Article
Biochemistry & Molecular Biology
Wen-Yu Zhao, Xin-Yue Zhang, Mei-Rong Zhou, Xiang-Ge Tian, Xia Lv, Hou-Li Zhang, Sa Deng, Bao-Jing Zhang, Cheng-Peng Sun, Xiao-Chi Ma
Summary: The inhibition of soluble epoxide hydrolase (sEH) is considered an effective treatment for inflammation-related diseases. Two novel sEH inhibitors were identified from Alisma orientate, providing potential leads for the development of sEH inhibitors based on protostane-type triterpenoids. In-depth studies revealed the mechanism of inhibition and highlighted the role of amino acid residue Ser374 in the activity of the inhibitors.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Cell Biology
Rebecca Charles, Philip Eaton
Summary: Cell responses to changes in redox state are mediated by reversible protein modifications, which can alter protein activities or interactions. These modifications are crucial for cells' homeostatic responses to environmental changes in redox state. The dysregulation of these redox regulatory mechanisms can contribute to pathophysiology. This review focuses on the redox control of soluble epoxide hydrolase (sEH), its different oxidative modifications, and their impact on cardiovascular physiology and disease progression during stress.
Article
Biochemistry & Molecular Biology
Wen-Yu Zhao, Juan-Juan Yan, Min Zhang, Chao Wang, Lei Feng, Xia Lv, Xiao-Kui Huo, Cheng-Peng Sun, Li-Xia Chen, Xiao-Chi Ma
Summary: The study found that the extract of Inula britanica exhibited inhibitory effects against sEH, leading to the isolation of several new compounds with significant inhibitory effects. Molecular docking and dynamics analysis suggested that compounds 10 and 13 could be potential candidates for the development of sEH inhibitors.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Nhien Nguyen, Christophe Morisseau, Dongyang Li, Jun Yang, Eileen Lam, D. Blake Woodside, Bruce D. Hammock, Pei-an Betty Shih
Summary: This study investigated the expression and activity of soluble epoxide hydrolase (sEH) in healthy women and women with anorexia nervosa. The results showed a correlation between sEH and body mass index, as well as a complex relationship with age and anxiety.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yun Ding, Svetlana Belyanskaya, Jennifer L. DeLorey, Jeffrey A. Messer, G. Joseph Franklin, Paolo A. Centrella, Barry A. Morgan, Matthew A. Clark, Steven R. Skinner, Jason W. Dodson, Peng Li, Joseph P. Marino, David I. Israel
Summary: The inhibition of soluble epoxide hydrolase (sEH) has emerged as a new approach to treat cardiovascular and respiratory diseases. Through structure-activity relationship studies, inhibitors based on 1,3,5-triazine chemotype have been discovered, leading to the identification of a clinical candidate for COPD.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Neurosciences
Dongyu Hua, Ailin Luo, Zifeng Wu, Chaoli Huang, Shan Li, Xiaolin Xu, Jiali Xu, Chun Yang, Di Wang, Cunming Liu
Summary: Anesthesia and surgery are found to cause cognitive dysfunction in patients, especially the elderly. Decreased Keap1-Nrf2 signaling in the medial prefrontal cortex, hippocampus, and liver may contribute to the onset of post-operative cognitive dysfunction (POCD). Sulforaphane shows potential in improving POCD symptoms by increasing Keap1-Nrf2 signaling.
BRAIN RESEARCH BULLETIN
(2022)
Article
Integrative & Complementary Medicine
Yan-qiong Zhang, Chun-xia Shi, Dan-mei Zhang, Lu-yi Zhang, Lu-wen Wang, Zuo-jiong Gong
Summary: The study found that sulforaphane has a protective effect on acute liver failure by reducing ferroptosis through the regulation of HDAC6 activity.
JOURNAL OF INTEGRATIVE MEDICINE-JIM
(2023)
Article
Chemistry, Medicinal
Fangyu Du, Wenjiao Sun, Christophe Morisseau, Bruce D. Hammock, Xuefei Bao, Qiu Liu, Chao Wang, Tan Zhang, Hao Yang, Jun Zhou, Wei Xiao, Zhongbo Liu, Guoliang Chen
Summary: A new series of sEH inhibitors has been designed with improved binding properties and higher inhibition potency, among which compound B401 demonstrated potential therapeutic efficacy in sepsis. Molecular docking and in vitro studies supported the favorable activity of B401, highlighting its promise as a potential treatment for sepsis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Fangyu Du, Ruolin Cao, Lu Chen, Jianwen Sun, Yajie Shi, Yang Fu, Bruce D. Hammock, Zhonghui Zheng, Zhongbo Liu, Guoliang Chen
Summary: A new memantyl urea derivative, A20, was identified as a potent sEH inhibitor that can alleviate pain and improve the health status of rats, making it a promising candidate for the treatment of neuropathic pain.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Biochemistry & Molecular Biology
Jang Hoon Kim, Yun-Chan Huh, Mok Hur, Woo Tae Park, Youn-Ho Moon, Tae Il Kim, Yong Il Kim, Seon Mi Kim, Jeonghoon Lee, Ik Soo Lee
Summary: A Glycyrrhiza uralensis extract showed potential inhibition of sEH, a target enzyme for treating inflammation and cardiovascular disease. Compounds 1-11 were isolated and tested, with compound 10 exhibiting the strongest inhibitory activity. Further evaluation in cells and animals is needed for compound 10.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Vladimir Burmistrov, Christophe Morisseau, Denis A. Babkov, Tatiana Golubeva, Dmitry Pitushkin, Elena Sokolova, Vladimir Vasipov, Yaroslav Kuznetsov, Sergey Bazhenov, Uliana S. Novoyatlova, Nikolay A. Bondarev, Ilya Manukhov, Victoria Osipova, Nadezhda Berberova, Alexander A. Spasov, Gennady M. Butov, Bruce D. Hammock
Summary: The newly synthesized inhibitor compounds showed effective inhibitory activity against inflammation and exhibited low cytotoxicity in cell assays.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Christian Grinan-Ferre, Julia Jarne-Ferrer, Aina Bellver-Sanchis, Sandra Codony, Dolors Puigoriol-Illamola, Coral Sanfeliu, Yumin Oh, Seulki Lee, Santiago Vazquez, Merce Pallas
Summary: This study found that inhibiting soluble epoxide hydrolase (sEH) is helpful in combating neuroinflammation, and it can achieve neuroprotection by modulating the eIF2 alpha/CHOP pathway, which is of potential significance for the treatment of Alzheimer's disease.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Food Science & Technology
Jiamin Dang, Shuangkui Du, Liying Wang
Summary: This study demonstrated the inhibitory properties of corn gluten peptides on soluble epoxide hydrolase (sEH). Through virtual screening and experimental testing, peptides with high inhibitory activity were identified, which may serve as candidates for novel natural inhibitors.
Article
Biochemistry & Molecular Biology
Weimin Yu, Siqi Li, Haixia Wu, Pingping Hu, Lili Chen, Chunyu Zeng, Xiaoyong Tong
Summary: The study showed that inhibiting sEH can alleviate atherosclerosis caused by endothelial Nox4 dysfunction, potentially through suppression of ER stress. Endothelial Nox4 dysfunction can lead to inflammation, and inhibiting sEH and ER stress is beneficial for alleviating atherosclerosis.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Plant Sciences
Yoo Kyong Han, Ji Sun Lee, Seo Young Yang, Ki Yong Lee, Young Ho Kim
Summary: Compounds isolated from Lycopus lucidus, such as methyl rosmarinate, martynoside, dimethyl lithospermate, and 9 '' methyl lithospermate, showed significant inhibitory activity against sEH, making them potential candidates for further development in cardiovascular disease prevention and treatment.
Article
Medicine, Research & Experimental
Ailin Luo, Zifeng Wu, Shan Li, Cindy B. McReynolds, Di Wang, Hanyu Liu, Chaoli Huang, Teng He, Xinying Zhang, Yuanyuan Wang, Cunming Liu, Bruce D. Hammock, Kenji Hashimoto, Chun Yang
Summary: This study investigated the relationship between chronic pain and depression and the potential benefits of inhibiting soluble epoxide hydrolase (sEH) signaling. The results showed that sEH expression was associated with pain and depression behaviors, and the sEH inhibitor TPPU improved the symptoms of both. The therapeutic effects of TPPU were mediated through the AHR and TSPO signaling pathways.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Neurosciences
Zhiqian Yu, Kazuko Ueno, Ryo Funayama, Mai Sakai, Naoki Nariai, Kaname Kojima, Yoshie Kikuchi, Xue Li, Chiaki Ono, Junpei Kanatani, Jiro Ono, Kazuya Iwamoto, Kenji Hashimoto, Kengo Kinoshita, Keiko Nakayama, Masao Nagasaki, Hiroaki Tomita
Summary: This study investigated the transcriptional profiles in the dorsolateral prefrontal cortex (DLPFC) to understand the clinical and biological differences of schizophrenia between males and females. The results showed that females with schizophrenia had more significantly changed genes compared to males, and these changes were mainly related to mitochondrial, ATP- and metal ion-binding relevant biological processes. The differentially expressed genes related to schizophrenia in females were involved in midbrain dopaminergic and GABA-ergic neurons and microglia. Additionally, analysis of a murine model revealed that the methylation and transcriptional expression of the ACSBG1 locus potentially impact the sex differences in gene transcription.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jie Guo, Di Qiu, Han-wen Gu, Xing-ming Wang, Kenji Hashimoto, Guang-fen Zhang, Jian-jun Yang
Summary: The perioperative administration of ketamine reduces postoperative depression and pain scores but increases the risk of adverse effects.
MOLECULAR PSYCHIATRY
(2023)
Article
Neurosciences
Xingming Wang, Akifumi Eguchi, Yong Yang, Lijia Chang, Xiayun Wan, Jiajing Shan, Youge Qu, Li Ma, Chisato Mori, Jianjun Yang, Kenji Hashimoto
Summary: Multiple sclerosis (MS) is a common demyelinating disease that affects the central nervous system. This study investigated the effects of subdiaphragmatic vagotomy (SDV) on demyelination in cuprizone (CPZ)-treated mice and found that SDV significantly improved demyelination and microglial activation in the brain. Analysis of gut microbiota composition and blood metabolites revealed that SDV also improved the abnormal levels in CPZ-treated mice. These findings suggest a link between the gut microbiota-brain axis and demyelination in the brain.
NEUROBIOLOGY OF DISEASE
(2023)
Correction
Neurosciences
X. Wang, A. Eguchi, Y. Yang, L. Chang, X. Wan, J. Shan, Y. Qu, L. Ma, C. Mori, J. Yang, K. Hashimoto
NEUROBIOLOGY OF DISEASE
(2023)
Article
Psychiatry
Youge Qu, Akifumi Eguchi, Xiayun Wan, Li Ma, Lijia Chang, Jiajing Shan, Yong Yang, Chisato Mori, Kenji Hashimoto
Summary: 3,4-Methylenedioxymethamphetamine (MDMA), the most widely used illicit compound worldwide, may contribute to stress resilience in mice subjected to chronic social defeat stress (CSDS) through the gut-microbiota-brain axis. The study found that MDMA treatment prevented the negative effects of CSDS, such as splenomegaly, anhedonia-like phenotype, and increased interleukin-6 (IL-6) levels in the mice. Gut microbiome analysis revealed differences between the saline + CSDS group and the MDMA + CSDS group, while metabolomics analysis showed altered plasma levels of N-epsilon-methyl-L-lysine in the saline + CSDS group compared to the control and MDMA + CSDS groups.
PSYCHIATRY RESEARCH
(2023)
Article
Clinical Neurology
Sai Chen, Jin-Jin Yang, Yue Zhang, Lei Lei, Di Qiu, Hui-Min Lv, Zhen-Tao Sun, Kenji Hashimoto, Jian-Jun Yang
Summary: This study investigated the effects of a single-dose of esketamine during anesthesia induction on emergence delirium (ED) in preschool children after minor surgery. The study found that the use of esketamine was associated with a higher incidence and score of ED, as well as a longer post-anesthesia care unit stay. However, there were no significant differences in other outcomes between the two groups. Therefore, the use of esketamine in preschool children for minor surgery should be noticed.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
(2023)
Review
Clinical Neurology
Kenji Hashimoto
Summary: Cognitive impairment is a common feature in various psychiatric disorders, and current therapeutic drugs do not effectively improve it. However, (R,S)-ketamine, particularly (R)-ketamine, has shown potential in improving cognitive impairment. The gut-microbiome-brain axis may also play a role in cognitive impairment in psychiatric disorders.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
(2023)
Editorial Material
Neurosciences
Kenji Hashimoto, Shigeyuki Chaki
Article
Neurosciences
Xiao-Hui Tang, Yu-Gang Diao, Zhuo-Yu Ren, Yan-Yu Zang, Guang-Fen Zhang, Xing-Ming Wang, Gui-Fang Duan, Jin-Chun Shen, Kenji Hashimoto, Zhi-Qiang Zhou, Jian-Jun Yang
Summary: Mouse models of depression-like behavior showed decreased levels of GABA and increased levels of glutamate in the hippocampus. Ketamine treatment reversed these alterations by increasing GABA levels and decreasing glutamate levels. These effects were mediated by changes in enzymes and transporters on GABAergic neurons and astrocytes.
Article
Neurosciences
Xiayun Wan, Akifumi Eguchi, Lijia Chang, Chisato Mori, Kenji Hashimoto
Summary: Patients with depression often have reduced bone mineral density. The new antidepressant arketamine has been shown to improve this reduction in mice. This study investigates the potential role of the gut microbiota and its metabolites in the beneficial effects of arketamine on behavioral and bone density changes in mice with chronic social defeat stress.
Article
Neurosciences
Yaoyu Pu, Qiuhong Wu, Qiuping Zhang, Tianwen Huang, Ji Wen, Long Wei, Kenji Hashimoto, Yi Liu
Summary: This study aimed to investigate the effect of mesenchymal stem-cell-derived microvesicles (MSC-MVs) in treating Parkinson's disease (PD). The results showed that single administration of MSC-MVs could alleviate the reduction of dopamine transporter and tyrosine hydroxylase expressions in the striatum and substantia nigra (SNr) of mice after MPTP injection. MSC-MVs also restored the abnormal gut microbiota composition induced by MPTP. Therefore, MSC-MVs have a new therapeutic potential for neurological disorders such as PD.
PSYCHOPHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Kenji Hashimoto
Summary: The COVID-19 pandemic caused by SARS-CoV-2 infection has resulted in various health issues, including persistent neurological and psychiatric symptoms known as long COVID or brain fog. The virus has been detected in the brains of patients who died from COVID-19, and Epstein-Barr virus reactivation and changes in the microbiome may contribute to long COVID symptoms. This article discusses the detrimental effects of COVID-19 on the brain and the biological mechanisms underlying long COVID, as well as potential therapeutic approaches targeting the gut-brain axis.
MOLECULAR PSYCHIATRY
(2023)
Review
Biochemistry & Molecular Biology
Kenji Hashimoto
Summary: The human body contains a diverse ecosystem of microorganisms, known as the microbiota, which includes bacteria, viruses, and fungi. Current research is focusing on the potential association between the microbiota and neuropsychiatric disorders. While the gut microbiota has received particular attention, the microbiota in other body tissues also influences the development and progression of these disorders. This article provides an overview of the role of the host microbiota in neuropsychiatric disorders and explores future research directions.
MOLECULAR PSYCHIATRY
(2023)
Article
Neurosciences
Yukihiko Shirayama, Masaaki Iwata, Kanako Miyano, Yuki Hirose, Yasunori Oda, Yuko Fujita, Kenji Hashimoto
Summary: Beta-hydroxybutyrate (BHB) has shown antidepressant-like effects in a rat model of depression. It activates the BDNF-TrkB signaling pathway and AMPA receptors, and is associated with the prefrontal cortex, hippocampus, and basolateral region of amygdala.