Volume 33, Issue 1 (3-2024)
JGUMS 2024, 33(1): 66-77 |
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Research code: A-10-2107-1
Ethics code: IR.PNU.REC.1400.273
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Parandin R, Abbasi F. Investigating the Antidepressant and Antioxidant Activity of the Alcoholic Extract of Melilotus Officinalis L. in Male Rats. JGUMS 2024; 33 (1) :66-77
URL: http://journal.gums.ac.ir/article-1-2595-en.html
URL: http://journal.gums.ac.ir/article-1-2595-en.html
1- Department of Biology, Faculty of Sciences, Payame Noor University, Tehran, Iran.
2- Department of Biology, Faculty of Sciences, Payame Noor University, Tehran, Iran., faezeabasi283@gmail.com
2- Department of Biology, Faculty of Sciences, Payame Noor University, Tehran, Iran., faezeabasi283@gmail.com
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Introduction
Depression is a common mental illness that can cause functional and social disorders [1]. According to the World Health Organization (WHO), major depressive disorder was the second leading cause of illness worldwide in 2020 [1]. This disease is considered as the most widespread problem in adolescents, and the increase in suicide attempts among adolescents can indicate the importance of this concern. According to several studies, the prevalence of major depressive disorder in adolescents is 4.6% among boys and 5.9% among girls, and its age at onset is 13-18 years. The global prevalence of depression is 16.2%. In general, the prevalence of depression in the general population is estimated between 4.2 and 37%. In Iran, due to the use of different measurement tools, the studies have reported different prevalence rates. Based on a national survey in 2011, prevalence of depression is about 23.6% [2, 3].
Melilotus officinalis L. belongs to the Fabaceae family. The main compounds of this plant include coumarin and melilotus [4]. The flowers of this plant have therapeutic properties for convulsions and chest pain. It removes the smell of urine and is also used in the treatment of rheumatism. This plant is used as a painkiller, disinfectant, and tonic and for the healing of burn wounds [5]. Due to the fact that there is little information about the effect of M. officinalis L. on depression, the present study aims to evaluate the possible effects of this plant on depression caused by reserpine injection in rats.
Methods
In this experimental study, the M. officinalis L. plant was first collected from the mountains around Kermanshah, Iran, in spring and dried in the shade in a suitable environment at a temperature of 23-27°C. Then the dried plant was turned into powder. Sixty grams of the resulting powder was separated and 300 cc of 80% ethanol was added to it and kept for 72 hours. After filtering using Whatman No. 1 paper, the obtained extract was dried, and the resulting powder was used to prepare the desired doses.
Forty-two male Syrian rats were divided into six groups of 7 including control (normal saline), negative control (reserpine), positive control (reserpine+fluoxetine) and three reserpine groups treated by intraperitoneal injection of 100, 200, 400 mg/kg doses of alcoholic extract of M. officinalis L. Behavioral tests including forced swim test (FST) and tail suspension test (TST) were used to evaluate depression, and the antioxidant capacity and malondialdehyde (MDA) level were also measured. The obtained data were analyzed in SPSS software, version 20, and the significance level was set as P<0.05. First, by using the Kolmogorov-Smirnov test, the normality of data distribution in each group was ensured. Then, one-way analysis of variance was used to compare the groups, followed by Tukey’s post hoc test for pairwise comparison.
Results
The FST results
The negative control group showed significantly longer mean immobility time compared to the control group (P=0.001). Positive control group showed significantly shorter mean immobility time compared to the negative control group (P=0.001). The dose of 100 mg/kg of the extract caused a significant increase compared to the negative control group (P<0.05). The doses of 200 and 400 mg/kg of the extract significantly reduced the duration of immobility compared to the negative control (P=0.001). The doses of 100 and 200 mg/kg significantly increased the duration of immobility compared to the positive control group (P=0.001).
The TST results
The negative control group showed significantly longer mean immobility time compared to the control group (P=0.001). The positive control showed significantly shorter mean immobility time compared to the control and negative control groups (P=0.001). The dose of 100 mg/kg of the extract caused a significant increase compared to the positive control group (P<0.05). The doses of 200 and 400 mg/kg of the extract significantly increased the duration of immobility compared to the negative control (P=0.001). The doses of 100 and 200 mg/kg significantly increased the duration of immobility compared to the positive control group (P=0.001).
Antioxidant capacity in the brain
The negative control group showed significantly lower antioxidant capacity in the brain compared to the control group (P=0.001). The positive control group showed significantly higher antioxidant capacity in the brain compared to the negative control (P=0.001). The doses of 100 and 400 mg/kg significantly reduced the antioxidant capacity compared to the positive control group (P=0.001). The dose of 200 mg/kg significantly increased the antioxidant capacity compared to the negative control group (P=0.001). The dose of 400 mg/kg increased the antioxidant capacity of the brain compared to the negative control group (P<0.01). The dose of 200 mg/kg extract reduced the antioxidant capacity of the brain in comparison with the positive control group (P<0.01).
The MDA level in the brain
The negative control group showed significantly higher MDA level compared to the control group (P=0.001). The positive control significantly reduced the mean brain MDA in comparison with the negative control (P=0.001). The dose of 100 mg/kg extract significantly increased the MDA level in the brain compared to the positive control group (P=0.001). The doses of 200 and 400 mg/kg extract significantly reduced the MDA level compared to the negative control group (P=0.001).
Conclusion
In both behavioral tests (FST and TST), reserpine significantly increased the immobility time in mice. The doses of 200 and 400 mg/kg of alcoholic extract of M. officinalis L. can significantly reduce immobility time in the FST compared to the negative control (reserpine). In the TST, the doses of 200 and 400 mg/kg extract can significantly increase the immobility time compared to the negative control. The dose of 400 mg/kg extract can significantly increase the antioxidant capacity in the brain compared to the negative control. The doses of 200 and 400 mg/kg of MDA extract significantly reduced the capacity of the brain in comparison with the negative control. The doses of 200 and 400 mg/kg of the extract can significantly reduce the MDA level in the brain compared to the negative control.
The obtained results revealed that the alcoholic extract of M. officinalis L. has anti-depressant effects, similar to fluoxetine, in Syrian rats with depression caused by the administration of reserpine, which can probably due to the presence of antioxidant compounds of this plant, which requires more extensive and deep research. The alcoholic extract of M. officinalis L. can be used as a medicine or supplement for the treatment of depression and similar symptoms.
Ethical Considerations
Compliance with ethical guidelines
This study was approved by Ethics Committee of Payame Noor University (Code: PNU.REC.1400.273).
Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.
Authors' contributions
All authors equally contribute to preparing all parts of the research.
Conflicts of interest
The authors declared no conflict of interest.
References
Depression is a common mental illness that can cause functional and social disorders [1]. According to the World Health Organization (WHO), major depressive disorder was the second leading cause of illness worldwide in 2020 [1]. This disease is considered as the most widespread problem in adolescents, and the increase in suicide attempts among adolescents can indicate the importance of this concern. According to several studies, the prevalence of major depressive disorder in adolescents is 4.6% among boys and 5.9% among girls, and its age at onset is 13-18 years. The global prevalence of depression is 16.2%. In general, the prevalence of depression in the general population is estimated between 4.2 and 37%. In Iran, due to the use of different measurement tools, the studies have reported different prevalence rates. Based on a national survey in 2011, prevalence of depression is about 23.6% [2, 3].
Melilotus officinalis L. belongs to the Fabaceae family. The main compounds of this plant include coumarin and melilotus [4]. The flowers of this plant have therapeutic properties for convulsions and chest pain. It removes the smell of urine and is also used in the treatment of rheumatism. This plant is used as a painkiller, disinfectant, and tonic and for the healing of burn wounds [5]. Due to the fact that there is little information about the effect of M. officinalis L. on depression, the present study aims to evaluate the possible effects of this plant on depression caused by reserpine injection in rats.
Methods
In this experimental study, the M. officinalis L. plant was first collected from the mountains around Kermanshah, Iran, in spring and dried in the shade in a suitable environment at a temperature of 23-27°C. Then the dried plant was turned into powder. Sixty grams of the resulting powder was separated and 300 cc of 80% ethanol was added to it and kept for 72 hours. After filtering using Whatman No. 1 paper, the obtained extract was dried, and the resulting powder was used to prepare the desired doses.
Forty-two male Syrian rats were divided into six groups of 7 including control (normal saline), negative control (reserpine), positive control (reserpine+fluoxetine) and three reserpine groups treated by intraperitoneal injection of 100, 200, 400 mg/kg doses of alcoholic extract of M. officinalis L. Behavioral tests including forced swim test (FST) and tail suspension test (TST) were used to evaluate depression, and the antioxidant capacity and malondialdehyde (MDA) level were also measured. The obtained data were analyzed in SPSS software, version 20, and the significance level was set as P<0.05. First, by using the Kolmogorov-Smirnov test, the normality of data distribution in each group was ensured. Then, one-way analysis of variance was used to compare the groups, followed by Tukey’s post hoc test for pairwise comparison.
Results
The FST results
The negative control group showed significantly longer mean immobility time compared to the control group (P=0.001). Positive control group showed significantly shorter mean immobility time compared to the negative control group (P=0.001). The dose of 100 mg/kg of the extract caused a significant increase compared to the negative control group (P<0.05). The doses of 200 and 400 mg/kg of the extract significantly reduced the duration of immobility compared to the negative control (P=0.001). The doses of 100 and 200 mg/kg significantly increased the duration of immobility compared to the positive control group (P=0.001).
The TST results
The negative control group showed significantly longer mean immobility time compared to the control group (P=0.001). The positive control showed significantly shorter mean immobility time compared to the control and negative control groups (P=0.001). The dose of 100 mg/kg of the extract caused a significant increase compared to the positive control group (P<0.05). The doses of 200 and 400 mg/kg of the extract significantly increased the duration of immobility compared to the negative control (P=0.001). The doses of 100 and 200 mg/kg significantly increased the duration of immobility compared to the positive control group (P=0.001).
Antioxidant capacity in the brain
The negative control group showed significantly lower antioxidant capacity in the brain compared to the control group (P=0.001). The positive control group showed significantly higher antioxidant capacity in the brain compared to the negative control (P=0.001). The doses of 100 and 400 mg/kg significantly reduced the antioxidant capacity compared to the positive control group (P=0.001). The dose of 200 mg/kg significantly increased the antioxidant capacity compared to the negative control group (P=0.001). The dose of 400 mg/kg increased the antioxidant capacity of the brain compared to the negative control group (P<0.01). The dose of 200 mg/kg extract reduced the antioxidant capacity of the brain in comparison with the positive control group (P<0.01).
The MDA level in the brain
The negative control group showed significantly higher MDA level compared to the control group (P=0.001). The positive control significantly reduced the mean brain MDA in comparison with the negative control (P=0.001). The dose of 100 mg/kg extract significantly increased the MDA level in the brain compared to the positive control group (P=0.001). The doses of 200 and 400 mg/kg extract significantly reduced the MDA level compared to the negative control group (P=0.001).
Conclusion
In both behavioral tests (FST and TST), reserpine significantly increased the immobility time in mice. The doses of 200 and 400 mg/kg of alcoholic extract of M. officinalis L. can significantly reduce immobility time in the FST compared to the negative control (reserpine). In the TST, the doses of 200 and 400 mg/kg extract can significantly increase the immobility time compared to the negative control. The dose of 400 mg/kg extract can significantly increase the antioxidant capacity in the brain compared to the negative control. The doses of 200 and 400 mg/kg of MDA extract significantly reduced the capacity of the brain in comparison with the negative control. The doses of 200 and 400 mg/kg of the extract can significantly reduce the MDA level in the brain compared to the negative control.
The obtained results revealed that the alcoholic extract of M. officinalis L. has anti-depressant effects, similar to fluoxetine, in Syrian rats with depression caused by the administration of reserpine, which can probably due to the presence of antioxidant compounds of this plant, which requires more extensive and deep research. The alcoholic extract of M. officinalis L. can be used as a medicine or supplement for the treatment of depression and similar symptoms.
Ethical Considerations
Compliance with ethical guidelines
This study was approved by Ethics Committee of Payame Noor University (Code: PNU.REC.1400.273).
Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.
Authors' contributions
All authors equally contribute to preparing all parts of the research.
Conflicts of interest
The authors declared no conflict of interest.
References
1.Jaisoorya TS, Bhaskarapillai B, Manoj L, Sunil Kumar G, Gokul GR, Thennarasu K. Risk estimates of anxiety and depressive disorders among primary care patients with chronic medical illness - A Indian study. Asian Journal of Psychiatry. 2022; 74:103190. [DOI:10.1016/j.ajp.2022.103190] [PMID]
2.Brailovskaia J, Margraf J. The relationship between burden caused by coronavirus (COVID-19), addictive social media use, sense of control and anxiety. Computers in Human Behavior. 2021; 119:106720. [DOI:10.1016/j.chb.2021.106720] [PMID]
3.Mohammadi M, Vaisi-Raygani A, Jalali R, Ghobadi A, Salalri N. [Prevalence of depression in soldiers of Iranian military centers: A meta-analysis (Persian)]. Ebnesina. 2020; 21(4):34-40. [Link]
4.Al-Snafi AE. Chemical constituents and pharmacological effects of melilotus officinalis-A review. International Journal of Current Pharmaceutical Research. 20190; 11(6):1-10. [DOI:10.22159/ijcpr.2019v11i6.36338]
5.Ilhan M, Ali Z, Khan IA, Küpeli Akkol E. A new isoflavane-4-ol derivative from melilotus officinalis (L.) Pall. Natural Product Research. 2019; 33(13):1856-61. [DOI:10.1080/14786419.2018.1477152] [PMID]
6.Stefanović OD, Tešić JD, Čomić LR. Melilotus albus and Dorycnium herbaceum extracts as source of phenolic compounds and their antimicrobial, antibiofilm, and antioxidant potentials. Journal of Food and Drug Analysis. 2015; 23(3):417-24. [DOI:10.1016/j.jfda.2015.01.003] [PMID]
7.Mahdian Dehkordi F, Kaboutari J, Zendehdel M, Javdani M. The antinociceptive effect of artemisinin on the inflammatory pain and role of GABAergic and opioidergic systems. The Korean Journal of Pain. 2019; 32(3):160-7. [DOI:10.3344/kjp.2019.32.3.160] [PMID]
8.Rashidi A, Jahandideh A, Hassanpour S, Asghari A. Anti-nociceptive mechanisms of melilotus officinalis linn. Ethanoic extract in mice: Involvement of opioidergic, nitrergic and muscarinic receptors. Journal of Basic and Clinical Pathophysiology. 2020; 8(2):7-14. [DOI:10.22070/jbcp.2020.13683.1136]
9.Matraszek-Gawron R, Chwil M, Terlecka P, Skoczylas MM. Recent studies on anti-depressant bioactive substances in selected species from the genera hemerocallis and gladiolus: A systematic review. Pharmaceuticals (Basel, Switzerland). 2019; 12(4):172. [DOI:10.3390/ph12040172] [PMID]
10.Lori-Gooini Z, Rabiei Z, Farhadi B, Bijad E, Azomon E, Rafieian- M, et al. [Investigation of chemical compounds and effects of Achilea wilhelmsii L essential oil on antioxidant and malondialdehyde levels of serum and brains of reserpined mice (Persian)]. Iranian Journal of Physiology and Pharmacology. 2018; 2(3):166-76. [Link]
11.Ikram H, Haleem DJ. Repeated treatment with reserpine as a progressive animal model of depression. Pakistan Journal of Pharmaceutical Sciences. 2017; 30(3):897-902. [PMID]
12.Salehi B, Gültekin-Özgüven M, Kirkin C, Özçelik B, Morais-Braga MFB, Carneiro JNP, et al. Antioxidant, antimicrobial, and anticancer effects of anacardium plants: An ethnopharmacological perspective. Frontiers in Endocrinology. 2020; 11:295. [DOI:10.3389/fendo.2020.00295] [PMID]
13.Zarghami Moghadd P, Zolfaghari MR, Allah Ghaemi E, Mazandarani M, Mansourian AR, Taheri SA. Negative performance of root extract of Onosma dichroanthum Boiss. on the burn wound healing in an animal model. Archives of Clinical Microbiology. 2011; 2(5):1-5. [DOI: 10:3823/238]
14.Rehman MU, Qureshi A, Baloch, MM. Extraction of hydroxyapatite from caprine bones and its anti-bacterial study. Mehran University Research Journal of Engineering and Technology. 2021; 40(4):867-73. [DOI:10.22581/muet1982.2104.16]
15.Mazandarani M, Makari S, Bajian GR, Zarghami MP, ABRODI M. Evaluation of phytochemical and antioxidant activity in different parts of heracleum gorganicum Rech. F. in Golestan Province of Iran. Iranian Journal of Plant Physiology. 2012; 2(2):381-6. [DOI: 10.30495/ijpp.2012.540771]
16.Abdollahi M, Farzamfar B, Salari P, Khoram Khorshid HR, Larijani B, Farhadi M, et al. Evaluation of acute and sub-chronic toxicity of Semelil (ANGIPARSTM), a new phytotherapeutic drug for wound healing in rodents. DARU Journal of Pharmaceutical Sciences. 2008; 16(1):7-14. [Link]
17.Hillhouse TM, Porter JH. A brief history of the development of antidepressant drugs: From monoamines to glutamate. Experimental and clinical Psychopharmacology. 2015; 23(1):1–21. [DOI:10.1037/a0038550] [PMID]
18.Baek SE, Lee GJ, Rhee CK, Rho DY, Kim DH, Huh S, et al. Decreased total antioxidant activity in major depressive disorder patients non-responsive to antidepressant treatment. Psychiatry Investigation. 2016; 13(2):222-6. [DOI:10.4306/pi.2016.13.2.222] [PMID]
19.Rabiei Z, Movahedi E, Rafieian Kopaei M, Lorigooini Z. [Antidepressant effects of trifolium pratense hydroalcholic extract in mice (Persian)]. Iranian Journal of Physiology and Pharmacology. 2018; 2(1):24-33. [Link]
2.Brailovskaia J, Margraf J. The relationship between burden caused by coronavirus (COVID-19), addictive social media use, sense of control and anxiety. Computers in Human Behavior. 2021; 119:106720. [DOI:10.1016/j.chb.2021.106720] [PMID]
3.Mohammadi M, Vaisi-Raygani A, Jalali R, Ghobadi A, Salalri N. [Prevalence of depression in soldiers of Iranian military centers: A meta-analysis (Persian)]. Ebnesina. 2020; 21(4):34-40. [Link]
4.Al-Snafi AE. Chemical constituents and pharmacological effects of melilotus officinalis-A review. International Journal of Current Pharmaceutical Research. 20190; 11(6):1-10. [DOI:10.22159/ijcpr.2019v11i6.36338]
5.Ilhan M, Ali Z, Khan IA, Küpeli Akkol E. A new isoflavane-4-ol derivative from melilotus officinalis (L.) Pall. Natural Product Research. 2019; 33(13):1856-61. [DOI:10.1080/14786419.2018.1477152] [PMID]
6.Stefanović OD, Tešić JD, Čomić LR. Melilotus albus and Dorycnium herbaceum extracts as source of phenolic compounds and their antimicrobial, antibiofilm, and antioxidant potentials. Journal of Food and Drug Analysis. 2015; 23(3):417-24. [DOI:10.1016/j.jfda.2015.01.003] [PMID]
7.Mahdian Dehkordi F, Kaboutari J, Zendehdel M, Javdani M. The antinociceptive effect of artemisinin on the inflammatory pain and role of GABAergic and opioidergic systems. The Korean Journal of Pain. 2019; 32(3):160-7. [DOI:10.3344/kjp.2019.32.3.160] [PMID]
8.Rashidi A, Jahandideh A, Hassanpour S, Asghari A. Anti-nociceptive mechanisms of melilotus officinalis linn. Ethanoic extract in mice: Involvement of opioidergic, nitrergic and muscarinic receptors. Journal of Basic and Clinical Pathophysiology. 2020; 8(2):7-14. [DOI:10.22070/jbcp.2020.13683.1136]
9.Matraszek-Gawron R, Chwil M, Terlecka P, Skoczylas MM. Recent studies on anti-depressant bioactive substances in selected species from the genera hemerocallis and gladiolus: A systematic review. Pharmaceuticals (Basel, Switzerland). 2019; 12(4):172. [DOI:10.3390/ph12040172] [PMID]
10.Lori-Gooini Z, Rabiei Z, Farhadi B, Bijad E, Azomon E, Rafieian- M, et al. [Investigation of chemical compounds and effects of Achilea wilhelmsii L essential oil on antioxidant and malondialdehyde levels of serum and brains of reserpined mice (Persian)]. Iranian Journal of Physiology and Pharmacology. 2018; 2(3):166-76. [Link]
11.Ikram H, Haleem DJ. Repeated treatment with reserpine as a progressive animal model of depression. Pakistan Journal of Pharmaceutical Sciences. 2017; 30(3):897-902. [PMID]
12.Salehi B, Gültekin-Özgüven M, Kirkin C, Özçelik B, Morais-Braga MFB, Carneiro JNP, et al. Antioxidant, antimicrobial, and anticancer effects of anacardium plants: An ethnopharmacological perspective. Frontiers in Endocrinology. 2020; 11:295. [DOI:10.3389/fendo.2020.00295] [PMID]
13.Zarghami Moghadd P, Zolfaghari MR, Allah Ghaemi E, Mazandarani M, Mansourian AR, Taheri SA. Negative performance of root extract of Onosma dichroanthum Boiss. on the burn wound healing in an animal model. Archives of Clinical Microbiology. 2011; 2(5):1-5. [DOI: 10:3823/238]
14.Rehman MU, Qureshi A, Baloch, MM. Extraction of hydroxyapatite from caprine bones and its anti-bacterial study. Mehran University Research Journal of Engineering and Technology. 2021; 40(4):867-73. [DOI:10.22581/muet1982.2104.16]
15.Mazandarani M, Makari S, Bajian GR, Zarghami MP, ABRODI M. Evaluation of phytochemical and antioxidant activity in different parts of heracleum gorganicum Rech. F. in Golestan Province of Iran. Iranian Journal of Plant Physiology. 2012; 2(2):381-6. [DOI: 10.30495/ijpp.2012.540771]
16.Abdollahi M, Farzamfar B, Salari P, Khoram Khorshid HR, Larijani B, Farhadi M, et al. Evaluation of acute and sub-chronic toxicity of Semelil (ANGIPARSTM), a new phytotherapeutic drug for wound healing in rodents. DARU Journal of Pharmaceutical Sciences. 2008; 16(1):7-14. [Link]
17.Hillhouse TM, Porter JH. A brief history of the development of antidepressant drugs: From monoamines to glutamate. Experimental and clinical Psychopharmacology. 2015; 23(1):1–21. [DOI:10.1037/a0038550] [PMID]
18.Baek SE, Lee GJ, Rhee CK, Rho DY, Kim DH, Huh S, et al. Decreased total antioxidant activity in major depressive disorder patients non-responsive to antidepressant treatment. Psychiatry Investigation. 2016; 13(2):222-6. [DOI:10.4306/pi.2016.13.2.222] [PMID]
19.Rabiei Z, Movahedi E, Rafieian Kopaei M, Lorigooini Z. [Antidepressant effects of trifolium pratense hydroalcholic extract in mice (Persian)]. Iranian Journal of Physiology and Pharmacology. 2018; 2(1):24-33. [Link]
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Received: 2023/02/18 | Accepted: 2023/10/24 | Published: 2024/04/1
Received: 2023/02/18 | Accepted: 2023/10/24 | Published: 2024/04/1
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