title: Revealing pharmacodynamics of medicinal plants using in silico approach: a case study with wet lab validation.
abstract: BACKGROUND
  Exploration of therapeutic mechanism is an integral part of medicinal plant based drug discovery for better understanding of pharmacological behavior of these agents. But, its study using conventional hit and trial wet laboratory experiments proves to be very tedious, time consuming and expensive, thus encouraging development of in silico techniques. Hence, an in silico technique has been devised using a computer software Prediction of Activity Spectra for Substances (PASS) to study pharmacodynamics of medicinal plants. The technique has been presented with a case study using Ficus religiosa L. (Moraceae) in which its anticonvulsant mechanism has been elucidated with PASS and further validated experimentally.
  
  
  METHODS
  Pentylenetetrazol (PTZ)-induced convulsion test was used to study the anticonvulsant effect of standardized bark extract of F. religiosa. Thereafter, structure of all the reported bioactive metabolites in the bark was subjected to PASS software to obtain biological activity spectrum of each compound. The mechanism signifying anticonvulsant effect was selected from the spectrum and was further validated using in vitro test.
  
  
  CONCLUSIONS
  The extract showed significant anticonvulsant effect in PTZ test. PASS analysis showed a high activity score for GABA aminotransferase (GABA-AT) inhibitory effect of the bioactive metabolites present in the bark. In vitro GABA-AT enzyme assay results were in concordance with the predicted mechanism by PASS for the observed anticonvulsant effect, as the extract showed potent inhibition of the enzyme. The results of present study showed the in silico technique to be useful for elucidation of unknown therapeutic mechanisms of medicinal plants.
authors: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India.
authors: Damanpreet
authors: D
authors: Singh
authors: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India.
authors: Dinesh Y
authors: DY
authors: Gawande
authors: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India.
authors: Tanveer
authors: T
authors: Singh
authors: Institute of Biomedical Chemistry of Russian Academy of Medical Sciences, 10, Pogodinskaya Street, Moscow 119121, Russia.
authors: Vladimir
authors: V
authors: Poroikov
authors: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India. Electronic address: goelrkpup@gmail.com.
authors: Rajesh Kumar
authors: RK
authors: Goel
mesh_terms: D000612:4-Aminobutyrate Transaminase; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D003292:Convulsants / Q000633:toxicity; D030681:Ficus; D008297:Male; D051379:Mice; D008954:Models, Biological; D008956:Models, Chemical; D015233:Models, Statistical; D010433:Pentylenetetrazole / Q000633:toxicity; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal; D015203:Reproducibility of Results; D012640:Seizures / Q000139:chemically induced
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D010936:Plant Extracts; D000612:4-Aminobutyrate Transaminase; D010433:Pentylenetetrazole
keywords: Anticonvulsant; Ficus religiosa L. (Moraceae); GABA aminotransferase; In silico predictions; Medicinal plants; Prediction of Activity Spectra for Substances (PASS)