title: Bioactivity guided isolation of antipsychotic constituents from the leaves of Rauwolfia tetraphylla L.
abstract: This study was undertaken to ascertain the antipsychotic properties of Rauwolfia tetraphylla L. leaves and to isolate and characterize the antipsychotic constituents. Among the MeOH extract and some alkaloidal fractions at different pHs, the alkaloidal CHCl(3) fraction at pH-9 (2C) showed the highest antipsychotic activity against dopaminergic (DA-D(2)) and serotonergic (5-HT(2A)) receptors in-vitro and amphetamine induced hyperactive mouse model in-vivo. The activity guided isolation of CHCl(3) fraction (2C) afforded six indole alkaloids: 10-methoxytetrahydroalstonine (1), isoreserpiline (2), an isomeric mixture of 11-demethoxyreserpiline (3) and 10-demethoxyreserpiline (4), α-yohimbine (5) and reserpiline (6). Given orally, alkaloids 3-6 showed significant antipsychotic activity in a dose dependent manner. None of the extract, alkaloidal fractions or alkaloids showed any extra pyramidal symptoms at the tested doses. It was also observed that MeOH extract was behaving similar to other clinically used novel atypical antipsychotics in having 5-HT(2A) occupancy greater than the DA-D(2) receptor at the tested doses. Further toxicity and safety evaluation studies of MeOH extracts of R. tetraphylla leaves at different doses (10, 100, 300 and 2000 mg/kg) on female Swiss albino mice showed that MeOH extract is non toxic. The isolated alkaloids, 3-6 could serve as a promising lead structure for drug development of treating psychotic conditions in human.
authors.affiliation: Medicinal Chemistry Department, Bioprospection Division, Central Institute of Medicinal and Aromatic Plants, Lucknow, India.
authors.forename: Shikha
authors.initials: S
authors.lastname: Gupta
authors.forename: Vinay Kumar
authors.initials: VK
authors.lastname: Khanna
authors.forename: Anupam
authors.initials: A
authors.lastname: Maurya
authors.forename: Dnyaneshwar Umrao
authors.initials: DU
authors.lastname: Bawankule
authors.forename: Rajendra Kumar
authors.initials: RK
authors.lastname: Shukla
authors.forename: Anirban
authors.initials: A
authors.lastname: Pal
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Srivastava
mesh_terms: D000661:Amphetamine; D000818:Animals; D014150:Antipsychotic Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006863:Hydrogen-Ion Concentration; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D026121:Indole Alkaloids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D018377:Neurotransmitter Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D011926:Rauwolfia / Q000737:chemistry*; D017982:Receptors, Biogenic Amine / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D026121:Indole Alkaloids; D018377:Neurotransmitter Agents; D010936:Plant Extracts; D017982:Receptors, Biogenic Amine; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D000661:Amphetamine