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.

A systematic review of treatment options for post-prostatectomy incontinence.

PURPOSE: Urinary incontinence remains common in men after prostatectomy. Current guidance suggests early corrective surgery to those that are still incontinent after trying Pelvic Floor Muscle Therapy, however, other treatments are now available. This review aims to evaluate all currently available treatment options for men with post-prostatectomy incontinence (PPI). METHODS: A search of MEDLINE and CENTRAL databases on 2/2/2021 produced 879 articles. Any study evaluating incontinence before and after a treatment protocol was eligible for inclusion. After screening, 17 randomized control trials were included, and pre-defined data points were collected. Due to heterogeneity, pooled analysis was not possible, and a descriptive synthesis was produced in accordance with PRISMA guidelines. Cochrane Risk of Bias (RoB) tool was used to evaluate all studies. The search protocol and methods for this study was registered on the PROSPERO database before the search began, ID:(CRD42021229749). RESULTS: 3/17(18%) of studies focussed on pharmacotherapy, 2/17(12%) on vibration therapies, 8/17(47%) on pelvic floor muscle therapy (PFMT), 3/17(18%) on electrical stimulation (ES), and 1/17 (6%) on extracorporeal magnetic innervation (ExMI) as their main intervention. The use of Duloxetine, Solifenacin, PFMT, ES, and ExMI all show effective reduction in incontinence in men suffering from PPI. No study in this review evaluated surgical managements for PPI. CONCLUSION: A large number of treatments are available for PPI using an array of different methods. For this reason, a variety of treatments could be considered before early invasive procedures, to prevent unnecessary surgery and its associated negative complications.

Designing a Pragmatic Intervention to Help Improve the Bladder Cancer Patient Experience.

Bladder cancer (BC) is the 10th most common malignancy worldwide and the patient experience is found to be worse than that for patients diagnosed with other cancer types. We aimed to develop a wellbeing intervention to help improve the bladder cancer patient experience by ameliorating their health-related Quality of Life (HRQoL). We followed the 3 phases of the modified Medical Research Council (MRC) Framework for development of complex interventions. Following a systematic review of the literature on mental, sexual, and physical wellbeing, we conducted discussion groups with patients and healthcare professionals on these 3 themes. A consultation phase was then conducted with all relevant stakeholders to co-design a wellbeing intervention as part of a feasibility study. A pragmatic wellbeing feasibility trial was designed based on the hypothesis that a wellbeing program will increase patient awareness and attendance to services available to them and will better support their needs to improve HRQoL. The primary feasibility endpoints are patient attendance to the services offered and changes in HRQoL. The principle of patient centered care has strengthened the commitment to provide a holistic approach to support BC patients. In this study, we developed a wellbeing intervention in collaboration with patients and healthcare professionals to meet an unmet need in terms of the BC patient experience.

Total phenolic and flavonoid contents and antihypertensive effect of the crude extract and fractions of Calamintha vulgaris.

BACKGROUND: Calamintha vulgaris L., has been used medicinally in the management hypertension. PURPOSE: To investigate the antihypertensive mechanisms of extract of C. vulgaris L., in Sprague-Dawley (SD) rat. STUDY DESIGN: Total phenol and total flavonoid contents were determined in the crude extract through HPLC. In vivo and in vitro pharmacological approaches were utilized to test the crude extract and fractions of C. vulgaris in Sprague-Dawley (SD) rats. The effect on mean arterial pressure (MAP) was compared in normotensive and high salt-induced hypertensive rats. METHODS: Crude extract and nHexane, chloroform, ethylacetate and aqueous fractions of C. vulgaris were tested. In vitro experiments were carried out in isolated rat and rabbit aortae, to probe vascular mechanism(s). Extract was also evaluated for acute toxicity study in mice. RESULTS: Crude extract and fractions of C. vulgaris induced a fall in MAP in normotensive and high salt-induced hypertensive rats at different doses. The effect was more significant in the hypertensive rats (Max. fall, 38.67 ± 2.17 vs 44.16 ± 4.67 mmHg). Among the fractions, chloroform was more effective (Max. fall, 53.20 ±â€¯1.23 mmHg) and aqueous the least (Max. fall, 38.66 ±â€¯1.12 mmHg). Normotensive rats pretreated with atropine (2 mg/kg) or L-NAME (100 µg/kg) ablated fall in MAP to the extract and fractions. In isolated rat aorta, extract induced endothelium-dependent vasodilatory effect, which was ablated with atropine (1 µM), L-NAME (10 µM), atropine + L-NAME, TEA (10 µM) pretreatment and denudation of aorta. Indomethacin (10 µM) pretreatment ablated vasodilatation at lower concentrations and unmasked a vasoconstrictor effect, followed by relaxation at higher concentrations. Extract and fractions inhibited high K+-precontractions and rightward shifted Ca+2 concentration response curves, similar to verapamil. Total phenolic and flavonoid contents were found 39.41 ± 0.18 (mg of GAE/g) and 12.03 ±â€¯0.23 (mg of QUE/g), respectively. HPLC analysis showed the presence of quercetin and rutin CONCLUSION: Results obtained indicate that the antihypertensive effect of C. vulgaris is the outcome of vasodilation, which is mediated through combination of muscarinic receptor-linked NO, activation of TEA-sensitive K+ channels, prostacyclin and Ca+2 antagonism.

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.

Mechanisms underlying the antihypertensive properties of Urtica dioica.

BACKGROUND: Urtica dioica has traditionally been used in the management of cardiovascular disorders especially hypertension. The aim of this study was to explore pharmacological base of its use in hypertension. METHODS: Crude methanolic extract of U. dioica (Ud.Cr) and its fractions (Ud.EtAc, Ud.nHex, Ud.Chl and Ud.Aq) were tested in vivo on normotensive and hypertensive rats under anesthesia for blood pressure lowering effect. In-vitro experiments on rat and rabbit aortae were employed to probe the vasorelaxation mechanism(s). The responses were measured using pressure and force transducers connected to PowerLab Data Acquisition System. RESULTS: Ud.Cr and fractions were found more effective antihypertensive in hypertensive rats than normotensive with remarkable potency exhibited by the ethyl acetate fraction. The effect was same in the presence of atropine. In isolated rat aortic rings, Ud.Cr and all its fractions exhibited L-NAME sensitive endothelium-dependent vasodilator effect and also inhibit K(+) (80 mM)-induced pre-contractions. In isolated rabbit thoracic aortic rings Ud.Cr and its fractions induced relaxation with more potency against K(+) (80 mM) than phenylephrine (1 µM) like verapamil, showing Ud.EtAc fraction the most potent one. Pre-incubation of aortic rings with Ud.Cr and its fractions exhibited Ca(2+) channel blocking activity comparable with verapamil by shifting Ca(2+) concentration response curves to the right. Ud.Cr and its fractions also ablated the intracellular Ca(2+) release by suppressing PE peak formation in Ca(2+) free medium. When tested on basal tension, the crude extract and all fractions were devoid of any vasoconstrictor effect. CONCLUSIONS: These data indicate that crude methanolic extract and its fractions possess antihypertensive effect. Identification of NO-mediated vasorelaxation and calcium channel blocking effects explain the antihypertensive potential of U. dioica and provide a potential pharmacological base to its medicinal use in the management of hypertension.