Anxiolytic effects of Plumeria rubra var. acutifolia (Poiret) L. flower extracts in the elevated plus-maze model of anxiety in mice

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Abstract

Interest in alternative medicine and plant-derived medications that affect the “mind” is growing rapidly since last two decades. The aim of the present study was to investigate the effects of ethanolic extract of flower of Plumeria rubra (PR) along with its fractions in the elevated plus-maze (EPM) model of anxiety. The P. rubra extract or its fractions was administered orally to male Swiss mice, at graded doses, 1 h prior to behavioural assessment. The PR extract at the dose of 100 mg/kg p.o., significantly increased the time spent in the open arms of the EPM. Further, the anxiolytic properties of hexane, chloroform and butanolic soluble and insoluble fractions at one-fifth of the original dose were also observed in the EPM task. Out of which butanol insoluble fraction showed significant anxiolytic activity comparable to standard anxiolytic drug, diazepam. Further, pretreatment with crude ethanolic extract and butane insoluble fraction showed no significant effects in the horizontal activity, total distance travelled and stereotypy count in the animal activity monitor and had no motor in-coordination side effects in the rotarod test in mice. These observations suggest that the flower extract of P. rubra and its insoluble butanolic fraction might possess significant anxiolytic potential to be pursued further for drug development process.

Highlights

► Sub-chronic administration of Plumeria rubra (PR), at 100 mg/kg p.o., increased the time spent in the open arms of the elevated plus maze test. ► The extract was further fractionated into hexane, chloroform, butane soluble and n-butane insoluble fractions. ► Out of which butanol insoluble fraction (BIF) showed significant anxiolytic activity comparable to standard anxiolytic drug, diazepam. ► Both PR and BIF did not show any significant alterations in the horizontal activity, total distance and stereotypy count in the activity monitor. ► No motor in-coordination side effects were observed after PR and BIF pre-treatment in the rotarod test in mice.

Introduction

Anxiety is one of the most prevalent psychiatric disorders. In any given year, approximately 40 million adults are affected by anxiety disorder and can also precipitate or aggravate cardiovascular and behavioural disorders (Weissman et al., 1990). Approximately two-thirds of the anxious patients respond to the currently available treatments but the magnitude of improvement is still disappointing, besides, they also produce various systemic side effects and exhibit dependence and tolerance on chronic treatment which now have become a major concern about the use of currently used medicines. At present, the benzodiazepines (BZDs) are the most commonly employed medicinal treatments for anxiety. BZDs produce their pharmacological actions via specific high affinity binding sites on a supramolecular complex composed of GABA-A and a BZD receptor coupled with a chloride ion channel. Besides, the potential for drug dependence and side effects, BZDs also cause drug interactions by potentiating the effect of other CNS depressants such as alcohol, hypnotics, and neuroleptics if taken together. Other anti-anxiety medications include antidepressants, buspirone and β-blockers which though effective in many cases, also possess side effects like nausea, light headedness, dizziness, headache, dry mouth, constipation, diarrhea, etc. (Smith et al., 2012). Therefore, there is an urgent need of drug which possesses greater efficacy, lesser undesirable effects with minimum or no tolerance and dependence. In order to overcome these adverse effects, investigations has been extended for the search of novel and better biocompatible molecules from plant sources.

Herbs are widely accepted sources of medicine, which play an important role in health care programme worldwide (Verma et al., 2010). The search for novel pharmacotherapy from medicinal plants for psychiatric illnesses has progressed significantly in the past decade and their therapeutic potential has been assessed in a variety of animal models (Carlini, 2003, Zhang, 2004, Chatterjee et al., 2012). Our previous studies also involved evaluation of some Indian medicinal plants like Ocimum sanctum (Chatterjee et al., 2011b) and Bacopa monera (Chatterjee et al., 2010) for their anxiolytic effects. In this study, we extended our search for such herbal medications to evaluate the neuropharmacological effects of flower extract of another Indian medicinal plant, Plumeria rubra. P. rubra (PR) syn. Plumeria acutifolia is also known as Plumeria tree, temple tree, West Indian jasmine or frangipani. This shrub or small tree is native to Mexico, and is well-known for its strongly perfumed flowers that can be of several colors. Various species of Plumeria has been previously shown to possess antioxidant (Ruiz-Terán et al., 2008), hypolipidemic (Merina et al., 2010), hypoglycemic (Zaheer et al., 2010), antimicrobial (Rasool et al., 2008) and cytotoxic activities (Kardono et al., 1990). The medicinal properties of plant also include protection against ulcers, skin diseases, inflammation, arthritis and constipation (Hamburger et al., 1991, Gupta et al., 2006, Zaheer et al., 2010).

Despite the widely popular use of this plant, the available scientific information about the potential effects of PR in animal models of psychiatric disorders especially in anxiety is limited. Therefore, the present study was conducted to evaluate the anxiolytic effect of PR in different models in mice.

Section snippets

Animals

All experimental protocols were approved by our Institutional Ethical Committee following the guidelines of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA). Albino male Swiss mice weighing 20–25 g were employed in the study. Mice were housed in six per cage at constant room temperature (22 ± 2 °C) and 12-h light/12-h dark (8:00 a.m.–8:00 p.m.). Mice were fed standard laboratory food and water was given ad libitum. Each animal was used once in the behaviour

Statistical analysis

The results were expressed as mean ± SEM. The statistical significance was determined by One-Way Analysis of Variance (ANOVA) followed by Dunnett's test, using Prism software version 5.0. P < 0.05 was considered to be statistically significant.

Effect of ethanolic flower extract of P. rubra in elevated plus maze test in mice

Graded doses (50–200 mg/kg, p.o.) of crude ethanolic flower extract was studied in the elevated plus maze model. As shown in the Fig. 2 (Table 1), a significant increase in the time spent in open arms was observed at both doses of 50 mg/kg (P < 0.01) and 100 mg/kg, p.o. (P < 0.001). However, no such effects were observed with the higher dose of 200 mg/kg. The results were compared with the standard drug diazepam (1.5 mg/kg, p.o.)

Effect of P. rubra fractions in elevated plus maze test in mice

We further evaluated the effects of hexane, chloroform, butanolic soluble

Discussion

The study analysed the therapeutic potential of P. rubra flower extract in experimental models of anxiety in mice. The PR extract showed promising anxiolytic effects without causing any neuromuscular side effects.

To study the anxiolytic profile of the extract we used the elevated plus maze model, which is currently one of the most frequently used models of animal anxiety (Hogg, 1996). The elevated plus maze is considered to be an etiologically valid animal model of anxiety because it uses

Role of funding source

The study was supported by the Council of Scientific and Industrial Research, New Delhi, India.

Contributors

M.C. carried out experiments, undertook the statistical analysis and prepared the first draft. M.C. and R.V. managed the literature searches, reviewed and finalized the draft. V.L. and A.M prepared and purified the plant extract. S.S. and A.V. carried out experiments. G.P. designed the study. All authors contributed to and have approved the final manuscript. M.C., R.V. and G.P. revised the manuscript.

Conflict of interests

Authors declare that they have no conflict of interests.

Acknowledgement

Authors are grateful to CSIR, New Delhi, India for financial support.

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