CD8+ tissue-resident memory T cells are essential in bleomycin-induced pulmonary fibrosis.

Human tissue-resident memory T (TRM) cells play a crucial role in protecting the body from infections and cancers. Recent research observed increased numbers of TRM cells in the lung tissues of idiopathic pulmonary fibrosis patients. However, the functional consequences of TRM cells in pulmonary fibrosis remain unclear. Here, we found that the numbers of TRM cells, especially the CD8+ subset, were increased in the mouse lung with bleomycin-induced pulmonary fibrosis. Increasing or decreasing CD8+ TRM cells in mouse lungs accordingly altered the severity of fibrosis. In addition, the adoptive transfer of CD8+ T cells containing a large number of CD8+ TRM cells from fibrotic lungs was sufficient to induce pulmonary fibrosis in control mice. Treatment with chemokine CC-motif ligand (CCL18) induced CD8+ TRM cell expansion and exacerbated fibrosis, whereas blocking C-C chemokine receptor 8 (CCR8) prevented CD8+ TRM recruitment and inhibited pulmonary fibrosis. In conclusion, CD8+ TRM cells are essential for bleomycin-induced pulmonary fibrosis, and targeting CCL18/CCR8/CD8+ TRM cells may be a potential therapeutic approach. NEW & NOTEWORTHY The role of CD8+ TRM cells in the development of pulmonary fibrosis was validated and studied in the classic model of pulmonary fibrosis. It was proposed for the first time that CCL18 has a chemotactic effect on CD8+ TRM cells, thereby exacerbating pulmonary fibrosis.

4-octyl itaconate alleviates cisplatin-induced ferroptosis possibly via activating the NRF2/HO-1 signalling pathway.

Ferroptosis, characterized by iron-dependent lipid reactive oxygen species (ROS) accumulation, plays a pivotal role in cisplatin-induced ototoxicity. Existing research has suggested that in cisplatin-mediated damage to auditory cells and hearing loss, ferroptosis is partially implicated. 4-Octyl itaconate (4-OI), derived from itaconic acid, effectively permeates cell membranes, showcasing potent anti-inflammatory as well as antioxidant effects in several disease models. Our study aimed to investigate the effect of 4-OI on cisplatin-induced ferroptosis and the underlying molecular mechanisms. The survival rates of HEI-OC1 cells and mice cochlea hair cells were measured by CCK8 and immunofluorescence, respectively. The auditory brainstem response (ABR) audiometry was used to detect changes in hearing thresholds in mice before and after treatment. Levels of ROS were evaluated by DCFH-DA. Real-time PCR quantified inflammatory cytokines TNF-α, IL-6 and IL-1ß. Network Pharmacology and RNA sequencing (RNA-seq) analysis of the potential mechanism of 4-OI resistance to cisplatin-induced ferroptosis. The expressions of ferroptosis-related factors (GPX4, SLC7A11 and PTGS2) and important antioxidant factors (NRF2, HO-1, GCLC and NQO1) were tested by real-time PCR, Western blot and immunofluorescence. Results demonstrated cisplatin-induced significant ROS and inflammatory factor release, reduced NRF2 expression, hindered nuclear translocation and activated ferroptosis. Pretreatment with 4-OI exhibited anti-inflammatory and antioxidant effects, along with resistance to ferroptosis, ultimately mitigating cisplatin-induced cell loss. In the present study, we show that 4-OI inhibits cisplatin-induced ferroptosis possibly through activation of the NRF2/HO-1 signalling pathway, thereby exerting a protective effect against cisplatin-induced damage to auditory cells, and providing a new therapeutic strategy for cisplatin-induced hearing loss.

Ligand Mediation for Tunable and Oxide Suppressed Surface Gold-Decorated Liquid Metal Nanoparticles.

Gallium-based liquid metal systems hold vast potential in materials science. However, maximizing their possibilities is hindered by gallium's native oxide and interfacial functionalization. In this study, small-molecule ligands are adopted as surfactants to modify the surface of eutectic gallium indium (EGaIn) nanoparticles and suppress oxidation. Different p-aniline derivatives are explored. Next, the reduction of chloroanric acid (HAuCl4 ) onto these p-aniline ligand modified EGaIn nanoparticles is investigated to produce gold-decorated EGaIn nanosystems. It is found that by altering the concentrations of HAuCl4 or the p-aniline ligand, the formation of gold nanoparticles (AuNPs) on EGaIn can be manipulated. The reduction of interfacial oxidation and presence of AuNPs enhances electrical conductivity, plasmonic performance, wettability, stability, and photothermal performance of all the p-aniline derivative modified EGaIn. Of these, EGaIn nanoparticles covered with the ligand of p-aminobenzoic acid offer the most evenly distributed AuNPs decoration and perfect elimination of gallium oxides, resulting in the augmented electrical conductivity, and highest wettability suitable for patterning, enhanced aqueous stability, and favorable photothermal properties. The proof-of-concept application in photothermal therapy of cancer cells demonstrates significantly enhanced photothermal conversion performance along with good biocompatibility. Due to such unique characteristics, the developed gold-decorated EGaIn nanodroplets are expected to offer significant potential in precise medicine.

Green synthesis and anti-tumor efficacy via inducing pyroptosis of novel 1H-benzo[e]indole-2(3H)-one spirocyclic derivatives.

Pyroptosis induction is anticipated to be a new approach to developing anti-tumor medications. A novel class of spirocyclic compounds was designed by hybridization of 1H-Benzo[e]indole-2(3H)-one with 1,4-dihydroquinoline and synthesized through a new green "one-pot" synthesis method using 10 wt% SDS/H2O as a solvent to screen novel tumor cell pyroptosis inducers. The anti-tumor activity of all compounds in vitro was determined by the MTT method, and a fraction of the compounds showed good cell growth inhibitory activity. The quantitative structure-activity relationship models of the compounds were established by artificial intelligence random forest algorithm (R2 = 0.9656 and 0.9747). The ideal compound A9 could, in a concentration-dependent manner, prevent ovarian cancer cells from forming colonies, migrating, and invading. Furthermore, A9 could significantly induce pyroptosis and upregulate the expression of pyroptosis-related proteins GSDME-N, in addition to inducing apoptosis and mediating the expression of apoptosis-related proteins in ovarian cancer cells. A9 (5 mg/kg) significantly reduced tumor volume and weight of ovarian cancer in vivo, decreased caspase-3 expression in tumor tissue, and induced the production of GSDME-N. This study provides a green and efficient atom-economic synthesis method for 1H-Benzo[e]indole-2(3H)-one spirocyclic derivatives and a promising pyroptosis inducer with anti-tumor activity.

Chicoric Acid Ameliorated Beta-Amyloid Pathology and Enhanced Expression of Synaptic-Function-Related Markers via L1CAM in Alzheimer's Disease Models.

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease. The accumulation of amyloid-beta (Aß) plaques is a distinctive pathological feature of AD patients. The aims of this study were to evaluate the therapeutic effect of chicoric acid (CA) on AD models and to explore its underlying mechanisms. APPswe/Ind SH-SY5Y cells and 5xFAD mice were treated with CA. Soluble Aß1-42 and Aß plaque levels were analyzed by ELISA and immunohistochemistry, respectively. Transcriptome sequencing was used to compare the changes in hippocampal gene expression profiles among the 5xFAD mouse groups. The specific gene expression levels were quantified by qRT-PCR and Western blot analysis. It was found that CA treatment reduced the Aß1-42 levels in the APPswe/Ind cells and 5xFAD mice. It also reduced the Aß plaque levels as well as the APP and BACE1 levels. Transcriptome analysis showed that CA affected the synaptic-plasticity-related genes in the 5xFAD mice. The levels of L1CAM, PSD-95 and synaptophysin were increased in the APPswe/Ind SH-SY5Y cells and 5xFAD mice treated with CA, which could be inhibited by administering siRNA-L1CAM to the CA-treated APPswe/Ind SH-SY5Y cells. In summary, CA reduced Aß levels and increased the expression levels of synaptic-function-related markers via L1CAM in AD models.

KBrO3-Promoted Cross-Dehydrogenative Coupling Reaction: An Odorless Regioselective Sulfenylation of Imidazoheterocycles in Water.

A regioselective metal-free sulfenylation of imidazoheterocycles with heterocyclic thiols or thiones has been achieved using a cross-dehydrogenative coupling method in water. In addition, the procedure has several advantages including green solvents, free of foul-smelling sulfur sources, and mild conditions, thus providing considerable application potential in the pharmaceutical industry.

MicroRNA-22-3p ameliorates Alzheimer's disease by targeting SOX9 through the NF-κB signaling pathway in the hippocampus.

BACKGROUND: Studies have suggested that many down-regulated miRNAs identified in the brain tissue or serum of Alzheimer's disease (AD) patients were involved in the formation of senile plaques and neurofibrillary tangles. Specifically, our previous study revealed that microRNA-22-3p (miR-22-3p) was significantly down-regulated in AD patients. However, the molecular mechanism underlying the down-regulation of miR-22-3p has not been comprehensively investigated. METHODS: The ameliorating effect of miR-22-3p on apoptosis of the Aß-treated HT22 cells was detected by TUNEL staining, flow cytometry, and western blotting. The cognition of mice with stereotaxic injection of agomir or antagomir of miR-22-3p was assessed by Morris water maze test. Pathological changes in the mouse hippocampus were analyzed using hematoxylin and eosin (HE) staining, Nissl staining, and immunohistochemistry. Proteomics analysis was performed to identify the targets of miR-22-3p, which were further validated using dual-luciferase reporter analysis and western blotting analysis. RESULTS: The miR-22-3p played an important role in ameliorating apoptosis in the Aß-treated HT22 cells. Increased levels of miR-22-3p in the mouse hippocampus improved the cognition in mice. Although the miR-22-3p did not cause the decrease of neuronal loss in the hippocampus, it reduced the Aß deposition. Proteomics analysis revealed Sox9 protein as the target of miR-22-3p, which was verified by the luciferase reporter experiments. CONCLUSION: Our study showed that miR-22-3p could improve apoptosis and reduce Aß deposition by acting on Sox9 through the NF-κB signaling pathway to improve the cognition in AD mice. We concluded that miR-22-3p ameliorated AD by targeting Sox9 through the NF-κB signaling pathway in the hippocampus.

Fundamentals and Applications of Photo-Cross-Linking in Bioprinting.

This review provides a detailed overview of the rapidly advancing field of biofabrication, particularly with regards to the use of photo-cross-linking (i.e., light-based) techniques. The major emphasis of this review is on the fundamentals of photo-cross-linking and key criteria identified for the successful design and implementation of photo-cross-linked bioinks and bioresins in extrusion-based and lithography-based bioprinting. The general mechanisms associated with photo-cross-linking (e.g., free-radical chain polymerization, thiol-ene, photomediated redox) of natural and synthetic materials are described to inform bioink and bioresin design, which includes the selection of polymers, functional group modifications, photoinitiators, and light sources that enable facile and cytocompatible photo-cross-linking. Depending on material selection and the bioprinting technique of interest, we describe the specific bioink or bioresin properties and criteria that must be achieved to ensure optimal printability and utility. Finally, examples of current state-of-the-art applications of light-based bioprinting for in vitro tissue models, tissue engineering, and regenerative medicine are provided to further motivate future opportunities within the bioprinting landscape that are facilitated with light.

The advances in nanomedicine for bone and cartilage repair.

With the gradual demographic shift toward an aging and obese society, an increasing number of patients are suffering from bone and cartilage injuries. However, conventional therapies are hindered by the defects of materials, failing to adequately stimulate the necessary cellular response to promote sufficient cartilage regeneration, bone remodeling and osseointegration. In recent years, the rapid development of nanomedicine has initiated a revolution in orthopedics, especially in tissue engineering and regenerative medicine, due to their capacity to effectively stimulate cellular responses on a nanoscale with enhanced drug loading efficiency, targeted capability, increased mechanical properties and improved uptake rate, resulting in an improved therapeutic effect. Therefore, a comprehensive review of advancements in nanomedicine for bone and cartilage diseases is timely and beneficial. This review firstly summarized the wide range of existing nanotechnology applications in the medical field. The progressive development of nano delivery systems in nanomedicine, including nanoparticles and biomimetic techniques, which are lacking in the current literature, is further described. More importantly, we also highlighted the research advancements of nanomedicine in bone and cartilage repair using the latest preclinical and clinical examples, and further discussed the research directions of nano-therapies in future clinical practice.

Expression and characterization of a novel organic solvent tolerant protease from Bacillus sphaericus DS11.

Organic solvent-tolerant proteases have many applications in the synthesis of peptides. In this study, we have developed a low-cost and convenient method to produce highly concentrated organic solvent-tolerant protease. Organic solvent tolerant protease (OSP) gene from Bacillus sphaericus DS11 was cloned and expressed in Bacillus subtilis WB800. The optimum pH of the recombinant protease was 9.0. The optimum temperature of the recombinant protease was 40 °C. The recombinant protease was purified by ethanol with the yield of (87.33%). The yield of OSP enriched by ethanol was higher than that of by Ni-chelating affinity chromatography, which indicated that precipitation of the recombinant OSP with ethanol is a relatively low-cost and fast method for organic solvent -tolerant protease preparation. These results showed that this enzyme could be very useful in different industrial applications.

Small but significant: Insights and new perspectives of exosomes in cardiovascular disease.

Cardiovascular diseases (CVDs) are a major health problem worldwide, and health professionals are still actively seeking new and effective approaches for CVDs treatment. Presently, extracellular vesicles, particularly exosomes, have gained its popularity for CVDs treatment because of their function as messengers for inter- and extra-cellular communications to promote cellular functions in cardiovascular system. However, as a newly developed field, researchers are still trying to fully understand the role of exosomes, and their mechanism in mediating cardiac repair process. Therefore, a comprehensive review of this topic can be timely and favourable. In this review, we summarized the basic biogenesis and characterization of exosomes and then further extended the focus on the circulating exosomes in cellular communication and stem cell-derived exosomes in cardiac disease treatment. In addition, we covered interactions between the heart and other organs through exosomes, leading to the diagnostic characteristics of exosomes in CVDs. Future perspectives and limitations of exosomes in CVDs were also discussed with a special focus on exploring the potential delivery routes, targeting the injured tissue and engineering novel exosomes, as well as its potential as one novel target in the metabolism-related puzzle.

Keratin 86 is up-regulated in the uterus during implantation, induced by oestradiol.

BACKGROUND: Uterine receptivity is one of the determinants of embryo implantation, which is responsible for pregnancy success. Aberrant embryo implantation due to disrupted uterine receptivity is usually found in ovarian hyperstimulation induced hyperoestrogen patients. RESULTS: This study identified keratin 86 (KRT86), a fibrous structural protein, which was upregulated in uterine endometrium during peri-implantation. Using a hyperoestrogen mouse model established in a previous study, we found abnormal oestradiol (E2) levels during pre-implantation could trigger high expression of Krt86 in the uterine epithelium. In an ovariectomised mouse model, combining oestrogen receptors ERα and ERß knockout mice models, uterine Krt86 was found to be up-regulated after E2 treatment, mediated by nuclear ERα. Furthermore, we found progesterone (P4) could ameliorate Krt86 expression, induced by abnormal E2. CONCLUSIONS: These results revealed the dynamic expression and regulation of Krt86, especially in hyperoestrogen treated mice, indicating it might act as a marker for non-receptive uterus.

Aqp-1 Gene Knockout Attenuates Hypoxic Pulmonary Hypertension of Mice.

Objective- Hypoxic pulmonary hypertension (HPH) is characterized by proliferative vascular remodeling. Abnormal pulmonary artery smooth muscle cells proliferation and endothelial dysfunction are the primary cellular bases of vascular remodeling. AQP1 (aquaporin-1) is regulated by oxygen level and has been observed to play a role in the proliferation and migration of pulmonary artery smooth muscle cells. The role of AQP1 in HPH pathogenesis has not been directly determined to date. To determine the possible roles of AQP1 in the pathogenesis of HPH and explore its possible mechanisms. Approach and Results- Aqp1 knockout mice were used, and HPH model was established in this study. Primary pulmonary artery smooth muscle cells, primary mouse lung endothelial cells, and lung tissue sections from HPH model were used. Immunohistochemistry, immunofluorescence and Western blot, cell cycle, apoptosis, and migration analysis were performed in this study. AQP1 expression was upregulated by chronic hypoxia exposure, both in pulmonary artery endothelia and medial smooth muscle layer of mice. Aqp1 deficiency attenuated the elevation of right ventricular systolic pressures and mitigated pulmonary vascular structure remodeling. AQP1 deletion reduced abnormal cell proliferation in pulmonary artery and accompanied with accumulation of HIF (hypoxia-inducible factor). In vitro, Aqp1 deletion reduced hypoxia-induced proliferation, apoptosis resistance, and migration ability of primary cultured pulmonary artery smooth muscle cells and repressed HIF-1α protein stability. Furthermore, Aqp1 deficiency protected lung endothelial cells from apoptosis in response to hypoxic injury. Conclusions- Our data showed that Aqp1 deficiency could attenuate hypoxia-induced vascular remodeling in the development of HPH. AQP1 may be a potential target for pulmonary hypertension treatment.

Endoplasmic Reticulum Targeting Ratiometric Fluorescent Probe for Carboxylesterase 2 Detection in Drug-Induced Acute Liver Injury.

Carboxylesterase 2 (CES2), an endoplasmic reticulum (ER) located phase I enzyme, plays a vital role in the metabolism of various endogenous and exogenous substances, and is regarded as an important target for the design of prodrugs. Unfortunately, superior highly selective ER targeting fluorescent probes for monitoring of CES2 are not currently available. Herein, we report an ER targeting CES2 selective and sensitive ratiometric fluorescent probe ERNB based on the ER localizing group p-toluenesulfonamide. ERNB possessed high specificity, sensitivity, and exhibited excellent subcellular localization when compared to commercial ER tracker, and was used to image CES2 in the ER of living cells. Additionally, using ERNB we evaluated the CES2 regulation under d,l-dithiothreitol and tunicamycin-induced ER stress. Furthermore, we determined the down regulation of CES2 activity and expression in the acetaminophen-induced acute liver injury model. On the basis of these results, we conclude that ERNB is a promising tool for highlighting the role of CES2 in the ER and in exploring the role of CES2 in the development of diseases associated with ER stress.

Indirect comparison of novel Oral anticoagulants among Asians with non-Valvular atrial fibrillation in the real world setting: a network meta-analysis.

BACKGROUND: The development of novel oral anticoagulants (NOACs) has changed the landscape of non-valvular atrial fibrillation (NVAF) management. In this study, the effectiveness and the safety of several NOACs were evaluated in a real-world setting among Asian patients with NVAF. METHODS: The literature search was conducted crossing different databases including Embase, MEDLINE, and the Cochrane Library from inception through March 1, 2019, for studies which included real-world perspectives comparing the individual NOACs with each other or with warfarin among Asians with NVAF. The primary outcomes were defined as stroke or systemic embolism (SSE) and major bleeding; ischemic stroke, all-cause death as well as intracranial bleeding were classified as the secondary outcomes. RESULTS: From sixteen real-world studies, a total of 312,827 Asian patients were included in this analysis. In comparison with warfarin, the utilization of apixaban, dabigatran, and rivaroxaban significantly lowered the risk of major bleeding (apixaban: HR 0.47, 95%CI 0.35-0.63; dabigatran: HR 0.59, 95%CI 0.47-0.73; rivaroxaban: HR 0.66, 95%CI 0.52-0.83) and lessened the all-cause death rate (apixaban: HR 0.29, 95%CI 0.16-0.52; dabigatran: HR 0.40, 95%CI 0.27-0.60; rivaroxaban: HR 0.42, 95%CI 0.28-0.65). Apixaban (HR 0.59; 95%CI 0.40-0.85) reduced the possibility of ischemic stroke when compared against dabigatran. Rivaroxaban showed a higher chance of causing an ischemic stroke (HR 1.61; 95%CI 1.08-2.41) and major bleeding (HR 1.39; 95%CI 1.02-1.90) than Apixaban. CONCLUSIONS: Apixaban, dabigatran and rivaroxaban were more effective than warfarin on reducing the risks of stroke and haemorrhage; meanwhile, apixaban was likely to lower the risk of major bleeding comparing to rivaroxaban. TRIAL REGISTRATION: PROSPERO registry number: CRD42018086914 .

Growth Factor Delivery Systems for Tissue Engineering and Regenerative Medicine.

Growth factors (GFs) are often a key component in tissue engineering and regenerative medicine approaches. In order to fully exploit the therapeutic potential of GFs, GF delivery vehicles have to meet a number of key design criteria such as providing localized delivery and mimicking the dynamic native GF expression levels and patterns. The use of biomaterials as delivery systems is the most successful strategy for controlled delivery and has been translated into different commercially available systems. However, the risk of side effects remains an issue, which is mainly attributed to insufficient control over the release profile. This book chapter reviews the current strategies, chemistries, materials and delivery vehicles employed to overcome the current limitations associated with GF therapies.

The Value of Computed Tomography in Differentiating Heterotopic Pancreas from Small Gastrointestinal Stromal Tumor.

BACKGROUND: It is critical for an accurate preoperative diagnosis of heterotopic pancreas (HP) and small gastrointestinal stromal tumor (GIST), given the unique treatment and prognosis of the two tumors. This study aims to investigate HP's computed tomography (CT) features and identify the distinguishing characteristics between HP and small GIST. METHODS: From January 2016 to August 2020, our hospital database was searched for confirmed histopathological results and CT scans for HP and GIST for further analysis. The statistically significant variables were determined by using Fisher's exact test, the Mann-Whitney U test, the receiver operating characteristic (ROC) curve and the inverse probability weighting method. RESULTS: CT images and clinical data were reviewed for 24 participants with HP and 34 patients with small GIST. Contour, border, relative enhancement grade, surface dimple, duct-like structure, short diameter (SD), attenuation of each lesion in the unenhanced phase (Lp), and the enhancement ratio of tumor in the venous phase (ER) were significant for differentiating HP from small GIST. Threshold values for SD and Lp were 1.40 cm and 42.33 Hounsfield units, respectively. Ill-defined border, surface dimple, ductlike structure, and Lp were independent factors that differentiated HP from small GIST. Additionally, SD and ER were also found to be independent factors. CONCLUSIONS: Contour, relative enhancement grade, SD, and Lp could effectively differentiate HP from small GIST, demonstrating improved diagnostic performance compared to other parameters. The presence of ductlike structures and surface dimples could further characterize HP. These findings may help distinguish HP from small GIST and avoid unnecessary invasive examination and therapy in individuals with asymptomatic HP.

Wearable Microneedle Patch for Colorimetric Detection of Multiple Signature Biomarkers in vivo Toward Diabetic Diagnosis.

Type 2 diabetes is rapidly emerging as a global public health problem. While blood glucose monitoring has been the primary method of managing diabetes for decades, the increasing global prevalence of the disease suggests that there might be a need to identify additional biomarkers for a more precise early diagnosis. Herein, a microneedle patch based wearable sensor is developed for the purpose of diabetic diagnosis. Utilizing methacrylic acid modified gelatin and polyvinyl alcohol in the fabrication of microneedles has improved their mechanical properties for skin penetration and increased swelling capacity for interstitial fluid extraction, thanks to the double crosslinking mechanism. The fabricated microneedles are further integrated with test paper functionalized with enzyme and dye molecules to detect multiple signature biomarkers of diabetes in vivo through a colorimetric reaction. Such a wearable microneedle patch  holds significant promise for the real-time monitoring of various biomarkers related to chronic diseases and aging.

Comparison of face-based and voice-based first impressions in a Chinese sample.

People often form first impressions of others based on face and/or voice cues. This study aimed to compare the first impressions formed under these two cues. First, we compared free descriptions based on face and voice cues and found differences in the content and frequency of the personality words. We then compiled three wordlists used for face-based and voice-based first impression evaluations separately or simultaneously. Second, using these wordlists, we compared face-based and voice-based first impression ratings and found that both had significant intra-rater and inter-rater reliability. However, using the mean of the actors' self-rating and their acquaintance rating as the validity criterion, only the ratings of 'ingenuous' and 'mature' traits in the face-based first impression evaluation were significantly correlated with the validity criterion. Factor analysis revealed that face-based first impression had the dimensions of capability and approachability, while voice-based first impression had capability, approachability and reliability. The findings indicate that stable first impressions can be formed by either face or voice cues. However, the specific composition of impressions will vary between the cues. These results also provide a foundation for studying first impressions formed by an integrated perception of voice and face cues.

Attenuated memory impairment and neuroinflammation in Alzheimer's disease by aucubin via the inhibition of ERK-FOS axis.

Alzheimer's disease (AD) is a degenerative illness accompanied by cognitive and memory loss. In addition to the widely accepted, convincing amyloid cascade hypothesis, the activation of glial cells and neuroinflammation, especially the microglia-mediated neuroinflammation, has an essential role in the development and progression of AD. Therefore, the anti-inflammatory treatment is becoming a promising therapeutic strategy. Aucubin (Au) is a natural product derived from many plants with anti-inflammatory and antioxidant activities. Up to now, no research has been conducted to investigate the anti-inflammatory effects of Au and its neuroprotective quality on AD and the potential molecular mechanisms of its medical roles. In our study, the results of network pharmacology revealed the potential therapeutic effect of Au on AD. The results of studies in vivo showed that Au improved the behaviors, counteracted cognitive and memory deficits, and ameliorated AD-like pathological features of the mouse brain, e.g., the deposition of Aß plaques, neuronal damage, and inflammatory responses induced by glial cell overactivation, in APP/PS1 mice. The transcriptome sequencing further confirmed that the pathological symptoms of AD could be reversed by inhibiting the ERK/FOS axis to alleviate the inflammatory response. The in vitro experiments revealed that Au suppressed the BV2 cell activation, inhibited the phosphorylation of ERK1/2 and the expression of c-FOS, and reduced the LPS-induced inflammatory mediator production by BV2 cells and primary astrocytes. Our study suggested that Au exerted its neuroprotective effects by inhibiting the inflammatory responses, which could be a promising treatment of AD.