Beneficial effects of combined administration of fluoxetine and mitochondria-targeted antioxidant at in behavioural and molecular studies in mice model of depression

Herbet, Mariola; Szumełda, Izabela; Piątkowska‐Chmiel, Iwona; Gawrońska‐Grzywacz, Monika; Dudka, Jarosław

doi:10.1016/j.bbr.2021.113185

Cited by 13 publications

(7 citation statements)

References 56 publications

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“…It is known that adenosine receptors play a large role in pathogenesis as well as in the treatment of depressive disorders. Studies in mice suggest that increased A1 expression may have an antidepressant effect that is directly related to the function of astrocytes [ 93 , 94 ]. It has also been shown in a model of transgenic mice with the conditioned upregulation of brain A1 receptors that increasing A1 expression induces resistance to depressive behavior in behavioral tests, with it also exerting an antidepressant effect in the chronic stress model [ 95 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Selen on the Antidepressant-like Activity of Agents Affecting the Adenosinergic Neurotransmission

et al. 2022

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The main goal of this study was to determine the antidepressant-like potential of the co-administration of sodium selenite (Se) and the selective adenosine A1 and A2A antagonists DPCPX and istradefylline (IST), respectively, in mice despair tests. Biochemical studies were performed to elucidate the action mechanisms of the investigated treatment strategies. The results confirmed that, when administered by itself, Se exerts an antidepressant-like effect in the FST and TST and that this activity is dose-dependent. Further experiments demonstrated that Se (0.25 mg/kg) significantly enhanced the activity of mice in both tests when co-administered with DPCPX (1 mg/kg) and IST (0.5 mg/kg) at doses which would be ineffective if administered individually. Our research revealed that neither DPCPX, IST, nor Se or combinations of the tested substances induced significant changes in the brain-derived neurotrophic factor (BDNF) levels in mice serum vs. the NaCl-treated group. However, we observed a decrease in the mRNA level of antioxidant defense enzymes. Molecular studies also showed changes in the expression of the Slc6a15, Comt, and Adora1 genes, particularly after exposure to the combination of Se and DPCPX, which indicates a beneficial effect and may help to explain the key mechanism of the antidepressant effect. The combination of Se with substances attenuating adenosine neurotransmission may become a new therapeutic strategy for patients with depression.

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Section: Discussionmentioning

confidence: 99%

Effects of Selen on the Antidepressant-like Activity of Agents Affecting the Adenosinergic Neurotransmission

et al. 2022

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“…So, we mainly explored the antioxidation-related mechanisms by KEGG pathway enrichment analysis. We found that antioxidant-related targets AKT1, NOS3, Nrf2, and KEAP1 have high research potential and KXS could activate the AKT/Nrf2 pathway to up-regulate the activity of several antioxidant systems, such as glutathione (GSH) system [ 34 ], reactive oxygen species (ROS) [ 35 ], heme oxygenase(HO) system [ 36 ], and Trx system. These antioxidant mechanisms may play an important role in the treatment of depression.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant Mechanism of Kaixinsan and Its Active Compounds Based on Upregulation of Antioxidant Thioredoxin

Wang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objectives. Kaixinsan (KXS), a traditional Chinese medicine formula, has been demonstrated to be effective in the treatment of depression. The present study applied a network pharmacology approach to dig out the new targets and mechanism of action of KXS and the active compounds in the treatment of depression. Methods. A network pharmacology approach based on public databases including ADME (absorption, distribution, metabolism, and excretion) evaluation, targets prediction, construction of networks, and molecule docking was used and validated the predicted new antioxidant targets and mechanisms in vitro. Based on an in vitro experiment, we verified the AKT1/Nrf2 pathway related to the thioredoxin (Trx) antioxidant mechanism. Results. The present study sorted 31 pharmacologically active components (kaempferol, ginsenoside rh2, ginsenoside rh4, stigmasterol, etc.) through the ADME algorithm from KXS. 136 potential molecular targets (AKT1, TNF, IL-1b, JUN, ESR1, NOS3, etc.) were predicted, of which there were 69 targets clearly related to depression. By compound-depression targets (C-DTs) network constructed, and protein-protein interaction networks (PPI) and KEGG pathway enrichment analyzed, we identified active compounds mediating depression-related targets to exert synergism on the predictive AKT1/Nrf2 pathway related to thioredoxin (Trx) antioxidant mechanism and other inflammation-related signaling pathways as well as neurotransmitter related signaling pathways. In the H2O2 induced SH-SY5Y cell damage model, this showed kaempferol and ginsenoside rh2 could enhance the activity of the Trx system by upregulation of AKT1 to activate Nrf2 in vitro. Conclusions. Taken together, by comprehensive systems pharmacology approach analysis, we found that KXS and its active compounds might exhibit antioxidant effects by stimulating the AKT1/Nrf2 pathway in the treatment of depression, which might shed new light on innovative therapeutic tactics for the new aspects for depression in traditional Chinese medicine in future studies.

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“…ROS result in the formation of unusual free radical oxidation products that react with cellular metabolites. This may result in cell death by apoptosis or necrosis [ 55 , 56 , 57 ]. The main source of ROS production is the mitochondrial respiratory chain.…”

Section: Oxidative Stress In Depression and Admentioning

confidence: 99%

“…The main source of ROS production is the mitochondrial respiratory chain. Due to its high level of energy consumption, the brain is highly dependent on mitochondrial activity [ 56 , 57 ]. A significant number of patients complain of persistent side effects after taking antidepressants, most commonly: “feeling foggy or detached, drowsiness, reduction in positive feelings, thoughts of suicide, addiction” [ 58 ].…”

Section: Oxidative Stress In Depression and Admentioning

confidence: 99%

Chronic Stress and Oxidative Stress as Common Factors of the Pathogenesis of Depression and Alzheimer’s Disease: The Role of Antioxidants in Prevention and Treatment

et al. 2021

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There is a growing body of scientific research showing the link between depression and dementia in Alzheimer’s disease (AD). The chronic stress contributes to the formation of oxidative stress in the parts of the brain involved in the development of depression and AD. The scientific literature reports the significant role of antioxidants, which are highly effective in treating these diseases. In this review, we have summarized the relationship between chronic stress, oxidative stress, and the changes in the brain they cause occurring in the brain. Among all the compounds showing antioxidant properties, the most promising results in AD treatment were observed for Vitamin E, coenzyme Q10 (CoQ10), melatonin, polyphenols, curcumin, and selenium. In case of depression treatment, the greatest potential was observed in curcumin, zinc, selenium, vitamin E, and saffron.

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Beneficial effects of combined administration of fluoxetine and mitochondria-targeted antioxidant at in behavioural and molecular studies in mice model of depression

Cited by 13 publications

References 56 publications

Effects of Selen on the Antidepressant-like Activity of Agents Affecting the Adenosinergic Neurotransmission

Effects of Selen on the Antidepressant-like Activity of Agents Affecting the Adenosinergic Neurotransmission

Antidepressant Mechanism of Kaixinsan and Its Active Compounds Based on Upregulation of Antioxidant Thioredoxin

Chronic Stress and Oxidative Stress as Common Factors of the Pathogenesis of Depression and Alzheimer’s Disease: The Role of Antioxidants in Prevention and Treatment

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