1. Pharmacological insights and prediction of lead bioactive isolates of Dita bark through experimental and computer-aided mechanism
- Author
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Mohammad Arman, Tommaso Venneri, Shaifullah Mansur Tanzil, Suhel Ahmed, A F M Irfan Uddin Zim, Mohammad Forhad Khan, Areeful Haque, Chadni Lyzu, Abdus Shukur Imran, Barbara Romano, Raffaele Capasso, Faisal Bin Kader, Shahenur Alam Sakib, Khan, M. F., Kader, F. B., Arman, M., Ahmed, S., Lyzu, C., Sakib, S. A., Tanzil, S. M., Zim, A. F. M. I. U., Imran, M. A. S., Venneri, T., Romano, B., Haque, M. A., and Capasso, R.
- Subjects
0301 basic medicine ,Male ,Anti-Inflammatory Agents ,Antidepressant ,Pharmacology ,Mice ,0302 clinical medicine ,GC–MS ,ADME ,biology ,Chemistry ,Depression ,General Medicine ,Antidepressive Agents ,Phytochemical ,030220 oncology & carcinogenesis ,Molecular docking ,Lipinski's rule of five ,Plant Bark ,Female ,Adult ,Alstonia scholaris (L.) R. Br ,medicine.drug_class ,Alstonia scholaris ,RM1-950 ,Anti-inflammatory ,Gas Chromatography-Mass Spectrometry ,03 medical and health sciences ,Young Adult ,Fibrinolytic Agents ,In vivo ,medicine ,Thrombolytic Agent ,Animals ,Humans ,Computer Simulation ,Dita bark ,Inflammation ,Dose-Response Relationship, Drug ,Plant Extracts ,Anticoagulant ,Thrombosis ,biology.organism_classification ,Tail suspension test ,Disease Models, Animal ,030104 developmental biology ,Therapeutics. Pharmacology ,Alstonia - Abstract
Dita bark (Alstonia scholaris (L.) R. Br.) is an ethnomedicine used for the management of various ailments. This study aimed to investigate the biological properties of methanol extract of A. scholaris bark (MEAS), through in vivo, in vitro and in silico approaches alongside its phytochemical profiling. Identification and nature of the bioactive secondary metabolites were studied by the established qualitative tests and GC-MS analysis. The antidepressant activity was determined by forced swimming test (FST) and tail suspension test (TST) in mice. The anti-inflammatory and thrombolytic effect was evaluated using inhibition of protein denaturation technique and clot lysis technique, respectively. Besides, computational studies of the isolated compounds and ADME/T analysis were performed by Schrodinger-Maestro (v11.1) software, and PASS prediction was conducted through PASS online tools. The GC-MS analysis revealed the presence of several secondary metabolites in MEAS. Treatment with MEAS revealed a significant reduction of immobility time in a dose-dependent manner in FST and TST. Besides, MEAS showed substantial anti-inflammatory effects at the higher dose (400 μg/mL) as well as revealed notable clot lysis effect as compared to control. In the case of computer-aided investigation, all compounds meet the condition of Lipinski's rule of five. PASS study also predicted for all compounds, and among these safe compound furazan-3-amine showed the most spontaneous binding energy for both antidepressant and thrombolytic activities, as well as 5-dimethylamino-6 azauracil, found promising for anti-inflammatory activity. Taken together, the investigation concludes that MEAS can be a potent source of antidepressant, anti-inflammatory, and thrombolytic agents.
- Published
- 2020