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Anxiolytic actions of Nardostachys jatamansi via GABA benzodiazepine channel complex mechanism and its biodistribution studies

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Abstract

Nardostachys jatamansi has profound applications against pharmacological interventions and is categorized as a hypno-sedative drug according to Ayurveda. In the present study probable mechanism of anxiolytic action of Nardostachys jatamansi extract (NJE) was studied using behavioral anxiolytic tests (Elevated plus maze, Open field test, Light dark box test, and Vogel’s conflict test) in mice. Mice were treated orally with NJE (250 mg/kg) for 3, 7 and 14 days or diazepam (1 mg/kg) followed by behavioral assessment and estimation of monoamine neurotransmitters, GABA, and antioxidant enzymes. Treatment of mice for 7 days caused an increase in time spent in open arms in elevated plus maze, number of line crossings in open field test, increased time spent in lit compartment of light-dark box test, an increase in number of licks made and shocks accepted in Vogel’s conflict test, with results comparable to diazepam and this treatment also caused a significant increase in monoamine neurotransmitters and GABA in brain and tissue antioxidant parameters. Co-treatment of NJE with flumazenil (GABA-benzodiazepine antagonist; 0.5 mg/kg i.p) or picrotoxin (GABAA gated chloride channel blocker; 1 mg/kg i.p) caused a blockage/antagonised anxiolytic actions of NJE by causing a significant reduction in time spent in open arms of elevated plus maze, an decrease in number of line crossing in open field test and also number of shocks and licks accepted in Vogel’s conflict test. Further, NJE was radiolabelled with technetium99m at their hydroxyl groups following which purity as well as in vivo and in vitro stability of radiolabelled formulations was evaluated. The blood kinetics and in vivo bio-distribution studies were carried out in rabbits and mice respectively. Labeled formulation was found to be stable in vitro (96 to 93% stability) and in vivo (96 to 92% stability). The labeled compound was cleared rapidly from blood (within 24 h) and accumulated majorly in kidneys (11.65 ± 1.33), liver (6.07 ± 0.94), and blood (4.03 ± 0.63) after 1 h. However, a small amount was observed in brain (0.1 ± 0.02) probably because of its inability to cross blood-brain barrier. These results highlight biodistribution pattern of NJE, and also indicated that a 7-day treatment with NJE produced significant anxiolytic effects in mice and also a significant increase in brain monoamine and GABA neurotransmitter levels and suggests that anxiolytic effects of NJE are primarily and plausibly mediated by activating GABAergic receptor complex.

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Authors and Affiliations

  1. Biochemistry and Nanosciences Discipline, Defence Food Research Laboratory, Mysore, Karnataka, 570011, India

    Sakina Razack, Hemanth Kumar Kandikattu, M. P. Venuprasad & Farhath Khanum

  2. Department of Seed Science and Technology, UAS, GKVK, Bangalore, India

    Narayanappa Amruta

  3. Department of Pharmaceuticals, Institute of Nuclear Medicine and Allied Sciences, Brigadier Mazumdar Marg, Timar Pur, Delhi, 110054, India

    Krishna Chuttani & Anil Kumar Mishra

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  1. Sakina Razack
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  2. Hemanth Kumar Kandikattu
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  3. M. P. Venuprasad
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  4. Narayanappa Amruta
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Razack, S., Kandikattu, H.K., Venuprasad, M.P. et al. Anxiolytic actions of Nardostachys jatamansi via GABA benzodiazepine channel complex mechanism and its biodistribution studies. Metab Brain Dis 33, 1533–1549 (2018). https://doi.org/10.1007/s11011-018-0261-z

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