antidepressant activity
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Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 533
Author(s):  
Małgorzata Jarończyk ◽  
Jarosław Walory

Antidepressants target a variety of proteins in the central nervous system (CNS), the most important belonging to the family of G-protein coupled receptors and the family of neurotransmitter transporters. The increasing number of crystallographic structures of these proteins have significantly contributed to the knowledge of their mechanism of action, as well as to the design of new drugs. Several computational approaches such as molecular docking, molecular dynamics, and virtual screening are useful for elucidating the mechanism of drug action and are important for drug design. This review is a survey of molecular targets for antidepressants in the CNS and computer based strategies to discover novel compounds with antidepressant activity.


2022 ◽  
Author(s):  
Jialin Liu ◽  
Yichao Fang ◽  
Lixun Cui ◽  
Zhongzhao Wang ◽  
Yusha Luo ◽  
...  

Abstract Background: Gut microbiota has emerged as a crucial target of gut-brain axis to influence brain and behavior and also has been closely connected with depression. Zhi-Zi-Chi decoctions (ZZCD), as a classic oral formula in clinic prescribed to clear heat and relieve restlessness traditionally, is widely applied in depression treatment nowadays. However, the underlying mechanism in the antidepressant activity of ZZCD remains largely unknown. Our previous study revealed that isoflavones, the bioactive constituents of Semen Sojae Praeparatum, benefited health by regulating the gut microbiota, which introduced the gut microbiota into understanding the mechanism of Traditional Chinese Medicine (TCM). Hence, in the present study, we aimed to investigate the antidepressant mechanism of ZZCD by focusing on the gut microbiota. Results: A classic depression model of chronic mild unpredictable stress (CUMS) was established in rats based on the results of behavioral tests and hippocampal histomorphology. 16S rRNA sequencing analysis indicated that ZZCD could increase short-chain fatty acid-producing and anti-inflammatory bacteria and reduce inflammatory and tryptophan-metabolizing bacteria, which reflected the changes of short-chain fatty acids (SCFAs), inflammation and tryptophan metabolism from the perspective of the gut microbiota. Furthermore, ZZCD reversed the alterations of BDNF, TNF-α, pro-inflammatory cytokines and neurotransmitters in the gut, blood and brain along the brain-gut axis and restored the decrease of butyrate in cecal content caused by CUMS. Then, butyrate was utilized to validate its ameliorative effect on pathological characteristics of depressive rats. Conclusions: Taken together, these results show that ZZCD exhibits antidepressant effect through modulating gut microbiota to facilitate the production of butyrate, which further regulate anti-inflammation, neurotransmitters, endocrine and BDNF along the gut-brain axis. Hence, this study fills the gap of the antidepressive mechanism of ZZCD in the light of the brain-gut axis and established a multi-targets and multi-levels platform eventually for further research into the mechanism of other TCM efficacy.


2022 ◽  
Vol 15 ◽  
Author(s):  
Gilberto Uriel Rosas-Sánchez ◽  
León Jesús German-Ponciano ◽  
Juan Francisco Rodríguez-Landa

Author(s):  
Shruti Mittal ◽  
Prashant Gupta ◽  
Vijay Nigam

Depressive disorder is a prevalent psychiatric disorder, which affects 21% of the world population. The presently using drugs can impose a variety of side-effects including cardiac toxicity, hypopiesia, sexual dysfunction, body weight gain, and sleep disorder. Ayurvedic medicine may be a powerful weapon given by our nature to cure disease. Considering the importance of plants as sources of drugs even today people are adopting different herbal drugs for the treatment of assorted diseases. During the last decade, there is a growing interest in the therapeutic effects of natural products on mental disorders. This study planned to assess antidepressant like activity of methanolic extract of Clitoria ternatea Linn. (fabaceae). Soxhlet extraction method was used for methanolic extraction. Antidepressant activity was studied using forced swimming test (FST) and tail suspension test (TST). Two doses 200 and 400 mg/kg of methanolic extract of flower were selected for testing. Imipramine (10 mg/kg, i.p.) were used as the reference standard drugs. Methanolic extract of Clitoria ternatea flower significantly reduced immobility time in both TST and FST. Extract increased the climbing behavior in FST, which is similar to effect observed with imipramine. The results of this study suggest that antidepressant like effect of Clitoria ternatea seems to be mediated by an increase in norepinephrine level in synapses. However further study is needed to understand mechanism of action and to isolate the active component responsible for antidepressant like activity.


2021 ◽  
Author(s):  
Yan-Na Ni ◽  
Xin-Li Du ◽  
Tao Wang ◽  
Yuan-Yuan Chen ◽  
Xiang-Qing Xu ◽  
...  

A total of 20 novel aryl piperazine derivatives were designed and synthesized, and their structures were confirmed by mass spectrometry and nuclear magnetic resonance analyses. Their 5-HT1A and sigma-1 receptor affinities were determined, and six of them showed high affinities (K i < 20 nmol/L) to both 5-HT1A and sigma-1 targets. Then, metabolic stability (T 1/2) tests of six compounds in rat and human liver microsomes were performed. Our data indicated that compound 27 has both high affinity for 5-HT1A and sigma-1 receptors (5-HT1A: K i = 0.44 nmol/L; sigma-1: K i = 0.27 nmol/L), and good metabolic stability (T 1/2 values are 21.7 and 24.6 minutes, respectively). Interestingly, results from the forced swimming test, mouse tail suspension test, and preliminary pharmacokinetic test suggested the marked antidepressant activity, good pharmacokinetic characteristics, and low toxicity of compound 27 in the two models. In conclusion, compound 27 has great value of further study as an active molecule of antidepressant drugs.


Author(s):  
Wojciech Ziemichod ◽  
Ewa Gibula-Tarlowska ◽  
Jolanta H. Kotlinska ◽  
Pawel Grochecki ◽  
Ewa Kedzierska

Abstract There is a number of diseases for which, scientists are constantly looking for a promising new treatments. Isolation of novel substances with biological activity from plants gives hope for its use in treatment. In this review, we focused on the biological activity of p-synephrine (4-(2-aminoethyl)phenol) which was previously confirmed during both in vitro and in vivo tests. The main part of the review is dedicated to the anti-obesity activity of p-synephrine, as obesity is a disease of contemporary civilization. However, synephrine also possesses anti-diabetic, anti-inflammatory and antidepressant activity and it is confirmed to be a hypotensive agent in portal hypertension. The review also emphasize that, based on current knowledge, the use of p-synephrine appears to be exceedingly safe with only limited range of side effects. Therefore, it seems that this substance may be of great importance in the pharmacotherapy of many disease states and further research is necessary.


2021 ◽  
Vol 11 ◽  
Author(s):  
Abdulhalim Serafi ◽  
Aisha Azmat ◽  
Muhammad Ahmed ◽  
Mohammed Bafail ◽  
Zahir Hussain

Background: Depression is common in hypertensive patients, and monotherapy may contribute for controlling depression in hypertensive patients and improving the socioeconomic outcomes. Previous studies have shown that Acacia tortilis possesses hypotensive activity. Objectives: Hence, the present study was planned to evaluate the hemodynamic activity and antidepressant effects of an ethanolic extract of Acacia tortilis leaves (ATEL) in salt-induced hypertensive rats. Methods: Sprague-Dawley rats were divided into 5 groups for experiments. The rats received respective treatment for 15 days: G1: Control (C); G2: Hypertensive control (HC: high dietary salt, 4% 10ml/kg); G3-5: HC+ ATEL (50, 100, 150mg/kg respectively). Cardiac hemodynamics (mean arterial blood pressure: MAP and heart rate: HR) were measured in the anaesthetized rats by an invasive method. For this method, one carotid artery was catheterized, a pressure catheter (pressure volume Millar microtip catheter connected to the Mikro-Tip Pressure-Volume System from Ultra Foundation Systems, PowerLab) was inserted, and the blood pressure (MAP in mm Hg) and HR (beats/min) were monitored continuously during the experiment. For the neuropharmacological studies, antidepressant activity was assessed by forced swim test on the 15th day. Results: A dose-dependent significant increase in mobility time was observed in rats (G3-5) treated with HC + different doses of ATEL (p < 0.05). However, the mobility time was significantly reduced by HC (G2) treatment compared with that of the control (p< 0.05). The hypertensive control (high dietary salt: HC) group showed significant increases in SP, DP, MAP, and HR (p<0.05) compared to the control (G1) group. At all doses (50, 100 and 150 mg/kg), MAP and HR were found to decrease significantly (p<0.05) when compared with the values in the HC (G2) group. Further analysis revealed an improvement in heart rate variability (HRV) in ATEL-treated hypertensive rats. Conclusion: The present research suggests that increased dietary salt intake not only increases blood pressure significantly but also increases depression. ATEL contains some efficacious constituents, N, N-dimethyltryptamine (DMT: a 5-HT1A agonist) with predominant antidepressant and antihypertensive activity. Hence, ATEL appears to be a valuable plant extract that can be useful, at least as an adjunct, for therapy in patients who suffer from both depression and hypertension. Objectives: Hence, the present study was planned to evaluate the hemodynamic activity and antidepressant effects of an ethanolic extract of Acacia tortilis leaves (ATEL) in salt-induced hypertensive rats. Methods: Sprague-Dawley rats were divided into 5 groups for experiments. The rats received respective treatment for 15 days: G1: Control (C); G2: Hypertensive control (HC: high dietary salt, 4% 10ml/kg); G3-5: HC+ ATEL (50, 100, 150mg/kg respectively). Cardiac hemodynamics (mean arterial blood pressure: MAP and heart rate: HR) were measured in the anaesthetized rats by an invasive method. For this method, one carotid artery was catheterized, a pressure catheter (pressure volume Millar microtip catheter connected to the Mikro-Tip Pressure-Volume System from Ultra Foundation Systems, PowerLab) was inserted, and the blood pressure (MAP in mm Hg) and HR (beats/min) were monitored continuously during the experiment. For the neuropharmacological studies, antidepressant activity was assessed by forced swim test on the 15th day. Results: A dose-dependent significant increase in mobility time was observed in rats (G3-5) treated with HC + different doses of ATEL (p < 0.05). However, the mobility time was significantly reduced by HC (G2) treatment compared with that of the control (p< 0.05). The hypertensive control (high dietary salt: HC) group showed significant increases in SP, DP, MAP, and HR (p<0.05) compared to the control (G1) group. At all doses (50, 100 and 150 mg/kg), MAP and HR were found to decrease significantly (p<0.05) when compared with the values in the HC (G2) group. Further analysis revealed an improvement in heart rate variability (HRV) in ATEL-treated hypertensive rats. Conclusion: The present research suggests that increased dietary salt intake not only increases blood pressure significantly but also increases depression. ATEL contains some efficacious constituents, N, N-dimethyltryptamine (DMT: a 5-HT1A agonist) with predominant antidepressant and antihypertensive activity. Hence, ATEL appears to be a valuable plant extract that can be useful, at least as an adjunct, for therapy in patients who suffer from both depression and hypertension.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander Spasov ◽  
Alexander Ozerov ◽  
Pavel Vassiliev ◽  
Vadim Kosolapov ◽  
Natalia Gurova ◽  
...  

AbstractThe Na+/H+ exchanger isoform 1 (NHE-1) attracts ongoing attention as a validated drug target for the management of cardiovascular and ocular diseases owing to cytoprotective, anti-ischemic and anti-inflammatory properties of NHE-1 inhibitors. Herein we report novel NHE-1 inhibitors realized via functionalization of N1-alkyl quinazoline-2,4(1H,3H)-dione and quinazoline-4(3H)-one with N-acylguanidine or 3-acyl(5-amino-1,2,4-triazole) side chain. Lead compounds show activity in a nanomolar range. Their pharmacophoric features were elucidated with neural network modeling. Several compounds combine NHE-1 inhibition with antiplatelet activity. Compound 6b reduces intraocular pressure in rats and effectively inhibits the formation of glycated proteins. Compounds 3e and 3i inhibit pro-inflammatory activation of murine macrophages, LPS-induced interleukin-6 secretion and also exhibit antidepressant activity similar to amiloride. Hence, novel compounds represent an interesting starting point for the development of agents against cardiovascular diseases, thrombotic events, excessive inflammation, long-term diabetic complications and glaucoma.


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