Photophysical Investigation of One Pot Synthesized Novel Indenofluorene Derivative (BDP) as a Fluorescent Chemosensor for the Detection of Fe3+ Ion.

An Indane-1-one derivative 11-(1-benzyl-1H-indol-3-yl)-10,12-dihydrodiindeno[1,2-b:2',1'-e]-pyridine (BDP) has been synthesized by the reaction of Indan-1-one with 1-benzyl-1H-indole-3-carbaldehyde. FT-IR, 1H-NMR, 13N-NMR and Mass spectroscopic techniques has been used to confirmed the structure of BDP. The observed photophysical changes in BDP across various solvents were associated. The impact of various interactions on photophysical parameters, including Stokes shift, dipole moment, oscillator strength, and fluorescence quantum yields, has been assessed in relation to solvent polarity. Moreover, BDP demonstrates potential as a selective fluorescent chemosensor for detecting Fe3+ ion within a range of cations in an aqueous DMSO environment. A thorough investigation into the recognition mechanism of BDP towards Fe3+ ion has been conducted using Benesi-Hildebrand and Stern-Volmer, measurements. BDP forms a 2:1 complex with the Fe3+ ion, exhibiting fluorescent quenching behaviour.

Salicylic Acid Priming Improves Cotton Seedling Heat Tolerance through Photosynthetic Pigment Preservation, Enhanced Antioxidant Activity, and Osmoprotectant Levels.

The escalating global temperatures associated with climate change are detrimental to plant growth and development, leading to significant reductions in crop yields worldwide. Our research demonstrates that salicylic acid (SA), a phytohormone known for its growth-promoting properties, is crucial in enhancing heat tolerance in cotton (Gossypium hirsutum). This enhancement is achieved through modifications in various biochemical, physiological, and growth parameters. Under heat stress, cotton plants typically show significant growth disturbances, including leaf wilting, stunted growth, and reduced biomass. However, priming cotton plants with 1 mM SA significantly mitigated these adverse effects, evidenced by increases in shoot dry mass, leaf-water content, and chlorophyll concentrations in the heat-stressed plants. Heat stress also prompted an increase in hydrogen peroxide levels-a key reactive oxygen species-resulting in heightened electrolyte leakage and elevated malondialdehyde concentrations, which indicate severe impacts on cellular membrane integrity and oxidative stress. Remarkably, SA treatment significantly reduced these oxidative stresses by enhancing the activities of critical antioxidant enzymes, such as catalase, glutathione S-transferase, and ascorbate peroxidase. Additionally, the elevated levels of total soluble sugars in SA-treated plants enhanced osmotic regulation under heat stress. Overall, our findings reveal that SA-triggered protective mechanisms not only preserve photosynthetic pigments but also ameliorate oxidative stress and boost plant resilience in the face of elevated temperatures. In conclusion, the application of 1 mM SA is highly effective in enhancing heat tolerance in cotton and is recommended for field trials before being commercially used to improve crop resilience under increasing global temperatures.

Extract of Chenopodium album lowers blood pressure in rats through endothelium-dependent and -independent vasorelaxation.

OBJECTIVES: To investigate the antihypertensive effect of crude extract of Chenopodium album (Ca.Cr), based on its medicinal use in hypertension. METHODS: Ca.Cr and its fractions were tested in-vivo in normotensive anesthetized rats for blood pressure-lowering effect. In-vitro experiments were performed on isolated rat aortae to explore the vascular mechanism(s). RESULTS: In normotensive anesthetized rats, Ca.Cr produced a dose-dependent (1-300mg/kg) fall (30%mmHg) in mean arterial pressure (MAP). Among the fractions, nHexane was the most potent (46% fall). In rat aortic rings precontracted with phenylephrine (PE), Ca.Cr and its fractions (except Ca.Aq) produced endothelium-dependent vasorelaxation, which was partially reversed with endothelium removal and by pretreating intact aortic rings with L-NAME (10µM) and atropine (1µM). This relaxation to Ca.Cr and fractions (nHexane, ethylacetate and chloroform) was also eliminated with indomethacin pretreatment, however, it unmasked a vasoconstriction effect with Ca.Cr only. Surprisingly, the aqueous fraction produced a calcium sensitive strong vasoconstriction instead of vasorelaxation. The crude extract and its fractions (except Ca.Aq) also antagonized vasoconstriction induced with high K+ (80mM), suggesting calcium antagonistic effect. The aqueous fraction produced mild vasorelaxation against high K+. This effect was further confirmed when pretreatment of the aortic rings with different concentrations of crude extract and fractions suppressed CaCl2 concentration response curves, similar to verapamil. In acute toxicity test, Ca.Cr extract was found safe up to 5g/kg body weight in mice. CONCLUSION: These findings suggest that crude extract and fractions of C. album produced vasorelaxant effect through muscarinic receptors linked-NO pathway, prostaglandin (endothelium-dependent) and calcium antagonism (endothelium-independent), which explains the blood pressure lowering effect of C. album in rats.

Esculetin unveiled: Decoding its anti-tumor potential through molecular mechanisms-A comprehensive review.

BACKGROUND: The growing complexity of cancer has made it a significant concern in the medical community. Although cancer research has advanced, it is still challenging to create new effective medications due to the limitations and side effects of existing treatment strategies. These are enforcing the development of some alternative drugs from natural compounds with fewer drawbacks and side effects. AIM: Therefore, this review aims to provide up-to-date, crucial, and all-encompassing data on esculetin's anticancer activity, including all relevant molecular and cellular processes based on in vivo and in vitro investigations. RESULTS: According to the literature review, esculetin is available in nature and is effective against 16 different types of cancer. The general mechanism shown by esculetin is modulating signaling cascades and its related pathways, like cell proliferation, cell growth, autophagy, apoptosis, necrosis, inflammation, angiogenesis, metastasis, invasion, and DNA damage. Nanoformulation of esculetin improves this natural product's efficacy by improving water solubility. Esculetin's synergistic effects with both natural substances and conventional treatments have been shown, and this method aids in reversing resistance mechanisms by modulating resistance-related proteins. In addition, it has fewer side effects on humans than other phytochemicals and standard drugs with some good pharmacokinetic features. CONCLUSION: Therefore, until standard chemotherapeutics are available in pharmaceutical markets, esculetin should be used as a therapeutic drug against various cancer types.

Ultrasound-Assisted Synthesis of Chalcone: A Highly Sensitive and Selective Fluorescent Chemosensor for the Detection of Fe3+ in Aqueous Media.

The chalcone compound DHPO was synthesized through a chemical reaction between 1-(2-hydroxyphenyl)-ethanone and 3,4-dimethoxy benzaldehyde under ultrasound irradiation. The interaction between the DHPO compound and several metal ions was studied using fluorescence behavior, revealing that the chalcone function as a "turn on and turn off" switch fluorescent sensor, for selectively and sensitively detecting Fe3+ ions. The process of fluorescence quenching and complexation of DHPO with Fe3+ ion was further studied using methods such as Benesi-Hildebrand, Stern-Volmer plot, and job plot.

Quantifying Myeloperoxidase-DNA and Neutrophil Elastase-DNA Complexes from Neutrophil Extracellular Traps by Using a Modified Sandwich ELISA.

Certain stimuli, such as microorganisms, cause neutrophils to release neutrophil extracellular traps (NETs), which are basically web-like structures composed of DNA with granule proteins, such as myeloperoxidase (MPO) and neutrophil elastase (NE), and cytoplasmic and cytoskeletal proteins. Although interest in NETs has increased recently, no sensitive, reliable assay method is available for measuring NETs in clinical settings. This article describes a modified sandwich enzyme-linked immunosorbent assay to quantitatively measure two components of circulating NETs, MPO-DNA and NE-DNA complexes, which are specific components of NETs and are released into the extracellular space as breakdown products of NETs. The assay uses specific monoclonal antibodies for MPO or NE as the capture antibodies and a DNA-specific detection antibody. MPO or NE binds to one site of the capture antibody during the initial incubation of samples containing MPO-DNA or NE-DNA complexes. This assay shows good linearity and high inter-assay and intra-assay precision. We used it in 16 patients with COVID-19 with accompanying acute respiratory distress syndrome and found that the plasma concentrations of MPO-DNA and NE-DNA were significantly higher than in the plasma obtained from healthy controls. This detection assay is a reliable, highly sensitive, and useful method for investigating the characteristics of NETs in human plasma and culture supernatants.

Relationship of serum lipid profiles in preeclampsia and normal pregnancy, Bangladesh.

Objective: The purpose of this present study to investigate the lipid profile levels and basal body mass index in preeclampsia and normal pregnancy in Bangladeshi women. Material and methods: This case-control study was conducted at Sheba Hospital Kaligonj Bangladesh with 70 participants among 35 normal pregnancy (control) and 35 preeclampsia women (case) were enrolled from August 2018 to July 2019. Blood samples were obtained for analysis of total cholesterol, triglyceride and high-density lipoprotein by enzymatic assays and low-density lipoprotein by using Fried Ewald's formula in between 22-36 weeks of gestation. Results: This study found the mean age of preeclampsia and normal pregnancy women were 24.71±2.56 and 23.09±2.1 respectively with significant (P= 0.005). Basal body mass index, total cholesterol, triglyceride and low-density lipoprotein significantly higher (P=0.002), (P= 0.000), (P= 0.022) and (P=0.000) in preeclampsia compared to normal pregnancy respectively. While high-density lipoprotein comparatively lower in preeclampsia than normal pregnancy and consider significant as (P=0.037). Conclusion: Abnormal lipid profile and increased body mass index is contributed to the development of preeclampsia. The frequent antenatal monitoring of lipid profiles provides the status which helps to require management and reduces the preeclampsia which enhances maternal and fetal wellbeing and fetal outcome.

Antihypertensive Potential of Tartaric Acid and Exploration of Underlying Mechanistic Pathways.

Tartaric acid is capable of balancing blood pressure. It is the main constituent of antihypertensive agents (grapes and wine) and has not been scientifically explored as an antihypertensive remedy. This study aimed to investigate the antihypertensive effect of a low-dose tartaric acid in vivo and explore underlying mechanisms in vitro. Intravenous administration of tartaric acid at the dose of 50 µg/kg caused a % fall in mean arterial pressure (MAP) in normotensive and hypertensive rats [51.5 ± 1.7 and 63.5 ± 2.9% mmHg]. This hypotensive effect was partially inhibited by atropine (1 mg/kg) and L-NAME (100 µg/kg) pretreatment. In hypertensive rats, oral administration of tartaric acid (.1, .5, 1, 5, and 10 mg/kg) for 2 weeks resulted in 65 ± 7.3 mmHg MAP at 10 mg/kg. This antihypertensive effect was comparable to the orally administered verapamil (10 mg/kg) for 2 weeks which caused a decrease in MAP 60.4 ± 3.8 mmHg. Tartaric acid relaxed phenylephrine (PE) and High K+-induced contractions with EC50 values of .157 (.043-.2) and 1.93 (.07-2) µg/mL in vitro. This endothelium-dependent relaxation was inhibited with atropine (1 µM) and L-NAME (10 µM) pretreatment. Tartaric acid also suppressed phenylephrine contractions in Ca+2 free/EGTA medium and on voltage-dependent calcium channels, causing the concentration-response curves toward right. Tartaric acid induced negative inotropic and chronotropic effects with EC50 values of .26 (.14-.4) and .60 (.2-.8) in rat atria. It showed its effect by complete blockade against atropine and partially in propranolol pretreatment. These findings provide scientific basis to low-dose tartaric acid as an antihypertensive and vasodilatory remedy through muscarinic receptor-linked nitric oxide (NO) pathway and Ca+2 channel antagonist.

Role of MicroRNAs in Cardiac Disease with Stroke in Pregnancy.

Pregnancy-related cardiovascular disease with stroke remains a considerable source of higher maternal morbidity and mortality occurs in periods of pregnancy, delivery, and postpartum. It is essential to counsel the mother before pregnancy by an expert cardiologist and obstetric team to discuss any event related to preexistent cardiac or past preeclampsia for estimation of maternal and fetal risks. In pregnancy, the cardiac state includes hypertensive disorders, ischemic heart disease, valvular disease, and postpartum stroke. The incidence of stroke is increasing in pregnancy, particularly in postpartum, and its strong relationship with hypertensive disorders of pregnancy (preeclampsia). The combined cardiologist and obstetrics team requires during pregnancy mainly due to the approach to the management of a cardiac disease that subsequently prevents stroke postpartum. Therefore, a general perception of cardiac disease during pregnancy, delivery, and postpartum should be a core knowledge extent for all cardiovascular and clinicians. Many studies provided linked that deregulation of microRNAs (miRNAs) in maternal circulation and placenta tissue may development of pregnancy complications including preeclampsia considered a diagnostic marker. The desire of this review provides a detailed outline of current knowledge and dealing in this field with strength on the physiological changes during pregnancy.

Overexpression of miR-126 Protects Hypoxic-Reoxygenation-Exposed HUVEC Cellular Injury through Regulating LRP6 Expression.

The aim of the study was to explore the clinical impact of circulatory miR-126 as a candidate for novel biomarker in patients with coronary artery disease (CAD) and its protective role against hypoxia/reoxygenation- (H/R-) exposed HUVEC cellular injury. A total of 278 subjects, which included 153 subjects with angiographically confirmed CAD, 70 unstable angina subjects, and 55 healthy individuals, along with 18-hour HR-induced HUVECs were recruited in this study. Plasma miR-126 levels were significantly downregulated in stable and unstable CAD patients as well as 18-hour HR-exposed HUVECs as compared with controls. Stable and unstable CAD subjects were significantly differentiated from healthy individuals with a predictive value of AUC 0.903 and 0.923, respectively. Moreover, peripheral circulatory miR-126 expressions in elderly (71-90 years) stable and unstable CAD patients were comparatively lower than younger (30-50 years) subjects. The caspase-3 activity, intracellular ROS concentrations, and cellular viabilities were evidently increased in 18-hour HR-exposed HUVECs than in normal cells (P < 0.001). On the contrary, mimic expressions of miR-126 prominently reduced caspase-3 activity and intracellular ROS levels and markedly enhanced HUVEC cellular viabilities (P < 0.001). LRP6 expressions were significantly elevated in HR-induced HUVECs, whereas overexpression of miR-126 remarkably decreased LRP6 expressions (P < 0.001). Plasma miR-126 could be used as a novel biomarker for early prediction of CAD subjects. Overexpression of miR-126 significantly improved HUVEC cellular viabilities by downregulation of LRP6 protein expression, suggesting a potential therapeutic target for CAD patients.

Evaluation of the Antiasthmatic Activity of Carissa opaca in Animal Models.

Carissa opaca Stapf ex Haines (C. opaca) fruit is used traditionally in the treatment of respiratory illnesses including asthma. However, there is no scientific evidence supporting its antiasthmatic activity. The current study was conducted to evaluate its antiasthmatic effects using in vivo and in vitro approaches. The methanolic crude extract of C. opaca fruit (Co.Cr.) was used and in vivo antiasthmatic activity was carried out using ovalbumin- (OVA-) sensitized and OVA-challenged BALB/c mice. In in vitro bronchorelaxant activity of crude extract, aqueous and n-hexane fractions of C. opaca were carried out on isolated rat tracheal strips. Co.Cr. (200 and 400 mg/kg) attenuated ovalbumin-induced changes in lung histochemistry with % decrease in peribronchial inflammation of 14.1 ± 0.21 and 65.8 ± 0.22 and % decrease in total inflammatory cell count of 35.7 ± 2.80 and 53.3 ± 2.30 in bronchoalveolar lavage fluid. Co.Cr., aqueous, and n-hexane fraction of C. opaca attenuated the precontractions induced by high K+ (80 mM) and carbachol (1 µM), respectively. In conclusion, the results showed that C. opaca possesses antiasthmatic activity via relaxant effect on bronchial smooth muscle which is mediated through calcium channel blockade and antimuscarinic activity. This study provides scientific evidence of the traditional use of C. opaca in the management of allergic asthma.

O Efeito Anti-Hipertensivo de Sauromatum Guttatum Mediado por Efeitos Vasorrelaxante e Depressivos Miocárdicos / Antihypertensive Activity of Sauromatum guttatum Mediated by Vasorelaxation and Myocardial Depressant Effects

Resumo Fundamento: A Sauromatum guttatum (S. guttatum) é utilizado no tratamento de doenças do sangue e supostamente tem atividade espasmolítica através da inibição dos canais de Ca2+. Objetivos: O objetivo deste estudo foi investigar o potencial anti-hipertensivo de S. guttatum em modelo de rato Sprague-Dawley (SD) com hipertensão induzida por dieta com alto teor de sal (HIDATS). Métodos: Ratos SD foram divididos em normotensos, hipertensos e grupos tratados com verapamil e S. guttatum. Extrato bruto de S. guttatum (Sg.B) (100, 150 e 300 mg/kg/dia) e verapamil (5, 10 e 15 mg/kg/dia) foram administrados por via oral junto com NaCl. Anéis aórticos e faixas do átrio direito de ratos normotensos foram utilizados para investigar os mecanismos subjacentes. O nível de significância estatística adotado foi de 5%. Resultados: A pressão arterial média diminuiu nos grupos hipertensos tratados com Sg.B e verapamil de forma dose-dependente (p <0,001). No estudo de reatividade vascular, a acetilcolina induziu relaxamentos com valor CE50 de 0,6 µg/mL (0,3-1,0) em ratos hipertensos tratados com Sg.B (300 mg/kg), sugerindo preservação endotelial. Em aorta isolada de rato normotenso, o Sg.B exibiu vasorrelaxamento com valor de CE50 de 0,15 mg/mL (0,10-0,20), após ablação por desnudamento endotelial ou pré-tratamento com L-NAME e atropina. O tratamento com Sg.B causou relaxamento contra contrações induzidas por K+ alto, como o verapamil. O Sg.B mostrou efeitos inotrópicos (82%) e cronotrópicos (56%) negativos em preparações isoladas atriais de ratos reduzidas com atropina. A avaliação fitoquímica indicou a presença de alcaloides, flavonoides e taninos. Conclusão: O S. guttatum possui efeito vasodilatador através da preservação da função endotelial, liberação de NO mediada pelo receptor muscarínico e inibição do movimento de Ca2+, enquanto o efeito depressor do miocárdio atrial pode estar ligado ao receptor muscarínico. Esses achados fornecem a base farmacológica para o uso do extrato de S. guttatum como um medicamento anti-hipertensivo.

Abstract Background: Sauromatum guttatum (S. guttatum) is used in the treatment of blood disorders and reportedly has a spasmolytic activity through Ca2+ channel inhibition. Objectives: The aim of this study was to investigate the antihypertensive potential of S. guttatum in high salt-induced hypertensive Sprague-Dawley (SD) rat model (HSHRs). Methods: SD rats were divided into normotensive, hypertensive, S. guttatum and verapamil treated groups. S. guttatum crude extract (Sg.Cr) (100, 150 and 300 mg/kg/day) and verapamil (5, 10 and 15 mg/kg/day) were administered orally along with NaCl. Aortic rings and right atrial strips from normotensive rats were used to investigate the underlying mechanisms. The level of statistical significance was set at 5%. Results: Mean arterial pressure decreased in the Sg.Cr and verapamil-treated hypertensive groups in a dose-dependent manner (p < 0.001). In the vascular reactivity study, acetylcholine induced relaxations with an EC50 value of 0.6 µg/mL (0.3-1.0) in Sg.Cr-treated hypertensive rats (300 mg/kg), suggesting endothelial preservation. In isolated normotensive rat aorta, Sg.Cr-treated rats showed vasorelaxation with an EC50 value of 0.15 mg/mL (0.10-0.20), ablated by endothelial denudation or pretreatment with L-NAME and atropine. Sg.Cr treatment caused relaxation against high K+-induced contractions, like verapamil. Sg.Cr showed negative inotropic (82%) and chronotropic effects (56%) in isolated rat atrial preparations reduced with atropine. The phytochemical investigation indicated presence of alkaloids, flavonoids and tannins. Conclusion: S. guttatum has a vasodilatory effect through endothelial function preservation, muscarinic receptor-mediated NO release and Ca2+ movement inhibition, while atrial myocardial depressant effect can be linked to the muscarinic receptor. These findings provide pharmacological base for using S. guttatum extract as an antihypertensive medication.

Gut Microbiota and Development of Vibrio cholerae-Specific Long-Term Memory B Cells in Adults after Whole-Cell Killed Oral Cholera Vaccine.

Cholera is a diarrheal disease caused by Vibrio cholerae that continues to be a major public health concern in populations without access to safe water. IgG- and IgA-secreting memory B cells (MBC) targeting the V. cholerae O-specific polysaccharide (OSP) correlate with protection from infection in persons exposed to V. cholerae and may be a major determinant of long-term protection against cholera. Shanchol, a widely used oral cholera vaccine (OCV), stimulates OSP MBC responses in only some people after vaccination, and the gut microbiota is a possible determinant of variable immune responses observed after OCV. Using 16S rRNA sequencing of feces from the time of vaccination, we compared the gut microbiota among adults with and without MBC responses to OCV. Gut microbial diversity measures were not associated with MBC isotype or OSP-specific responses, but individuals with a higher abundance of Clostridiales and lower abundance of Enterobacterales were more likely to develop an MBC response. We applied protein-normalized fecal supernatants of high and low MBC responders to THP-1-derived human macrophages to investigate the effect of microbial factors at the time of vaccination. Feces from individuals with higher MBC responses induced significantly different IL-1ß and IL-6 levels than individuals with lower responses, indicating that the gut microbiota at the time of vaccination may "prime" the mucosal immune response to vaccine antigens. Our results suggest the gut microbiota could impact immune responses to OCVs, and further study of microbial metabolites as potential vaccine adjuvants is warranted.

Therapeutic Value of miRNAs in Coronary Artery Disease.

Atherosclerotic ischemic coronary artery disease (CAD) is a significant community health challenge and the principal cause of morbidity and mortality in both developed and developing countries for all ethnic groups. The progressive chronic coronary atherosclerosis is the main underlying cause of CAD. Although enormous progress occurred in the last three decades in the management of cardiovascular diseases, the prevalence of CAD continues to increase worldwide, indicating the need for discovery of deeper molecular insights of CAD mechanisms, biomarkers, and innovative therapeutic targets. Recently, several research groups established that microRNAs essentially regulate various cardiovascular development and functions, and a deregulated cardiac enriched microRNA profile plays a vital role in the pathogenesis of CAD and its biological aging. Numerous studies established that over- or downregulation of a single miRNA gene by ago-miRNA or anti-miRNA is enough to modify the CAD disease process, significantly prevent age-dependent cardiac cell death, and markedly improve cardiac function. In the light of more recent experimental and clinical evidences, we briefly reviewed and discussed the involvement of miRNAs in CAD and their possible diagnostic/therapeutic values. Moreover, we also focused on the role of miRNAs in the initiation and progression of the atherosclerosis plaque as the strongest risk factor for CAD.

Relationship of COVID-19 with pregnancy.

COVID-19 a pandemic disease caused by the SARS-CoV2 virus, which has been emerged in Wuhan city China from early December 2019 which subsequently spreading globally. As a consequence of the physiological adaptive changes and immunosuppressive condition during pregnancy are more susceptible to respiratory tract infection and pneumonia that perhaps makes them more at risk to COVID-19. There is scarce information available on COVID-19 pregnancy and no reliable evidence for vertical transmission. It is a concern that newborns are risk from postpartum contamination. Meanwhile, there was no vaccine and specific therapeutic drugs for COVID19. The Multidisciplinary team will manage by close supervision, isolated negative pressure room, and routinely fetal monitoring. The timing and mode of delivery depend on the critical condition of the mother and fetal. The newborns need a14 days period of precautionary isolation. In the present study, addressed the most recent data on 149 pregnant women and 96 newborns with typical symptoms and planning of management which response to COVID-19 that will help for frontline doctor to the management of COVID-19 associated pregnancy and newborns baby. Repeated testing, contact tracing and self-isolation will assist to control the spread of SARS-CoV2 infection and COVID-19 disease until specific vaccine and pharmaceuticals drugs of COVID-19 are available.

Antihypertensive Activity of Sauromatum guttatum Mediated by Vasorelaxation and Myocardial Depressant Effects. / O Efeito Anti-Hipertensivo de Sauromatum Guttatum Mediado por Efeitos Vasorrelaxante e Depressivos Miocárdicos.

BACKGROUND: Sauromatum guttatum (S. guttatum) is used in the treatment of blood disorders and reportedly has a spasmolytic activity through Ca2+ channel inhibition. OBJECTIVES: The aim of this study was to investigate the antihypertensive potential of S. guttatum in high salt-induced hypertensive Sprague-Dawley (SD) rat model (HSHRs). METHODS: SD rats were divided into normotensive, hypertensive, S. guttatum and verapamil treated groups. S. guttatum crude extract (Sg.Cr) (100, 150 and 300 mg/kg/day) and verapamil (5, 10 and 15 mg/kg/day) were administered orally along with NaCl. Aortic rings and right atrial strips from normotensive rats were used to investigate the underlying mechanisms. The level of statistical significance was set at 5%. RESULTS: Mean arterial pressure decreased in the Sg.Cr and verapamil-treated hypertensive groups in a dose-dependent manner (p < 0.001). In the vascular reactivity study, acetylcholine induced relaxations with an EC50 value of 0.6 µg/mL (0.3-1.0) in Sg.Cr-treated hypertensive rats (300 mg/kg), suggesting endothelial preservation. In isolated normotensive rat aorta, Sg.Cr-treated rats showed vasorelaxation with an EC50 value of 0.15 mg/mL (0.10-0.20), ablated by endothelial denudation or pretreatment with L-NAME and atropine. Sg.Cr treatment caused relaxation against high K+-induced contractions, like verapamil. Sg.Cr showed negative inotropic (82%) and chronotropic effects (56%) in isolated rat atrial preparations reduced with atropine. The phytochemical investigation indicated presence of alkaloids, flavonoids and tannins. CONCLUSION: S. guttatum has a vasodilatory effect through endothelial function preservation, muscarinic receptor-mediated NO release and Ca2+ movement inhibition, while atrial myocardial depressant effect can be linked to the muscarinic receptor. These findings provide pharmacological base for using S. guttatum extract as an antihypertensive medication.

FUNDAMENTO: A Sauromatum guttatum (S. guttatum) é utilizado no tratamento de doenças do sangue e supostamente tem atividade espasmolítica através da inibição dos canais de Ca2+. OBJETIVOS: O objetivo deste estudo foi investigar o potencial anti-hipertensivo de S. guttatum em modelo de rato Sprague-Dawley (SD) com hipertensão induzida por dieta com alto teor de sal (HIDATS). MÉTODOS: Ratos SD foram divididos em normotensos, hipertensos e grupos tratados com verapamil e S. guttatum. Extrato bruto de S. guttatum (Sg.B) (100, 150 e 300 mg/kg/dia) e verapamil (5, 10 e 15 mg/kg/dia) foram administrados por via oral junto com NaCl. Anéis aórticos e faixas do átrio direito de ratos normotensos foram utilizados para investigar os mecanismos subjacentes. O nível de significância estatística adotado foi de 5%. RESULTADOS: A pressão arterial média diminuiu nos grupos hipertensos tratados com Sg.B e verapamil de forma dose-dependente (p <0,001). No estudo de reatividade vascular, a acetilcolina induziu relaxamentos com valor CE50 de 0,6 µg/mL (0,3­1,0) em ratos hipertensos tratados com Sg.B (300 mg/kg), sugerindo preservação endotelial. Em aorta isolada de rato normotenso, o Sg.B exibiu vasorrelaxamento com valor de CE50 de 0,15 mg/mL (0,10-0,20), após ablação por desnudamento endotelial ou pré-tratamento com L-NAME e atropina. O tratamento com Sg.B causou relaxamento contra contrações induzidas por K+ alto, como o verapamil. O Sg.B mostrou efeitos inotrópicos (82%) e cronotrópicos (56%) negativos em preparações isoladas atriais de ratos reduzidas com atropina. A avaliação fitoquímica indicou a presença de alcaloides, flavonoides e taninos. CONCLUSÃO: O S. guttatum possui efeito vasodilatador através da preservação da função endotelial, liberação de NO mediada pelo receptor muscarínico e inibição do movimento de Ca2+, enquanto o efeito depressor do miocárdio atrial pode estar ligado ao receptor muscarínico. Esses achados fornecem a base farmacológica para o uso do extrato de S. guttatum como um medicamento anti-hipertensivo.

Antihypertensive effect of the methanolic extract from Eruca sativa Mill., (Brassicaceae) in rats: Muscarinic receptor-linked vasorelaxant and cardiotonic effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Eruca sativa Mill., (Brassicaceae) is a popular remedy for the treatment of hypertension in Pakistan. However, direct effect of the extract and its fractions on blood pressure and vascular tone are unknown. AIM OF THE STUDY: This investigation was aimed to explore the pharmacological base for the traditional use of E. sativa in hypertension. MATERIALS AND METHODS: In-vivo blood pressure study was carried out using normotensive and high salt-induced hypertensive rats under anaesthesia. The cardiovascular mechanisms were explored using rat aorta and atria in-vitro. Preliminary phytochemical analysis, spectrophotometric detection of total phenols, flavonoids and HPLC analysis of crude extract were performed using quercetin and erucin as marker compounds. RESULTS: Intravenous injection of crude extract induced a fall in mean arterial pressure (MAP) in both normotensive (max fall: 41.79 ±â€¯1.55% mmHg) and hypertensive (max fall: 58.25 ±â€¯0.91% mmHg) rats. Atropine (1 mg/kg) pretreatment attenuated this effect significantly (p < 0.001), suggesting the involvement of muscarinic receptor in its antihypertensive effect. Fractions also induced atropine-sensitive antihypertensive effect. Similarly, oral administration of crude and aqueous extracts resulted a fall in MAP in the hypertensive rats. In isolated rat aortic rings from normotensive rats, crude extract and fractions induced an endothelium-dependent relaxation. This relaxation was partially inhibited with L-NAME and atropine pretreatment and with denudation of aortic rings, indicating involvement of muscarinic receptor-linked nitric oxide (NO). In aorta from the hypertensive rats, crude extract and fractions induced endothelium-independent relaxation. This relaxation was not affected by pretreatment with L-NAME or atropine. Crude extract and fractions also suppressed phenylephrine contractions in Ca+2 free/EGTA medium. In isolated rat atrial preparations, crude extract and fractions induced negative inotropic and chronotropic effects with a positive inotropic effect by the n-hexane fraction, which were not affected with atropine pretreatment. Phytochemical screening and spectrophotometric analysis indicated the presence of phenols and flavonoids, whereas HPLC analysis of crude extract revealed the presence of quercetin (flavonoid) and erucin (isothiocyanate). CONCLUSION: The results suggest that E. sativa is an antihypertensive remedy which is mainly due to its vasodilatory and partly cardiac effects. Muscarinic receptors-linked NO release and dual inhibitory effect on Ca+2 influx and release underlie the vasodilation. This finding provides pharmacological base to the traditional use of E. sativa in hypertension. The presence of quercetin and erucin further support this finding.

Vascular mechanisms underlying the hypotensive effect of Rumex acetosa.

CONTEXT: Rumex acetosa L. (Polygonaceae) is well known in traditional medicine for its therapeutic efficacy as an antihypertensive. OBJECTIVE: The study investigates antihypertensive potential of crude methanol extract (Ra.Cr) and fractions of Rumex acetosa in normotensive and hypertensive rat models and probes the underlying vascular mechanisms. MATERIALS AND METHODS: Ra.Cr and its fractions were tested in vivo on normotensive and hypertensive Sprague-Dawley rats under anaesthesia for blood pressure lowering effect. In vitro experiments on rat and Oryctolagus cuniculus rabbit aortae were employed to probe the underlying vasorelaxant mechanism. RESULTS: In normotensive rats under anaesthesia, Ra.Cr caused fall in MAP (40 mmHg) at 50 mg/kg with % fall of 27.88 ± 4.55. Among the fractions tested, aqueous fraction was more potent at the dose of 50 mg/kg with % fall of 45.63 ± 2.84. In hypertensive rats under similar conditions, extract and fractions showed antihypertensive effect at same doses while aqueous fraction being more potent, exhibited 68.53 ± 4.45% fall in MAP (70 mmHg). In isolated rat aortic rings precontracted with phenylephrine (PE), Ra.Cr and fractions induced endothelium-dependent vasorelaxation, which was partially blocked in presence of l-NAME, indomethacin and atropine. In isolated rabbit aortic rings pre-contracted with PE and K+-(80 mM), Ra.Cr induced vasorelaxation and shifted Ca2+ concentration-response curves to the right and suppressed PE peak formation, similar to verapamil, in Ca2+-free medium. DISCUSSION AND CONCLUSIONS: The data indicate that l-NAME and atropine-sensitive endothelial-derived NO and COX enzyme inhibitors and Ca2+ entry blocking-mediated vasodilator effect of the extract explain its antihypertensive potential.

The Opposite Effect of Water and N-Methyl-2-Pyrrolidone Cosolvents on the Nanostructural Organization of Ethylammonium Butanoate Ionic Liquid: A Small- and Wide-Angle X-Ray Scattering and Molecular Dynamics Simulations Study.

Two series of mixtures of ethylammoniumbutanoate (EAB, [N0 0 0 2][C3CO2]) in water and N-methyl-2-pyrrolidone (NMP) have been prepared at different molar fractions to assess the effect of these two polar solvents on the nanostructural order present in [N0 0 0 2][C3CO2]. The small- and wide-angle X-ray scattering (SWAXS) pattern of the liquid in neat state shows a prepeak at Q = 0.513 Å-1, which is associated with the aggregation of nonpolar alkyl chains of both cations and anions. Interestingly, the two solvents affect the nanostructure of [N0 0 0 2][C3CO2] differently, though both are polar. In the case of water addition to the mixture, the prepeak shifts to lower Q values, while in NMP, it moves toward higher values. Also, the principal peaks move in opposite direction in both solvents. The underlying expansion (water) or contraction (NMP) of the solutions observed by the scattering experiments is discussed in terms of molecular dynamics (MD) simulations, which are in very good agreement with the observed patterns.