scholarly journals Involvement of Muscarinic Receptors in Hypotensive and Diuretic Effects of Aqueous Soluble Fraction from Asphodelus tenuifolius Cav.

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Waqas Younis ◽  
Alamgeer ◽  
V. B. Schini-Kerth ◽  
Samara Requena Nocchi ◽  
Denise Brentan Silva ◽  
...  

Background. Asphodelus tenuifolius Cav. (Asphodelaceae) is widely used in Pakistan traditional medicine as a hypotensive and diuretic agent. Despite the cardioprotective effects described for A. tenuifolius, the mechanisms involved in its probable hypotensive and diuretic effects have never been evaluated. Firstly, different extracts from A. tenuifolius seeds were obtained, and their antioxidant profiles and chemical constituents by LC-DAD-were determined, including molecular networking by the GNPS platform. Then, to evaluate changes in blood pressure, different groups of anesthetized normotensive rats were intravenously treated with the crude extract (AT-Cr, 1–50 mg/kg), aqueous (AS-AT, 1–25 mg/kg), n-butanol (BS-AT, 1–50 mg/kg), and dichloromethane fraction (DS-AT, 1–80 mg/kg). The diuretic effects of AT-Cr, AS-AT, BS-AT, and DS-AT at 100, 200, and 300 mg/kg, p.o. doses, were also evaluated in comparison with hydrochlorothiazide (HCTZ, 10 mg/kg, p.o). The urinary volume, sodium, potassium, and pH were estimated in the sample collected for 6 h from saline-loaded rats. Using pharmacological antagonists or inhibitors, we determine the involvement of acetylcholine, prostaglandins, and nitric oxide in A. tenuifolius-induced hypotensive and diuresis action. In addition, the activities of angiotensin-converting enzyme, erythrocyte carbonic anhydrase, and renal Na+/K+/ATPase were evaluated in vitro. Acute treatment with crude extract and fractions of A. tenuifolius exhibited significant hypotensive and diuretic potential in normotensive rats. However, AS-AT produced the most potent and significant dose-dependent hypotension and diuretic effects in normotensive rats. Previous treatment with atropine significantly reduced the hypotensive and diuretic action of AS-AT, but pretreatment with indomethacin or L-NAME did not affect these effects. Moreover, the 7-day treatment with AS-AT did not reduce activities of serum angiotensin-converting enzyme, erythrocyte carbonic anhydrase, and renal Na+/K+/ATPase. AS-AT showed four major compound node clusters, which included sugars, alkaloids, nucleoside, amino acid, and glycosylated flavonoids. This research supports and extends the traditional use of A. tenuifolius as a hypotensive and diuretic agent. The results showed that AS-AT from A. tenuifolius could present compounds responsible for hypotensive and diuretic activities through the activation of muscarinic receptors.

1977 ◽  
Vol 5 (1) ◽  
pp. 1-9 ◽  
Author(s):  
R A Vukovich ◽  
D A Willard ◽  
L J Brannick

One of several novel peptidic inhibitors of angiotensin converting enzyme (CEI) has been studied intravenously both in normal male volunteers and severely hypertensive patients without any clinically significant adversity or intolerance. Hypertensive patients experienced a significant yet gradual reduction in resting arterial pressure without hypotension. The addition of a diuretic agent was observed to potentiate this antihypertensive effect. Normal, sodium replete volunteers received this nonapeptide intravenously in doses up to 2·0 mg/kg without any significant cardiovascular effect. Both patients and normal subjects exhibited reversible dose related increases in angiotensin I and renin levels after receiving the peptide. The plasma renin response to tilting was also potentiated by CEI. These findings suggest that intravenous CEI may be of value in the treatment of severely elevated hypertension and as a tool to evaluate vasoconstrictor and volume factors in hypertension.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Nazim Uddin Emon ◽  
Md. Munsur Alam ◽  
Irin Akter ◽  
Saima Akhter ◽  
Anjuman Ara Sneha ◽  
...  

Abstract Background COVID-19 has mutation capability, and there are no specific drug therapies that are available to fight or inhibit the proteins of this virus. The present study aims to investigate the binding affinity of the bioactive and synthetic compounds with the main protease (Mpro) enzymes and angiotensin-converting enzyme 2 (ACE 2) by computational approach. PASS prediction, pharmacokinetics, and toxicological properties prediction studies were performed through the Google PASS prediction and Swiss ADME/T website. Besides, molecular docking studies were accomplished by BIOVIA Discovery Studio 2020, UCSF Chimera, and PyRx autodock vina. Results The docking scores were inferred and the selected compounds showed results varying from −3.2 to −9.8 (kcal/mol). Theaflavin scored the highest docking score to the 5REB, 6VW1, and 1R42 enzymes and showed the binding affinity as −6.3 kcal/mol, −9.8 kcal/mol, and −8.6 kcal/mol, respectively. Again, kaempferol showed the best binding affinity to the 7BQY (−7.1 kcal/mol) and 6Y2FB (−6.6 kcal/mol) enzymes. All the chemical constituents showed better probability in action in pass prediction analysis. Besides, no ligands (except theaflavin) have any conflict with Lipinski’s rules of five, which authorized the drug probability of these ligands. Conclusion Therefore, the selected compounds could be considered a potential herbal treatment source against SARS-CoV-2.


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