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1.
Mol Neurobiol ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38356095

RESUMO

Exosomes, as membranous vesicles generated by multiple cell types and secreted to extracellular space, play a crucial role in a range of brain injury-related brain disorders by transporting diverse proteins, RNA, DNA fragments, and other functional substances. The nervous system's pathogenic mechanisms are complicated, involving pathological processes like as inflammation, apoptosis, oxidative stress, and autophagy, all of which result in blood-brain barrier damage, cognitive impairment, and even loss of normal motor function. Exosomes have been linked to the incidence and progression of brain disorders in recent research. As a result, a thorough knowledge of the interaction between exosomes and brain diseases may lead to the development of more effective therapeutic techniques that may be implemented in the clinic. The potential role of exosomes in brain diseases and the crosstalk between exosomes and other pathogenic processes were discussed in this paper. Simultaneously, we noted the delicate events in which exosomes as a media allow the brain to communicate with other tissues and organs in physiology and disease, and compiled a list of natural compounds that modulate exosomes, in order to further improve our understanding of exosomes and propose new ideas for treating brain disorders.

2.
Metab Brain Dis ; 38(7): 2443-2456, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37382831

RESUMO

Neuroinflammation is a critical feature in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Hesperetin can exert anti-inflammatory, antioxidant and other neuroprotective effects. In this study, the scopolamine (SCOP)-induced cognitive dysfunction in mice model was used to evaluate the neuroprotective effects of hesperetin. Behavioral tests (Morris water maze, open field, and novel object recognition tests) were conducted to evaluate the effect of hesperetin on cognitive dysfunction behaviors. Nissl staining and Immunofluorescence were used to evaluate hippocampal neuronal damage and microglial activation in mice. The levels of proinflammatory factors, oxidant stress, and the cholinergic neurotransmitter were detected by real-time quantitative fluorescence PCR (RT-qPCR) or biochemical reagent kits. Western blotting was used to detect the relative protein expression of the sirtuin 6 (SIRT6) / NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway. Results showed that hesperetin could ameliorate SCOP-induced cognitive impairment and neuronal damage, and regulate the levels of cholinergic neurotransmitters in the hippocampal of AD mice. Hesperetin could also enhance antioxidant defense by regulating the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). Hesperetin exerted anti-neuroinflammation effects through inhibiting of microglia activation and down-regulating the mRNA transcript levels of inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Meanwhile, hesperetin could attenuate the expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), thioredoxin-interacting protein (TXNIP), and caspase-1 p20 and upregulate the expression of SIRT6 in SCOP-induced mice. Overall, our study suggested that hesperetin might ameliorate SCOP-induced cognitive dysfunction by improving cholinergic system dysfunction and suppressing oxidative stress and attenuating neuroinflammation via SIRT6/NLRP3 pathway in mice.


Assuntos
Disfunção Cognitiva , Fármacos Neuroprotetores , Sirtuínas , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Antioxidantes , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Escopolamina , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico
3.
Artigo em Inglês | MEDLINE | ID: mdl-36310618

RESUMO

Objective: Traditional Chinese medicine formula Kai-Xin-San (KXS) is used to treat psychiatric disorders, especially in anxiety and depression. However, the precise molecular mechanism of action remains unclear. In this study, we investigated the antidepressant effect of KXS on inhibiting inflammation and oxidative stress in corticosterone (CORT)-induced depression. Methods: The therapeutic efficacy of KXS was evaluated in a mouse model of depression induced by CORT. Behavioral tests were conducted to evaluate the effectiveness of KXS in treating depressive-like behavior. Nissl staining and ß-galactosidase staining were used to assess the effects of KXS on neuronal injury in depressed mice. To screen key potential therapeutic targets of KXS, transcriptome sequences and data analysis were performed. Then, Iba1 immunofluorescence staining and their relative inflammatory factors mRNA expression were conducted to assess the effect of KXS in inhibiting microglial inflammation activation response. Concurrently, the measurement of 4-Hydroxynonenal (4-HNE) immunohistochemistry staining, malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were performed to evaluate the effect of KXS on anti-oxidative stress of depression in vivo. Besides, nitric oxide (NO), relative inflammatory factors mRNA expression, JC-1 staining, and ROS were used to evaluate the effect of KXS by lipopolysaccharide (LPS)/interferon-gamma (IFNγ)-induced BV2 cells. Results: KXS significantly relieved the depressive-like symptoms induced by CORT, as well as ameliorating the neuronal damage, which decreased microglia inflammatory activation response of IL-1ß, IL-6, and tumor necrosis factor α (TNFα) in vivo or in vitro too. Transcriptome Sequencing and Data Analysis showed that KXS mainly by regulating immune system and transduction pathways decreased CORT-induced depression in mice. And showed that there were 19 Principal components and 10 genes in the main regulatory position with the strongest correlation in depression mice. Meanwhile, KXS effectively decreased senescence, the expression of 4-HNE, MDA content, and the production of ROS, while increasing the SOD activity in CORT-induced mice. Besides, KXS significantly reversed the mitochondrial membrane potential loss and excessive ROS production in LPS/IFNγ-induced BV2 cells. Conclusion: Our research suggested that KXS might protect depressed mice against CORT-induced neuronal injury by inhibiting microglia activation and oxidative stress.

4.
Drug Des Devel Ther ; 16: 2981-2993, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105321

RESUMO

Introduction: Breast cancer (BC) is the leading female malignancy, with one million new cases diagnosed worldwide per year. However, the current treatment options for BC patients have difficulty achieving satisfactory efficacy. Ferroptosis is a new mode of regulated cell death that plays a key role in the inhibition of tumorigenesis. Levistilide A (LA), as an active compound extracted from Chuanxiong Rhizoma, might prevent the development of tumors by regulating the critical cellular processes of ferroptosis. Methods: In this study, the underlying mechanisms of LA on ferroptosis in BC were explored in vitro. The effect of LA on the viability and mitochondrial function of BC cells was determined. Moreover, the effect of LA on the expression levels of key molecules involved in ferroptosis and the nuclear factor erythroid-2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway was evaluated. Results: LA significantly reduced cell viability and damaged the mitochondrial structure and function of BC cells in a dose-dependent manner. Furthermore, LA treatment markedly enhanced reactive oxygen species (ROS)-induced ferroptosis by activating the Nrf2/HO-1 signaling pathway. Conclusion: These findings suggest that LA may be a potential lead compound for breast cancer therapy by inducing ferroptosis in tumor cells.


Assuntos
Neoplasias da Mama , Ferroptose , Neoplasias da Mama/tratamento farmacológico , Feminino , Heme Oxigenase-1/metabolismo , Compostos Heterocíclicos de Anel em Ponte , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais
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