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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 5  |  Issue : 1  |  Page : 73-76

Anxiolytic activity of Berberis aristata root extract in mice


Department of Pharmacology, GMC, Amritsar, Punjab, India

Date of Submission18-Nov-2019
Date of Decision25-Jan-2020
Date of Acceptance27-Jan-2020
Date of Web Publication08-Jul-2020

Correspondence Address:
Dr. Divya Goel
1154/A, Sector 32, Chandigarh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bjhs.bjhs_71_19

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  Abstract 


BACKGROUND: Anxiety is a common emotional response in humans and it is one of most common psychiatric illnesses. Interest in herbal drugs is growing nowadays for the optimum treatment of anxiety. The aim of the present study was to explore the anxiolytic effect of berberine chloride (BER).
MATERIALS AND METHODS: Elevated plus maze model was used to know its anxiolytic effect and possible mechanism on acute administration in mice. Six groups of mice with six in each group were used. Group I served as control group; Group II received diazepam (0.5 mg/kg); and Groups III, IV, and V received BER in doses of 2.5, 5, and 10 mg/kg, respectively. Group VI received BER 5 mg/kg after flumazenil 5 mg/kg.
RESULTS: As compared to control, berberine chloride solution at all three doses 2.5 mg/kg (P < 0.01), 5 mg/kg (P < 0.01), and 10 mg/kg (P < 0.01) increased the total entries into open arms entries as well as total time spent in open arms.
CONCLUSION: Anxiolytics effect of berberine is comparable to diazepam, likely to be mediated by gamma-aminobutyric acid A – Cl channel complex as effects of berberine were blocked by prior administration of flumazenil. Further studies are needed to identify the phytoconstituents of the berberine which mediated the observed anxiolytic effects.

Keywords: Antianxiety, berberine extract, diazepam, elevated plus maze


How to cite this article:
Goel D. Anxiolytic activity of Berberis aristata root extract in mice. BLDE Univ J Health Sci 2020;5:73-6

How to cite this URL:
Goel D. Anxiolytic activity of Berberis aristata root extract in mice. BLDE Univ J Health Sci [serial online] 2020 [cited 2020 Aug 15];5:73-6. Available from: http://www.bldeujournalhs.in/text.asp?2020/5/1/73/289205



Anxiety is very common emotional response in humans and encompasses various behavioral, affective, and cognitive responses in anticipation of some danger. However, when these responses are excessive in absence of any danger, they result in psychological impairment. Various studies have found anxiety prevalence median value in adult population to be 18.5/1000.[1] As it is the most common psychiatric illness, optimizing its pharmacotherapy is need of the hour. The introduction of benzodiazepines (BZD) has revolutionized the treatment of anxiety disorder.[2] Although BZDs have quick onset of action and large therapeutic index, but at the same time, they are associated with the number of side effects, i.e., sedation, memory loss, and impaired concentration. Moreover, long-term treatment with BZDs leads to development of tolerance and dependence.[3] A number of drugs for the treatment of anxiety are in pipeline, but still we are not able to optimize its pharmacotherapy. To fill the void, many herbal drugs are being used across the globe for their antianxiety effect, i.e., Gingko biloba, Lavandula angustifolia, Hypericum perforatum, Valerina officinalis, Eschscholzia californica, Matricaria recutita, and Piper methysticum, but more scientifically planned studies are required to document their effects.[4]

Berberine is quaternary ammonium compound found in many plants, i.e., Berberis vulgaris, Berberis aristata, and Coptis chinensis.[5] Indian berberine is berberine aristata found in sub-Himalayan region and has been widely used in Ayurveda for numerous health conditions because of its multiple effects, i.e., anti-inflammatory,[6] antimicrobial,[7] antidiabetic,[8] and anticancer.[9] In addition, many studies have shown the sedative effects of berberine.[10] This study was planned to know whether berberine can be used as anxiolytic and also to know extent and site of anxiolytic effect.


  Materials and Methods Top


Drugs and chemicals used

Berberine chloride-pure yellow-colored berberine powder of berberine aristata root.

Diazepam (5 mg/ml) Intas Pharmaceuticals, Ahmedabad, India).

Flumazenil (5 mg/ml) Sigma-Aldrich, Bengaluru, India).

Normal saline for negative control and distilled water as vehicle for preparing various doses of the drugs.

Site of study

The study was conducted in the Department of Pharmacology in Central Research Lab of MMIMSR after getting approval from IAEC on January 30, 2016.

Animals

Healthy Swiss Albino mice (either sex, weighing 20–25 g) were procured from animal house of MMIMSR. The experiment was performed after obtaining permission from IAEC as per the CPCSEA, India, guidelines. Six mice per cage were kept for a minimum of 5 days prior to pharmacological experiments, were maintained under 12 h light/dark cycle and temperature (24°C ± 1°C), and were fed commercial feed and water ad libitum. Prior to experimentation, animals were acclimatized to laboratory conditions for 1 week. The animals were transferred to the central research lab at least 1 h prior to the start of the experiment. Experiments were performed during the daytime (8:00 AM–3:00 PM).

Acute oral toxicity studies

Acute toxicity test was performed according to the Organization for Economic Co-operation and Development guidelines test; berberine chloride solution at 5, 50, 300, and 2000 mg/kg was orally administered to female mice for each dose. The animals were observed for signs of toxicity such as hyperactivity, grooming, convulsion, sedation, and hypothermia continuously for 2 h, and mortality up to 24 h, after administration of the doses.

Groups

Mice were divided into 6 groups, each group had 6 mice. Group I (negative control) was injected normal saline (1 ml/kg, i.p), Group II (positive control) was injected diazepam (0.5 mg/kg, i.p), Group III was injected berberine chloride solution (2.5 mg/kg, i.p), Group IV was injected berberine chloride solution (5 mg/kg, i.p), Group V was injected berberine chloride solution (10 mg/kg, i.p), and Group VI was injected berberine chloride solution (5 mg/kg, i.p) + flumazenil (5 mg/kg, i.p).

Elevated plus maze model

To know the anxiolytic effect of berberine chloride, elevated plus maze (EPM) test was conducted.[11] The plus maze apparatus consists of platform (5 cm × 5 cm), elevated 40 cm above the floor and two open arms (5 cm × 10 cm) and two closed arms (5 cm × 10 cm × 15 cm) emerging from the platform. Half an hour after administration of drugs, each mouse was placed individually at the center of the EPM with its head facing toward the open arm. Each animal was observed for 5-min experiment for following parameters:

  1. Total number of entries in open as well as in closed arm entries (entry in to any arm was defined as the point when mouse put all four paws inside the arm)
  2. Total time spent in open and closed arms.


After each experiment, the apparatus was cleaned with 5% ethanol.

Statistical analysis

All the data were tabulated as mean ± standard error of mean. It was analyzed using one-way analysis of variance with post hoc Tukey's test. P < 0.05 was considered statistically significant.


  Results Top


Acute oral toxicity studies

Acute toxicity studies revealed that berberine chloride solution was safe at all doses. No lethal or toxic reaction was seen, but animals showed slight sedation after 1 h of administration.

Elevated plus-maze test

Administration of diazepam (0.5 mg/kg) significantly increased the number of open arm entries as compared to saline-treated group (P < 0.01) in the EPM model; similar effect has been shown by berberine chloride solution. Number of open arm entries increased significantly as compared to saline solution at 2.5 mg/kg (P < 0.01) and at 5 mg/kg (P < 0.05), while at 10 mg/kg increase in open arm entries was nonsignificant with berberine. As compared to diazepam (0.5 mg/kg), number of open arm entries was less with berberine at 2.5 mg/kg (P < 0.01), 10 mg/kg (P < 0.01), and more at 5 mg/kg (P > 0.05) [Table 1]. Both diazepam and berberine at all doses led to decrease in percentage of closed arm entries [Figure 1]. Significant increase in the time spent in the open arms was seen with the standard drug diazepam as compared to the saline control group (P < 0.01); similar effect had been shown by berberine chloride solution at all three doses 2.5 mg/kg (P < 0.01), 5 mg/kg (P < 0.01), and at 10 mg/kg (P < 0.01). As compared to diazepam, berberine at dose 5 mg/kg and 10 mg/kg showed statistical increased in the time spent in the open arms (P < 0.01) [Table 2]. Both diazepam and berberine extract solution decreased the time spent in the closed arms [Table 2].
Table 1: Effect of different treatments in the open arm entries by mice in elevated plus maze model (single-dose administration)

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Figure 1: Effect of drugs on number of closed arm entries

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Table 2: Effect of drugs on behavior of rats in elevated plus maze on single-dose administration (acute study)

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Berberine showed maximum increase in entries and time spent in open arm at 5 mg/kg; this dose was selected to know about the site of action of berberine after giving flumazenil (5 mg/kg). As compared to berberine, berberine + flumazenil statistically decreased the open arm entries and the total time spent in open arms [Table 1] and [Table 2].


  Discussion Top


The aim of the present study was to evaluate the antianxiety effect of berberine as compared to diazepam. For more than 40 years, BZDs are being used for the treatment of the anxiety disorders, but due to their side effects, there is a need for more safe and effective drugs.[12] Herbs could be good source to find such new remedy, as many drugs have been discovered from plants.[13] Anxiety disorders are manifested by change in behavior, which can be easily measured. The fear of height in EPM model induces anxiety in the animals which manifest as decrease in the motor activity and tendency to remain in the safe closed places.[14],[15] Anxiolytic drugs increase the motor activity and increase the exploratory activity of the animals which can be measured by number of open arm entries and total time spent in the open arms. Berberine at all the three doses increased the number of entries and time spent in the open arms compared to control. Behavioral changes were comparable to diazepam, A dose-dependent anxiolytic action was observed with berberine in this model. Berberine at higher doses 10 mg/kg increased the total time spent in the open arms, but decreased the number of open arm entries, which could be because of sedative effect at higher dose. It is a well-known fact that many drugs such as BZDs possess anxiolytic as well as sedative effect.

Berberine is a benzodioxoloquinolizine alkaloid, and berberine chloride solution also contains other different chemicals such as berbamine, aromoline, palmatine, oxycanthine, oxyberberine, calumbamine, umballiatine, jatrorrhizine, hydrastine, karachine, and taxilamine.[16],[17] Berberine aristata is found to have hepatoprotective,[18] anti-inflammatory,[19] antidiabetic,[20] antimicrobial,[21] anti-osteoporotic,[22] and anticancerous activities.[23] These beneficial effects might be due to presence of different chemicals in its extract.

Emotions are related to change in neurotransmitter levels in brain. In order to investigate the relationship between the anxiolytic-like effect of berberine and the GABAergic neurotransmission, flumazenil was given before berberine and it antagonized all the anxiolytic effects of berberine. As flumazenil is antagonist of (gamma-aminobutyric acid) A receptor, berberine appeared to mediate its anxiolytic action predominantly through this receptor.


  Conclusion Top


The result of present study suggests that berberine possess anxiolytic activity, its mechanism might be related to GABAergic neurotransmission. As berberine contains number of constituents, we cannot say which constituent or combination of constituent is responsible for its anxiolytic effect. Further studies are required to find out active phytochemical responsible for such action.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Pellow S, Chopin P, File SE, Briley M. Validation of open: Closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 1985;14:149-67.  Back to cited text no. 11
    
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Rai S, Pai PG, Shastry R, Ullal SD, Nishith RS, Belagali Y. Evaluation of anxiolytic effect of chronic administration of Mucuna pruriens in Wistar albino rats. Am J PharmTech Res 2014;4:611-9.  Back to cited text no. 15
    
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Sharma K, Ranjan B, Neelam C, Birendra S, Kumar SN. Berberis aristata. Int J Res Ayurveda Pharm 2011;2:383-8.  Back to cited text no. 16
    
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Mokhber-Dezfuli N, Saeidnia S, Gohari AR, Kurepaz-Mahmoodabadi M. Phytochemistry and pharmacology of berberis species. Pharmacogn Rev 2014;8:8-15.  Back to cited text no. 17
    
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Tiwari BK, Khosa RL. Evaluation of the hepatoprotective and antioxidant effect of Berberis asiatica against experimentally induced liver injury in rats. Int J Pharm Pharm Sci 2010;2:92-7.  Back to cited text no. 18
    
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Akhter MH, Sabir M, Bhide NK. Anti-inflammatory effect of berberine in rats injected locally with cholera toxin. Indian J Med Res 1977;65:133-41.  Back to cited text no. 19
    
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Semwal BC, Gupta J, Singh S, Kumar Y, Giri M. Antihyperglycemic activity of root of Berberis aristata DC. in alloxan-induced diabetic rats. Int J Green Pharm 2009;3:259-62.  Back to cited text no. 20
  [Full text]  
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Yogesh HS, Chandrashekhar VM, Katti HR, Ganapaty S, Raghavendra HL, Gowda GK, et al. Anti-osteoporotic activity of aqueous-methanol extract of Berberis aristata in ovariectomized rats. J Ethnopharmacol 2011;134:334-8.  Back to cited text no. 22
    
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    Figures

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    Tables

  [Table 1], [Table 2]



 

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