scholarly journals PACAP and VIP Modulate LPS-induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells

2021 ◽  
Author(s):  
Jocelyn Karunia ◽  
Aram Niaz ◽  
Mawj Mandwie ◽  
Sarah Thomas Broome ◽  
Kevin A Keay ◽  
...  
Keyword(s):  
Cell Migration ◽  
Microglial Activation ◽  
Activation Markers ◽  
Bv2 Cells ◽  
Bv2 Microglia ◽  
Cell Subpopulations ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Phenotypic Shift ◽  
Bv2 Microglial Cells

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two structurally-related immunosuppressive peptides. However, the underlying mechanisms through which these peptides regulate microglial activity are not fully understood. Using lipopolysaccharide (LPS) to induce an inflammatory challenge, we tested whether PACAP or VIP differentially affected microglial activation, morphology and cell migration. We found that both peptides attenuated LPS-induced expression of the microglial activation markers Iba1 and iNOS (###p<0.001), as well as the pro-inflammatory mediators IL-1β, IL-6, Itgam and CD68 (###p<0.001). In contrast, treatment with PACAP or VIP exerted distinct effects on microglial morphology and migration. PACAP reversed LPS-induced soma enlargement and increased the percentage of small-sized, rounded cells (54.09% vs 12.05% in LPS-treated cells), whereas VIP promoted a phenotypic shift towards cell subpopulations with mid-sized, spindle-shaped soma (48.41% vs 31.36% in LPS-treated). Additionally, PACAP was more efficient than VIP in restoring LPS-induced impairment of cell migration and the expression of urokinase plasminogen activator (uPA) in BV2 cells compared with VIP. These results suggest that whilst both PACAP and VIP exert similar immunosuppressive effects in activated BV2 microglia, each peptide triggers distinctive shifts towards phenotypes of differing morphologies and with differing migration capacities.

scholarly journals PACAP and VIP Modulate LPS-Induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells

2021 ◽  
Vol 22 (20) ◽  
pp. 10947
Author(s):  
Jocelyn Karunia ◽  
Aram Niaz ◽  
Mawj Mandwie ◽  
Sarah Thomas Broome ◽  
Kevin A. Keay ◽  
...  
Keyword(s):  
Cell Migration ◽  
Microglial Activation ◽  
Activation Markers ◽  
Bv2 Cells ◽  
Bv2 Microglia ◽  
Cell Subpopulations ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Phenotypic Shift ◽  
Bv2 Microglial Cells

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two structurally related immunosuppressive peptides. However, the underlying mechanisms through which these peptides regulate microglial activity are not fully understood. Using lipopolysaccharide (LPS) to induce an inflammatory challenge, we tested whether PACAP or VIP differentially affected microglial activation, morphology and cell migration. We found that both peptides attenuated LPS-induced expression of the microglial activation markers Iba1 and iNOS (### p < 0.001), as well as the pro-inflammatory mediators IL-1β, IL-6, Itgam and CD68 (### p < 0.001). In contrast, treatment with PACAP or VIP exerted distinct effects on microglial morphology and migration. PACAP reversed LPS-induced soma enlargement and increased the percentage of small-sized, rounded cells (54.09% vs. 12.05% in LPS-treated cells), whereas VIP promoted a phenotypic shift towards cell subpopulations with mid-sized, spindle-shaped somata (48.41% vs. 31.36% in LPS-treated cells). Additionally, PACAP was more efficient than VIP in restoring LPS-induced impairment of cell migration and the expression of urokinase plasminogen activator (uPA) in BV2 cells compared with VIP. These results suggest that whilst both PACAP and VIP exert similar immunosuppressive effects in activated BV2 microglia, each peptide triggers distinctive shifts towards phenotypes of differing morphologies and with differing migration capacities.

scholarly journals TGF-β-Induced CCR8 Promoted Macrophage Transdifferentiation into Myofibroblast-Like Cells

2021 ◽  
Author(s):  
Haijun Liu ◽  
Qingzhou Guan ◽  
Peng Zhao ◽  
Jiansheng Li
Keyword(s):  
Cell Migration ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Activation ◽  
The Body ◽  
Dependent Manner ◽  
Whole Process ◽  
Autophagy Inhibitor ◽  
Underlying Mechanisms ◽  
And Migration

Abstract Background: Idiopathic pulmonary fibrosis (IPF) is an unknown interstitial disease characterized by tissue fibrosis for which there currently is no effective treatment. Macrophages, as the main immune cells in lung tissue, are involved in the whole process of pulmonary fibrosis. In recent years, intercellular transformation has been widespread concerned in pulmonary fibrosis researchers. The macrophages which have flexible heterogeneity and plasticity participate in different physiological processes of the body. Cell chemokine receptor 8 (CCR8) expressed in a variety of cells plays a significant chemotactic role in inducing cell activation and migration. And it could also promote the differentiation of macrophages under certain environmental conditions. The current study is intended to explore the role of CCR8 in macrophage transdifferentiation into myofibroblast cells in idiopathic pulmonary fibrosis.Methods: We conducted experiments using Ccr8-specific small interfering RNA (siRNA), autophagy inhibitor (3-methyladenine,3-MA) and agonist (rapamycin) to explore the underlying mechanisms of macrophage transdifferentiation into myofibroblast cells in TGF-β induced pulmonary fibrosis. Results: The results indicated that TGF-β treatment increased the CCR8 protein level in a time- and a dose-dependent manner in MH-S, as well as macrophage transdifferentiation-related markers, including Vimentin, Collagen 1, and a-SMA, and cell migration. In addition, levels of autophagy were enhanced in macrophages treated with TGF-β. We found that 3-MA, an autophagy inhibitor decreased the expression levels of macrophage transdifferentiation-related markers and attenuated the cell migration. Furthermore, inhibition of CCR8 through using Ccr8-specific siRNA reduced the levels of autophagy and macrophage transdifferentiation-related markers, and inhibited the cell migration. Enhancing autophagy with rapamycin attenuated the inhibition effect of Ccr8-specific siRNA on macrophage migration and the increase of myofibroblast marker proteins.Conclusions: Our findings showed that the macrophages exposed to TGF-β had the potential to transdifferentiate into myofibroblasts and CCR8 was involved in the process. The effect of CCR8 in TGF-β-induced macrophage transdifferentiation occurs mainly through autophagy. Targeting the CCR8 may become a novel therapeutic strategy for the treatment of IPF.

scholarly journals Suppression of LPS-Induced Inflammation and Cell Migration by Azelastine through Inhibition of JNK/NF-κB Pathway in BV2 Microglial Cells

2021 ◽  
Vol 22 (16) ◽  
pp. 9061
Author(s):  
Phuong Linh Nguyen ◽  
Bich Phuong Bui ◽  
Men Thi Hoai Duong ◽  
Kyeong Lee ◽  
Hee-Chul Ahn ◽  
...  
Keyword(s):  
Cell Migration ◽  
Inflammatory Mediators ◽  
Nuclear Translocation ◽  
Drug Repurposing ◽  
Microglial Cells ◽  
Potential Candidate ◽  
Jnk Pathway ◽  
Bv2 Cells ◽  
Parkinson’S Diseases ◽  
Bv2 Microglial Cells

The c-Jun N-terminal kinases (JNKs) are implicated in many neuropathological conditions, including neurodegenerative diseases. To explore potential JNK3 inhibitors from the U.S. Food and Drug Administration-approved drug library, we performed structure-based virtual screening and identified azelastine (Aze) as one of the candidates. NMR spectroscopy indicated its direct binding to the ATP-binding site of JNK3, validating our observations. Although the antihistamine effect of Aze is well documented, the involvement of the JNK pathway in its action remains to be elucidated. This study investigated the effects of Aze on lipopolysaccharide (LPS)-induced JNK phosphorylation, pro-inflammatory mediators, and cell migration in BV2 microglial cells. Aze was found to inhibit the LPS-induced phosphorylation of JNK and c-Jun. It also inhibited the LPS-induced production of pro-inflammatory mediators, including interleukin-6, tumor necrosis factor-α, and nitric oxide. Wound healing and transwell migration assays indicated that Aze attenuated LPS-induced BV2 cell migration. Furthermore, Aze inhibited LPS-induced IκB phosphorylation, thereby suppressing nuclear translocation of NF-κB. Collectively, our data demonstrate that Aze exerts anti-inflammatory and anti-migratory effects through inhibition of the JNK/NF-κB pathway in BV2 cells. Based on our findings, Aze may be a potential candidate for drug repurposing to mitigate neuroinflammation in various neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases.

scholarly journals Aquilariae Lignum Methylene Chloride Fraction Attenuates IL-1β-Driven Neuroinflammation in BV2 Microglial Cells

2020 ◽  
Vol 21 (15) ◽  
pp. 5465
Author(s):  
Jin-Seok Lee ◽  
Yoo-Jin Jeon ◽  
Ji-Yun Kang ◽  
Sam-Keun Lee ◽  
Hwa-Dong Lee ◽  
...  
Keyword(s):  
Methylene Chloride ◽  
Underlying Mechanism ◽  
Microglial Cells ◽  
Bv2 Cells ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Bv2 Microglial Cells ◽  
Methylene Chloride Fraction

Microglial hyperactivation and neuroinflammation are known to induce neuronal death, which is one of the main causes of neurodegenerative disorders. We previously found that Aquilariae Lignum extract attenuated both neuronal excitotoxicity and neuroinflammation in vivo and in vitro. For further analysis, we extracted the methylene chloride fraction of Aquilariae Lignum to determine the bioactive compounds. In this study, we investigated the anti-neuroinflammatory effects and underlying mechanisms of the Aquilariae Lignum fraction (ALF) using lipopolysaccharide (LPS)-stimulated BV2 microglial cells. BV2 cells were pretreated with ALF (0.5, 1, and 2.5 μg/mL) before treatment with LPS (1 μg/mL). Pretreatment with ALF significantly attenuated the LPS-induced overproductions of nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and interleukin (IL)-1β. These anti-inflammatory effects were supported by ALF-mediated modulation of the nuclear factor-kappa B (NF-κB) pathway. Furthermore, ALF exerted strong anti-inflammasome effects, as shown by IL-1β-specific inhibitory activity, but not activity against tumor necrosis factor (TNF)-α, along with inhibition of caspase-1 activity and NACHT, LRR, and PYD domain-containing protein 3 (NLRP3)-related molecules. These results indicate the potent anti-neuroinflammatory activity of ALF and that its underlying mechanism may involve the regulation of NLRP3 inflammasome-derived neuroinflammation in microglial cells.

scholarly journals Gualou Guizhi Granule Suppresses LPS-induced Inflammatory Response of Microglia and Protects Against Microglial-Mediated Neurotoxicity in HT22 via Akt/NF-κB Signaling Pathways

2020 ◽  
Author(s):  
Yuqin Zhang ◽  
Yaojun Liu ◽  
Liming Fan ◽  
Lihong Nan ◽  
Wei Xu ◽  
...  
Keyword(s):  
Conditioned Medium ◽  
Neuronal Apoptosis ◽  
Neuroprotective Effect ◽  
Microglial Cells ◽  
Nuclear Factor ◽  
Ht22 Cells ◽  
Nuclear Factor Kappa ◽  
Bv2 Cells ◽  
Bv2 Microglia ◽  
Bv2 Microglial Cells

Abstract Background Neuroinflammation plays a crucial part in the commence and advancement of ischemic stroke. Gualou Guizhi Granule (GLGZG) is known to exhibit well neuroprotective effect, but it is not known whether GLGZG can regulate inflammatory process at the cellular level in BV2 microglia cells and protect against microglial-mediated neurotoxicity in neurons. Herein, we aimed to investigate the anti-inflammatory effects of GLGZG on BV2 microglia cells and protection against microglial-mediated neurotoxicity in neurons. Methods Cell model of neuroinflammation was constructed by lipopolysaccharide (LPS) to observe the effect of GLGZG in the presence or absence of GLGZG. The production of nitric oxide (NO), inflammatory mediators were detected. Moreover, potential mechanisms associated with anti-inflammatory effect, such as inhibition of microglial activation, the nuclear factor kappa B (NF-κB) were also investigated. In addition, to prove whether GLGZG protects against microglial-mediated neurotoxicity, neuronal HT22 cells were cultured in conditioned medium. And cell survivability, neuronal apoptosis of HT22 were evaluated. Results It was found that a main regulator of inflammation, NO, is suppressed by GLGZG in BV2 microglial cells. Moreover, GLGZG dose-dependently decreased the mRNA and protein levels of inducible NO synthase (iNOS) in LPS-stimulated BV2 cells. Additionally, GLGZG inhibited the expression and secretion of proinflammatory cytokines in BV2 microglial cells. And, GLGZG inhibited LPS-activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in BV2 microglial cells at the intracellular level. GLGZG negatively affected Akt phosphorylation: phosphorylated forms of Akt decreased. To check whether GLGZG protects against microglial-mediated neurotoxicity, neuronal HT22 cells were incubated in the conditioned medium. GLGZG showed a neuroprotective effect by promoting cell survivability, suppressing neuronal apoptosis. Conclusions GLGZG exerted its potential effects on suppressing inflammatory responses in LPS-induced BV2 cells by attenuating NF-κB and Akt pathways. In addition, GLGZG could protect against microglial-mediated neurotoxicity in HT22.

scholarly journals trans-Cinnamaldehyde Inhibits Microglial Activation and Improves Neuronal Survival against Neuroinflammation in BV2 Microglial Cells with Lipopolysaccharide Stimulation

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yan Fu ◽  
Pin Yang ◽  
Yang Zhao ◽  
Liqing Zhang ◽  
Zhangang Zhang ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Microglial Activation ◽  
Neuronal Damage ◽  
Neuronal Survival ◽  
Microglial Cells ◽  
Neuroprotective Effects ◽  
Bv2 Cells ◽  
Parkinson’S Diseases ◽  
Cox 2 ◽  
Bv2 Microglial Cells

Background.Microglial activation contributes to neuroinflammation and neuronal damage in neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. It has been suggested that neurodegenerative disorders may be improved if neuroinflammation can be controlled.trans-cinnamaldehyde (TCA) isolated from the stem bark ofCinnamomum cassiapossesses potent anti-inflammatory capability; we thus tested whether TCA presents neuroprotective effects on improving neuronal survival by inhibiting neuroinflammatory responses in BV2 microglial cells.Results.To determine the molecular mechanism behind TCA-mediated neuroprotective effects, we assessed the effects of TCA on lipopolysaccharide- (LPS-) induced proinflammatory responses in BV2 microglial cells. While LPS potently induced the production and expression upregulation of proinflammatory mediators, including NO, iNOS, COX-2, IL-1β, and TNF-α, TCA pretreatment significantly inhibited LPS-induced production of NO and expression of iNOS, COX-2, and IL-1βand recovered the morphological changes in BV2 cells. TCA markedly attenuated microglial activation and neuroinflammation by blocking nuclear factor kappa B (NF-κB) signaling pathway. With the aid of microglia and neuron coculture system, we showed that TCA greatly reduced LPS-elicited neuronal death and exerted neuroprotective effects.Conclusions.Our results suggest that TCA, a natural product, has the potential of being used as a therapeutic agent against neuroinflammation for ameliorating neurodegenerative disorders.

scholarly journals Potassium Channels Kv1.3 and Kir2.1 But Not Kv1.5 Contribute to BV2 Cell Line and Primary Microglial Migration

2021 ◽  
Vol 22 (4) ◽  
pp. 2081 ◽  
Author(s):  
Ruxandra Anton ◽  
Mihail Ghenghea ◽  
Violeta Ristoiu ◽  
Christophe Gattlen ◽  
Marc-Rene Suter ◽  
...  
Keyword(s):  
Cell Migration ◽  
Potassium Channels ◽  
Nerve Injury ◽  
Cellular Migration ◽  
Microglial Cells ◽  
Spared Nerve Injury ◽  
Cell Functions ◽  
Injury Model ◽  
Bv2 Cells ◽  
Underlying Mechanisms

(1) Background: As membrane channels contribute to different cell functions, understanding the underlying mechanisms becomes extremely important. A large number of neuronal channels have been investigated, however, less studied are the channels expressed in the glia population, particularly in microglia. In the present study, we focused on the function of the Kv1.3, Kv1.5 and Kir2.1 potassium channels expressed in both BV2 cells and primary microglia cultures, which may impact the cellular migration process. (2) Methods: Using an immunocytochemical approach, we were able to show the presence of the investigated channels in BV2 microglial cells, record their currents using a patch clamp and their role in cell migration using the scratch assay. The migration of the primary microglial cells in culture was assessed using cell culture inserts. (3) Results: By blocking each potassium channel, we showed that Kv1.3 and Kir2.1 but not Kv1.5 are essential for BV2 cell migration. Further, primary microglial cultures were obtained from a line of transgenic CX3CR1-eGFP mice that express fluorescent labeled microglia. The mice were subjected to a spared nerve injury model of pain and we found that microglia motility in an 8 µm insert was reduced 2 days after spared nerve injury (SNI) compared with sham conditions. Additional investigations showed a further impact on cell motility by specifically blocking Kv1.3 and Kir2.1 but not Kv1.5; (4) Conclusions: Our study highlights the importance of the Kv1.3 and Kir2.1 but not Kv1.5 potassium channels on microglia migration both in BV2 and primary cell cultures.

scholarly journals Rhein Suppresses Neuroinflammation via Multiple Signaling Pathways in LPS-Stimulated BV2 Microglia Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Piao Zheng ◽  
Xuefei Tian ◽  
Wei Zhang ◽  
Zhaoyu Yang ◽  
Jing Zhou ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathways ◽  
Protein Levels ◽  
Bv2 Microglia ◽  
Mrna And Protein Expression ◽  
Underlying Mechanisms ◽  
Bv2 Microglial Cells ◽  
Multiple Signaling ◽  
Natural Agent

As a bioactive absorbed compound of rhubarb, Rhein is applied for the treatment of brain injury. However, the underlying pharmacological mechanisms remain unclear. In this study, we aimed to explore antineuroinflammatory functions and underlying mechanisms of Rhein in vitro. BV2 microglia cells were chosen and irritated by LPS. The influence of Rhein on cell viability was determined using MTT assay. We finely gauged the proinflammatory cytokines of TNF-α and IL-1β through tests of immunofluorescence staining, ELISA, RT-qPCR, and western blot. Additionally, mediators including IL-6, IL-12, iNOS, and IL-10 were surveyed by ELISA. Furthermore, protein levels of the underlying signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF-κB) were tested adopting western blot. We found that Rhein reduced the secretion of pivotal indicators including TNF-α and IL-1β, effectively restraining their mRNA and protein expression in LPS-activated BV2 microglial cells. Besides, Rhein treatment demoted the production of IL-6, IL-12, and iNOS and promoted the excretion of IL-10. Subsequent mechanistic experiments revealed that Rhein obviously downregulated the phosphorylation levels of PI3K, Akt, p38, and ERK1/2 and simultaneously upregulated the PTEN expression. In addition, Rhein antagonized the increase of TLR4, p-IκBα, and NF-κB. In summary, Rhein suppresses neuroinflammation via multiple signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF-κB) in LPS-stimulated BV2 microglia cells. This study highlights a natural agent for prevention and treatment of neuroinflammation.

scholarly journals Gualou Guizhi Granule Suppresses LPS-Induced Inflammatory Response of Microglia and Protects against Microglia-Mediated Neurotoxicity in HT-22 via Akt/NF-κB Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xiaona Chang ◽  
Yaling Fang ◽  
Yuqin Zhang ◽  
Yaojun Liu ◽  
Liming Fan ◽  
...  
Keyword(s):  
Conditioned Medium ◽  
Neuronal Apoptosis ◽  
Neuroprotective Effect ◽  
Microglial Cells ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Bv2 Cells ◽  
Bv2 Microglia ◽  
Anti Inflammatory ◽  
Bv2 Microglial Cells

Neuroinflammation plays a crucial part in the commencement and advancement of ischemic stroke. Gualou Guizhi granule (GLGZG) is known to well exhibit neuroprotective effect, but it is not known whether GLGZG can regulate the inflammatory process at the cellular level in BV2 microglia cells and protect against microglia-mediated neurotoxicity in neurons. Herein, we aimed to investigate the anti-inflammatory effects of GLGZG on BV2 microglia cells and protection against microglia-mediated neurotoxicity in neurons. Methods. The cell model of neuroinflammation was constructed by lipopolysaccharide (LPS) to observe the effect of GLGZG in the presence or absence of GLGZG. The production of nitric oxide (NO), inflammatory mediators, was detected. Moreover, potential mechanisms associated with the anti-inflammatory effect, such as inhibition of microglial activation and nuclear factor kappa B (NF-κB), were also investigated. In addition, to prove whether GLGZG protects against microglia-mediated neurotoxicity, neuronal HT-22 cells were cultured in the conditioned medium. And cell survivability and neuronal apoptosis of HT-22 were evaluated. Results. It was found that a main regulator of inflammation, NO, is suppressed by GLGZG in BV2 microglial cells. Moreover, GLGZG dose dependently decreased the mRNA and protein levels of inducible NO synthase (iNOS) in LPS-stimulated BV2 cells. Additionally, GLGZG inhibited the expression and secretion of proinflammatory cytokines in BV2 microglial cells. Also, GLGZG inhibited LPS-activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in BV2 microglial cells at the intracellular level. GLGZG significantly affected Akt phosphorylation: phosphorylated forms of Akt increased. To check whether GLGZG protects against microglia-mediated neurotoxicity, neuronal HT-22 cells were incubated in the conditioned medium. GLGZG showed a neuroprotective effect by promoting cell survivability and suppressing neuronal apoptosis. Conclusions. GLGZG exerted its potential effects on suppressing inflammatory responses in LPS-induced BV2 cells by regulating NF-κB and Akt pathways. In addition, GLGZG could protect against microglia-mediated neurotoxicity in HT-22.

scholarly journals Atractylodis Rhizoma Alba Attenuates Neuroinflammation in BV2 Microglia upon LPS Stimulation by Inducing HO-1 Activity and Inhibiting NF-κB and MAPK

2019 ◽  
Vol 20 (16) ◽  
pp. 4015 ◽  
Author(s):  
Yun Hee Jeong ◽  
Wei Li ◽  
Younghoon Go ◽  
You-Chang Oh
Keyword(s):  
Nitric Oxide ◽  
High Performance ◽  
Microglial Activation ◽  
Molecular Mechanisms ◽  
Ethanolic Extract ◽  
Brain Diseases ◽  
Inflammatory Factors ◽  
Bv2 Cells ◽  
Mitogen Activated Protein ◽  
Bv2 Microglia

Microglial activation and the resulting neuroinflammation are associated with a variety of brain diseases, such as Alzheimer’s disease and Parkinson’s disease. Thus, the control of microglial activation is an important factor in the development of drugs that can treat or prevent inflammation-related neurodegenerative disorders. Atractylodis Rhizoma Alba (ARA) has been reported to exhibit antioxidant, gastroprotective, and anti-inflammatory effects. However, the effects of ARA ethanolic extract (ARAE) on microglia-mediated neuroinflammation have not been fully elucidated. In this work, we explored the anti-neuroinflammatory properties and underlying molecular mechanisms of ARAE in lipopolysaccharide (LPS)-stimulated microglial BV2 cells. Our results showed that ARAE significantly attenuates the production of nitric oxide (NO) and inflammatory cytokines induced by LPS. ARAE treatment also inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 without causing cytotoxicity. ARAE markedly attenuated the transcriptional activities of nuclear factor (NF)-κB and mitogen-activated protein kinases (MAPK) phosphorylation, and induced heme oxygenase (HO)-1 expression. High-performance liquid chromatography (HPLC) analysis showed that ARAE contains three main components—atractylenolide I, atractylenolide III, and atractylodin—all compounds that significantly inhibit the production of inflammatory factors. These findings indicate that ARAE may be a potential therapeutic agent for the treatment of inflammation-related neurodegenerative diseases.

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