E-ISSN 2636-834X
 

Original Research 


Antidepressant-Like Effect of the Polymethoxylated Flavone Tangeretin from Citrus Peels: The Role of Serotonergic Mechanisms

Özgür Devrim Can, Nesime İnci Güner.


Abstract
Objective: Depression is a mood disorder characterized by a set of emotional, cognitive, physical and behavioral symptoms. Low response rate to antidepressant treatment in patients with depression, late onset of action, side effects due to long-term drug use, and pharmacogenetic variations limit the effectiveness and tolerability of these drugs and lead to compliance problems in patients. Therefore, studies on the discovery and development of new antidepressant drugs continue, and molecules of natural origin are becoming the focus of attention of researchers. Tangeretin, which is commonly found in citrus peels and has a pentamethoxyflavone structure, is an important member of flavonoids. Since it lacks a glycoside structure, it is easily absorbed from the intestines and can easily pass through the blood-brain barrier due to its lipophilic structure. Previous studies indicating that tangeretin may be effective on the central nervous system suggest that it may be possible for this phytochemical to have an effect on mood. Based on this idea, this study aimed to investigate the possible antidepressant-like effects of tangeretin and to elucidate the pharmacological mechanisms mediating this effect.
Methods: Male Balb/c mice of the same age, weighing 30-35 g, were used for the experiments. The antidepressant-like effect of tangeretin (10, 20 ve 40 mg/kg, p.o.) was examined by tail suspension and modified forced swimming tests, while its effect on the motor coordination of experimental animals was evaluated using the Rota-rod method.
Results: The data obtained revealed that doses of 10 and 20 mg/kg tangeretin decreased the immobility time of mice in tail suspension test and immobility number of mice in modified forced swimming tests compared to control animals not receiving tangeretin. These findings indicated that tangeretin showed an antidepressant-like activity comparable to the reference drug fluoxetine (30 mg/kg) when administered at doses of 10 and 20 mg/kg. Tangeretin, at the same doses, did not alter the climbing number of mice in modified forced swimming tests, but significantly increased their swimming number. The 40 mg/kg dose of this flavonoid did not cause a statistically significant effect in either test. While α-methyl-para-tyrosine methyl ester (an inhibitor of catecholamine synthesis; 100 mg/kg i.p.) and ondansetron (a 5-HT3 receptor antagonist; 0.3 mg/kg i.p.) pretreatments did not change the antidepressant-like activity induced by 20 mg/kg dose of this flavonoid in the tail suspension tests; pretreatment of p-chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis; 100 mg/kg i.p., administered for 4-consecutive days), NAN-190 (a 5-HT1A receptor antagonist; 0.5 mg/kg i.p.) and ketanserin (a 5-HT2A/2C receptor antagonist; 1 mg/kg i.p.), reversed this activity. These findings indicated that tangeretin has antidepressant-like activity mediated by the serotonergic system and that 5-HT1A and 5-HT2A/5-HT2C serotonergic receptor subtypes participate in this effect.
Conclusion: The findings of this study suggest that tangeretin may be a useful drug candidate in the treatment of depression. However, it is clear that for tangeretin to be considered an antidepressant agent, the antidepressant-like activity presented in this preclinical study must be confirmed by well-designed clinical studies conducted on various groups of patients with depressive disorders.

Key words: Tangeretin, Antidepressant-Like Effect, Tail Suspension Test, Modified Forced Swimming Test, Rota-Rod Test, Serotonergic System


 
ARTICLE TOOLS
Abstract
PDF Fulltext
How to cite this articleHow to cite this article
Citation Tools
Related Records
 Articles by Özgür Devrim Can
Articles by Nesime İnci Güner
on Google
on Google Scholar


How to Cite this Article
Pubmed Style

Can OD, Guner N. Antidepressant-Like Effect of the Polymethoxylated Flavone Tangeretin from Citrus Peels: The Role of Serotonergic Mechanisms. PBS. 2024; 14(1): 48-57. doi:10.5455/PBS.20231210094357


Web Style

Can OD, Guner N. Antidepressant-Like Effect of the Polymethoxylated Flavone Tangeretin from Citrus Peels: The Role of Serotonergic Mechanisms. https://www.pbsciences.org/?mno=180772 [Access: April 07, 2024]. doi:10.5455/PBS.20231210094357


AMA (American Medical Association) Style

Can OD, Guner N. Antidepressant-Like Effect of the Polymethoxylated Flavone Tangeretin from Citrus Peels: The Role of Serotonergic Mechanisms. PBS. 2024; 14(1): 48-57. doi:10.5455/PBS.20231210094357



Vancouver/ICMJE Style

Can OD, Guner N. Antidepressant-Like Effect of the Polymethoxylated Flavone Tangeretin from Citrus Peels: The Role of Serotonergic Mechanisms. PBS. (2024), [cited April 07, 2024]; 14(1): 48-57. doi:10.5455/PBS.20231210094357



Harvard Style

Can, O. D. & Guner, . N. . (2024) Antidepressant-Like Effect of the Polymethoxylated Flavone Tangeretin from Citrus Peels: The Role of Serotonergic Mechanisms. PBS, 14 (1), 48-57. doi:10.5455/PBS.20231210094357



Turabian Style

Can, Ozgur Devrim, and Nesime İnci Guner. 2024. Antidepressant-Like Effect of the Polymethoxylated Flavone Tangeretin from Citrus Peels: The Role of Serotonergic Mechanisms. Psychiatry and Behavioral Sciences, 14 (1), 48-57. doi:10.5455/PBS.20231210094357



Chicago Style

Can, Ozgur Devrim, and Nesime İnci Guner. "Antidepressant-Like Effect of the Polymethoxylated Flavone Tangeretin from Citrus Peels: The Role of Serotonergic Mechanisms." Psychiatry and Behavioral Sciences 14 (2024), 48-57. doi:10.5455/PBS.20231210094357



MLA (The Modern Language Association) Style

Can, Ozgur Devrim, and Nesime İnci Guner. "Antidepressant-Like Effect of the Polymethoxylated Flavone Tangeretin from Citrus Peels: The Role of Serotonergic Mechanisms." Psychiatry and Behavioral Sciences 14.1 (2024), 48-57. Print. doi:10.5455/PBS.20231210094357



APA (American Psychological Association) Style

Can, O. D. & Guner, . N. . (2024) Antidepressant-Like Effect of the Polymethoxylated Flavone Tangeretin from Citrus Peels: The Role of Serotonergic Mechanisms. Psychiatry and Behavioral Sciences, 14 (1), 48-57. doi:10.5455/PBS.20231210094357