Nitric Oxide Levels Research Articles

Protective Effect of Lavandula officinalis on Pentylenetetrazol-Induced Epilepsy in Mice: Expression of NOS Genes and Caspase-3

Abstract Objective Given the incidence of epilepsy and the adverse effects of unconventional antiepileptic medicines, there is a need for a novel medical treatment strategy for epileptic patients. Material and Methods The current study involved the selection of 80 male mice, which were then separated into 10 experimental groups: pentylenetetrazol (PTZ), negative control which received normal saline, treatment which received Lavandula officinalis in two doses of 200 and 400 mg/kg, L. officinalis 200 mg/kg and 1400 w, L. officinalis 200 mg/kg and 7-NI, L. officinalis 200 mg/kg and diphenylene iodonium chloride (DPI), L. officinalis 400 mg/kg and 1400 w, L. officinalis 400 mg/kg and 7-nitroindazole (7-NI) and group which received L. officinalis 400 mg/kg and DPI. Each group was stimulated with an 11-day injection cycle (every 48 hours) of PTZ at a dosage of 35 mg/kg. All groups underwent PTZ challenge dosage (75 mg/kg) testing during the 12th injection. Ultimately, the brains of all mice were extracted, and the activity of genes related to neuronal nitric oxide, inducible nitric oxide, and endothelial nitric oxide was assessed. The enzyme-linked immunosorbent assay (ELISA) method was used to assess the quantity of caspase-3 in the groups. Results Lavandula officinalis decreased the severity of seizures. The findings of our study demonstrated that the extract had a suppressive effect on the expression of inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS; p < 0.05), while it had a stimulatory effect on endothelial NOS (eNOS; p < 0.05). In addition, L. officinalis reduced caspase-3 levels in the groups who were administered the extract. Conclusion The hydroalcoholic extract of L. officinalis has been found to be effective. Lavandula officinalis enhanced the expression of endothelial nitric oxide and reduced the levels of neuronal and inducible nitric oxide to a greater extent in brain tissue affected by epilepsy. The groups receiving extract derived from L. officinalis exhibited a reduction in the level of caspase-3.

JNK inhibitor and ferroptosis modulator as possible therapeutic modalities in Alzheimer disease (AD)

Alzheimer disease (AD) is among the most prevalent neurodegenerative diseases globally, marked by cognitive and behavioral disruptions. Ferroptosis is a form of controlled cell death characterized by intracellular iron accumulation associated with lipid peroxide formation, which subsequently promotes AD initiation and progression. We hypothesized that targeting the ferroptosis pathway may help in AD management. Therefore, our study aimed to evaluate the potential neuroprotective effect of the antifungal Ciclopirox olamine (CPX-O) that acts through iron chelation. We employed CPX-O separately or in combination with the JNK inhibitor (SP600125) in a mice model of AlCl3-induced AD. Animals underwent examination for behavioral, biochemical, histological, and immunohistochemical findings. Our results revealed that AlCl3 was associated with disruptions in learning and memory parameters, neuronal degeneration in the hippocampus, increased immunoreactivity of amyloid-β and tau proteins, a significant rise in iron, nitric oxide (NO), malondialdehyde (MDA), JNK, and P53 levels, along with the significant decrease in glutathione peroxidase activity. Interestingly, the administration of CPX-O alone or in combination with SP600125 in the AlCl3-induced AD model caused an improvement in the previously described examination findings. Therefore, CPX-O may be a promising candidate for AD treatment, and future clinical trials will be required to confirm these preclinical findings.

Engineered microparticles modulate arginine metabolism to repolarize tumor-associated macrophages for refractory colorectal cancer treatment

BackgroundArginase is abundantly expressed in colorectal cancer and disrupts arginine metabolism, promoting the formation of an immunosuppressive tumor microenvironment. This significant factor contributes to the insensitivity of colorectal cancer to immunotherapy. Tumor-associated macrophages (TAMs) are major immune cells in this environment, and aberrant arginine metabolism in tumor tissues induces TAM polarization toward M2-like macrophages. The natural compound piceatannol 3ʹ-O-glucoside inhibits arginase activity and activates nitric oxide synthase, thereby reducing M2-like macrophages while promoting M1-like macrophage polarization.MethodsThe natural compounds piceatannol 3ʹ-O-glucoside and indocyanine green were encapsulated within microparticles derived from tumor cells, termed PG/ICG@MPs. The enhanced cancer therapeutic effect of PG/ICG@MP was assessed both in vitro and in vivo.ResultsPG/ICG@MP precisely targets the tumor site, with piceatannol 3ʹ-O-glucoside concurrently inhibiting arginase activity and activating nitric oxide synthase. This process promotes increased endogenous nitric oxide production through arginine metabolism. The combined actions of nitric oxide and piceatannol 3ʹ-O-glucoside facilitate the repolarization of tumor-associated macrophages toward the M1 phenotype. Furthermore, the increase in endogenous nitric oxide levels, in conjunction with the photodynamic effect induced by indocyanine green, increases the quantity of reactive oxygen species. This dual effect not only enhances tumor immunity but also exerts remarkable inhibitory effects on tumors.ConclusionOur research results demonstrate the excellent tumor-targeting effect of PG/ICG@MPs. By modulating arginine metabolism to improve the tumor immune microenvironment, we provide an effective approach with clinical translational significance for combined cancer therapy.

A Holistic View on Erectile Dysfunction: South African Medicinal Plants as Sustainable Alternative Therapies

Erectile dysfunction is a common problem affecting men worldwide, especially as they age. This condition is characterized by the inability to achieve or maintain an erection firm enough for sexual intercourse and may result from various factors, including vascular, neurogenic, hormonal, and psychological. Common first-line treatment options for the disease have relied on phosphodiesterase-5 inhibitors such as sildenafil (Viagra), which are costly, inaccessible, and sometimes result in adverse health effects. Consequently, there has been increasing interest in exploring medicinal plants as alternative remedies because of their easy access and affordability. In South Africa, 75 plant species with properties that affect testosterone levels, luteinizing hormone, and follicle-stimulating hormone are used as aphrodisiacs. Some plant extracts can increase blood testosterone concentrations and stimulate penile erection by maintaining nitric oxide levels. This paper presents current information about the possible utilization of South African medicinal plants as viable and readily available therapeutic alternatives for managing erectile dysfunction. In addition, it discusses in detail the various mechanisms of action of medicinal plants in managing the disease. The information on the efficacy of African medicinal plants in managing erectile dysfunction provided in this review will help increase awareness of the sustainable use of natural products. It may serve as a basis for including indigenous herbal remedies in the guidelines for erectile dysfunction management as potential treatment options in Africa.

Oxidative stress disrupts vascular microenvironmental homeostasis affecting the development of atherosclerosis.

Atherosclerosis is primarily an inflammatory reaction of the cardiovascular system caused by endothelial damage, leading to progressive thickening and hardening of the vessel walls, as well as extensive necrosis and fibrosis of the surrounding tissues, the most necessary pathological process causing cardiovascular disease. When the body responds to harmful internal and external stimuli, excess oxygen free radicals are produced causing oxidative stress to occur in cells and tissues. Simultaneously, the activation of inflammatory immunological processes is followed by an elevation in oxygen free radicals, which directly initiates the release of cytokines and chemokines, resulting in a detrimental cycle of vascular homeostasis abnormalities. Oxidative stress contributes to the harm inflicted upon vascular endothelial cells and the decrease in nitric oxide levels. Nitric oxide is crucial for maintaining vascular homeostasis and is implicated in the development of atherosclerosis. This study examines the influence of oxidative stress on the formation of atherosclerosis, which is facilitated by the vascular milieu. It also provides an overview of the pertinent targets and pharmaceutical approaches for treating this condition.

Trial of the cerebral perfusion response to sodium nitrite infusion in patients with acute subarachnoid haemorrhage using arterial spin labelling MRI

Aneurysmal subarachnoid haemorrhage (SAH) is a devastating subset of stroke. One of the major determinants of outcome is an evolving multifactorial injury occurring in the first 72 hours, known as early brain injury. Reduced nitric oxide (NO) bioavailability and an associated disruption to cerebral perfusion is believed to play an important role in this process. We sought to explore this relationship, by examining the effect on cerebral perfusion of the in vivo manipulation of NO levels using an exogenous NO donor (sodium nitrite).We performed a double blind placebo controlled randomised experimental medicine study of the cerebral perfusion response to sodium nitrite infusion during the early brain injury period in 15 low grade (World Federation of Neurosurgeons grade 1–2) SAH patients. Patients were randomly assigned to receive sodium nitrite at 10 mcg/kg/min or saline placebo. Assessment occurred following endovascular aneurysm occlusion, mean time after ictus 66h (range 34–90h). Cerebral perfusion was quantified before infusion commencement and after 3 hours, using multi-post labelling delay (multi-PLD) vessel encoded pseudocontinuous arterial spin labelling (VEPCASL) magnetic resonance imaging (MRI).Administration of sodium nitrite was associated with a significant increase in average grey matter cerebral perfusion. Group level voxelwise analysis identified that increased perfusion occurred within regions of the brain known to exhibit enhanced vulnerability to injury. These findings highlight the role of impaired NO bioavailability in the pathophysiology of early brain injury.

Attenuating susceptibility to ascites in cold-stressed broiler chickens fed canola meal-based diets by supplementing arginine or guanidinoacetic acid, either alone or in combination with phenylalanine.

The purpose of this study was to determine the effects of dietary supplementation of arginine (ARG) or guanidinoacetic acid (GAA), with or without phenylalanine (PHE), on the ascites susceptibility in the cold-stressed broilers fed canola meal (CM)-based diet. A total of 450 one-day-old male broiler chicks were randomly allocated to 30 floor pens with 6 replications for each of the 5 treatments. The dietary treatments were as follows: CM-based diet (control), CM-based diet+2.57g/kg ARG, CM-based diet+1.8g/kg GAA, CM-based diet+2.57g/kg ARG+1.5g/kg PHE and CM-based diet+1.8g/kg GAA+1.5g/kg PHE. The groups experienced cold stress induction starting at 32°C on day one, with gradual reductions to 15°C on days 21. The temperature was then held at 15°C for the remainder of the experiment. The supplements ARG+PHE and GAA+PHE resulted in improved feed conversion ratios (FCR) when compared to the control group. In comparison with the control group, supplementation of ARG and ARG+PHE decreased the ascites mortality by increasing the plasma nitric oxide level (NO), blood O2 partial pressure, blood O2 saturation (SO2), and decreasing the blood CO2 partial pressure (PCO2) and right ventricle to total ventricle (RV:TV) ratio. Supplementation of GAA and GAA+PHE also declined ascites mortality by reducing blood PCO2 while increasing blood SO2 and plasma NO levels. Although plasma corticosterone level and RV:TV ratio were similar between the GAA and control groups, adding GAA+PHE significantly reduced both compared to the control group. In summary, supplementing cold-stressed broiler chicken diets with 2.57g/kg ARG may alleviate hypertension. Additionally, 1.8g/kg GAA proves to be an effective substitute for dietary ARG in low-ARG diets, alleviating adverse effects from cold stress. Proper PHE formulation, at 1.5g/kg in this study, is crucial when using ARG and GAA supplements.

Ethiopian coffee (Coffea arabica) improves glucose uptake and modulates metabolic enzyme activities linked to hyperglycemia-induced infertility in isolated rats’ testes

The present study evaluated the inhibitory effect of Ethiopian coffee (Coffea arabica) on carbohydrate digestive enzymes and its protective effect against glucose-induced testicular dysfunction using in vitro and in silico study models. Testicular oxidative stress was initiated by co-incubating testocular tissue collected from male Sprague-Dawley rats in glucose solution with different concentrations of Ethiopian coffee aqueous extracts (hot and cold) for 2 h at 37ºC. Glucose-mediated oxidative stress significantly (p < 0.05) depleted reduced glutathione and total glycogen levels while it lowered catalase and superoxide dismutase (SOD) activities in the testicular tissue. Concomitantly, this led to elevated malondialdehyde and nitric oxide levels while it also increased glycogen phosphorylase, fructose-1,6-bisphosphatase, ATPase, and acetylcholinesterase activities. Treatment with different concentrations of coffee aqueous extracts restored the enzymes’ and markers’ levels and activities. Although both the cold and hot coffee extracts strongly inhibited α-glucosidase and α-amylase enzymes, the former showed better activities. The subjection of the coffee extracts to LC-MS analysis indicated the presence of several compounds, including chlorogenic acid, caffeic acid, cafestol, kahweol, caffeine, quinic acid, ferulic acid, and catechol which were further docked with the carbohydrate digestive enzymes. The in silico results displayed that among the various metabolites, chlorogenic acid strongly interacted and had the best binding affinity with α-glucosidase and α-amylase. Our findings implied that Ethiopian coffee may have a preventive effect against glucose-induced testicular damage. These are evidenced by the capacity of the plant product to decrease oxidative stress and protect against testicular dysfunction.Graphical

Nitric oxide participates in sucrose-TOR signaling during meristem activation in Arabidopsis thaliana.

This study provides evidence about the relationship between Target of Rapamycin (TOR) kinase and the signal molecule nitric oxide (NO) in plants. We showed that sucrose (SUC)-mediated TOR activation of root apical meristem (RAM) requires NO and that NO, in turn, participates in the regulation of TOR signaling. Nitric oxide (NO) constitutes a signal molecule that regulates important target proteins related to growth and development and also contributes to metabolic reprogramming that occurs under adverse conditions. Taking into account the important role of NO and its relationship with Target of Rapamycin (TOR) signaling in animals, we wondered about the putative link between both pathways in plants. With this aim, we studied a TOR-dependent process which is the reactivation of the root apical meristem (RAM) in Arabidopsis thaliana. We used pharmacological and genetic tools to evaluate the relationship between NO and TOR on the sugar induction of RAM, using SNP as NO donor, cPTIO as NO scavenger and the nitrate reductase (NR) mutant nia2. The results showed that sucrose (SUC)-mediated TOR activation of the RAM requires NO and that NO, in turn, participates in the regulation of TOR signaling. Interestingly, TOR activation induced by sugar increased the NO levels. We also observed that NO could mediate the repression of SnRK1 activity by SUC. By computational prediction we found putative S-nitrosylation sites in the TOR complex proteins and the catalytic subunit of SnRK1, SnRK1.1. The present work demonstrates for the first time a link between NO and TOR revealing the complex interplay between the two pathways in plants.

Exploring the protective role of green tea extract against cardiovascular alterations induced by chronic REM sleep deprivation via modulation of inflammation and oxidative stress

BackgroundChronic Rapid eye movement (REM) sleep deprivation has been associated with various cardiovascular alterations, including disruptions in antioxidant defense mechanisms, lipid metabolism, and inflammatory responses. This study investigates the therapeutic potential of green tea extract (GTE) in mitigating these adverse effects.MethodsA total of 24 male Wistar albino rats were used in this study and divided into the control group (n = 8), Chronic-REM Sleep Deprivation (CRSD) Group (n = 8) and Chronic-REM SD + Green Tea 200 (CRSD + GTE200) Group (n = 8). After 21 days, a comprehensive analysis of paraoxonase (PON1), arylesterase (ARE), malondialdehyde (MDA), glutathione (GSH), nitric oxide (NOx), proinflammatory cytokines, and lipid profiles in aortic tissue, heart tissue, and serum was conducted in a sleep-deprived rat model.ResultsChronic REM sleep deprivation led to a significant reduction in PON1 and ARE levels in aortic (p = 0.046, p = 0.035 respectively) and heart tissues (p = 0.020, p = 0.019 respectively), indicative of compromised antioxidant defenses. MDA levels increased, and NOx levels decreased, suggesting oxidative stress and impaired vascular function. Lipid profile alterations, including increased triglycerides and total cholesterol, were observed in serum. Elevated levels of inflammatory cytokines (IL-6 and TNF-alpha) further indicated an inflammatory response (p = 0.007, p = 0.018 respectively). GTE administration demonstrated a protective role, restoring antioxidant enzyme levels, suppressing lipid peroxidation, and improving NOx levels.ConclusionThese findings suggest the therapeutic potential of GTE in alleviating the cardiovascular impairments of chronic REM sleep deprivation, emphasizing its candidacy for further clinical exploration as a natural intervention in sleep-related disorders and associated cardiovascular risks.

Effects of Amphotericin B-Conjugated Functionalized Carbon Nanoparticles in the Treatment of Cutaneous Leishmaniasis.

Leishmaniasis is a parasitic disease spread by the bite of an infected sandfly and caused by protozoan parasites of the genus Leishmania. Currently, there is no vaccine available for leishmaniasis in humans, and the existing chemotherapy methods face various clinical challenges. The majority of drugs are limited to a few toxic compounds, with some parasite strains developing resistance. Therefore, the discovery and development of a new anti-leishmanial compound is crucial. One promising strategy involves the use of nanoparticle delivery systems to accelerate the effectiveness of existing treatments. In this study, Amphotericin B (AmB) was incorporated into functionalized carbon nanotube (f-CNT) and evaluated for its efficacy against Leishmania major in vitro and in a BALB/c mice model. The increase in footpad thickness was measured, and real-time PCR was used to quantify the parasite load post-infection. Levels of nitric oxide and cytokines IL-4 and IFN-γ were also determined. We found that f-CNT-AmB significantly reduced the levels of promastigotes and amastigotes of the Leishmania parasite. The nanoparticle showed strong anti-leishmanial activity with an IC50 of 0.00494 ± 0.00095 mg/mL for promastigotes and EC50 of 0.00294 ± 0.00065 mg/mL for amastigotes at 72 h post-infection, without causing harm to mice macrophages. Treatment of infected BALB/c mice with f-CNT-AmB resulted in a significant decrease in cutaneous leishmania (CL) lesion size in the foot pad, as well as reduced Leishmania burden in both lymph nodes and spleen. The levels of nitric oxide and IFN-γ significantly increased in the f-CNT-AmB treated groups. Also, our results showed that the level of IL-4 significantly decreased after f-CNT-AmB treatment in comparison to other groups. In conclusion, our results demonstrate that AmB loaded into f-CNT is significantly more effective than AmB alone in inhibiting parasite propagation and promoting a shift towards a Th1 response.

The Regulatory Effect of Remifentanil on JNK Signaling during Remission of Flap Ischemia-Reperfusion Injury.

The impact of remifentanil on hypogastric flap function following ischemia-reperfusion (I/R) injury remains largely unknown, limiting its potential clinical application in flap surgery. This study investigated the therapeutic effects of remifentanil on hypogastric flap I/R injury. Aortic endothelial cells were extracted from the hypogastric flap I/R injury models established in-house using Sprague-Dawley rats, and were treated under hypoxic conditions. The cells were treated with 0.1, 1, 10 and 100 ng/mL remifentanil and 10 ng/mL anisomycin (the activator of c-Jun N-terminal kinase [JNK]). Histopathological changes and tumor necrosis factor alpha (TNF-α) content of the flaps were observed after hematoxylin-eosin staining and immunohistochemistry. Immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and flow cytometry were employed for apoptosis evaluation. Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were utilized to assess the protein and gene expression levels of TNF receptor 1 (TNFR1), JNK1, phosphorylated (p)-JNK1, malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO) and TNF-α in the flaps and cells. The endothelial necrosis and cell apoptosis of rat flaps induced by I/R injury were ameliorated by remifentanil, and declining aortic endothelial cell viability and augmented apoptosis induced by hypoxia were reversed by remifentanil (10, 100 ng/mL) (p < 0.05). Remifentanil reversed the increased expressions of TNFR1, JNK1, p-JNK1, MDA and TNF-α induced by I/R injury or hypoxia in the flaps and cells (p < 0.05), and counteracted the decreased levels of NO and SOD induced by I/R injury in the flaps (p < 0.05). Anisomycin reversed the effects of remifentanil on suppressing TNFR1, JNK1 and p-JNK1 levels and apoptosis in the cells (p < 0.05). Remifentanil ameliorates cell apoptosis and vascular endothelial necrosis induced by I/R injury in the hypogastric flap, likely by downregulating the TNF-α/TNFR1 pathway and JNK1 signaling. These findings suggest that remifentanil may be a promising therapeutic agent for improving hypogastric flap survival in clinical settings.

Effects of the Slow-release Curcumin-loaded Selenium Nanoparticles on Experimental Peritonitis

Background: New pharmaceutical forms of natural compounds such as curcumin can be an effective intervention to control peritonitis and abdominal adhesion. Objectives: This study investigates the effects of slow-release curcumin-loaded selenium nanoparticles (Cur@S.N) on some inflammatory biomarkers in experimental peritonitis. Methods: After synthesizing selenium nanoparticles (S.N) and (Cur@S.N), experimental peritonitis was surgically induced in 80 adult male rats. The control group received no treatment, whereas the other groups received single intraperitoneal doses of 0.25 mg/kg S.N, 50 mg/kg curcumin, and 0.25+50 mg/kg (Cur@S.N). Blood malondialdehyde (MDA), nitric oxide (NO), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNFα) were measured on days 3, 7 and 14, and also intra-abdominal adhesion assessment was done. Results: On day 3, NO levels in all treatment groups significantly decreased (P&gt;0.05), while the lowest level was seen on day 14 in the S.N group (P˂0.05). MDA was significantly lower in the S.N and Cur@S.N groups than in the control on days 3, 7 and 14 (P˂0.05). TNF-α levels in S.N and Cur@S.N groups were significantly lower than in the control group on day 3 (P≤0.05). Meanwhile, the S.N group had the lowest level on day 14. IL-6 significantly decreased on days 3 and 7 in the Cur@S.N and curcumin groups compared to the control group (P˂0.05). Conclusion: Cur@S.N group possesses significant anti-inflammatory efficacy by reducing MDA, NO, IL-6 and TNF-α, decreasing peritonitis and intra-abdominal adhesion.

Effect of low-molecular-weight heparin calcium combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function and pregnancy outcome in early-onset severe preeclampsia.

This paper was aimed at unveiling the effect of low-molecular-weight heparin calcium (LMWH) combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function, and pregnancy outcome in early-onset severe preeclampsia (EOSP). Pregnant women with EOSP were divided into the control group and the study group, each with 62 cases. Patients in the control group were treated with labetalol and magnesium sulfate, and those in the study group were treated with LMWH in combination with the control grou Blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), 24-h urine protein, coagulation indices [D-dimer (D-D), plasma fibrinogen (Fg), prothrombin time (PT), activated partial thromboplastin time (APTT), and prothrombin time (TT)], endothelial function [endothelin (ET-1) and nitric oxide (NO)], oxidative stress indices [oxidized low-density lipoproteins (ox-LDL), lipid peroxidation (LPO), superoxide dismutase (SOD), and malondialdehyde (MDA)], pregnancy outcome, and adverse effects occurred in the two groups were compared. After treatment, lower SBP, DBP, and 24-h urine protein levels; lower Fg and D-D levels; higher PT, APPT, and TT levels; higher NO levels; lower ET-1 levels; lower ox-LDL, MDA, and LPO levels; higher SOD levels; and lower incidence of adverse pregnancy and adverse reactions were noted in the study group in contrast to the control group. EOSP patients given with LMWH combined with magnesium sulfate and labetalol can effectively reduce the patient's blood pressure and urinary protein level; improve coagulation function, oxidative stress, and vascular endothelial function indices; reduce the adverse pregnancy outcomes; and improve the safety of treatment.

The Role of Inducible Nitric Oxide Synthase in Assessing the Functional Level of Coronary Artery Lesions in Chronic Coronary Syndrome.

Chronic coronary syndrome (CCS) is a long-term manifestation of coronary artery disease, marked by stable but recurring chest pain and myocardial ischemia due to the gradual buildup of atherosclerotic plaques in the coronary arteries. It is a metabolic disorder of coronary arteries characterized by oxidative stress, endothelial dysfunction, inflammation, and hyperlipidemia. The imbalance in oxidative-antioxidative status contributes to stable ischemic heart disease. Oxidative stress involves reactive oxygen and nitrogen species, leading to low-density lipoprotein (LDL) oxidation. Endothelial dysfunction, marked by reduced nitric oxide (NO) bioavailability, is an early onset of CCS, affecting vasodilation, cell proliferation, and inflammatory responses. Enzyme myeloperoxidase (MPO), traditionally considered protective, plays a dual role in initiating and progressing inflammatory diseases. MPO interacts with NO, modulating its catalytic activity. Elevated NO levels inhibit MPO through a reversible complex formation, preventing NO-induced inhibition by inducible nitric oxide synthase (iNOS). MPO also inactivates endothelial nitric oxide synthase (eNOS) and reacts with L-arginine, hindering NO synthesis. The interplay between MPO and NO significantly influences inflammation sites, impacting peroxidation rates and oxidation reactions. Peroxynitrite, a reactive species, contributes to nitration of tyrosine residues and lipid peroxidation. Mechanistic pathways suggest MPO enhances iNOS catalytic activity, influencing CCS development. iNOS, implicated in inflammation and atherosclerosis, is connected to NO regulation. This review analyzes the complex interplay of MPO, iNOS, and NO that affects plaque morphology, oxidative stress, and inflammation, contributing to atherosclerosis progression. Therefore, it is possible that the phenotypes of atherosclerotic plaques, focal and diffuse coronary artery disease, could be defined by the relationship between MPO and iNOS.

Chrysin Enhances Anti-Cancer Activity of Jurkat T Cell and NK-92 Cells Against Human Breast Cancer Cell Lines.

Chrysin, a naturally occurring flavonoid in plant and bee products, demonstrates notable biological activities, including anti-cancer effects. These properties are partially attributed to its capability to activate immune cells. This study focused on exploring the immunomodulatory potential of chrysin on NK-92 and Jurkat-T cells targeting breast cancer cells (BCC). Chrysin leads to activation of NK-92 and T cells facilitated by the addition of human recombinant IL-2 and PHA-M. The anti-cancer efficacy of chrysin on these immune cells was evaluated in a co-culture setup with EGF-stimulated MCF-7 and MDA-MB-231 cells. Findings revealed that chrysin notably increased the cytotoxicity of NK-92 and T cells towards MCF-7 and MDA-MB-231 cells, with the most significant impact observed on MCF-7 cells (20 %). The activation of NK-92 cells, marked by increased IFN-γ production and CD56 expression, correlated with enhanced secretion of cytokines. Additionally, the activation of these cells against BCC was linked with elevated levels of granzyme-B, TNF-α, and nitric oxide (NO). Similarly, the cytotoxic activation of Jurkat-T cells against BCC was characterized by increased production of granzyme-B, IL-2, and IFN-γ. Consequently, these results support the hypothesis that chrysin significantly contributes to the activation and functional enhancement of NK-92 and T-cells against two distinct BCC lines.

Investigation of blood pressure regulatory effect of bioactive peptides in complex enzyme-assisted hydrolysate from Paralichthys olivaceus

This study aimed to identify the bioactive peptides of protamex-pepsin hydrolysate obtained from Paralichthys olivaceus (POppH) and to investigate their potential vasorelaxation and blood pressure regulatory properties, both in vitro and in vivo. The effects of the peptides on endothelium-derived relaxing factors (EDRFs), such as nitric oxide and hydrogen sulfate levels, were analyzed in EA.hy926 cells, and the vasorelaxation-related PI3K/AKT/eNOS pathway activity was analyzed in EA. hy926 cells. An in vitro study revealed that POppH and leucine-glutamic acid-arginine (IER) peptide did not show any cytotoxic effects and significantly increased EDRF production via the regulation of vasorelaxation-associated PI3K/AKT/eNOS protein expression in EA.hy926 cells. An in vivo study suggested that oral administration of IER reduced systolic, diastolic, and mean arterial blood pressure in a spontaneously hypertensive rat model. The bioactive peptide IER derived from Paralichthys olivaceus could be used in the development of functional food products with blood pressure regulatory properties.

Aloe ferox leaf gel extracts attenuate redox imbalance in oxidative renal injury and stimulates glucose uptake, whilst inhibiting key enzymes linked to diabetes and obesity

The worldwide prevalence of diabetes and obesity is growing rapidly. Both metabolic disorders are linked to chronic adverse complications, which include kidney dysfunctions. Medicinal plants play a crucial role in traditional healthcare, especially in developing countries. Aloe ferox, native to South Africa, has a long history of medicinal use, but its pharmacological potential is less studied compared to other Aloe species, necessitating further investigation. Therefore, the present study was conducted to determine the antioxidative, anti-obesogenic, and antidiabetic effects of A. ferox leaf gel extracts using in vitro, ex vivo, and in silico experimental models, with oxidative renal damage induced by ferrous sulfate (FeSO4). A. ferox leaf gel extracts exhibited strong antioxidant activity, inhibited digestive enzymes, and significantly improved glucose uptake. The aqueous extract demonstrated better antioxidant efficacy, leading to higher reduced glutathione (GSH) level, and superoxide dismutase (SOD) and catalase enzymes activity, along with a concurrent reduction of nitric oxide (NO) and malondialdehyde (MDA) levels. Likewise, the aqueous extract showed more potent in vitro DPPH, NO, and OH• radical scavenging activity with IC50 values of 3.64 ±0.3 μg/mL, 110.73±0.1 μg/mL, and 331.13 ±0.7 μg/mL, respectively. The aqueous extract had better inhibition of the enzyme α-amylase (IC50 = 25.73±2.5 µg/mL), whilst the ethanolic extract inhibited α-glucosidase (IC50 =663.2±0.3 µg/ml), and pancreatic lipase (IC50 =122.01±5.9 µg/mL) more strongly. Incubation of the extracts with yeast cells stimulated glucose uptake dose dependently, when ethanolic extract (IC50 = 308.01±0.7 µg/mL) showed the better activity compared to the aqueous extract (IC50 = 338.79±7.05 µg/mL). Furthermore, LC-MS analysis led to the identification of many compounds, when chlorogenic acid demonstrated a stronger molecular interaction with the active site amino acids of α-amylase and catalase compared to other compounds. However, Aloin B showed the highest affinity with α-glucosidase and 5-Hydroxyaloin A showed the lowest binding energy with lipase, and SOD enzyme. These results suggest the reno-protective effects of A. ferox leaf gel extracts against FeSO4-induced oxidative stress along with its anti-hyperglycaemic activity. Given these observed effects, A. ferox leaf gel could indeed be valuable in developing natural therapies and potential drug development for the management of these disorders. Further studies in animal models are needed to ascertain the results of this study.

Intranasal Administration of Standardized Extract of Gotu Kola Leaves Against Nitroglycerine-Induced Recurrent Migraine-Like Pain in Rats

The present study aimed to determine the efficacy of intranasal administration of a standardized extract of Gotu kola, i.e., Centella asiatica (L.) Urban (INDCA-NS) with marker triterpenoids for the prevention of nitroglycerine- (NTG)-induced recurrent migraine in rats. Adult rats of both sexes in a group of 12 were administered intraperitoneal NTG (10 mg/kg) on alternate days (D1 to D9) and once daily intranasal solutions of either vehicle (saline, 50 µL/rat/day), sumatriptan (80 µL/rat/day of 12 mg/ml) as positive control, or INDCA-NS (10, 30, or 100 µg/rat/day) for 21 days. Behavioral and biochemical parameters related to concurrent migraine pain (facial expressions on the grimace scale, thermal hyperalgesia, mechanical allodynia, and plasma and brain levels of pituitary adenylate cyclase-activating polypeptide and nitric oxide), and stress (photophobia and cortisol levels in the brain and serum) were measured. The intranasal administration of INDCA-NS prevented NTG-induced migraine-like pain, photophobia, and stress in a dose-dependent manner. At the same time, sumatriptan alleviated pain and anxiety but not photophobia. In conclusion, the intranasal administration of INDCA-NS showed prophylactic efficacy against recurrent NTG-induced migraine pain in rats.

Evaluation of anti-hypertensive activity of Quercus leucotrichophora A. camus methanolic extract on DOCA-salt induced hypertensive rats

Quercus leucotrichophora A. camus, commonly known as Banj oak or Ban tree, belongs to the Fagaceae family and is abundantly found in the regions of Shimla, Kullu-Manali, and upper Mandi in Himachal Pradesh. This study explores the medicinal properties of plant seeds, known for their antioxidant and diuretic activity, traditionally utilized in the treatment of hypertension and hypolipidemic, hepatoprotective conditions. PurposeTo investigate the antihypertensive effect of methanolic extract of Quercus leucotrichophora A. camus seeds in DOCA sat induced rats. Material and methodsGround seeds of Quercus leucotrichophora A. camus were stored in an airtight container. A total of 100 gs of dried seed powder were subjected to extraction using 250 ml of methanol and a Soxhlet extractor maintained at 60–65 °C for five hours. The resulting dried extract (5 gs) was stored in an airtight container in a refrigerator at low temperature and administered by rats to test its antihypertensive impact. The assessment of obtained extract impact on hypertension induced by DOCA-salt was conducted through blood pressure measurement and biochemical analysis. ResultsOur study revealed that the methanolic extract of Quercus leucotrichophora A. camus seeds exerted blood pressure-lowering effects, associated with an increase in serum Nitric Oxide (NO) levels. The attenuation of hypertension by extract was further linked to the normalization of serum Na+ and K+concentrations, indicating an improvement in electrolyte imbalance. Additionally, the antioxidant properties of Quercus leucotrichophora A. camus were evident through increased activities of Glutathione (GSH), Glutathione Peroxidase (GHPx), Superoxide Dismutase (SOD), and decrease activity of Thiobarbituric acid reactive substances (TBARS). ConclusionThe findings of our investigation suggest that the antihypertensive action of Quercus leucotrichophora A. camus is correlated with enhanced endothelial nitric oxide synthase (eNOS) activation and an augmented antioxidant defense system. This sheds light on the potential therapeutic benefits of plant under investigation in managing hypertension, emphasizing its role in promoting cardiovascular health. Further research is warranted to elucidate the underlying mechanisms and to explore the full pharmacological potential of Quercus leucotrichophora A. camus in the field of cardiovascular medicine.