Effect of 25-methoxy hispidol A isolated from Poncirus trifoliate against bacteria-induced anxiety and depression by targeting neuroinflammation, oxidative stress and apoptosis in mice

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. It is characterized by static tremors, stiffness, slow movements, and gait disturbances, but it is also accompanied by anxiety and depression. Our previous study showed that statins, especially atorvastatin, could reduce the risk of PD, but the mechanism is still unclear. Results In this paper, we used an animal model of PD in which depression was determined by a tail suspension test, followed by an elevated plus-maze test to determine anxiety levels, and muscle status was measured by a rotarod test. We found that atorvastatin can increase muscle capacity and the coordination of movement and improved anxiety and depression，which mechanism may be related to decrease the expression of α-synuclein Ser129 and NADPH oxidase 2 (NOX2), and increase the protein expression of LC-3II/LC3-I, and promote autophagy flow. To further confirm that atorvastatin protection was achieved by inhibiting NOX2, we injected the midbrain substratum with NOX2 shRNA (M) lentivirus and found that silent NOX2 produced the same effect as atorvastatin. Further research found that atorvastatin could reduce MPTP-induced oxidative stress damage by increasing Nrf2, NQO-1 and HO-1, while inhibiting NOX2 decreased the antioxidative stress effect of atorvastatin. Conclusions： Our results suggest that atorvastatin can improve muscle capacity, anxiety and depression by inhibiting NOX2, which may be related to NOX2-mediated oxidative stress and autophagy in dopaminergic neurons. Atorvastatin may be identified as a drug that can effectively improve behavioral disorders in PD mice. NOX2 may be a potential gene target for new drug development in PD.

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Neuroprotective Effects of dl-3-n-Butylphthalide against Doxorubicin-Induced Neuroinflammation, Oxidative Stress, Endoplasmic Reticulum Stress, and Behavioral Changes

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/9125601 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 21

Author(s):

Dehua Liao ◽

Daxiong Xiang ◽

Ruili Dang ◽

Pengfei Xu ◽

Jiemin Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Therapeutic Potential ◽

Interleukin 1 ◽

Behavioral Changes ◽

Anxiety And Depression ◽

Stress Markers ◽

Neural Apoptosis

Doxorubicin (DOX) is a broad-spectrum antitumor drug while its use is limited due to its neurobiological side effects associated with depression. We investigated the neuroprotective efficacy of dl-3-n-butylphthalide (dl-NBP) against DOX-induced anxiety- and depression-like behaviors in rats. dl-NBP was given (30 mg/kg) daily by gavage over three weeks starting seven days before DOX administration. Elevated plus maze (EPM) test, forced swimming test (FST), and sucrose preference test (SPT) were performed to assess anxiety- and depression-like behaviors. Our study showed that the supplementation of dl-NBP significantly mitigated the behavioral changes induced by DOX. To further explore the mechanism of neuroprotection induced by dl-NBP, several biomarkers including oxidative stress markers, endoplasmic reticulum (ER) stress markers, and neuroinflammatory cytokines in the hippocampus were quantified. The results showed that dl-NBP treatment alleviated DOX-induced neural apoptosis. Meanwhile, DOX-induced oxidative stress and ER stress in the hippocampus were significantly ameliorated in dl-NBP pretreatment group. Our study found that dl-NBP alleviated the upregulation of malondialdehyde (MDA), nitric oxide (NO), CHOP, glucose-regulated protein 78 kD (GRP-78), and caspase-12 and increased the levels of reduced glutathione (GSH) and activities of catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx) in the hippocampus of rats exposed to DOX. Additionally, the gene expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) and protein levels of inducible nitric oxide synthase (iNOS) were significantly increased in DOX-treated group, whereas DOX-induced neuroinflammation was significantly attenuated in dl-NBP supplementation group. In conclusion, dl-NBP could alleviate DOX-induced anxiety- and depression-like behaviors via attenuating oxidative stress, ER stress, inflammatory reaction, and neural apoptosis, providing a basis as a therapeutic potential against DOX-induced neurotoxicity.

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Quercetin mitigates Adriamycin-induced anxiety- and depression-like behaviors, immune dysfunction, and brain oxidative stress in rats

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-014-1008-y ◽

2014 ◽

Vol 387 (10) ◽

pp. 921-933 ◽

Cited By ~ 35

Author(s):

Sameha Merzoug ◽

Mohamed Lamine Toumi ◽

Abdelkrim Tahraoui

Keyword(s):

Oxidative Stress ◽

Immune Dysfunction ◽

Anxiety And Depression ◽

Brain Oxidative Stress

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Analysis of the association between anxiety and depression levels and oxidative stress levels

Annals of Medical Research ◽

10.5455/annalsmedres.2019.12.819 ◽

2020 ◽

Vol 27 (4) ◽

pp. 1193

Author(s):

Atakan Savrun ◽

Seyda Savrun ◽

Ali Aygun ◽

Emre Gokcen ◽

Yeliz Arici ◽

...

Keyword(s):

Oxidative Stress ◽

Anxiety And Depression ◽

Stress Levels ◽

And Oxidative Stress

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Beneficial effects of vitamin D on anxiety and depression-like behaviors induced by unpredictable chronic mild stress by suppression of brain oxidative stress and neuroinflammation in rats

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-020-02002-0 ◽

2020 ◽

Author(s):

Hossein Bakhtiari-Dovvombaygi ◽

Saeed Izadi ◽

Mostafa Zare Moghaddam ◽

Milad Hashemzehi ◽

Mahmoud Hosseini ◽

...

Keyword(s):

Oxidative Stress ◽

Vitamin D ◽

Chronic Mild Stress ◽

Anxiety And Depression ◽

Mild Stress ◽

Unpredictable Chronic Mild Stress ◽

Beneficial Effects ◽

Brain Oxidative Stress

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Protective Effects of Two Halophilic Crude Extracts from Pseudomonas zhaodongensis and Bacillus stratosphericus against Memory Deficits and Anxiety- and Depression-Like Behaviors in Methionine-Induced Schizophrenia in Mice Focusing on Oxidative Stress Status

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/8852418 ◽

2020 ◽

Vol 2020 ◽

pp. 1-18

Author(s):

Yousra Massaoudi ◽

Jaouad Anissi ◽

Radu Lefter ◽

Andrei Lobiuc ◽

Khalid Sendide ◽

...

Keyword(s):

Oxidative Stress ◽

Negative Symptoms ◽

Forced Swimming Test ◽

Anxiety And Depression ◽

Protective Effects ◽

Crude Extracts ◽

Y Maze ◽

Plus Maze ◽

Oxidative Stress Status ◽

Swimming Test

Recently, the implication of oxidative stress in behavioral-like disorders has received a lot of attention. Many studies were interested in searching for new natural compounds with protective effects on behavioral-like disorders by focusing on oxidative stress as the main causal factor. Here, we assess the potential effect of cell-free extracts from halophilic bacteria on memory, anxiety, and depression-related behaviors in mice, as well as on cognitive deficits, negative symptoms, and some oxidative stress biomarkers in methionine-induced mice models of schizophrenia. Firstly, crude extracts of bacteria isolated from the Dead Sea were screened for their effects on memory and anxiety- and depression-like behaviors through Y-maze, elevated plus maze, and forced swimming test, respectively, using two doses 60 mg/kg and 120 mg/kg. Then, 120 mg/kg of two bacterial crude extracts, from two strains designated SL22 and BM20 and identified as Bacillus stratosphericus and Pseudomonas zhaodongensis, respectively, with significant contents of phenolic and flavonoid-like compounds, were selected for the assessment of cognitive and negative symptom improvement, as well as for their effects on oxidative stress status in methionine-induced mice models of schizophrenia using six groups (controls, methionine, crude extracts solely, and combinations of crude extracts and methionine). Results showed that the administration of the crude extracts caused a significant increase in the spontaneous alternations in the Y-maze task, the time spent in open arms of the elevated plus maze, and a decrease in immobility time in the forced swimming test in comparison with the control group. Furthermore, the administration of bacterial extracts seemed to diminish disorders related to cognitive and negative symptoms of schizophrenia and to improve the oxidative state in the temporal lobes, in comparison with the methionine group. Our findings suggest substantial antioxidant and anti-neuropsychiatric effects of the crude extracts prepared from Pseudomonas zhaodongensis strain BM20 and Bacillus stratosphericus strain SL22 and that further studies are needed to purify and to determine the active fraction from the extracts.

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