|Year : 2011 | Volume
| Issue : 2 | Page : 152-156
Antidepressant like activity of Lagenaria siceraria (Molina) Standley fruits by evaluation of the forced swim behavior in rats
Rakesh Prajapati1, Rahul Umbarkar1, Sachin Parmar2, Navin Sheth2
1 Department of Pharmaceutical sciences, Bhagwan Mahavir College of Pharmacy, Surat, Gujarat, India
2 Department of Pharmaceutical Sciences, Saurashtra University, Rajkot, Gujarat, India
|Date of Submission||24-Dec-2010|
|Date of Acceptance||19-Mar-2011|
|Date of Web Publication||23-Aug-2011|
Department of Pharmaceutical sciences Bhagwan Mahavir College of Pharmacy, Surat, Gujarat
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Context : In current stressful routine life, depression has become the second most common chronic condition in clinical psychology practice. Lagenaria siceraria (Molina) Standley (LS), commonly known as ''bottle gourd'' (English), possesses several medicinal properties; little is known about its traditional use as nerve tonic. Objective: The purpose of the study was to evaluate the antidepressant activity of methanolic extract of Lagenaria siceraria (Molina) Standley fruits (MLSF) using forced swim (behavior despair) models. Materials and Methods: LS fruit slices were dried and extracted with methanol in Soxhlet apparatus for 5-6 h. Adult Wistar albino rats were subjected to behavior despair test. Imipramine was used as reference standard drug. Results and Discussion: The MLSF (50, 100, and 200 mg/kg, p.o.) showed dose-dependent significant reduction in duration of immobility (P < 0.01) in behavior despair test. The phytochemical screening revealed the presence of phytoconstituents, such as flavonoids, saponins, and sterols in the fruits. Conclusions: The results of the study for show that the plant possesses antidepressant activity, confirming the traditional claims. Future research should focus on the isolation and identification of the phytoconstituents responsible for the antidepressant activity of LS .
Keywords: Behavior despair test, depression, duration of immobility, lagenaria siceraria, phytochemical screening
|How to cite this article:|
Prajapati R, Umbarkar R, Parmar S, Sheth N. Antidepressant like activity of Lagenaria siceraria (Molina) Standley fruits by evaluation of the forced swim behavior in rats. Int J Nutr Pharmacol Neurol Dis 2011;1:152-6
|How to cite this URL:|
Prajapati R, Umbarkar R, Parmar S, Sheth N. Antidepressant like activity of Lagenaria siceraria (Molina) Standley fruits by evaluation of the forced swim behavior in rats. Int J Nutr Pharmacol Neurol Dis [serial online] 2011 [cited 2019 Aug 17];1:152-6. Available from: http://www.ijnpnd.com/text.asp?2011/1/2/152/84206
| Introduction|| |
Depression constitutes the second most common chronic condition in clinical practice and will become the second leading cause of death or disability worldwide by the year 2020. , Approximately two-thirds of the anxious or depressed patients respond to the currently available treatments but the magnitude of improvement is still disappointing.  Although there are many effective antidepressants available today, the current armentarium of therapy is often inadequate with unsatisfactory results in about one-third of all subjects treated. This necessitates the development of newer and more effective antidepressants from traditional medicinal plants whose psychotherapeutic potential has been assessed in a variety of animal models. 
Lagenaria siceraria (Molina) Standley (LS) syn. L. leucantha Rusby; (Family: Cucurbitaceae) is commonly known as ''Bottle gourd'', an excellent fruit in the nature having composition of all the essential constituents that are required for normal and good health of humans.  LS fruits are traditionally used for its cardioprotective, cardiotonic, nervine tonic, aphrodisiac and acts as alternate purgative, diuretic. , It also cures pain, ulcers, fever, and used for pectoral cough, asthma, and other bronchial disorders.  The fruits are edible and considered as good source of vitamin C, β-carotene, vitamin B-complex, pectin and also contain highest choline level-a lipotropic factor. , Modern phytochemical screening methods showed the presence of triterpenoid cucurbitacins B, D, G, H, fucosterol, campesterol, and flavone C-glycosides. ,,[-11]
Considering the available information and folklore use of the plant the present study was designed to evaluate antidepressant activity of MLSF by using forced swimming model. The MLSF was also studied for its acute toxicity effects and preliminary phytochemical screening.
| Materials and Methods|| |
Collection and authentication of plant materials
Fresh fruits of LS were purchased from local market of Rajkot, Gujarat. The plant was identified and authenticated by Professor P. J. Parmar, Botanical Survey of India, Jodhpur. A specimen voucher (SU/DPS/Herb/05) of the plant has been deposited at Department of Pharmaceutical Sciences, Saurashtra University, Rajkot for future reference.
Preparation of fruit extract
LS fruits were properly cleaned and cut in thin-round slices and dried. The dried plant material was then subjected to coarse powder. The coarsely powdered dried fruits of LS were extracted with methanol by hot extraction process (Soxhlet extraction) for 5--6 h. After completion of extraction the solvent was removed by distillation and concentrated in vaccuo and stored at freeze temperature. The test extracts were prepared freshly in sodium carboxy methyl cellulose (SCMC) solution just prior to experiment. Moreover, the MLSF was also subjected to phytochemical investigations for the detection of various plant constituents. 
Male Wistar albino rats (250--300 g) were subjected to behavior despair tests (n = 5). All the animals were housed in groups in polypropylene cages and placed in climate controlled central animal house having temperature 22 ± 2 °C, relative humidity 60 ± 5%, and a 12 h light/dark cycle (lights on at 08:00 h and off at 20:00 h). The animals were fed standard pellet diet (Amrut, Pranav Agro Industries Ltd., India) and water ad libitum. The experimental protocol was approved (approval no.- SU/DPS/IAEC/9001) by Institutional Animal Ethics Committee (IAEC) of the Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA), Ministry of Environment and Forests, Government of India.
Drugs and chemicals
Imipramine, the reference standard tricyclic antidepressant drug, was obtained as a gift sample from Torrent Research Centre, India. The solvents used in study were of analytical grade and purchased from Merch Ltd., Mumbai.
Administration of drugs
Imipramine was dissolved in distilled water, while MLSF was prepared as suspension in distilled water using 0.5% SCMC as the suspending agent. Animals were assigned to different treatment groups (n = 6). The control group received the vehicle (0.5% SCMC, 1 ml/kg) per os (p.o.), whereas different treatment groups received freshly prepared MLSF and imipramine just prior to experiment. All the doses of MLSF were administered orally, whereas imipramine was administered intraperitoneally (i.p.).
Acute toxicity study
The acute toxicity study was performed as per the method described by Litchfield and Wilcoxonand LD 50 was calculated accordingly.  All the drugs were suspended in distilled water using 0.5% SCMC as the suspending agent Briefly, the MLSF in the dose range of 10--1600 mg/kg was administered intraperitoneally to different groups of mice (n = 10). The animals were examined every 30 min up to a period of 3 h and then, occasionally for additional period of 4 h; finally, overnight mortality was recorded. All tests on rats were performed at three dose levels 50, 100, and 200 mg/kg, p.o. body weight corresponding to 5, 10, and 20% of LD 50 value (1000 mg/kg, i.p.), respectively.
Behavior despair test
The procedure described by Porsolt et alwas followed with slight modification of deep water level suggested by Detke et alto ensure that rats could not support themselves by touching the bottom with their feet. , Male rats were used for this test. , Swimming sessions were conducted by placing rats in individual glass cylinder (35 cm Χ 25 cm) containing water (25 ± 1 °C) having 27 cm depth. Two swimming sessions were conducted between 9:00 and 16:00 h. All the rats were subjected to an initial 15 min pretest followed 25 h later by a 5 min test. Drugs were administered three times during the period between these two sessions, first immediately after pretest session and then, after 6 and 23 h of the first dose. Following both swimming sessions, the rats were removed from the cylinder, dried with paper towels, placed in the cages under a heating source (15 min), and returned to their home cages. The immobility period in seconds was measured in each test session of 5 min. The water in the cylinder was changed after every other trial. Imipramine (12.5 mg/kg, i.p.) served as standard drug in this model. 
Spontaneous locomotor activity
Since the forced behavioral experiment was affected by changes in locomotor activity, an additional experiment was carried out with the specific aim of monitoring the activity. Separately from the experiment with the forced swim test, spontaneous locomotor activity was measured using actophotometer. Actophotometer registers the number of times infrared photobeams of light were broken as the rat moved around inside the cage. Each rat was placed in the centre of the metal cage of actophotometer and its ambulatory activity was measured for at 5-min interval for the next 15 min. 
| Statistical Analysis|| |
All the data were expressed as mean ± SEM from five animals. The data obtained was analyzed using the one-way ANOVA followed by Student--Newman--Keuls test for determining the level of significance and P < 0.05 was considered statistically significant.
| Results|| |
Acute toxicity studies
The acute toxicity studies showed that the LD 50 of the MLSF in mice was 1000 mg/kg by i.p. route. So accordingly three dose levels 50, 100, and 200 mg/kg, p.o. body weight were selected to perform test, corresponding to 5, 10, and 20% of LD 50 value (1000 mg/kg, i.p.), respectively.
Preliminary phytochemical screening
Preliminary phytochemical screening of the methanolic extract of LS showed the presence of flavonoids, saponins, sterols, proteins, tannins and carbohydrates [Table 1].
|Table 1: Result of phytochemical screening of methanolic extract of Lagenaria Siceraria fruits|
Click here to view
Behavior despair (forced swim behavior) test
[Table 2] shows the antidepressant effect of MLSF and imipramine in the experimental animals. The control animals remained immobile for most of the time during the test session. MLSF (50, 100, and 200 mg/kg, p.o.) induced a dose-dependent significant reduction in the immobility time of rats (P < 0.5; P < 0.01) as compared to the control group. In the same experimental conditions, the antidepressant activity of the reference drug imipramine (12.5 mg/kg, i.p.) was clearly evident (P < 0.01). The antidepressant effect produced by MLSF (100 and 200 mg/kg, p.o.) was comparable to that of imipramine [Figure 1]
|Table 2: Effect of methanolic extract of Lagenaria siceraria fruits on the immobility period during behavior despair testa|
Click here to view
|Figure 1: Effect of MLSF on immobility period in behavior despair test. Values are expressed as mean ± SEM (n = 5). *P < 0.05, **P < 0.01, compared with control (one-way ANOVA followed by Student--|
Click here to view
Spontaneous locomotor activity (actophotometer)
As shown in [Figure 2] the locomotor activity count measured in 15 min of the test was significantly decreased by diazepam (5 mg/kg). Locomotor activity was not changed in animals pretreated with MLSF (100 mg/kg) compared with that in the control group. However, at 200 and 400 mg/kg, MLSF slightly inhibited locomotor activity, but at lesser extent than diazepam [Figure 2].
|Figure 2: Effect of Lagenaria siceraria fruit extract on spontaneous locomotor activity.|
Click here to view
| Discussion|| |
LS is traditionally used for the treatment of depression, and other CNS disorders. Scientific data on this property of the plant are not available. Therefore, we investigated the antidepressant effect of different doses of MLSF using forced swimming model (behavior despair test). The behavior despair test has been validated as a suitable tool to evaluate drugs with putative antidepressant effects. ,, In this model, when rodents are forced to swim in a confined space, they tend to become immobile after vigorous activity (struggling). This inescapable stressful situation leads to depression.  In the present study, administration of MLSF significantly reduced total immobility time and enhanced struggling behavior in dose-dependent manner, suggesting antidepressant effect.
Spontaneous locomotor activity is considered as an index of alertness and can be helpful to confirm the general depressive activity of any drug. The decrease in motor activity gives an indication of the level of excitability of the CNS  and this decrease may be related to sedation resulting from depression of CNS.  However, in the present study the MLSF was found to have no effect on the locomomotor activity in actophotometer.
It is reported that GABA, an inhibitory neurotransmitter is involved in the pathophysiology of depression.  Moreover, neurochemical research has revealed that the monoamines (5-HT, NA, and dopamine) have a crucial role in the development of the depression syndrome.  It has been found that flavonoids isolated from plant species such as Hypericum perforatum showed antidepressant activity.  Thus, it is likely that flavonoids present in MLSF may be responsible for the observed antidepressant effect. The antidepressant effect shown by MLSF suggests etiological similarity in the development depression. Several hypotheses have been proposed to explain this aspect. The serotonergic theory postulates excessive functioning of the serotonergic neurotransmission for the prevention of the cause of depression.  It can be hypothesised that MLSF may have acted by modulating one or more of the above-mentioned neurotransmitters. Moreover, cholinergic transmission also plays the promising role in CNS. Based on its irregular distribution within the CNS and the observation that peripheral cholinergic drugs could produce marked behavioral effects after central administration.  Therefore, it can be predicted that the higher level of choline in LS fruits may be responsible to act on cholinergic transmission in CNS and may be helpful to prevent depression.
Phytochemical screening of MLSF revealed presence of flavonoids, saponins, sterols, proteins, tannins and carbohydrates. Moreover triterpepenoids (steroidal compounds) are present in the fruits, those are able to cross blood brain barrier (BBB) due to their lipophilic nature and so it can be assumed that such steroidal compounds might also be responsible to elicit antidepressant and other neuropharmacological activities at molecular level in CNS (brain). ,
| Conclusions|| |
The present study for the first time provides evidence for the antidepressant activity of MLSF in experimental animals. The presence of flavonoids, saponins and sterols in MLSF could be responsible for this activity. The need of the hour is to identify and isolate the phytoconstituents responsible for the observed antidepressant effect in animals and to understand their molecular mechanisms.
We are grateful to the Head, Department of Pharmaceutical Sciences, Saurashtra University, Rajkot, Gujarat, India for providing the facilities during the course of this study. Gift sample of imipramine by Torrent Ltd, Gandhinagar, India is gratefully acknowledged. Special thanks to Professor P. J. Parmar, Botanical Survey of India for identification and authentication of the plant.
| Acknowledgements|| |
| References|| |
|1.||Whooley MA, Simon GE. Managing depression in medical outpatients. New Eng J Med 2005;343:194250. |
|2.||WHO. WHO Director-General unveils new global strategies for mental health. Press Release 1999; WHO/99-67. Available from: http://www.who.int/inf-pr-1999/en/pr99-67.html. |
|3.||Mora S, Nillian R, Lungenstrassb H, Morian G, Herrera-Ruiz M, Tortoriello T. The hydroalcoholic extract of Salvia elegans induces anxiolytic and antidepressant like effects in rats. J Ethno 2006;106:76-81. |
|4.||Zhang ZJ. Therapeutic effects of herbal extracts and constituents in animal models of psychiatric disorders. Life Sci 2004;75:1659-99. |
|5.||Rahman AS. Bottle Gourd (Lagenaria siceraria)- A vegetable for good health. Nat Prod Rad 2003;2:249-50. |
|6.||Shinrajan VV, Balachandra I. Ayurvedic Drugs and their plant source. New Delhi, India: Oxford and IBH Publishers,1996. p. 176-7. |
|7.||Kirtikar KR. Indian medicinal Plants. Dehradun, India: Oriental Enterprises; 2001. p. 722-3. |
|8.||Chopra RN, Chopra IC, Verma BS. Supplement of Glossary of Indian Medicinal plants. New Delhi, India: Council of Scientific and Industrial Research; 1992. p. 51. |
|9.||Aranowska MK, Cisowski W. High Performance Liquid Chromatographic determination of Flavone C-glycosides in some species of the Curcubiraceae family. J Chromato A 1994;675:240-3. |
|10.||Shirwaikar A, Sreenivasan KK. Chemical investigation and anti-hepatotoxic activity of the fruits of Lagenaria siceraria. Ind J Pharm Sci 1996;58:197-202. |
|11.||Sonja S, Hermann S. Analysis of curcubitacins in medicinal Plants by HPLC-MS. Phytochem Analysis 2000;11:121. |
|12.||Khandelwal KR. Preliminary phytochemical screening. Practical Pharmacognosy. 6 th ed. Pune, India: Nirali Prakashan2006. p. 149-53. |
|13.||Litchfield JT, Wilcoxon F. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 1949;96:99-113. |
|14.||Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioral despair in rats: A new model sensitive to antidepressant treatments. Eur J Pharmacol 1978;47:379-91. |
|15.||Detke MJ, Lucki I, Rickels M. Active behaviours in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacol 1995;121:66-72. |
|16.||Padovan CM, Guimaraes FS. Antidepressant-like effects of NMDA-receptorsantagonist injected into the dorsal hippocampus of rats. Pharmacol Biochem Behav 2004;77:15-9. |
|17.||Calil CM, Marcondes FK. The comparison of immobility time in experimental rat swimming models. Life Sci 2006;79:1712-9. |
|18.||Bhattamisra SK, Khanna VK, Agrawal AK, Singh PN, Singh SK. Antidepressant activity of standardised extract of Marsiela minuta Linn. J Ethnopharmacol 2008;117:51-7. |
|19.||Turner RA. Depressants of the Central Nervous System. Screening procedure in pharmacology. New York: Academic press; 1972. p. 78. |
|20.||Anisman H, Matheson K. Stress, depression, and anhedonia: Caveats concerning animal models. Neurosci Biobehav Revnone 2005;29:525-46. |
|21.||Matthews K, Christmas D, Swan J, Sorrell E. Animal models of depression: Navigating through the clinical fog. Neurosci Biobehav Rev 2005;29:503-13. |
|22.||Porsolt RD, Bertin A, Jalfre M. "Behavioral despair" in rats and mice: Strain differences and the effects of imipramine. Eur J Pharmacol 1978;51:291-4. |
|23.||Masur J, Martz RM, Carlini EA. Effects of acute and chronic administration of Cannabis sativa and (−)9-trans tetrahydrocannabinol on behavior of rats in open-field arena. Psychopharmacol 1971;19:338- 97. |
|24.||Ozturk Y, Aydini S, Beis R, Baser KH. Effect of Hypericum perforatum L. and Hypericum calycinum L. extracts on the central nervous system in mice. Phytomed 1996;3:139-46. |
|25.||Lloyd KG, Zivkovic B, Scatton B, Morselli PL, Bartholoni G. The GABAergic hypothesis of depression. Prog Neuropsychopharmacol Biol Psych 1989;13:341-51. |
|26.||Naughton M, Mulrooney JB, Leonard BE. A review of the role of serotonin receptors in psychiatric disorders. Hum Psychopharmacol 2000;15:397-415. |
|27.||Butterweck V, Jurgenliemk G, Nahrstedt A, Winterhoff H. Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test. Planta Med 2000;66:3-6. |
|28.||Deakin JF. Role of serotogenic system in escape, avoidance and other behaviors. In: Cooper SJ, editor. Theory in Psychopharmacology. London: Academic Press; 1983. p. 149-93. |
|29.||Shepherd GM. The Synaptic Organization of the Brain. New York: Oxford University Press; 2003. |
|30.||Librowaski P, Czarapki R, Mendyk A, Jastrzebska M. Influence of new monoterpene homologous of GABA on the CNS activity in mice. Pol J Pharmacol 2000;52:317-21. |
[Figure 1], [Figure 2]
[Table 1], [Table 2]
|This article has been cited by|
||Lagenaria siceraria Fruit Pedicle Extracts as a Remedy against Microbial Infections
| ||Dildar Ahmed,Neelam Ashiq |
| ||International Journal of Vegetable Science. 2018; : 1 |
|[Pubmed] | [DOI]|
||Biosynthesis, mechanism of action, and clinical mportance of neuroactive steroids: Pearls from literature
| ||MirzaShiraz Baig,PratishthaVijaykumar Banga,KantilalChainkaran Chandaliya,GauravAnil Deshmukh,SudhakarraoMalhar Doifode,ChetanYuvraj Patil |
| ||International Journal of Nutrition, Pharmacology, Neurological Diseases. 2013; 3(2): 77 |
|[Pubmed] | [DOI]|