Vasodilatory Properties Research Articles

Imperatorin inhibits oxidative stress injury and neuroinflammation via the PI3K/AKT signaling pathway in the MPTP-induced Parkinson's disease mouse.

Parkinson's disease (PD) is a disorder of neurodegeneration. Imperatorin is an active natural furocoumarin characterized by antioxidant, anti-inflammatory, and potent vasodilatory properties. Therefore, we aimed to investigate the biological functions of imperatorin and its mechanisms against PD progression. C57BL/6 mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg) daily for 5 consecutive days to mimic PD conditions in vivo. The MPTP-induced PD model mice were intraperitoneally injected with imperatorin (5 mg/kg) for 25 consecutive days after MPTP administration. The motor and cognitive functions of mice were examined by rotarod test, hanging test, narrow beam test and Morris water maze test. After analysis of MWM test, the expression levels of tyrosine hydroxylase and Iba-1 in the substantia nigra pars compacta were measured by immunohistochemistry staining, immunofluorescence staining and western blotting. The expression levels of striatal dopamine and its metabolite 3,4-dihydroxyphenylacetic acid were also measured. The protein levels of inducible nitric-oxide synthase, cyclooxygenase-2, phosphorylated phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (Akt) in the mouse striatum were estimated by western blotting. The expression levels of proinflammatory cytokines including tumor necrosis factor, interleukin (IL)-1β and IL-6 in the mouse striatum were measured by ELISA kits. The expression levels of superoxide dismutase, malondialdehyde and glutathione in the mouse midbrains were measured with commercially available kits. TUNEL staining was performed to identify the apoptosis of midbrain cells. Histopathologic changes in the mouse striata were assessed by hematoxylin-eosin staining. Imperatorin treatment markedly improved spatial learning and memory abilities of MPTP-induced PD mice. The MPTP-induced dopaminergic neuron loss in the mouse striata was inhibited by imperatorin. Imperatorin also suppressed neuroinflammation and neuronal oxidative stress in the midbrains of MPTP-induced PD mice. Mechanistically, imperatorin treatment inhibited the MPTP-induced reduction in the PI3K/Akt pathway. Imperatorin treatment can prevent dopaminergic neuron degeneration and improve cognitive functions via its potent antioxidant and anti-inflammatory properties in an MPTP-induced PD model in mice by regulating the PI3K/Akt pathway.

On the cardiovascular effects mechanism of humic nature macromolecular compounds

Introduction. The search for new drugs to reduce effectively myocardial damage during ischemia and reoxygenation is relevant considering that many pharmacological drugs have a number of limitations for patients and their use is accompanied by negative side effects.Aim: To assess the NO-synthase possible role in the cardiovascular effects mechanism of the standardized active pharmaceutical substance (AFS) of the humic acids (HA) isolated from peat.Material and Methods. The experiments were carried out on the isolated perfused rat heart model using the Langendorff method. We studied the effect of a standardized sample of peat HA at concentrations of 0.001; 0.01; 0.1 mg/ml on coronary perfusion rate and myocardial contractility parameters. To assess the NO-synthase value in the HA effects realization, the enzyme was pre-inhibited using L-NAME (10 µM/L) before the test sample addition.Results. HA sample using contributed to an effective increase in the heart coronary perfusion rate due to the NO-synthase signaling mechanism activation. There was some decrease in contractility and end-diastolic pressure associated with the NOsynthase activation because the enzyme inhibition with L-NAME removed all effects of the test HA sample.Conclusion. The obtained data show to the peat HA have vasodilating properties associated with the NO-synthase activation. The such effect presence indicates on the prospects for further investigation of these compounds cardiotropic properties in the order developing new effective means for improving intracardiac hemodynamics and limiting Ca2+ overload of cardiomyocytes in conditions of ischemia and reperfusion.

Uporedno spektrofotometrijsko određivanje 3-hidroksiflavona bazirano na kompleksima cinka i aluminijuma i njihovi antioksidatni profili

Flavonoids, as plant-derived compounds, were essential active components in traditional medicine for centuries. Their potential or confirmed effects include antiviral, antimutagenic, antiinflammatory, antibacterial, vasodilatory, and anticancer properties. The promotion of a plantbased diet, along with the benefits of consuming flavonoids, has recently become increasingly attractive. 3-Hydroxyflavone (3HF) is the structural spine of flavonols, an important subgroup of flavonoids. Although 3HF itself does not exist in plants per se, it exerts many of its effects because of its characteristics that allow it to prevent free radical generation. This work is focused on the characterization of 3HF complexes with zinc(II) and aluminium(III) ions (Zn-3HF and Al-3HF, respectively). Besides this, a simple, fast, and low-priced spectrophotometric method for 3HF determination, with very low LOD and LOQ, based on Zn-3HF and Al-3HF formation, was established. A slight advantage is given to the modification with Al3+ ion on pH 4.91, due to very low LOD and LOQ values of 1.83×10-7 molL-1 , and 5.50×10-7 molL-1 , respectively, and a high correlation coefficient, R =0.99986. Furthermore, the antioxidant ability of Zn-3HF, Al-3HF, and parent 3HF was examined by the ABTS and DPPH tests. They brought the Zn-3HF complex to the fore as a potential antioxidative agent.

Impact of vasodilators on diuretic response in patients with congestive heart failure: A mechanistic trial of cimlanod (BMS-986231).

To investigate the effects of Cimlanod, a nitroxyl donor with vasodilator properties, on water and salt excretion after an administration of an intravenos bolus of furosemide. In this randomized, double-blind, mechanistic, crossover trial, 21 patients with left ventricular ejection fraction <45%, increased plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and receiving loop diuretics were given, on separate study days, either an 8 h intravenous (IV) infusion of cimlanod (12 μg/kg/min) or placebo. Furosemide was given as a 40 mg IV bolus four hours after the start of infusion. The primary endpoint was urine volume in the 4 h after the bolus of furosemide during infusion of cimlanod compared with placebo. Median NT-proBNP at baseline was 1487 (interquartile range: 847-2665) ng/L. Infusion of cimlanod increased cardiac output and reduced blood pressure without affecting cardiac power index consistent with its vasodilator effects. Urine volume in the 4 h post-furosemide was lower with cimlanod (1032 ± 393 ml) versus placebo (1481 ± 560 ml) (p = 0.002), as were total sodium excretion (p = 0.004), fractional sodium excretion (p = 0.016), systolic blood pressure (p < 0.001), estimated glomerular filtration rate (p = 0.012), and haemoglobin (p = 0.010), an index of plasma volume expansion. For patients with heart failure and congestion, vasodilatation with agents such as cimlanod reduces the response to diuretic agents, which may offset any benefit from acute reductions in cardiac preload and afterload.

Effect of beta blockers on optical coherence tomography angiography in normal, suspect, and glaucomatous eyes: A prospective study.

The study aimed to assess the effect of hypertension, and use of systemic beta blockers (BB) and other antihypertensives on ocular perfusion by optical coherence tomography angiography (OCTA) in normal, suspect, and glaucomatous eyes. Cross-sectional study in tertiary eye care center. Prospectively recruited consenting subjects between 18 and 90 years with or without glaucoma. Measured the optic nerve peripapillary perfusion and flux and macular vessel density (MVD: 6 × 6 and 3 × 3 mm) in the superficial retinal layer using OCTA. Included 200 eyes (112 patients). Compared to nonhypertensives or those on non-BB antihypertensives (NBB), hypertensives on BB had lower peripapillary perfusion (43.45,43.40, 42.05%, P = 0.003), and MVD (6 × 6 mm: 16.65, 16.70,15.75 mm/mm 2 , P = 0.002; 3 × 3 mm: 18.70, 18.50, 18.00 mm/mm 2 , P = 0.025). Those on systemic BB with vasodilatory properties had similar perfusion parameters as nonhypertensives and NBB. Those on systemic BB without vasodilating properties had significantly lower peripapillary perfusion (42.05 vs 43.30%, P = 0.011) and MVD (6 × 6 mm: 15.15 vs 16.60 mm/mm 2 , P < 0.001; 3 × 3 mm: 17.40 vs 18.70 mm/mm 2 , P = 0.005) compared to nonhypertensives. On multivariate analysis, peripapillary perfusion increased with increase in diastolic blood pressure (β:0.051, p: 0.04) and increasing age was the only factor found to be significantly associated with decreased peripapillary and macular perfusion parameters. Systemic BB users have worse ocular perfusion parameters compared to those on other medications or nonhypertensives on univariate analysis but similar perfusion on multivariate analysis. Those on BB with vasodilation have better ocular perfusion parameters. All BB cannot be considered equally detrimental to ocular perfusion. Further well-controlled prospective studies are needed to reassess the effects of BB with or without vasodilation on ocular perfusion.

FORCED DEGRADATION STUDIES OF VINCAMINE BY HPTLC

Vincamine is an alkaloid with vasodilator properties. Vinpocetine, a semi-synthetic vincamine derivative alkaloid, is used to treat cerebrovascular diseases like stroke and dementia. Being an important molecule, the current research work examines the forced degradation studies of vincamine using planar chromatography, HPTLC using stability studies parameters such as degradation by acid and base hydrolysis, oxidative stress degradation, hydrolytic induced degradation, photolytic degradation and dry heat degradation. The compound was found to be stable to oxidative stress, but significant degradation occurred under acid hydrolysis, base hydrolysis, water hydrolysis, and to a lesser extent, under thermal stress and photolytic stress. The percentage recovery of vincamine was found to be lower in acidinduced degradation (31.8 %), and base-induced degradation (8.2 %) than in UV-induced degradation (94.9 %) and dry heat-induced degradation (93.1 %). In pharmaceutical research and development, forced degradation experiments are essential for predicting long-term stability.

The selective Rho Kinase 2 inhibitor Chroman-1, is a potent vasodilator but does not compromise left ventricular function in-vivo

Abstract Background In the field of cardioprotection, focus is turning to limiting microvascular obstruction (MVO) post myocardial infarction. The development of MVO carries a poor prognosis, which is independent of infarct burden [1]. Commonly used vasodilators in the treatment of MVO e.g., Ca2+ blockers, beta-blockers can induce negatively inotropic effects. This is a serious problem as hypotension and shock during acute MI are harmful. Rho kinase (ROCK) inhibitors induce vasodilation by inhibiting the phosphorylation of myosin light chain kinase (MLC2) in vascular smooth muscle (VSMC) [2]. ROCK1/2 inhibitors are known to cause transient negative inotropic effects [3]. However, the potential side-effects of the selective ROCK2i, Chroman-1 (Ch1) are unknown. Purpose We aimed to i) Confirm the expression of ROCK2 mRNA in aorta and coronary vasculature, ii) To investigate the vasodilatory properties of Ch1 iii) To confirm that Ch1 does not acutely impair left ventricular ejection fraction (LVEF%) and blood pressure in-vivo. Methods RNA scope in-situ hybridisation was performed with a fluorescent, multiplex assay for ROCK1/2 &amp; VSMC mRNA in whole hearts, coronary vasculature and aorta from male SD rats. Thoracic aorta was dissected and 3mm segments suspended into a tissue bath. Vascular rings were constricted with 1µM PE and treated with [10-12]-[10-5]mM Ch1. In a separate set of in-vivo experiments, male SD rats 250-300g were anaesthetised with isoflurane, intubated and ventilated. LVEF% was measured in a closed chest model, following the addition of Ch1 (30-300µg/kg) or DMSO vehicle, administered i.p at 15-minute intervals. Mean arterial pressure (MAP, mmHg) and heart rate (BPM) were measured throughout. Results ROCK2 mRNA was localised to myocardium, aorta and coronary circulation VSMC. Figure 1 demonstrates that Ch1 induced dose dependent vasodilation of PE constricted aortic rings vs control (EC50 Ch1 95% CI [5.1e-008, 2.2e-007] n=6). In-vivo, Ch1 at all doses (30-300µg/kg) did not significantly affect LVEF% (p&amp;gt;0.05, n=5) nor average MAP at doses 30-100µg/kg (p&amp;gt;0.05, n=5). At the highest dose, i.e 300µg/kg, Ch1 decreased average MAP (mmHg) compared to control +/-SEM (76+/-7.1 vs 92+/-2.8, p=0.02, n=5), but not below 70mmHg threshold. Ch1 did not significantly affect mean heart rate at any dose (p&amp;gt;0.05, n=5). Conclusion The selective ROCK2 inhibitor Ch1, induces potent arterial vasodilation, without compromising LVEF% or haemodynamics. It is therefore, a suitable drug for further preclinical studies of MVO in ischaemia/reperfusion (I/R).Figure 1:Ch1 induces dose dependent vasodilation of aortic rings, **p&amp;lt;0.005, ***p&amp;lt;0.001

Abstract 16882: Comparison of Regadenoson and Adenosine in First Pass Quantitative Perfusion Cardiovascular Magnetic Resonance in Subjects With Suspected Coronary Microvascular Disease

Introduction: Regadenoson and adenosine are commonly used vasodilators in myocardial perfusion imaging for detection of coronary artery disease. There are no comparative studies of the vasodilator properties of two agents in subjects with suspected coronary microvascular disease (CMD). We aimed to compare the potency of two vasodilators by quantifying myocardial perfusion in subjects with suspected CMD. Methods: Subjects with angina and more than two risk factors for CMD (females, or males with diabetes, metabolic syndrome, HTN, hyperlipidemia, and smoking) who had no obstructive coronary disease by invasive coronary angiography or CT angiography were enrolled for first-pass perfusion images using dual sequence. Stress perfusion images were acquired on 1.5T or 3.0T GE Healthcare during adenosine infusion or regadenoson. Rest perfusion images were acquired either 10 minutes following the cessation of adenosine or reversal with aminophylline. Myocardial blood flow (MBF) in ml/min/g and myocardial perfusion reserve (MPR) were quantified using Fermi deconvolution. Results: A total of thirty-two subjects were recruited with a mean age of 62±11 years, 53% men, history of hypertension in 91%, diabetes in 72%, hyperlipidemia in 75%, and tobacco use in 16%. Twenty (63%) of subjects underwent adenosine, while twelve (38%) of subjects underwent regadenoson. Regadenoson produced similar stress MBF compared to adenosine (2.30 ± 0.54 vs. 2.35 ± 0.61 ml/min/g, p = 0.66). Rest MBF was higher in the regadenoson group compared to adenosine group (1.35±0.35 vs. 1.12±0.26 ml/min/g, p=0.07). MPR was non-significantly lower in regadenoson compared to adenosine 1.72±0.70 vs.1.89±0.53 ml/g/min, p=0.13). Conclusions: Based on fully quantitative perfusion using CMR, regadenoson and adenosine have similar vasodilator efficacy in subjects with risk factors for CMD. However, resting blood flows are slightly higher when regadenoson is used which may impact quantification of MPR.

Abstract 12468: One-Year Effects of Randomized High-Intensity Statin versus Placebo on the Bioactive Lipidome: Findings From the JUPITER Trial

Introduction: Statin effects extend LDL-C reduction, with the potential to modulate the metabolism of bioactive lipids (BALs), crucial metabolites for biological signaling and inflammation. Hypothesis: Statin allocated participants will have a different BAL profile with cardioprotective properties compared to placebo. Aim: To investigate the impact of high-intensity statin therapy versus placebo on plasma BALs in the JUPITER trial (NCT00239681), a randomized double-blinded primary prevention trial involving individuals with LDL-C &lt;130 mg/dL and high-sensitivity C-reactive protein ≥ 2 mg/L. Methods: Using a non-targeted mass spectrometry approach, over 15500 lipid features were assayed from baseline (BL) and 1-year (Y1) plasma samples from non-CVD cases from 2 nested JUPITER sub-studies: JUPITER discovery (N=589) and JUPITER validation (N=409). The effect of rosuvastatin 20mg vs . placebo on BALs was examined by fitting a linear regression with delta values (ΔBAL=BAL Y1 -BAL BL ) that adjusted for age (years) and baseline BAL level. Significant associations in discovery were carried over for validation. Multiple comparisons were adjusted using a two-stage overall False Discovery Rate (FDR) &lt;.05. Results: We identified 569 associations significantly validated (overall FDR&lt;.05), including 27 BALs with putative annotation. Statins increased levels of 302 BALs, such as specialized pro-resolving mediators (SPMs) and eicosanoids with anti-inflammatory activity in the vasculature (e.g. 5,6-diHETE), arterial vasodilation properties (hepoxilins), and a precursor of leukotrienes (5-HpETE). Among 267 BALs lowered by statins, there were arachidonic acid and inflammation-related lipid mediators (10 HDoHE, 5-HEPE, 11-HETE, 9-HODE, 11d-TXB2) (Fig1 A and B). Conclusions: Statins had pleiotropic effects on BAL metabolites, predominantly increasing anti-inflammatory and pro-resolution BALs and decreasing BALs with pro-inflammatory properties.

Electrochemistry of Flavonoids: A Comprehensive Review.

Flavonoids represent a large group of aromatic amino acids that are extensively disseminated in plants. More than six thousand different flavonoids have been isolated and identified. They are important components of the human diet, presenting a broad spectrum of health benefits, including antibacterial, antiviral, antimicrobial, antineoplastic, anti-mutagenic, anti-inflammatory, anti-allergic, immunomodulatory, vasodilatory and cardioprotective properties. They are now considered indispensable compounds in the healthcare, food, pharmaceutical, cosmetic and biotechnology industries. All flavonoids are electroactive, and a relationship between their electron-transfer properties and radical-scavenging activity has been highlighted. This review seeks to provide a comprehensive overview concerning the electron-transfer reactions in flavonoids, from the point of view of their in-vitro antioxidant mode of action. Flavonoid redox behavior is related to the oxidation of the phenolic hydroxy groups present in their structures. The fundamental principles concerning the redox behavior of flavonoids will be described, and the phenol moiety oxidation pathways and the effect of substituents and experimental conditions on flavonoid electrochemical behavior will be discussed. The final sections will focus on the electroanalysis of flavonoids in natural products and their identification in highly complex matrixes, such as fruits, vegetables, beverages, food supplements, pharmaceutical compounds and human body fluids, relevant for food quality control, nutrition, and healthcare research.

Therapeutic Potential of Myrtenal and Its Derivatives-A Review.

The investigation of monoterpenes as natural products has gained significant attention in the search for new pharmacological agents due to their ability to exhibit a wide range in biological activities, including antifungal, antibacterial, antioxidant, anticancer, antispasmodic, hypotensive, and vasodilating properties. In vitro and in vivo studies reveal their antidepressant, anxiolytic, and memory-enhancing effects in experimental dementia and Parkinson's disease. Chemical modification of natural substances by conjugation with various synthetic components is a modern method of obtaining new biologically active compounds. The discovery of new potential drugs among monoterpene derivatives is a progressive avenue within experimental pharmacology, offering a promising approach for the therapy of diverse pathological conditions. Biologically active substances such as monoterpenes, for example, borneol, camphor, geraniol, pinene, and thymol, are used to synthesize compounds with analgesic, anti-inflammatory, anticonvulsive, antidepressant, anti-Alzheimer's, antiparkinsonian, antiviral and antibacterial (antituberculosis) properties. Myrtenal is a perspective monoterpenoid with therapeutic potential in various fields of medicine. Its chemical modifications often lead to new or more pronounced biological effects. As an example, the conjugation of myrtenal with the established pharmacophore adamantane enables the augmentation of several of its pivotal properties. Myrtenal-adamantane derivatives exhibited a variety of beneficial characteristics, such as antimicrobial, antifungal, antiviral, anticancer, anxiolytic, and neuroprotective properties, which are worth examining in more detail and at length.

Testosterone, atherosclerosis and cardiovascular risks

The study highlighted the most significant scientific works that examined the influence of androgen deficiency and its drug correction in coronary heart disease. The effects of androgens on metabolic parameters, development of atherosclerosis, inflammation, coagulation and thromboembolism, blood pressure, and development of cardiovascular complications were also evaluated. The importance of conducting long-term randomized international studies evaluating the effects of testosterone in men with androgen deficiency and cardiovascular diseases, a cautious approach to androgen replacement therapy, and the need for individualization of therapy were discussed. Cardiovascular diseases are the leading cause of mortality. Thus, the study of the role of sex steroids in the development of atherosclerosis and coronary heart disease is of great interest. Testosterone is the main sex hormone that determines a mans health. With age, testosterone levels gradually decrease, and mortality from cardiovascular complications increases. Low testosterone levels are associated with erectile dysfunction, decreased libido, decreased skeletal muscle mass, metabolic disorders, osteoporosis, and depression, and the importance of androgens for the circulatory system remains insufficiently studied. Many men receive testosterone replacement therapy, which leads to the improvement of well-being, sexual function, surge of strength, and favorable metabolic changes. The scientific literature describes the possible cardioprotective effect of testosterone, and it is believed to have vasodilating properties, shorten the QT interval, and normalize the ratio of fat and muscle mass. However, the expediency and safety of prescribing testosterone drugs to patients with hypogonadism and high cardiovascular risk is debatable because only several studies have described an increase in the number of cardiovascular complications in the androgen therapy group relative to the placebo group. Most studies on testosterone replacement therapy did not assess cardiovascular risks and excluded people with a recent stroke, heart attack, or severe heart failure. In addition, data interpretation is complicated by the lack of generally accepted international standards of testosterone for men of different ages, and most studies do not consider the change in androgen status relative to peak values at a young age and features of the receptor apparatus.

Eupatorin from Orthosiphon aristatus: A Review of The Botanical Origin, Pharmacological Effects and Isolation Methods

Abstract: Orthosiphon aristatus has been known for its medicinal uses. One of the compounds responsible for the pharmacological activities of O. aristatus is a flavonoid called Eupatorin (EUP). EUP has been studied for its pharmacological activities, including anti-inflammatory, vasodilating, antiproliferative, hepatoprotective, analgesic, and antidiabetic properties. Despite its importance and abundance, currently, there is no published paper that reviews the characteristics, pharmacological activities and isolation methods of EUP. This review summarizes the botanical origin, phytochemical characteristics, pharmacological activities, isolation, as well as identification and characterization methods of EUP from O. aristatus. This paper also compares different isolation methods based on the parameters and the resulting yields. Various isolation methods had been used to obtain EUP. Reverse-phase high-performance liquid chromatography (HPLC) is the most commonly used method to isolate EUP, followed by preparative thin layer chromatography (TLC) and crystallization for the purification. Various spectroscopic methods, including UV-Vis, FT-IR, Mass, and NMR spectroscopy have been commonly used to identify and characterize EUP. This paper provides a comprehensive insight into EUP from O. aristatus which might be beneficial for future research using this compound.

Hepatic ischemia-reperfusion syndrome and its effect on the cardiovascular system: The role of treprostinil, a synthetic prostacyclin analog.

Hepatic ischemia-reperfusion syndrome has been the subject of intensive study and experimentation in recent decades since it is responsible for the outcome of several clinical entities, such as major hepatic resections and liver transplantation. In addition to the organ's post reperfusion injury, this syndrome appears to play a central role in the dysfunction of distant tissues and systems. Thus, continuous research should be directed toward finding effective therapeutic options to improve the outcome and reduce the postoperative morbidity and mortality rates. Treprostinil is a synthetic analog of prostaglandin I2, and its experimental administration has shown encouraging results. It has already been approved by the Food and Drug Administration in the United States for pulmonary arterial hypertension and has been used in liver transplantation, where preliminary encouraging results showed its safety and feasibility by using continuous intravenous administration at a dose of 5 ng/kg/min. Treprostinil improves renal and hepatic function, diminishes hepatic oxidative stress and lipid peroxidation, reduces hepatictoll-like receptor 9 and inflammation, inhibits hepatic apoptosis and restores hepatic adenosine triphosphate (ATP) levels and ATP synthases, which is necessary for functional maintenance of mitochondria. Treprostinil exhibits vasodilatory properties and antiplatelet activity and regulates proinflammatory cytokines; therefore, it can potentially minimize ischemia-reperfusion injury. Additionally, it may have beneficial effects on cardiovascular parameters, and much current research interest is concentrated on this compound.

Puerarin prevents sepsis-associated encephalopathy by regulating the AKT1 pathway in microglia

BackgroundPrevious studies have reported that puerarin possesses cardioprotective, vasodilatory, anti-inflammatory, anti-apoptotic, and hypoglycemic properties. However, the impact of puerarin on sepsis-associated encephalopathy (SAE) remains unexplored. In this study, we explored whether puerarin can modulate microglia-mediated neuroinflammation for the treatment of SAE and delved into the underlying mechanisms. MethodsWe established a murine model of SAE through intraperitoneal injection of lipopolysaccharide (LPS). The puerarin treatment group received pretreatment with puerarin. For in vitro experiments, BV2 cells were pre-incubated with puerarin for 2 h before LPS exposure. We employed network pharmacology, the Morris Water Maze (MWM) test, Novel Object Recognition (NOR) test, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), Western blotting, and quantitative real-time PCR (qRT-PCR) to elucidate the molecular mechanism of underlying puerarin's effects in SAE treatment. ResultsOur findings demonstrate that puerarin significantly reduced the production of inflammatory cytokines (TNF-α and IL-6) in the peripheral blood of LPS-treated mice. Moreover, puerarin treatment markedly ameliorated sepsis-associated cognitive impairment. Puerarin also exhibited inhibitory effects on the release of TNF-α and IL-6 from microglia, thereby preventing hippocampal neuronal cell death. Network pharmacology analysis identified AKT1 as a potential therapeutic target for puerarin in SAE treatment. Subsequently, we validated these results in both in vitro and in vitro experiments. Our study conclusively demonstrated that puerarin reduced LPS-induced phosphorylation of AKT1, with the AKT activator SC79 reversing puerarin's anti-inflammatory effects through the activation of the AKT1 signaling pathway. ConclusionPuerarin exerts an anti-neuroinflammatory effect against SAE by modulating the AKT1 pathway in microglia.

Cocoa Shell Extract Reduces Blood Pressure in Aged Hypertensive Rats via the Cardiovascular Upregulation of Endothelial Nitric Oxide Synthase and Nuclear Factor (Erythroid-Derived 2)-like 2 Protein Expression.

Cocoa shell is a by-product of cocoa manufacturing. We obtained an aqueous extract (CSE) rich in polyphenols and methylxanthines with antioxidant and vasodilatory properties. We aimed to evaluate the effects of CSE supplementation in aged hypertensive rats on blood pressure and the mechanism implicated. Eighteen-month-old male and female rats exposed to undernutrition during the fetal period who developed hypertension, with a milder form in females, were used (MUN rats). Systolic blood pressure (SBP; tail-cuff plethysmography) and a blood sample were obtained before (basal) and after CSE supplementation (250 mg/kg; 2 weeks, 5 days/week). Plasma SOD, catalase activity, GSH, carbonyls, and lipid peroxidation were assessed (spectrophotometry). In hearts and aortas from supplemented and non-supplemented age-matched rats, we evaluated the protein expression of SOD-2, catalase, HO-1, UCP-2, total and phosphorylated Nrf2 and e-NOS (Western blot), and aorta media thickness (confocal microscopy). MUN males had higher SBP compared with females, which was reduced via CSE supplementation with a significant difference for group, sex, and interaction effect. After supplementation with plasma, GSH, but not catalase or SOD, was elevated in males and females. Compared with non-supplemented rats, CSE-supplemented males and females exhibited increased aorta e-NOS and Nrf2 protein expression and cardiac phosphorylated-Nrf2, without changes in SOD-2, catalase, HO-1, or UCP-2 in cardiovascular tissues or aorta remodeling. In conclusion, CSE supplementation induces antihypertensive actions related to the upregulation of e-NOS and Nrf2 expression and GSH elevation and a possible direct antioxidant effect of CSE bioactive components. Two weeks of supplementation may be insufficient to increase antioxidant enzyme expression.

Rosmarinus officinalis Essential Oil Increases Hair Length and Follicle Diameter of Ultraviolet B-exposed Mice Through VEGF

BACKGROUND: Ultraviolet (UVB) radiation induces hair photoaging by triggering oxidative stress, causing alterations in hair diameter and length, which contribute to the development of senile alopecia. Development of alternative anti-photoaging agents to prevent hair loss from various materials, including natural products, is currently being explored. Rosmarinus officinalis essential oil (ROEO) has been known to have antioxidant and vasodilation properties. However, the effect and mechanism of ROEO on UVB-exposed hair are still unclear. Therefore, this study was conducted to evaluate the effects of ROEO on the hair length and follicle diameter in UVB-exposed mice as well as the skin vascular endothelial growth factor (VEGF) level.METHODS: Thirty male Swiss mice were treated topically with/without paraffin oil, 2% minoxidil, or various concentrations of ROEO, every day for 21 days. Meanwhile, UVB exposure was performed 3×/week. On day 21, the hair length was measured, the skin tissue was collected for hair follicle diameter and VEGF measurements.RESULTS: ROEO contained phenolic, including flavonoids and tannins, as well as non-phenolic antioxidants, including 1.8-cineole, α-pinene, and camphor. The IC50 value of ROEO was 15.977 ppm. Significant higher hair length, follicle diameter, and VEGF level of 10% ROEO+UVB-treated mice were observed, compared with the ones of mice exposed with UVB merely (LSD test, p&lt;0.05).CONCLUSION: Since 10% ROEO could significantly increase hair length, follicle diameter and VEGF level, and contained antioxidant compounds, it can be suggested that ROEO might increase hair length, follicle diameter, and VEGF level through its antioxidant component.KEYWORDS: Rosmarinus officinalis, hair follicle diameter, hair length, VEGF, ultraviolet B, antioxidant

Benzodiazepines Reduce Blood Pressure in Short Term: A Systematic Review and Meta-analysis.

Benzodiazepines, due to their anxiolytic properties, are prescribed to reduce anxiety and insomnia. They might have hypotensive effect via potentiation of the inhibitory effect of gamma-amino butyric acid (GABA) in the central nervous system and vasodilatory properties. However, studies comparing the effect of benzodiazepines in lowering blood pressure (BP) are equivocal. This systematic review and meta-analysis was planned to assess the efficacy of benzodiazepines in reducing blood pressure in short term among hypertensive patients. Various trials and retrospective analysis conducted previously have reported that benzodiazepines cause short- as well as long-term BP reduction in patients with increased anxiety with hypertension. On the other hand, several studies investigating the efficacy of benzodiazepines in patients with hypertension have reported inconclusive results. The primary question about the effect of benzodiazepines in lowering BP remains unanswered. In this meta-analysis of seven studies, benzodiazepines were found comparable to standard drugs in reducing systolic and diastolic BP in patients having hypertension. Although, the mean difference in systolic BP with benzodiazepines and placebo was statistically not significant, the difference can be considered as clinically meaningful. The current review offers preliminary evidence that benzodiazepines may have antihypertensive properties and may be used as add-on antihypertensive in a subset of patients in short term. The existing data are encouraging, but more clinical trials and mechanistic research are required to ascertain the long-term benefits.

Acute nitric oxide synthase inhibition induces greater increases in blood pressure in female versus male Wistar Kyoto rats.

Nitric oxide (NO) contributes to blood pressure (BP) regulation via its vasodilatory and anti-inflammatory properties. We and others previously reported sex differences in BP in normotensive and hypertensive rat models where females have lower BP than age-matched males. As females are known to have greater NO bioavailability than age-matched males, the current study was designed to test the hypothesis that anesthetized female normotensive Wistar Kyoto rats (WKY) are more responsive to acute NOS inhibition-induced increases in BP compared to male WKY. Twelve-week-old male and female WKY were randomized to infusion of the nonspecific NOS inhibitor NG -nitro-L-arginine methyl ester (L-NAME, 1 mg/kg/min) or selective NOS1 inhibition with vinyl-L-NIO (VNIO, 0.5 mg/kg/min) for 60 min. Mean arterial BP, glomerular filtration rate (GFR), urine volume, and electrolyte excretion were assessed before, and during L-NAME or VNIO infusion. L-NAME and VNIO significantly increased BP in both sexes; however, the increase in BP with L-NAME infusion was greater in females versus males compared to baseline BP values. Acute infusion of neither L-NAME nor VNIO for 60 min altered GFR in either sex. However, urine volume, sodium, chloride and potassium excretion levels increased comparably in male and female WKY with L-NAME and VNIO infusion. Our findings suggest sex differences in BP responses to acute non-isoform-specific NOS inhibition in WKY, with females being more responsive to L-NAME-induced elevations in BP relative to male WKY. However, sex differences in the BP response did not coincide with sex differences in renal hemodynamic responses to acute NOS inhibition.

Conventional and advanced extraction methods of some bioactive compounds with health benefits of food and plant waste: A comprehensive review

AbstractFood bioactive compounds have a beneficial biological effect on human health, fending off cancer, cardiovascular disease, metabolic syndrome, and neurodegenerative disease, among other noncommunicable diseases and neurodegenerative disorders. Secondary metabolites like polyphenols, glucosinolates, carotenoids, vitamins, terpenoids, saponins, and fibers have been linked to these health benefits due to their antioxidant, antiatherogenic, anti‐inflammatory, antimicrobial, cardioprotective, and vasodilator properties. This review comprehensively illustrates the extraction of bioactive compounds in food formulations along plant wastes and provides insight into the efficient delivery systems for health‐promoting compounds. There is an insight into how to choose which bioactive to use, how to extract them in a bioavailable state, and how to include and deliver them. Grapes, garlic, sweet potato leaves, cactus pears, beetroot, amaranth, Picea abies bark waste, olive leaves, and black plum are discussed comprehensively in terms of extraction and health benefits. The novel and emerging technologies are discussed in detail, and a comprehensive review and comparison with conventional methods are presented. The significant health benefits associated with bioactive compounds are also discussed.