDNA sequencing analyses, Hyperoside-2-hydroxypropyl-ß-cyclodextrin may have an anti-inflammatory effect by increasing the abundance of beneficial bacteria (e.g. Firmicuria) and decreasing the proportion of harmful bacteria (e.g. Bacteroidetes) to balance the colon's microbiota.

The efficacy and potential mechanism of Danggui Buxue Decoction in treating diabetic nephropathy: A meta-analysis and network pharmacology.

BACKGROUND: To evaluate the efficacy and potential pharmacological mechanisms of Danggui Buxue Decoction (DGBXD) in the treatment of diabetic nephropathy. METHODS: Meta-analysis was used to conduct a comprehensive search of the literature for randomized controlled trials of DGBXD for diabetic nephropathy, followed by identification of quantitative literature based on inclusion and exclusion criteria, and statistical analysis of the included data using Review Manager. The network pharmacology technique was used to screen the chemical components of DGBXD and their targets, disease targets, shared targets, and other associated information, and then apply bioinformatics technologies to annotate the key pathways. Using AutoDock and PyMol software, the 6 core targets were docked with the 7 main active components of DGBXD. RESULTS: DGBXD complementary treatment significantly reduced 24 hours UTP, SCr and BUN levels and lowered blood glucose and lipid levels, improving clinical outcomes and modulating inflammatory factor levels. 22 active ingredients and 209 active targets were obtained for DGBXD, 245 core targets were obtained for diabetic nephropathy. The molecular docking results showed that all 7 components of DGBXD docked with 6 core targets had binding energies below -5. CONCLUSIONS: The findings suggest that DGBXD affects diabetic nephropathy through a multi-target, multi-component and multi-pathway mechanism.

Antioxidant and Antiapoptotic Properties of n-Butanol Fraction the Acanthopanax senticosus Extracts in H2O2-RAW264.7 Cells and CCl4-Induced Liver Injury in Mice.

The Acanthopanax senticosus has been shown to have a wide range of pharmacological activities, which are associated with health benefits, such as antioxidant, anti-inflammatory, and antiapoptotic properties. A previous study has shown that the n-butanol fraction of A. senticosus extract had the strongest antioxidant effect in vitro. This study aimed to investigate the effects that the n-butanol fraction of A. senticosus extract could relieve oxidative stress damage through antioxidant and antiapoptotic in the H2O2-stimulated RAW264.7 macrophages and the CCl4-induced liver injury. The result showed that the n-butanol fraction extract could relieve damage by increasing the intracellular antioxidant enzymes (SOD) level, decreasing intracellular ROS and MDA levels, and regulating antioxidant and antiapoptotic-related gene expression levels. The morphological observation of HE, TUNE, and immunohistochemistry staining of liver tissue verified that the n-butanol fraction extract is though anti-oxidative and antiapoptotic to alleviate cellular oxidative damage. The RT-PCR assay showed that the Keap1-Nrf2-ARE and the Bax/Bcl-2 signaling pathway were related to the molecular mechanism of action. The experimental results show that Acanthopanax senticosus extract has a good effect in treating liver injury and enhancing the antioxidant capacity of the body.

Jiedu Tongluo Baoshen formula enhances renal tubular epithelial cell autophagy to prevent renal fibrosis by activating SIRT1/LKB1/AMPK pathway.

Renal fibrosis, an important pathological change in the development of diabetic kidney disease (DKD), urgently needs new treatment methods clinically. The Jiedu Tongluo Baoshen (JTBF) formula was created based on the theory of toxic damage to the kidney collaterals, and a variety of active ingredients in JTBF have inhibitory effects on epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM). In this study, the Ultra Performance Liquid Chromatography (UPLC) was employed to analyze the effective ingredients in the JTBF formula. After screening in the PubChem database, we identified 94 active compounds of JTBF and predicted the SIRT1 pathway as potential targets through network pharmacology. In addition, in the high fat diet (HFD)+Streptozocin (STZ)-induced DKD rat model and high glucose (HG)-induced NRK-52E cell model, JTBF treatment activates the phosphorylation of LKB1 and AMPK and enhances the autophagy activity of NRK-52E cells, thereby reducing the accumulation of EMT and ECM. These results have been confirmed in vivo and in vitro experiments. JTBF enhances the autophagy activity of renal tubular epithelial cells and inhibits the progression of DKD renal fibrosis by activating the SIRT1/LKB1/AMPK signal pathway. This study provides new insights into the molecular mechanism of JTBF to prevent and treat DKD renal fibrosis.

P T symmetry in a superconducting hybrid quantum system with longitudinal coupling.

We propose a scheme consisting of coupled nanomechanical cantilever resonators and superconducting flux qubits to engineer a parity-time- (P T-) symmetric phononic system formed by active and passive modes. The effective gain (loss) of the phonon mode is achieved by the longitudinal coupling of the resonator and the fast dissipative superconducting qubit with a blue-sideband driving (red-sideband driving). A P T-symmetric to broken-P T-symmetric phase transition can be observed in both balanced gain-to-loss and unbalanced gain-to-loss cases. Applying a resonant weak probe field to the dissipative resonator, we find that (i) for balanced gain and loss, the acoustic signal absorption to amplification can be tuned by changing the coupling strength between resonators; (ii) for unbalanced gain and loss, both acoustically induced transparency and anomalous dispersion can be observed around Δ = 0, where the maximum group delay is also located at this point. Our work provides an experimentally feasible scheme to design P T-symmetric phononic systems and a powerful platform for controllable acoustic signal transmission in a hybrid quantum system.

Contribution of Chinese herbal medicine in the treatment of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis of randomized controlled trials.

Coronavirus disease 2019 (COVID-19) has become a global epidemic, and there is no specific treatment for anti-COVID-19 drugs. However, treatment of COVID-19 using Chinese herbal medicine (CHM) has been widely practiced in China. PubMed, Embase, Cochrane Library, CNKI, Wanfang and VIP databases were searched to evaluate the efficacy and safety of CHM in the treatment of COVID-19. Twenty-six studies were included in this meta-analysis. The included cases were all patients diagnosed with COVID-19 according to the "New Coronary Virus Pneumonia Diagnosis and Treatment Program," with a total of 2,407 cases. Patients were treated with CHM, including 36 prescriptions, and 105 flavors of CHM were included. The results of the meta-analysis showed that the CHM group improved in lung CT, clinical cure rate, clinical symptom score and time to negative for viral nucleic acid. However, this study still has many limitations due to the limited number of included studies. Therefore, high-quality RCT studies are needed to provide more reliable evidence for CHM treatment of COVID-19. In conclusion, CHM may significantly improve the clinical manifestations and laboratory indicators of patients with COVID-19. In addition, no serious adverse reactions were found after CHM treatment. Therefore, CHM may be used as a potential candidate for COVID-19. HIGHLIGHTS: COVID-19 has become a global epidemic, and there is no specific treatment for anti-COVID-19 drugs. CHM has made a new breakthrough in the treatment of COVID-19. CHM may relieve lung CT images of COVID-19 patients. CHM may improve clinical symptoms of COVID-19 patients. CHM may inhibit the expression of inflammatory factors in patients with COVID-19.

The critical role of the Hippo signaling pathway in kidney diseases.

The Hippo signaling pathway is involved in cell growth, proliferation, and apoptosis, and it plays a key role in regulating organ size, tissue regeneration, and tumor development. The Hippo signaling pathway also participates in the occurrence and development of various human diseases. Recently, many studies have shown that the Hippo pathway is closely related to renal diseases, including renal cancer, cystic kidney disease, diabetic nephropathy, and renal fibrosis, and it promotes the transformation of acute kidney disease to chronic kidney disease (CKD). The present paper summarizes and analyzes the research status of the Hippo signaling pathway in different kidney diseases, and it also summarizes the expression of Hippo signaling pathway components in pathological tissues of kidney diseases. In addition, the present paper discusses the positive therapeutic significance of traditional Chinese medicine (TCM) in regulating the Hippo signaling pathway for treating kidney diseases. This article introduces new targets and ideas for drug development, clinical diagnosis, and treatment of kidney diseases.

The critical role of dysregulated autophagy in the progression of diabetic kidney disease.

Diabetic kidney disease (DKD) is one of the major public health problems in society today. It is a renal complication caused by diabetes mellitus with predominantly microangiopathy and is a major cause of end-stage renal disease (ESRD). Autophagy is a metabolic pathway for the intracellular degradation of cytoplasmic products and damaged organelles and plays a vital role in maintaining homeostasis and function of the renal cells. The dysregulation of autophagy in the hyperglycaemic state of diabetes mellitus can lead to the progression of DKD, and the activation or restoration of autophagy through drugs is beneficial to the recovery of renal function. This review summarizes the physiological process of autophagy, illustrates the close link between DKD and autophagy, and discusses the effects of drugs on autophagy and the signaling pathways involved from the perspective of podocytes, renal tubular epithelial cells, and mesangial cells, in the hope that this will be useful for clinical treatment.

Oxytocin-induced endothelial nitric oxide dependent vasorelaxation and ERK1/2-mediated vasoconstriction in the rat aorta.

Oxytocin is a neuropeptide produced primarily in the hypothalamus and plays an important role in the regulation of mammalian birth and lactation. It has been shown that oxytocin has important cardiovascular protective effects. Here we investigated the effects of oxytocin on vascular reactivity and underlying the mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and in rat aorta ex vivo. Oxytocin increased phospho-eNOS (Ser 1177) and phospho-Akt (Ser 473) expression in HUVECs in vitro and the aorta of rat ex vivo. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), inhibited oxytocin-induced Akt and eNOS phosphorylation. In the rat aortic rings, oxytocin induced a biphasic vascular reactivity: oxytocin at low dose (10-9-10-8 M) initiated a vasorelaxation followed by a vasoconstriction at high dose (10-7 M). L-NAME (a nitric oxide synthase inhibitor), endothelium removal or wortmannin abolished oxytocin-induced vasorelaxation, and slightly enhanced oxytocin-induced vasoconstriction. Atosiban, an oxytocin/vasopressin 1a receptor inhibitor, totally blocked oxytocin-induced relaxation and vasoconstriction. PD98059 (ERK1/2 inhibitor) partially inhibited oxytocin-induced vasoconstriction. Oxytocin also increased aortic phospho-ERK1/2 expression, which was reduced by either atosiban or PD98059, suggesting that oxytocin-induced vasoconstriction was partially mediated by oxytocin/V1aR activation of ERK1/2. The present study demonstrates that oxytocin can activate different signaling pathways to cause vasorelaxation or vasoconstriction. Oxytocin stimulation of PI3K/eNOS-derived nitric oxide may participate in maintenance of cardiovascular homeostasis, and different vascular reactivities to low or high dose of oxytocin suggest that oxytocin may have different regulatory effects on vascular tone under physiological or pathophysiological conditions.