Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders

Shan, Jiajing; Hashimoto, Kenji

doi:10.3390/ijms23094951

Cited by 19 publications

(11 citation statements)

References 140 publications

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“…It cannot be ignored that the soluble epoxide hydrolase (sEH) is a key enzyme in the metabolism of PUFA and plays a key role in the inflammation that is involved in depression 96,97 . Meanwhile, epoxy fatty acids such as epoxyeicosatrienoic acids (EETs) and epoxyeicosapentaenoic acids (EDPs) have been found to exert neuroprotective effects through potent anti‐inflammatory actions 98 . Unfortunately, the present study did not observe the content of sEH and epoxy fatty acids, which may further explain the antidepressant effect of TMS.…”

Section: Discussionmentioning

confidence: 99%

rTMS ameliorates depressive‐like behaviors and regulates the gut microbiome and medium‐ and long‐chain fatty acids in mice exposed to chronic unpredictable mild stress

et al. 2023

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IntroductionRepetitive transcranial magnetic stimulation (rTMS) is a clinically useful therapy for depression. However, the effects of rTMS on the metabolism of fatty acids (FAs) and the composition of gut microbiota in depression are not well established.MethodsMice received rTMS (15 Hz, 1.26 T) for seven consecutive days after exposure to chronic unpredictable mild stress (CUMS). The subsequent depressive‐like behaviors, the composition of gut microbiota of stool samples, as well as medium‐ and long‐chain fatty acids (MLCFAs) in the plasma, prefrontal cortex (PFC), and hippocampus (HPC) were evaluated.ResultsCUMS induced remarkable changes in gut microbiotas and fatty acids, specifically in community diversity of gut microbiotas and PUFAs in the brain. 15 Hz rTMS treatment alleviates depressive‐like behaviors and partially normalized CUMS induced alterations of microbiotas and MLCFAs, especially the abundance of Cyanobacteria, Actinobacteriota, and levels of polyunsaturated fatty acids (PUFAs) in the hippocampus and PFC.ConclusionThese findings revealed that the modulation of gut microbiotas and PUFAs metabolism might partly contribute to the antidepressant effect of rTMS.

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Section: Discussionmentioning

confidence: 99%

rTMS ameliorates depressive‐like behaviors and regulates the gut microbiome and medium‐ and long‐chain fatty acids in mice exposed to chronic unpredictable mild stress

et al. 2023

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“…Previous studies have suggested that the effect of n‐3 PUFAs on depression was related to its metabolic mechanism. It is believed that n‐3 PUFAs are metabolized by soluble epoxide hydrolase, and soluble epoxide hydrolase plays a key role in inflammation, so that it may also play a role in the pathogenesis of mental illness 29,30 …”

Section: Discussionmentioning

confidence: 99%

“…It is believed that n-3 PUFAs are metabolized by soluble epoxide hydrolase, and soluble epoxide hydrolase plays a key role in inflammation, so that it may also play a role in the pathogenesis of mental illness. 29,30 However, the pathogenesis of depression is complex, which includes a variety of molecular mechanisms and signaling pathways, studies have found that TLR4 signaling pathway was activated in the peripheral circulatory system or central nervous system (CNS) of depression patients and depression animal models. 31 TLR4 is mainly expressed in brain microglia, and adult nerves in the subgranular region of the hippocampus dentate gyrus were involved in the process of learning, memory and emotional management.…”

Section: Tlr4 Activation Partially Reversed the Inhibition Of N-3 Puf...mentioning

confidence: 99%

n‐3 polyunsaturated fatty acids improve depression‐like behavior by inhibiting hippocampal neuroinflammation in mice via reducing TLR4 expression

Zeng

Yang

et al. 2022

Immunity Inflam & Disease

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Introduction n‐3 polyunsaturated fatty acids (PUFAs) are believed to be implicated in the pathogenesis of many inflammation‐related diseases, including depression. Methods The mouse model of depression was established through chronic unpredictable mild stress (CUMS), the mice were intervened with n‐3 PUFAs, and then the expression of toll‐like receptor 4 (TLR4) was stimulated with lipopolysaccharides (LPS). Tail suspension test (TST), forced swimming test (FST) and sucrose preference test were performed to monitor the depression behavior of mice. Microglia activation was detected by Iba1 immunofluorescence, and neuronal injury was detected by Nissl staining. Concentrations of tumor necrosis factor (TNF)‐α, Interleukin (IL)‐6 and IL‐1β in the hippocampus were assessed via enzyme linked immunosorbent assay (ELISA). Quantitative real time polymerase chain reaction was used to detect IL‐6, IL‐1β and TNF‐α messenger RNA levels. Western blot was utilized for detection of TLR4 protein expression. Results CUMS significantly reduced the sucrose preference in mice, while increased the immobility time in FST and TST. Moreover, CUMS significantly aggravated microglia activation and neuronal damage in mice and increased the levels of IL‐6, IL‐1β and TNF‐α in hippocampal tissues, however, intervention with n‐3 PUFAs could improve the above effects. Further, the increased TLR4 induced by LPS partially reversed the inhibition of n‐3 PUFAs on depression‐like behaviors, microglial activation and inflammatory injury of hippocampal neurons. Conclusion n‐3 PUFAs may ameliorate depression‐like behaviors via reducing hippocampal neuroinflammation in CUMS‐induced mice by regulating TLR4 expression, suggesting that n‐3 PUFAs may be an effective antidepressant, which provides evidence for future treatment of depression.

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“…Soluble epoxide hydrolase (sEH) is a therapeutic target considered for the treatment of inflammation-based diseases, and various pathologies, including cardiovascular diseases and neuropsychiatric disorders [ 78 , 79 ]. A methanol extract of AR was shown to attenuate the decrease in epoxide hydrolase induced in rats intoxicated with bromobenzene [ 80 ].…”

Section: Pharmacological Properties Of Alisolsmentioning

confidence: 99%

Pharmacological Properties and Molecular Targets of Alisol Triterpenoids from Alismatis Rhizoma

Bailly

2022

Biomedicines

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More than 100 protostane triterpenoids have been isolated from the dried rhizomes of Alisma species, designated Alismatis rhizoma (AR), commonly used in Asian traditional medicine to treat inflammatory and vascular diseases. The main products are the alisols, with the lead compounds alisol-A/-B and their acetate derivatives being the most abundant products in the plant and the best-known bioactive products. The pharmacological effects of Ali-A, Ali-A 24-acetate, Ali-B, Ali-B 23-acetate, and derivatives have been analyzed to provide an overview of the medicinal properties, signaling pathways, and molecular targets at the origin of those activities. Diverse protein targets have been proposed for these natural products, including the farnesoid X receptor, soluble epoxide hydrolase, and other enzymes (AMPK, HCE-2) and functional proteins (YAP, LXR) at the origin of the anti-atherosclerosis, anti-inflammatory, antioxidant, anti-fibrotic, and anti-proliferative activities. Activities were classified in two groups. The lipid-lowering and anti-atherosclerosis effects benefit from robust in vitro and in vivo data (group 1). The anticancer effects of alisols have been largely reported, but, essentially, studies using tumor cell lines and solid in vivo data are lacking (group 2). The survey shed light on the pharmacological properties of alisol triterpenoids frequently found in traditional phytomedicines.

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Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders

Cited by 19 publications

References 140 publications

rTMS ameliorates depressive‐like behaviors and regulates the gut microbiome and medium‐ and long‐chain fatty acids in mice exposed to chronic unpredictable mild stress

rTMS ameliorates depressive‐like behaviors and regulates the gut microbiome and medium‐ and long‐chain fatty acids in mice exposed to chronic unpredictable mild stress

n‐3 polyunsaturated fatty acids improve depression‐like behavior by inhibiting hippocampal neuroinflammation in mice via reducing TLR4 expression

Pharmacological Properties and Molecular Targets of Alisol Triterpenoids from Alismatis Rhizoma

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