Elsevier

Chemico-Biological Interactions

Volume 260, 25 December 2016, Pages 208-218
Chemico-Biological Interactions

Asparagus adscendens root extract enhances cognition and protects against scopolamine induced amnesia: An in-silico and in-vivo studies

https://doi.org/10.1016/j.cbi.2016.10.007Get rights and content

Highlights

  • Phytoconstituents of AAE (Asparagus adscendens extract) showed excellent score for nootropic and antioxidant activities.

  • AAE administration showed nootropic activity in behavioral studies (radial arm maze and passive shock avoidance paradigm).

  • Pretreatment with AAE significantly reduced the acetylcholinesterase activity.

  • Pretreatment with AAE significantly reduced the oxidative stress.

Abstract

Asparagus adscendens Roxb. commonly known as safed musli and belonging to the Liliaceae family is cultivated mainly in Asian countries. In traditional medicine, safed musli is recommended as nerve tonic and remedy for memory impairment. The present study was aimed to evaluate nootropic and antiamnesic activities of Asparagus adscendens extract (AAE) using in silico and in vivo approach. Phytoconstituents of A. adscendens root reported in literature were subjected to in silico prediction using PASS and Pharmaexpert. The radial arm maze and passive shock avoidance paradigm were employed to evaluate nootropic activity. Subsequently, the anti-amnesic activity was evaluated in scopolamine induced amnesia model. To elucidate the mechanism of nootropic activity, the effect of AAE on the activities of acetylcholinesterase and antioxidant enzymes in the cortex and hippocampus of mice were also evaluated. In silico activity spectrum for all of A. adscendens phytoconstituents exhibited excellent prediction score for nootropic activity. Pretreatment with AAE (50, 100 & 200 mg/kg, i.p.) for 15 days showed significant decrease in working memory error, reference memory error and retrieval latency in radial arm maze and decrease in step down latency in passive shock avoidance paradigm were observed. Further, AAE significantly reduced acetylcholinesterase and oxidative stress parameters in cortex and hippocampus of mice. Thus, in silico and in vivo results suggest that A. adscendens root may exert its nootropic activity through both anti-acetylcholinesterase and antioxidant activities.

Introduction

Alzheimer's disease (AD) is a neurodegenerative disorder has been characterized by a progressive loss of cognitive abilities, leading to learning and memory dysfunctioning in everyday activities [1], [2]. According to the WHO, it affects nearly 47.5 million people worldwide, which is likely to be increased to 75.6 million by 2030 [3]. Dysfunctioning of cholinergic system and elevated oxidative stress in forebrain and hippocampus appears to play a critical role in the pathogenesis of Alzheimer's disease [4], [5], [6]. Currently, acetylcholinesterase inhibitors such as physostigmine, tacrine and donepezil are widely used for the treatment of AD, which are known to increase the availability of acetylcholine in cholinergic synapses [7], [8]. However, the adverse effects such as loss of appetite, vomiting, headache, diarrhea, narrow therapeutic range, hepatotoxicity etc. limit their use [9], [10]. Therefore, it is an urgent need to find complementary and alternative medicines (CAM) for the management of AD. Several medicinal plants and their phytoconstituents have shown the neuroprotective and cognition enhancing properties in experimental model of AD [11], [12], [13].

Asparagus adscendens Roxb. (Liliaceae) commonly known as safed musali or dholi musali, is a climbing herb found mainly in Asian countries. It has been attributed to a number of therapeutic uses in traditional medicine system such as diarrhea, dysentery, sexual debilities, nerve tonic and as a remedy in memory impairment [14]. The literature revealed that A. adscendens roots have been investigated for antifilarial [15], Insulin enhancing [16], antistress [17], Chemomodulatory [18], aphrodisiac [19] and antioxidant activities [18], [20], [21]. Moreover, the available literature reveals that this plant has not been explored with respect to its therapeutic potential as nootropic activity. Also, nowadays the virtual screening of the phytochemical is believed to be a useful tool for drug discovery beyond their ethnic use [22]. Therefore, an effort has been made to explore the pharmacological activities of A. adscendens root using Prediction of Activity Spectra for Substances (PASS) and Pharmaexpert. A PASS based analysis (Table 1) revealed the presence of different bioactive phytoconstituents which might be responsible for nootropic potential with the most significant possibility of getting effective in the management of Alzheimer's disease. Hence, based on traditional knowledge and in silico support the present study was envisaged to evaluate nootropic and anti-amnesic activities of Asparagus adscendens extract (AAE).

Section snippets

Drugs and chemicals

Shatavarin IV was procured from Natural Remedies Private Limited (Bangalore, India), Piracetam was obtained as a gift sample from Micro Labs Ltd. (Bangalore, India) and Griess reagent was procured from Sigma-Aldrich, Company (St. Louis, MO, USA). All other chemicals used in the present study were of analytic grade.

Animals

Swiss albino mice, weighing 20–30 g were purchased from Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, Haryana. The animals were housed on a 12 h light/dark

In silico screening of A. adscendens root phytoconstituents

So far, 23 phytoconstituents have been reported as per literature, 3-heptadecanone, 8-hexadecenoic acid, methyl pentacosanoate, tetratriacontane, tritriacontane, methyl palmitate, tetracosyl tetracosanoate, palmitic acid, stearic acid, asparanin C, asparanin D, asparoside C, asparoside D, 3-β-O-{β-D-2-tetracosylxylopyranosyl}-stigmasterol, 3-β-O-{β-d-glucopyranosyl (1–2)-α-l-arabinopyranosyl}-stigmasterol, β-sitosterol-β-D-glucoside, Shatavarin IV, stigmasterol, sarsasapogenin, xanthophyll,

Discussion

The PASS prediction spectra of phytoconstituents present in Asparagus adscendens roots revealed the excellent score for nootropic potential. Also, the above predicted nootropic potential was further supported by relevant mechanisms as analyzed by Pharmaexpert. The predictive values of these in silico tools have been validated in our laboratory as well as by other laboratories too [24], [41], [42], [43]. Therefore, based on the excellent score in PASS prediction, the nootropic and anti-amnesic

Acknowledgement

The authors are deeply grateful to the Council of Scientific and Industrial Research (CSIR), Pusa, New Delhi, India for providing financial assistance [Vide F.No. 38(1339)/12/EMR-II] for the project, and project fellowship to Miss. Priyanka Pahwa. We are also thankful to Dr. Bikram Singh, CSIR- Institute of Himalayan Bioresource Technology, Palampur, H.P. for the authentication of plant material.

References (77)

  • S. Surveswaran et al.

    Systematic evaluation of natural phenolic antioxidants from 133 Indian medicinal plants

    Food. Chem.

    (2007)
  • D.Y. Gawande et al.

    Pharmacological validation of in silico guided novel nootropic potential of Achyranthes aspera L

    J. Ethnopharmacol.

    (2015)
  • N.W. Dunham et al.

    A note on a simple apparatus for detecting neurological deficit in rats and mice

    J. Am. Pharm. Assoc. Am. Pharm. Assoc. Balt.

    (1957)
  • R.A. Turner

    Depressants of the central nervous system

  • O. Cioanca et al.

    Cognitive-enhancing and antioxidant activities of inhaled coriander volatile oil in amyloid β (1-42) rat model of Alzheimer's disease

    Physiol. Behav.

    (2013)
  • K.D. Oakes et al.

    Utility of TBARS assay in detecting oxidative stress in white sucker (Catostomus commersoni) populations exposed to pulp mill effluent

    Aquat. Toxicol.

    (2003)
  • B. Chance et al.

    Assay of catalase and peroxidases

    Met. Enzymol.

    (1955)
  • K.M. Choudhary et al.

    Ameliorative effect of Curcumin on seizure severity, depression like behavior, learning and memory deficit in post pentylenetetrazole-kindled mice

    Eur. J. Pharmacol.

    (2013)
  • G.L. Ellman et al.

    A new and rapid colorimetric determination of acetylcholinesterase activity

    Biochem. Pharmacol.

    (1961)
  • D. Singh et al.

    Revealing pharmacodynamics of medicinal plants using in silico Approach: a case study with wet lab validation

    Comput. Biol. Med.

    (2014)
  • M.M. Al-Amin et al.

    Astaxanthin ameliorates aluminum chloride-induced spatial memory impairment and neuronal oxidative stress in mice

    Eur. J. Pharmacol.

    (2016)
  • E.D. Levin

    Learning about cognition risk with the radial-arm maze in the developmental neurotoxicology battery

    Neurotoxicol. Teratol.

    (2015)
  • K. Yamada et al.

    Hippocampal AP5 treatment impairs both spatial working and reference memory in radial maze performance in rats

    Eur. J. Pharmacol.

    (2015)
  • A.D.J. Titus et al.

    Hypobaric hypoxia-induced dendritic atrophy of hippocampal neurons is associated with cognitive impairment in adult rats

    Neurosci

    (2007)
  • D. Braida et al.

    An inverted U-shaped curve for heptylphysostigmine on radial maze performance in rats: comparison with other cholinesterase inhibitors

    Eur. J. Pharmacol.

    (1996)
  • G. Pepeu et al.

    Cholinesterase inhibitors and memory

    Chem. Biol. Interact.

    (2010)
  • D.L. Marcus et al.

    Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer's disease

    Exp. Neurol.

    (1998)
  • M.F. Chen et al.

    Noradrenergic mediation of the memory-enhancing effect of corticotropin-releasing factor in the locus coeruleus of rats

    Psychoneuroendocrinology

    (1992)
  • C.F. Murchison et al.

    A distinct role for norepinephrine in memory retrieval

    Cell.

    (2004)
  • WHO. Dementia. Fact Sheet. World Health Organisation. April...
  • R.T. Bartus et al.

    The cholinergic hypothesis of geriatric memory dysfunctioning

    Science

    (1982)
  • Q. Ding et al.

    Oxidative damage, protein synthesis, and protein degradation in Alzheimer's diasease

    Curr. Alzheimer’s. Res.

    (2007)
  • G.M. Bores et al.

    Pharmacological evaluation of novel Alzheimer's disease therapeutics: acetylcholinesterase inhibitors related to galanthamine

    J. Pharmacol. Exp. Ther.

    (1996)
  • R. Singh et al.

    Potential antifilarial activity of roots of Asparagus adscendens Roxb, against setaria cervi in vitro

    Indian. J. Exp. Biol.

    (1997)
  • J.N. Mathews et al.

    Asparagus adscendens (Shweta musli) stimulates insulin secretion, insulin action and inhibits starch digestion

    Br. J. Nutr.

    (2006)
  • A.S. Kanwar et al.

    Effects of Chlorophytum arundinaceum, Asparagus adscendens and Asparagus racemosus on pro-inflammatory cytokine and corticosterone levels produced by stress

    Phytother. Res.

    (2010)
  • M. Singh et al.

    Chemomodulatory potential of Asparagus adscendens against murine skin and forestomach papillomagenesis

    Eur. J. Cancer. Prev.

    (2011)
  • F.W. Bansode et al.

    Dose-dependent effects of Asparagus adscendens root (AARR) extract on the anabolic, reproductive and sexual behavioural activity in rats

    Pharm. Biol.

    (2015)
  • Cited by (17)

    • Ameliorative effect of deoxyvasicine on scopolamine-induced cognitive dysfunction by restoration of cholinergic function in mice

      2019, Phytomedicine
      Citation Excerpt :

      In order to further elucidate the underlying mechanism of memory improving effects of DVAS in the scopolamine-treated mice, alterations of histopathology, cholinergic system, BDNF excretion, inflammation and oxidative stress were assessed. Moreover, histopathologic changes, attenuated cholinergic function, elevated inflammation and oxidative stress were found in the scopolamine-induced mice as previous reports (Li et al., 2018b; Pahwa and Goel, 2016). Huperzine-A is used as a Chinese marketed drug to improve the cognition and memory of AD patients and as a memory enhancing dietary supplement in USA (Damar et al., 2017), and it can remarkedly ameliorate these changes in scopolamine-treated mice and enhance their learning and memory in this study.

    View all citing articles on Scopus
    View full text