|Year : 2014 | Volume
| Issue : 2 | Page : 118-124
Antidepressant activity of aqueous extract of Phaseolus vulgaris (black bean) in rodent models of dep ression
Madhu Devi, Ramica Sharma
Department of Pharmacology, Rayat Institute of Pharmacy, Railmajra, Shahid Bhagat Singh Nagar, Punjab, India
|Date of Submission||18-Sep-2013|
|Date of Acceptance||05-Dec-2013|
|Date of Web Publication||29-Mar-2014|
Department of Pharmacology, Rayat Institute of Pharmacy, Railmajra, Shahid Bhagat Singh Nagar - 144 533, Punjab
Source of Support: None, Conflict of Interest: None
| Abstract|| |
The aim of this study was to investigate the potential antidepressive effect of aqueous extract of Phaseolus vulgaris (AEPV) and its mechanism of the antidepressant-like action in validated models of depression. Force swim test (FST) in rats and 5-hydroxytryptophan (5-HTP)-induced head-twitch responses (HTRs) in mice were performed to assess the potential antidepressant-like activity of AEPV. Oral administration of AEPV markedly reduced the duration of immobility during the FST in dose-dependent (250 and 500 mg/kg) manner and these effects were similar to that of imipramine. However, AEPV at a dose of 500 mg/kg, p.o. potentiate 5-HTP-induced HTR in mice, as similar to that of fluoxetine (FLU). In conclusion, this study depicts the antidepressant-like effect of AEPV in animal models of depression.
Keywords: Antidepressive, depression, head twitch, immobility, Phaseolus vulgaris
|How to cite this article:|
Devi M, Sharma R. Antidepressant activity of aqueous extract of Phaseolus vulgaris (black bean) in rodent models of dep ression. Int J Nutr Pharmacol Neurol Dis 2014;4:118-24
|How to cite this URL:|
Devi M, Sharma R. Antidepressant activity of aqueous extract of Phaseolus vulgaris (black bean) in rodent models of dep ression. Int J Nutr Pharmacol Neurol Dis [serial online] 2014 [cited 2020 Jan 28];4:118-24. Available from: http://www.ijnpnd.com/text.asp?2014/4/2/118/129603
| Introduction|| |
Depression is a psychiatric disorder clinically characterized by a low mood, loss of interest, or pleasure in daily activities, and low self-esteem with a high suicidal tendency. ,,, It's a disease that affects the quality of life of many people, and has become a major cause of suicidal death.  Depression is the most common of the affective disorders and is a major cause of disability and premature death worldwide among the disorders of mood not thought or cognition.  Although depression is prevalent, and carries a large burden of disease, the pathogenesis of depression is poorly understood. The underlying pathophysiology of depression has not been clearly defined. Current evidence suggested that there is a complex interaction between neurotransmitter availability, receptor regulation and sensitivity underlying the affective symptoms. From the clinical and preclinical trials data it is suggested that there is disturbance in central nervous system serotonin 5-hydroxytryptamine (5-HT) activity which is an important factor. Other neurotransmitters include norepinephrine (NE) or noradrenaline (NA), dopamine (DA), glutamate, and brain-derived neurotrophic factor (BDNF).  While synthetic antidepressant drugs do exist, they are not ideal, as only a segment of patients are effectively treated and the therapeutic onset is delayed. ,, Several classes of medications are available for treatment of depression. Despite the availability of sophisticated structural and functional brain imaging, physicians must choose antidepressants using clinical judgment and past experience.  Available technology does not allow the physician to determine which class of medications is most effective for a particular patient. Antidepressant medications can be chosen for effectiveness, toxicity, expense, and ease of administration. , The pharmacological treatment of depression in the patient begins with a careful assessment to determine the cause of depression and identification of potential target symptoms for medications. 
Herbal medicines used prominently for depression  and most of the people suffering from depression try complementary medicines.  The clinically depressed patients used a number of synthetic drugs as standard treatment and those synthetic drugs have adverse effects that can compromise the therapeutic treatment and also provide a chance for alternative remedies based on natural products.  Beans are grains that have a high nutritional value due to their protein content. They also contain an elevated concentration of complex carbohydrates, soluble fibers, essential vitamins, metals, and polyphenols such as flavonoids and isoflavones. ,, In addition to these compounds, black beans also contain tryptophan. Tryptophan increases the concentration of 5-HTP in the brain and is helpful in preventing depression.  Hence, battery of behavioral tests were used namely; forced swim test (FST) in rats and 5-hydroxytryptophan (5-HTP) potentiation in mice to provide significant information on antidepressant like activity of AEPV.
| Materials and Methods|| |
Procurement of extract
Standardized dry AEPV (seed extract) was obtained from S.V. Agro Food (Delhi, India). It can also be prepared by the extraction process using water as a solvent.
Swiss albino rats/mice, of either sex were obtained from Punjab University, Chandigarh and were housed under standard light/dark cycle, with food, and water provided ad libitum. The experiments were performed between 09:00 and 16:00 hours. The experimental protocols were approved by the Institutional Animal Ethics Committee and conducted according to the guidelines of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), New Delhi, India. The standard animal feed was obtained from Ashirwad Industries, Punjab (India).
Drugs and chemicals
All of the drug solutions were freshly prepared before use. 5,5-Dithiobis (2-nitrobenzoic acid) (DTNB) reduced glutathione (GSH) standard was purchased from Sanjay Biologial Lab, Amritsar. N-(1-Naphthyl) ethylenediamine (NEDA) and trichloroacetic acid (TCA) was purchased from S D Fine-Chem Ltd (SDFCL), Mumbai. Thiobarbituric acid (TBA) was purchased from Loba Chemie Pvt Ltd., Mumbai and sulfanilamide was purchased from Titan Biotech Limited. Imipramine tablets were procured from Pfizer Pvt. Ltd. Mumbai, India and fluoxetine (FLU) capsules from Pharma Pvt. Ltd., Ahmedabad, Gujarat, India. 5-HTP was procured as a gift sample from Chemical Resources (Panchkula, India). All other reagents used in the present study were of analytical grade.
Force swim test in rats
The method was described by Porsolt et al., 1977, 1978, 1979. ,, Animals were randomly allocated into three different groups (five to six animals/group). Group I animals served as the control group and were administered with the vehicle, distilled water (1 ml/100 g, p.o.). Animals in Group II served as standard group and were administered with imipramine (10 mg/kg, p.o.). Group III served as the drug-treated control (aqueous extract of Phaseolus vulgaris (AEPV)), which were administered orally with 250 mg/kg (Group IIIa) and 500 mg/kg (Group IIIb) doses of AEPV. Behavioral parameter such as duration of immobility was measured in each animal.
Immobility was measured after 1 h of the vehicle, imipramine and AEPV administration. It was carried out by observing the motor activity of the rats, which were placed in a pool of water. A glass cylinder, 18 cm in diameter, height 40 cm, was filled with water to a height of 15 cm. The temperature of water was 25 ± 1C. Measurement was carried out for 5 min. Immobility time is the time during which the animal floated on the surface with front paws together and made only those movements which were necessary to keep afloat. Shorter immobility time is an indicator of the stronger antidepressant effect of the tested substance.
5-HTP potentiation in mice
The method was described by Shelkunov, 1978.  Mice were randomly allocated into four groups of five to six animals in each group. Animals of Group I served as the normal control group and was administered with saline (1 ml/kg, i.p.) as vehicle. Group II animals served as the negative control and were administered with reserpine (dissolved in few drops of glacial acetic acid and final volume made up with distilled water) at a single dose of 2.5 mg/kg (i.p.). Group III consisted of animals which received combined treatment of standard drug (FLU; 40 mg/kg, p.o.) followed by 5-HTP at a dose of 200 mg/kg, i.p. FLU were administered orally twice 24 h and 30 min prior to 5-HTP, and 30 min later the mice were injected intraperitoneally with 5-HTP (200 mg/kg). Animals of Group IV received combined treatment of drug (AEPV; 500 mg/kg, p.o.) followed by 5-HTP at a dose of 200 mg/kg, i.p. AEPV were administered orally twice 24 h and 30 min prior to 5-HTP, and 30 min later the mice were i.p. injected with 5-HTP (200 mg/kg). Parameters like head twitch response (HTR; mentioned in 3.4.4) were counted in each animal.
The numbers of HTR were counted for 8 min (from 15 to 23 min) after the injection of 5-HTP in each group.
Brain homogenate preparation
Mice were sacrificed under ether anesthesia and their brains were removed and weighed. A 10% (w/v) tissue homogenate was prepared in 0.1 M phosphate buffer (pH 7.4). The homogenates were centrifuged and the clear supernatant was used for biochemical estimations mentioned below.
Estimation of tissue TBA reactive substance level
Whole brain TBARS level was measured by the method of Okhawa et al., with slight modifications. The absorbance was measured spectrophotometrically at 532 nm. 
Estimation of reduced GSH
The whole brain GSH level was measured by the method of Beutler et al., with slight modifications. The absorbance was noted spectrophotometrically at 412 nm. 
Estimation of tissue nitrite content
Nitrite concentration was measured by the method of Sastry et al., and absorbance was measured spectrophotometrically at 545 nm. 
The data was expressed as mean ± standard error of the mean (SEM) and analyzed by one-way analysis of variance (ANOVA) followed by Tukey test. In all the test the criterion for statistical significance was P < 0.05.
| Results|| |
Effect of AEPV on duration of immobility-induced by FST in rats
The duration of immobility in control group (Group I) was found to be 168-190 s for 5 min after 1 h of vehicle treatment; whereas, animals treated with imipramine (standard drug) (Group II) showed immobility for 82-99 sec for 5 min after 1 h of the imipramine treatment. The results thus indicate that imipramine produced a significant decrease in immobility (P < 0.001) in Group II as compared to the control group.
Further, a significant (P < 0.001) dose-dependent decrease in duration of immobility observed in animals treated with 250 and 500 mg/kg (Groups IIIa and IIIb, respectively) doses of AEPV, with a greater effect at 500 mg/kg dose (Group IIIb) when compared to control group (Group I). Whereas, AEPV-treated animals (Groups IIIa and IIIb) showed a significant (P < 0.001 and P < 0.05, respectively) difference as compared to imipramine-treated group (Group II). However, greater effect elicted at a dose of 500 mg/kg (Group IIIb). Animals of Groups IIIa and IIIb showed the average duration of immobility for almost 135 and 107 s, respectively for a period of 5 min after 1 h of the AEPV treatment [Figure 1].
|Figure 1: Effect of aqueous extract of Phaseolus vulgaris on duration of immobility-induced by (force swim test) FST in rats. All the values are expressed as mean ± standard error of the mean and analyzed by one-way analysis of variance followed by Tukey's multiple comparisons test. n = 6, where a*** represents P < 0.001 vs normal control group; b*** represents P < 0.001 vs imipramine (10 mg/kg) standard group; b* represents P < 0.05 vs imipramine (10 mg/kg) standard group|
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Effect of AEPV on 5-HTP-induced HTRs in mice:
Vehicle-treated normal control group (Group I) animals showed no head twitches. Therefore, the average HTR was zero. Animals of 5-HTP-treated (200 mg/kg) negative control group (Group II) showed the average HTR of 46 ± 3.530. Thus, 5-HTP produced significant head twitches (P < 0.001) in animals of Group II as compared to the vehicle-treated control group (Group I).
There was a significant (P < 0.001) increase in HTR in animals treated with FLU 40 mg/kg followed by 5-HTP (Group III) when compared to 5-HTP-treated negative control group (Group II). Animals treated with 500 mg/kg dose of AEPV followed by 5-HTP (Group IV) showed the significant (P < 0.001) increase in HTR when compared to 5-HTP-treated negative control group (Group II). However, AEPV followed by 5-HTP (Group IV) showed the marked (P < 0.01) potent effect when compared to FLU followed by 5-HTP-treated group (Group III). Animals of Groups III and IV showed the mean HTR of about 98 and 84, respectively [Figure 2].
|Figure 2: Effect of AEPV on 5-hydroxytryptophan-induced head-twitch response in mice. All the values are expressed as mean ± SEM and analyzed by ANOVA followed by Tukey's multiple comparisons t-test. n = 6, where a*** represents P < 0.001 vs normal control group; b*** represents P < 0.001 vs 5-HTP (200 mg/kg) negative control group, and c** represents P < 0.01 vs fluoxetine (40 mg/kg) +5-HTP-treated group|
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Effect of AEPV on TBARS level in 5-HTP-induced HTR in mice
Administration of 5-HTP (200 mg/kg) to mice showed the significant increase in the level of TBARS when compared to normal control group. Treatment with AEPV at a dose of 500 mg/kg followed by 5-HTP showed a significant decrease in the level of TBARS in brain. Thus elicited the antioxidant effect [Figure 3].
|Figure 3: Effect of AEPV on thiobarbituric acid reactive substances level in 5-HTP-induced HTR in mice. All the values are expressed as mean ± SEM and analyzed by ANOVA followed by Tukey's multiple comparison t-test. n = 6, where a*** represents P < 0.001 vs normal control group; b*** represents P < 0.001 vs 5-HTP (200 mg/kg) negative control group and c** represents P < 0.01 vs fluoxetine (40 mg/kg) + 5-HTP-treated group|
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Effect of AEPV on GSH level in 5-HTP-induced HTR in mice
The level of GSH in mice was significantly decreased after the administration of 5-HTP (200 mg/kg) as compared to normal control group. Treatment with AEPV at a dose of 500 mg/kg followed by 5-HTP (200 mg/kg) showed a significant increase in the level of GSH in brain [Figure 4].
|Figure 4: Effect of AEPV on glutathione level in 5-HTP-induced HTR in mice. All the values are expressed as mean ± SEM and analyzed by ANOVA followed by Tukey's multiple comparisons t-test. n = 6, where a*** represents P < 0.001 vs normal control group; b*** represents P < 0.001 vs 5-HTP (200 mg/kg) negative control group, and c*** represents P < 0.001 vs fluoxetine (40 mg/kg) + 5-HTP-treated group|
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Effect of AEPV on nitrite level in 5-HTP-induced HTR in mice
Mice administered with 5-HTP (200 mg/kg) showed a marked increase in the level nitrite when compared to normal control group. Treatment with AEPV at a dose of 500 mg/kg followed by 5-HTP showed a significant decrease in the level of nitrite in brain [Figure 5].
|Figure 5: Effect of AEPV on nitrite level in 5-HTP-induced HTR in mice. All the values are expressed as mean ± SEM and analyzed by ANOVA followed by Tukey's multiple comparisons t-test. n = 6, where a*** represents P < 0.001 vs normal control group; b*** represents P < 0.001 vs 5-HTP (200 mg/kg) negative control group, and c** represents P < 0.01 vs fluoxetine (40 mg/kg) followed by 5-HTP standard group|
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| Discussion|| |
Depression is a serious, psychiatric disorder that exerts great imputation on the quality of everyday life. The most common symptom is a long-term depressed mood, accompanied by attention and cognition impairment.  Literature survey record that clinical depression, affects up to 14 million people in the US in any given year. , Depression is mediated by brain neurotransmitters and agreeable to treatment that alters neurotransmitter regulation via their synthesis, reuptake, or degradation. Serotonin and NE have been primarily implicated with a lesser role for DA in depression. ,
The present study has been designed to depict the antidepressant property of AEPV, an herbal protectant traditionally used for depression, in rodents by using various experimental models such as FST in rats, 5-HTP potentiation in mice, and the various biochemical parameters assessment.
In FST, rats are forced to swim in a restricted and inescapable space show characteristic alternating behavior. The immobility signifies behavior resembling a state of depression reduced by several antidepressants effective in human depression. This model widely used to screen newer antidepressant drugs. Drugs that potentiate central dopaminergic and α-adrenergic systems reduce the immobility time in rodents. In the present study, the immobility produced by FST significantly reduced by the treatment with AEPV, an herbal protectant, dose-dependently increase the duration of immobility. The protective effect of AEPV at the doses of 250 and 500 mg/kg suggested that this plant has influence on the monoaminergic receptor mediated neurotransmission.
Further, one of the major pharmacological mechanisms of antidepressants is the enhancement of synaptic concentrations of monoamines, particularly 5-HTP. 5-HTP, the immediate precursor of 5-HT had been observed to increase the intensity of spontaneous irregularly occurring head twitches in mice when administered in large doses  that occur due to stimulation of central 5-HTz receptors located in brain stem. This has been well supported in also our study that the 5-HTP administered mice exhibited markedly and significantly more HTR than normal control. Treatment with FLU (40 mg/kg), a standard antidepressant and AEPV (500 mg/kg) the mice exhibited markedly more HTR than 5-HTP control. FLU is a selective serotonin reuptake inhibitor. It restores the levels of 5-HT in the synaptic cleft and thus helpful in preventing depression.
Oxidative stress, which is defined as a disturbance in the balance between the production of reactive oxygen species (ROS) and endogenous antioxidant defense systems, has also been shown to play a vital role in the pathogenesis of neuropsychiatric disorders. , Furthermore, preclinical studies have demonstrated that the inhibition of oxidative stress may contribute to the therapeutic effects of some antidepressant drugs  Excessive ROS can cause damages to the major macromolecules in cells, including lipids, proteins, and nucleic acids, culminating in neuronal dysfunction and depression. Malondialdehyde (MDA) is a byproduct of lipid peroxidation, is produced under oxidative stress and is regarded as index of oxidative stress.  Assay of TBARS measures MDA present in the sample. It has been reported that brain MDA level was significantly increased in rodents when exposed to chronic stress, which could be reversed by antidepressants.  The lipid peroxidation measured in terms of TBARS was noted to be increased significantly in 5-HTP-treated mice when compared with normal control mice. However, treatment with FLU and AEPV significantly attenuated the level of TBARS in comparison to 5-HTP-treated group. GSH plays an important role in the endogenous antioxidant system. GSH peroxidase catalyzes the conversion of reduced GSH present in the peroxisomes of cytoplasm to oxidized GSH which is toxic to the cells.  The result depicts that there is a significant decrease in GSH level in 5-HTP-treated group when compared with normal control animals. However, treatment with FLU and AEPV significantly increased the level of reduced GSH as compared to the 5-HTP-treated group.
NO produced by inducible nitric oxide synthase (i-NOS) is a multifunction free radical species that is implicated in a variety of physiological and pathological processes such as modulation of NE, DA, Glut, and 5-HT, the major neurotransmitters involved in the neurobiology of major depression. This contention is supported by our results that a significant increase in nitrite level was observed in 5-HTP-treated mice when compared with normal control animals. However, treatment with FLU and AEPV significantly decrease the level of nitrite as compared to 5-HTP-treated group, thus exploring anti-inflammatory potential of AEPV. Phenolics, flavonoids, omega-3 fatty acids, and tryptophan are the major constituents noted in Phaseolus vulgaris which are helpful in preventing depression [Table 1].
| Conclusion|| |
From the above study, it can be concluded that AEPV possess a therapeutic effect against the depression in FST, and 5-HTP-induced depression animal models. AEPV contains the natural constituents like tryptophan, omega-3 fatty acids, etc., which are helpful in protecting depression. Further, studies with different extracts and their fractions are encouraged to identify the chemical constituents responsible for antidepressant activity. Also clinical studies to prove this effect is needed for its applicability in humans for treatment of depression.
| Acknowledgment|| |
The authors would like to thank The Director, Rayat Institute of Pharmacy (Punjab) for providing the necessary facilities for the research work. They would also thankful to the Chemical Resources, Panchkula, India for providing the sample of 5-hydroxytryptophan.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]