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Article ; Online: Bullatine A exerts anti-inflammatory effects by inhibiting the ROS/JNK/NF-κB pathway and attenuating systemic inflammatory responses in mice

Liu, Shuhan / Che, Na / Ou, Wen / Yan, Meichen / Liao, Yajin / Cheng, Yong

Pharmaceutical Biology. 2022 Dec. 31, v. 60, no. 1 p.1840-1849

2022

Abstract: Aconiti brachypodi Radix (Xue-shang-yi-zhi-hao) is a traditional Chinese herbal medicine that is capable of anti-analgesic and anti-inflammatory effects. Bullatine A (BA) is one of the major active ingredients of this plant, and most of the previous ... ...

Abstract	Aconiti brachypodi Radix (Xue-shang-yi-zhi-hao) is a traditional Chinese herbal medicine that is capable of anti-analgesic and anti-inflammatory effects. Bullatine A (BA) is one of the major active ingredients of this plant, and most of the previous studies reported that it has anti-analgesic effects. However, the mechanism of BA anti-inflammatory remains unclear. This study investigates the anti-inflammatory activities of BA, both in vitro and in vivo, and elucidates its mechanism. In vitro, BA (10, 20, 40 and 80 μM) was added to 1 µg/mL of lipopolysaccharide (LPS)-activated microglia BV2 cells and immortalized murine bone marrow-derived macrophages, respectively. After 6 h, the mRNA and protein levels of inflammatory factors were determined by real-time quantitative PCR and western blotting. In vivo, C57BL/6 mice were randomly divided into control, model (5 mg/kg dose of LPS) and treated groups (LPS with 5, 10 or 20 mg/kg dose of BA) to evaluate the anti-inflammatory efficacy of BA. BA significantly inhibited LPS-induced expression of inflammatory factors, such as IL-1β, IL-6, TNF-α, inducible nitric oxide synthase (iNOS) and COX-2. Further investigations showed that BA reduced the translocation of NF-κB p65 (38.5%, p < 0.01). BA also reduced the phosphorylation of c-Jun N-terminal kinase (JNK) (11.2%, p < 0.05) and reactive oxygen species (ROS) generation (24.2%, p < 0.01). Furthermore, BA treatment attenuated the LPS-primed inflammatory response and liver and lung damage in vivo. BA can inhibit the inflammatory response in part through the ROS/JNK/NF-κB signalling pathway, providing a theoretical basis for the clinical application of BA in the treatment of periphery inflammatory diseases.
Keywords	Oriental traditional medicine ; inducible nitric oxide synthase ; inflammation ; interleukin-6 ; lipopolysaccharides ; liver ; lungs ; macrophages ; mice ; mitogen-activated protein kinase ; models ; neuroglia ; phosphorylation ; quantitative polymerase chain reaction ; reactive oxygen species ; Aconiti brachypodi Radix ; LPS ; BV-2 ; macrophage ; MAPKs
Language	English
Dates of publication	2022-1231
Size	p. 1840-1849.
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	1440131-9
ISSN	1744-5116 ; 1388-0209
ISSN (online)	1744-5116
ISSN	1388-0209
DOI	10.1080/13880209.2022.2121410
Database	NAL-Catalogue (AGRICOLA)

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Article: The Molecular Determinants of Mitochondrial Membrane Contact With ER, Lysosomes and Peroxisomes in Neuronal Physiology and Pathology.

Liao, Yajin / Dong, Yuan / Cheng, Jinbo

Frontiers in cellular neuroscience

2020 Volume 14, Page(s) 194

Abstract: Membrane tethering is an important communication method for membrane-packaged organelles. Mitochondria are organelles with a bilayer membrane, and the membrane contact between mitochondria and other organelles is indispensable for maintaining cellular ... ...

Abstract	Membrane tethering is an important communication method for membrane-packaged organelles. Mitochondria are organelles with a bilayer membrane, and the membrane contact between mitochondria and other organelles is indispensable for maintaining cellular homeostasis. Increased levels of molecular determinants that mediate the membrane contact between mitochondria and other organelles, and their functions, have been revealed in recent years. In this review article, we aim to summarize the findings on the tethering between mitochondria and other organelles in physiological or pathological conditions, and discuss their roles in cellular homeostasis, neural activity, and neurodegenerative diseases.
Language	English
Publishing date	2020-08-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2020.00194
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Article ; Online: Bullatine A exerts anti-inflammatory effects by inhibiting the ROS/JNK/NF-κB pathway and attenuating systemic inflammatory responses in mice.

Liu, Shuhan / Che, Na / Ou, Wen / Yan, Meichen / Liao, Yajin / Cheng, Yong

Pharmaceutical biology

2022 Volume 60, Issue 1, Page(s) 1840–1849

Abstract: Context: Aconiti brachypodi: Objective: This study investigates the anti-inflammatory activities of BA, both : Materials and methods: In vitro: Results: BA significantly inhibited LPS-induced expression of inflammatory factors, such as IL-1β, ... ...

Abstract	Context: Aconiti brachypodi Objective: This study investigates the anti-inflammatory activities of BA, both Materials and methods: In vitro Results: BA significantly inhibited LPS-induced expression of inflammatory factors, such as IL-1β, IL-6, TNF-α, inducible nitric oxide synthase (iNOS) and COX-2. Further investigations showed that BA reduced the translocation of NF-κB p65 (38.5%, Conclusions: BA can inhibit the inflammatory response in part through the ROS/JNK/NF-κB signalling pathway, providing a theoretical basis for the clinical application of BA in the treatment of periphery inflammatory diseases.
MeSH term(s)	Alkaloids ; Animals ; Anti-Inflammatory Agents/therapeutic use ; Cyclooxygenase 2/metabolism ; Diterpenes ; Drugs, Chinese Herbal/therapeutic use ; Inflammation/metabolism ; Interleukin-6/metabolism ; JNK Mitogen-Activated Protein Kinases/metabolism ; Lipopolysaccharides/toxicity ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type II/genetics ; RNA, Messenger ; Reactive Oxygen Species/metabolism ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Alkaloids ; Anti-Inflammatory Agents ; Diterpenes ; Drugs, Chinese Herbal ; Interleukin-6 ; Lipopolysaccharides ; NF-kappa B ; RNA, Messenger ; Reactive Oxygen Species ; Tumor Necrosis Factor-alpha ; bullatine A ; Nitric Oxide (31C4KY9ESH) ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Cyclooxygenase 2 (EC 1.14.99.1) ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2022-10-06
Publishing country	England
Document type	Journal Article
ZDB-ID	1440131-9
ISSN	1744-5116 ; 1388-0209
ISSN (online)	1744-5116
ISSN	1388-0209
DOI	10.1080/13880209.2022.2121410
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Associations of Sleep Disorders With Depressive Symptoms in Early and Prodromal Parkinson's Disease.

Ma, Jiangnan / Dou, Kaixin / Liu, Ruize / Liao, Yajin / Yuan, Zengqiang / Xie, Anmu

Frontiers in aging neuroscience

2022 Volume 14, Page(s) 898149

Abstract: Background: Non-motor symptoms, including sleep disorders and depression, are common in Parkinson's disease (PD). The purpose of our study is to explore the effect of sleep disorders, including the probable rapid eye movement (REM) sleep behavior ... ...

Abstract	Background: Non-motor symptoms, including sleep disorders and depression, are common in Parkinson's disease (PD). The purpose of our study is to explore the effect of sleep disorders, including the probable rapid eye movement (REM) sleep behavior disorder (pRBD) and the daytime sleepiness, on depressive symptoms in patients with early and prodromal PD. Methods: A total of 683 participants who obtained from the Parkinson Progression Markers Initiative (PPMI) were included, consisting of 423 individuals with early PD, 64 individuals with prodromal PD, and 196 healthy controls (HCs), who were followed up to 5 years from baseline. Multiple linear regression models and linear mixed-effects models were conducted to explore the relationship between sleep disorders and depression at baseline and longitudinally, respectively. Multiple linear regression models were used to further investigate the association between the change rates of daytime sleepiness score and depression-related score. Mediation analyses were also performed. Results: At baseline analysis, individuals with early and prodromal PD, who had higher RBD screening questionnaire (RBDSQ) score, or who were considered as pRBD, or who manifested specific behaviors of RBD (things falling down when sleep or disturbance of sleep), showed significantly the higher score of depression-related questionnaires. Our 5-year follow-up study showed that sleep disorders, including pRBD and daytime sleepiness, were associated with the increased depressive-related score in individuals with early and prodromal PD. Interestingly, we also found that the increased possibilities of daytime sleepiness were associated with depressive-related score. Finally, mediation analysis demonstrated that the relationship between RBD and depressive symptoms was partially mediated by autonomic symptoms, such as postural hypertension, salivation, dysphagia, and constipation. Conclusion: Our study shows that sleep disorders, including pRBD and daytime sleepiness, are associated with depression at baseline and longitudinally, which is partially mediated by the autonomic dysfunction in early and prodromal PD, with an implication that sleep management is of great value for disease surveillance.
Language	English
Publishing date	2022-06-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2022.898149
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Article ; Online: Bergapten alleviates depression-like behavior by inhibiting cyclooxygenase 2 activity and NF-κB/MAPK signaling pathway in microglia.

Yan, Meichen / Bo, Xuena / Zhang, Jingdan / Liu, Shuhan / Li, Xiaoheng / Liao, Yajin / Liu, Qingshan / Cheng, Yong / Cheng, Jinbo

Experimental neurology

2023 Volume 365, Page(s) 114426

Abstract: Major depressive disorder (MDD) is a common psychiatric disorder that severely affects human life and health. However, the pathological mechanism of MDD is unclear, and effective treatment strategies are urgently needed. Microglia-mediated ... ...

Abstract	Major depressive disorder (MDD) is a common psychiatric disorder that severely affects human life and health. However, the pathological mechanism of MDD is unclear, and effective treatment strategies are urgently needed. Microglia-mediated neuroinflammation is closely associated with the pathophysiology of depression. Bergapten (BG) is a natural pharmaceutical monomer with anti-inflammatory effects; however, its role in neuroinflammation and depression remains unclear. In this study, we employed a lipopolysaccharide (LPS) injection-induced acute depression mouse model, and found that treatment with BG significantly alleviated LPS-induced depression-like behavior in mice. BG administration largely decreased the increase in microglial numbers and rescued the microglial morphological changes induced by LPS injection. Furthermore, transcriptomic changes revealed a protective role of BG in the hippocampus of mice. Mechanistically, we found that BG directly inhibited cyclooxygenase 2 (COX2) activity, and suppressed nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in microglia. Together, these results highlight the important role of BG in microglial activation, neuroinflammation, and depression-like behavior, thus providing a new candidate drug for depression treatment.
MeSH term(s)	Animals ; Humans ; Mice ; 5-Methoxypsoralen/pharmacology ; Cyclooxygenase 2/metabolism ; Depression/drug therapy ; Depression/chemically induced ; Depressive Disorder, Major/metabolism ; Lipopolysaccharides/toxicity ; Microglia/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Neuroinflammatory Diseases ; NF-kappa B ; Signal Transduction
Chemical Substances	5-Methoxypsoralen (4FVK84C92X) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Lipopolysaccharides ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; NF-kappa B
Language	English
Publishing date	2023-04-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207148-4
ISSN	1090-2430 ; 0014-4886
ISSN (online)	1090-2430
ISSN	0014-4886
DOI	10.1016/j.expneurol.2023.114426
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: OTUB1/NDUFS2 axis promotes pancreatic tumorigenesis through protecting against mitochondrial cell death.

Huang, Xiao-Dong / Du, Li / Cheng, Xiao-Chen / Lu, Yu-Xin / Liu, Qiao-Wei / Wang, Yi-Wu / Liao, Ya-Jin / Lin, Dong-Dong / Xiao, Feng-Jun

Cell death discovery

2024 Volume 10, Issue 1, Page(s) 190

Abstract: Pancreatic cancer is one of the most fatal cancers in the world. A growing number of studies have begun to demonstrate that mitochondria play a key role in tumorigenesis. Our previous study reveals that NDUFS2 (NADH: ubiquinone oxidoreductase core ... ...

Abstract	Pancreatic cancer is one of the most fatal cancers in the world. A growing number of studies have begun to demonstrate that mitochondria play a key role in tumorigenesis. Our previous study reveals that NDUFS2 (NADH: ubiquinone oxidoreductase core subunit S2), a core subunit of the mitochondrial respiratory chain complex I, is upregulated in Pancreatic adenocarcinoma (PAAD). However, its role in the development of PAAD remains unknown. Here, we showed that NDUFS2 played a critical role in the survival, proliferation and migration of pancreatic cancer cells by inhibiting mitochondrial cell death. Additionally, protein mass spectrometry indicated that the NDUFS2 was interacted with a deubiquitinase, OTUB1. Overexpression of OTUB1 increased NDUFS2 expression at the protein level, while knockdown of OTUB1 restored the effects in vitro. Accordingly, overexpression and knockdown of OTUB1 phenocopied those of NDUFS2 in pancreatic cancer cells, respectively. Mechanically, NDUFS2 was deubiquitinated by OTUB1 via K48-linked polyubiquitin chains, resulted in an elevated protein stability of NDUFS2. Moreover, the growth of OTUB1-overexpressed pancreatic cancer xenograft tumor was promoted in vivo, while the OTUB1-silenced pancreatic cancer xenograft tumor was inhibited in vivo. In conclusion, we revealed that OTUB1 increased the stability of NDUFS2 in PAAD by deubiquitylation and this axis plays a pivotal role in pancreatic cancer tumorigenesis and development.
Language	English
Publishing date	2024-04-23
Publishing country	United States
Document type	Journal Article
ISSN	2058-7716
ISSN	2058-7716
DOI	10.1038/s41420-024-01948-x
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Article: Mangiferin Alleviates Postpartum Depression-Like Behaviors by Inhibiting MAPK Signaling in Microglia.

Yan, Meichen / Bo, Xuena / Zhang, Xinchao / Zhang, Jingdan / Liao, Yajin / Zhang, Haiyan / Cheng, Yong / Guo, Junxia / Cheng, Jinbo

Frontiers in pharmacology

2022 Volume 13, Page(s) 840567

Abstract: Postpartum depression (PPD), a severe mental health disorder, is closely associated with decreased gonadal hormone levels during the postpartum period. Mangiferin (MGF) possesses a wide range of pharmacological activities, including anti-inflammation. ... ...

Abstract	Postpartum depression (PPD), a severe mental health disorder, is closely associated with decreased gonadal hormone levels during the postpartum period. Mangiferin (MGF) possesses a wide range of pharmacological activities, including anti-inflammation. Growing evidence has suggested that neuroinflammation is involved in the development of depression. However, the role of MGF in the development of PPD is largely unknown. In the present study, by establishing a hormone-simulated pregnancy PPD mouse model, we found that the administration of MGF significantly alleviated PPD-like behaviors. Mechanistically, MGF treatment inhibited microglial activation and neuroinflammation. Moreover, we found that MGF treatment inhibited mitogen-activated protein kinase (MAPK) signaling
Language	English
Publishing date	2022-06-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.840567
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Article: The XPO1 Inhibitor KPT-8602 Ameliorates Parkinson's Disease by Inhibiting the NF-κB/NLRP3 Pathway.

Liu, Shuhan / Wang, Shengxiang / Gu, Runze / Che, Na / Wang, Jing / Cheng, Jinbo / Yuan, Zengqiang / Cheng, Yong / Liao, Yajin

Frontiers in pharmacology

2022 Volume 13, Page(s) 847605

Abstract: Exportin 1 (XPO1) is an important transport receptor that mediates the nuclear export of various proteins and RNA. KPT-8602 is a second-generation inhibitor of XPO1, demonstrating the lowest level of side effects, and is currently in clinical trials for ... ...

Abstract	Exportin 1 (XPO1) is an important transport receptor that mediates the nuclear export of various proteins and RNA. KPT-8602 is a second-generation inhibitor of XPO1, demonstrating the lowest level of side effects, and is currently in clinical trials for the treatment of cancers. Previous studies suggest that several first-generation inhibitors of XPO1 demonstrate anti-inflammation activities, indicating the application of this drug in inflammation-related diseases. In this study, our results suggested the potent anti-inflammatory effect of KPT-8602
Language	English
Publishing date	2022-06-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.847605
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Article: Hematopoietic Cell Kinase (HCK) Is Essential for NLRP3 Inflammasome Activation and Lipopolysaccharide-Induced Inflammatory Response

Kong, Xiangxi / Liao, Yajin / Zhou, Lujun / Zhang, Ying / Cheng, Jinbo / Yuan, Zengqiang / Wang, Shukun

Frontiers in pharmacology

2020 Volume 11, Page(s) 581011

Abstract: Activation of the NLRP3 inflammasome results in caspase 1 cleavage, which subsequently leads to IL- ... ...

Abstract	Activation of the NLRP3 inflammasome results in caspase 1 cleavage, which subsequently leads to IL-1
Language	English
Publishing date	2020-09-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.581011
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Article ; Online: The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders.

Liao, Yajin / Dong, Yuan / Cheng, Jinbo

International journal of molecular sciences

2017 Volume 18, Issue 2

Abstract: The mitochondrial calcium uniporter (MCU)-a calcium uniporter on the inner membrane of mitochondria-controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine ... ...

Abstract	The mitochondrial calcium uniporter (MCU)-a calcium uniporter on the inner membrane of mitochondria-controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders.
MeSH term(s)	Adenosine Triphosphate/biosynthesis ; Animals ; Biological Transport ; Calcium/metabolism ; Calcium Channel Blockers/pharmacology ; Calcium Channel Blockers/therapeutic use ; Calcium Channels/metabolism ; Calcium Signaling ; Humans ; Inflammation/metabolism ; Iron Overload/metabolism ; Iron Overload/pathology ; Mitochondria/drug effects ; Mitochondria/metabolism ; Molecular Targeted Therapy ; Neurodegenerative Diseases/drug therapy ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Neurons/metabolism ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Signal Transduction
Chemical Substances	Calcium Channel Blockers ; Calcium Channels ; Reactive Oxygen Species ; mitochondrial calcium uniporter ; Adenosine Triphosphate (8L70Q75FXE) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2017-02-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms18020248
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