Dataset Information

Molecular docking and ex vivo pharmacological evaluation of constituents of the leaves of Cleistanthus collinus (Roxb.) (Euphorbiaceae).

ABSTRACT: OBJECTIVE: To investigate the involvement of alpha adrenergic receptors in hypotension induced by cleistanthin A and cleistanthin B. MATERIALS AND METHODS: Cleistanthins A and B were isolated from the leaves of Cleistanthus collinus using a column chromatographic method and purified. Structures were confirmed by spectroscopic analysis. The compounds were prepared for molecular docking studies using Ligprep 2.3 module and Induced Fit Docking was carried out against ?-1 adrenergic receptors using Glide. The ex vivo experiments were carried out on male Wistar rats. Under anaesthesia, the femoral vein and carotid artery were cannulated for drug administration and for monitoring the blood pressure, respectively. The effect of epinephrine, norepinephrine, acetylcholine, histamine and dopamine were recorded before and after the administration of cleistanthin A or cleistanthin B. The molecular docking studies showed favorable molecular interactions, glide score, energy and emodel. RESULT: Cleistanthins A and B per se reduced the mean blood pressure and the effect was dose dependent. Both the compounds reduced the effect of epinephrine, norepinephrine and ?-1 receptor activity of dopamine. Cleistanthin B significantly increased the duration of action of acetylcholine on mean blood pressure. CONCLUSION: The molecular docking and ex vivo studies conclude that cleistanthin A and cleistanthin B have significant ?-1 adrenergic receptor antagonist effect on the peripheral vascular system.

SUBMITTER: Parasuraman S

PROVIDER: S-EPMC3326912 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Molecular docking and ex vivo pharmacological evaluation of constituents of the leaves of Cleistanthus collinus (Roxb.) (Euphorbiaceae).

Parasuraman Subramani S Raveendran Ramasamy R Vijayakumar Balakrishnan B Velmurugan Devadasan D Balamurugan Subramani S

Indian journal of pharmacology 20120301 2

<h4>Objective</h4>To investigate the involvement of alpha adrenergic receptors in hypotension induced by cleistanthin A and cleistanthin B.<h4>Materials and methods</h4>Cleistanthins A and B were isolated from the leaves of Cleistanthus collinus using a column chromatographic method and purified. Structures were confirmed by spectroscopic analysis. The compounds were prepared for molecular docking studies using Ligprep 2.3 module and Induced Fit Docking was carried out against α-1 adrenergic rec ...[more]

PMID: 22529475

Similar Datasets

Project description:Zhi zhu xiang (ZZX) is the root and rhizome of Valeriana jatamansi Jones ex Roxb. Recent studies have shown that ZZX can exert antianxiety, antidepressant, and sedative effects. Because post-traumatic stress disorder (PTSD) is similar to depression and anxiety in terms of its etiology, pathogenesis, and clinical manifestations, it is possible that ZZX may also be useful for the prevention and treatment of PTSD. In this study, a mouse model of PTSD was established and used to study the pharmacological action of a 95% ethanol extract of ZZX on PTSD via a series of classic behavioral tests. We found that a 95% ethanol extract of ZZX was indeed effective for relieving the symptoms of PTSD in mice. Moreover, network pharmacology analysis was used to predict the potential active ingredients, targets, and possible pathways of ZZX in the treatment of PTSD. The neurotransmitter system, the hypothalamic-pituitary-adrenal (HPA) axis, and the endocannabinoid (eCB) system were identified to be the most likely pathways for anti-PTSD action in ZZX. Due to the lack of a falsification mechanism in network pharmacology, in vivo tests were carried out in mice, and the expression levels of neurotransmitters, hormones, and genes of key targets were detected by enzyme-linked immunosorbent assay and real-time PCR to further verify this inference. Analysis showed that the levels of norepinephrine, 5-hydroxytryptamine, and glutamic acid were increased in the hippocampus, prefrontal cortex, and amygdala of PTSD mice, while the levels of dopamine and γ-aminobutyric acid were decreased in these brain regions; furthermore, ZZX could restore the expression of these factors, at least to a certain extent. The levels of adrenocorticotropic hormone, corticosterone, and corticotropin-releasing hormone were increased in these different brain regions and the serum of PTSD mice; these effects could be reversed by ZZX to a certain extent. The expression levels of cannabinoid receptor 1 and diacylglycerol lipase α mRNA were decreased in PTSD mice, while the levels of fatty acid amide hydrolase and monoacylglycerol lipase mRNA were increased; these effects were restored by ZZX to a certain extent. In conclusion, our findings suggest that ZZX may provide new therapeutic pathways for treating PTSD by the regulation of neurotransmitters, the HPA, and expression levels of eCB-related genes in the brain.

Project description:The aim of the study was to conduct phytochemical and pharmacological investigations of Wrightia coccinea (Roxb. ex Hornem.) Sims via several in vitro, in vivo, and in silico models. A total of four compounds were identified and isolated from the methanol extract of the bark and the methanol extract of the seed pulp of W. coccinea through successive chromatographic techniques and were characterized as 3β-acetyloxy-olean-12-en-28-ol (1), wrightiadione (2), 22β-hydroxylupeol (3), and β-sitosterol (4) by spectroscopic analysis. The aqueous fraction of the bark and chloroform fraction of the fruits provided the most potent antioxidant capacity (IC50 = 7.22 and 4.5 µg/mL, respectively) in DPPH free radical scavenging assay compared with the standard ascorbic acid (IC50 = 17.45 µg/mL). The methanol bark extract and the methanol fruit coat extract exerted anti-diarrheal activity by inhibiting 74.55 ± 0.67% and 77.78 ± 1.5% (mean ± SEM) of the diarrheal episode in mice, respectively, after four hours of loading the samples. In the hypoglycemic test, the methanol bark extract and the methanol fruit coat extract (400 mg/kg) produced a significant (p < 0.05) reduction in the blood glucose level in mice. Both doses of the plant extracts (200 mg/kg and 400 mg/kg) used in the study induced a significant (p < 0.05) increase in pain reaction time. The in vitro and in vivo findings were supported by the computational studies. The isolated compounds exhibited higher binding affinity compared with the standard drugs towards the active binding sites of glutathione reductase, epidermal growth factor receptor (EGFR), kappa opioid receptor, glucose transporter 3 (GLUT 3), Mu opioid receptor, and cyclooxygenase 2 (COX-2) proteins due to their potent antioxidant, cytotoxic, anti-diarrheal, hypoglycemic, and central and peripheral analgesic properties, respectively. The current findings concluded that W. coccinea might be a potential natural source for managing oxidative stress, diarrhea, hyperglycemia, and pain. Further studies are warranted for extensively phytochemical screening and establishing exact mechanisms of action.

Dataset Information

Molecular docking and ex vivo pharmacological evaluation of constituents of the leaves of Cleistanthus collinus (Roxb.) (Euphorbiaceae).

Publications

Molecular docking and ex vivo pharmacological evaluation of constituents of the leaves of Cleistanthus collinus (Roxb.) (Euphorbiaceae).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets