Neuroinflammation inhibition and neuroprotective effects of purpurin, a potential anti-AD compound, screened via network proximity and gene enrichment analyses.

Alzheimer's disease (AD) is a complex neurodegenerative disease without any effective preventive or therapeutic drugs. Natural products with stable structures and pharmacological characteristics are valuable sources for the development of novel drugs for many complex diseases. This study aimed to discover potential natural compounds for the treatment of AD using new technologies and methods and explore the efficacy and mechanism of candidate compounds. AD-related large-scale genetic datasets were collated to construct disease-PPIs and natural products were collected from six databases to construct compound-protein interactions (CPIs). Potential relationships between natural compounds and AD were predicted via network proximity and gene enrichment analyses. Then, five AD-related cell models and d-galactose-induced aging rat model were established to evaluate the neuroprotective effects of candidate compounds in vitro and in vivo. We identified that 267 natural compounds were predicted to have close connections with AD and 19 compounds could exert protective effect in at least one cell model. Notably, purpurin exerted protective effect in three cell models and significantly improved the cognitive learning and memory functions, reduced the oxidative stress injuries and neuroinflammation, and enhanced the synaptic plasticity and neurotrophic effect in the brain of d-galactose-treated rats. In this study, AD-related natural compounds were identified via network proximity and gene enrichment analyses. In vivo and in vitro experiments revealed the therapeutic potential of purpurin for AD treatment, laying the foundation for further in-depth research and providing valuable information for the development of novel anti-AD drugs.

TarKG: A Comprehensive Biomedical Knowledge Graph for Target Discovery.

MOTIVATION: Target discovery is a crucial step in drug development, as it directly affects the success rate of clinical trials. Knowledge graphs (KGs) offer unique advantages in processing complex biological data and inferring new relationships. Existing biomedical KGs primarily focus on tasks such as drug repositioning and drug-target interactions, leaving a gap in the construction of KGs tailored for target discovery. RESULTS: We established a comprehensive biomedical KG focusing on target discovery, termed TarKG, by integrating seven existing biomedical KGs, nine public databases, and traditional Chinese medicine knowledge databases. TarKG consists of 1,143,313 entities and 32,806,467 relations across 15 entity categories and 171 relation types, all centered around three core entity types: Disease, Gene, Compound. TarKG provides specialized knowledges for the core entities including chemical structures, protein sequences or text descriptions. By using different KG embedding algorithms, we assessed the knowledge completion capabilities of TarKG, particularly for disease-target link prediction. In case studies, we further examined TarKG's ability to predict potential protein targets for Alzheimer's disease (AD) and to identify diseases potentially associated with the metallo-deubiquitinase CSN5, using literature analysis for validation. Furthermore, we provided a user-friendly web server (https://tarkg.ddtmlab.org) that enables users to perform knowledge retrieval and relation inference using TarKG. AVAILABILITY: TarKG is accessible at https://tarkg.ddtmlab.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SLAMF1 as a novel molecule mediating the causal association between rheumatoid arthritis and interstitial lung disease: A Mendelian randomization study combined with transcriptomics and in vivo validation.

BACKGROUND: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a common complication of rheumatoid arthritis (RA) that result in significant morbidity and mortality. Understanding the molecular mechanisms underlying RA-ILD is crucial for effective prevention. This study aims to identify the specific molecule that mediate the causal association between RA and ILD, as well as to explore its potential mechanisms in the pathogenesis of RA-ILD. METHODS: Using two-sample Mendelian randomization (MR) analyses, we investigated the causal relationship among 16,987 blood genes, RA and ILD. Subsequently, a two-step MR technique was employed to identify significant genes that mediate the association between RA and ILD, and to quantify their proportion of mediation effect. To validate the genes as mediators, the replication MR analysis was conducted and the in vivo experiment was performed using an established animal model of RA-ILD. Furthermore, integrated bioinformatic analyses were conducted to elucidate the specific biological functions of the determined mediator in pathogenesis of RA-ILD. RESULTS: Nine genes, namely MAPK8IP2, TAF11, SLAMF1, DAB2IP, GLUL, SLC4A10, PRSS35, NFX1, and PLK3, were identified as mediators. Among them, SLAMF1 was validated as the most significant mediator, accounting for 4.693% of the mediating effect on the causal relationship between RA and ILD. Upregulated mRNA expression of SLAMF1 was observed in the animal model of RA-ILD compared to controls. Bioinformatic analyses revealed that SLAMF1 was overexpressed in patients with lung fibrosis and correlated with a poor prognosis. Specifically, SLAMF1 was found to be predominantly overexpressed in T cells in lung tissues of patients with lung fibrosis. Additionally, the functional role of SLAMF1 was associated with multiple immune cell infiltrations and the biological process of extracellular matrix synthesis in pulmonary tissues from patients with lung fibrosis. CONCLUSION: SLAMF1 may play a crucial role as a molecular mediator in the causal association between RA and ILD, and participate in multiple mechanisms underlying the pathogenesis of RA-ILD. This research provides insights into how the development of RA influences the risk of ILD and offers potential interventional targets against RA-ILD.

[Chemical components and in vitro anti-aging activity of Yangxue Qingnao Wan based on UPLC-Q-TOF-MS/MS].

The main chemical components of Yangxue Qingnao Wan(YXQNW) were analyzed and identified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS). According to the mass spectrometry information, Mass Hunter 10.0 analysis software was used to compare the collected quasi-molecular ion peaks and secondary fragment ions with literature and reference substances. A total of 131 compounds were identified from YXQNW, including 11 phenylpropanoids, 11 flavonoids, 42 nitrogen-containing compounds, 12 terpenoids, 17 phthalides, 23 quinones, and 15 other compounds. The anti-aging activity of YXQNW and six compounds from YXQNW, including rosmarinic acid, gallic acid, rutin, umbelliferone, hyperoside, and vanillic acid, were evaluated by D-galactose(D-gal)-induced HT22 cell senescence model. The effects of the compounds on HT22 cell damage and individual cell proliferation ability were observed from overall and individual perspectives by the Beyo Click~(TM) EdU-555 cell proliferation kit, and apoptosis was detected by the Annexin V-FITC/PI double staining apoptosis detection kit. Finally, the anti-aging effect of the compounds was tested by a cell senescence ß-galactosidase staining kit. This study provides a more comprehensive analysis of the chemical components of YXQNW and evaluates its anti-aging effect, which will provide a scientific basis for basic research on the efficacy of YXQNW for the treatment of various neurological diseases, such as Alzheimer's disease(AD), headache, and memory loss.

Network Medicine Approach Unravels Endophenotype Signature in Alzheimer's Disease through Large-Scale Comparative Proteomics Analysis: Vascular Dysfunction as a Prime Example.

Alzheimer's disease (AD) is the most common neurodegenerative disease burdening public health. We proposed a network-based infrastructure to identify protein signatures for five AD pathological endophenotypes: amyloidosis, tauopathy, vascular dysfunction, lysosomal dysfunction, and neuroinflammation. We analyzed 23 proteomic data sets from AD patients and transgenic mouse models, using network proximity to measure associations between endophenotype modules and differentially expressed proteins (DEPs) in the integrated AD proteome. We focused on the vascular dysfunction signature with 21 DEPs by integrating RNA-seq, single-cell transcriptomics, GWAS, and literature. Experiments on APP/PS1 and MCAO models highlighted three proteins (SEPT5, SNAP25, STXBP1) as novel AD biomarker candidates. This study demonstrates a network medicine framework for deciphering endophenotype signatures in AD.

Network Medicine: A Potential Approach for Virtual Drug Screening.

Traditional drug screening methods typically focus on a single protein target and exhibit limited efficiency due to the multifactorial nature of most diseases, which result from disturbances within complex networks of protein-protein interactions rather than single gene abnormalities. Addressing this limitation requires a comprehensive drug screening strategy. Network medicine is rooted in systems biology and provides a comprehensive framework for understanding disease mechanisms, prevention, and therapeutic innovations. This approach not only explores the associations between various diseases but also quantifies the relationships between disease genes and drug targets within interactome networks, thus facilitating the prediction of drug-disease relationships and enabling the screening of therapeutic drugs for specific complex diseases. An increasing body of research supports the efficiency and utility of network-based strategies in drug screening. This review highlights the transformative potential of network medicine in virtual therapeutic screening for complex diseases, offering novel insights and a robust foundation for future drug discovery endeavors.

Associations of dichlorophenols, trichlorophenols, and ortho-phenylphenol with the risk and prognosis of diabetes and prediabetes: A population-based study.

2,4-dichlorophenol (2,4-DCP), 2,5-DCP, 2,4,5-trichlorophenol (2,4,5-TCP), 2,4,6-TCP, and ortho-phenylphenol (OPP) are widely present in the environment. However, their associations with risk and prognosis of diabetes and prediabetes remains unclear. We investigated the associations of these five phenols with the risk of diabetes and prediabetes, and with all-cause and cardiovascular disease (CVD) mortality, in adults with diabetes or prediabetes (n=6419). Information on diabetes and prediabetes indicators, and mortality data was collected from the National Health and Nutrition Examination Survey. Logistic and Cox regression models were used to explore the associations of the five phenols with risk and prognosis of diabetes and prediabetes. Participants in the highest urinary 2,4-DCP and 2,5-DCP tertiles had higher odds of diabetes [adjusted odds ratio (aOR), 1.34, 95 % confidence interval (CI): 1.10, 1.62; aOR, 1.29, 95 % CI: 1.07, 1.56, respectively] than those in the lowest tertiles. Participants with urinary OPP concentrations above the limit of detection (LOD), but below median had an aOR of 1.25 (95 % CI: 1.08, 1.46) for prediabetes compared to those with concentrations below the LOD. In adults with diabetes, the highest 2,4-DCP and 2,5-DCP tertiles were associated with all-cause mortality [adjusted hazard ratio (aHR), 1.49; 95 % CI: 1.08, 2.06; aHR, 1.49; 95 % CI: 1.08, 2.05, respectively] and CVD mortality (aHR, 2.58; 95 % CI: 1.33, 4.97; aHR, 1.96; 95 % CI: 1.06, 3.60, respectively) compared with the lowest tertiles. Compared with 2,4,5-TCP concentrations below the LOD, those above median were associated with all-cause mortality (aHR: 1.75; 95 % CI: 1.24, 2.48) and CVD mortality (aHR: 2.34; 95 % CI: 1.19, 4.63) in adults with prediabetes. Furthermore, the associations between these phenols and mortality were strengthened in some subgroups. Environmental exposure to 2,4-DCP, 2,5-DCP, 2,4,5-TCP, and OPP increases the risk or adverse prognosis of diabetes or prediabetes in adults in the US. Further studies are required to confirm these findings.

Network-based identification and mechanism exploration of active ingredients against Alzheimer's disease via targeting endoplasmic reticulum stress from traditional chinese medicine.

Alzheimer's disease is a neurodegenerative disease that leads to dementia and poses a serious threat to the health of the elderly. Traditional Chinese medicine (TCM) presents as a promising novel therapeutic therapy for preventing and treating dementia. Studies have shown that natural products derived from kidney-tonifying herbs can effectively inhibit AD. Furthermore, endoplasmic reticulum (ER) stress is a critical factor in the pathology of AD. Regulation of ER stress is a crucial approach to prevent and treat AD. Thus, in this study, we first collected kidney-tonifying herbs, integrated chemical ingredients from multiple TCM databases, and constructed a comprehensive drug-target network. Subsequently, we employed the endophenotype network (network proximity) method to identify potential active ingredients in kidney-tonifying herbs that prevented AD via regulating ER stress. By combining the predicted outcomes, we discovered that 32 natural products could ameliorate AD pathology via regulating ER stress. After a comprehensive evaluation of the multi-network model and systematic pharmacological analyses, we further selected several promising compounds for in vitro testing in the APP-SH-SY5Y cell model. Experimental results showed that echinacoside and danthron were able to effectively reduce ER stress-mediated neuronal apoptosis by inhibiting the expression levels of BIP, p-PERK, ATF6, and CHOP in APP-SH-SY5Y cells. Overall, this study utilized the endophenotype network to preliminarily decipher the effective material basis and potential molecular mechanism of kidney-tonifying Chinese medicine for prevention and treatment of AD.

Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets.

BACKGROUND/AIMS: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets. METHODS: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options. RESULTS: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018-1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193, 1.048- 1.357). On the other hand, CFHR1 (0.621, 0.497-0.776) and CFHR2 (0.824, 0.703-0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707-0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036-1.314). Additionally, C1S (0.111, 0.018-0.672), C7 (1.631, 1.190-2.236), and CFHR2 (1.279, 1.059-1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network. CONCLUSION: Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development.

Assessing the Global, Regional, and National Impact of High Body Mass Index on Alzheimer's Disease and Other Dementias Between 1990 and 2019.

BACKGROUND: Obesity significantly increases Alzheimer's disease (AD) and dementia risk. Understanding the link between a high body mass index (BMI) and these conditions is crucial for effective management and prevention. OBJECTIVE: We aimed to estimate the burden of AD and other dementias attributed to high BMI from 1990 to 2019 based on sex, age, and socio-demographic indicators (SDI) at global, regional, and national levels. METHODS: We collected data on deaths, disability-adjusted life years (DALYs), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) from the 2019 Global Burden of Disease study for AD and dementia attributed to high BMI. We explored the correlation between SDI levels and ASDR. RESULTS: In 2019, there were 198,476.2 deaths (95% UI: 32,695.4-593,366.4) and 3,159,912.4 DALYs (848,330.5-8,042,531) attributed to high BMI. Numbers of deaths, DALYs, ASMR, and ASDR increased since 1990. Females had higher deaths, ASMR, and ASDR than males. Mortality and DALYs rates increased with age. ASMR and ASDR increased across five SDI levels, with the highest rise in Low-middle SDI. High-income North America had the most deaths [30,993.9 (5,101.7-89,912.9)], while North Africa and the Middle East had the highest ASMR [4.61 (0.79-13.64)] and ASDR [72.56 (20.98-181.16)] in 2019. CONCLUSIONS: The burden of AD and other dementias attributed to high BMI increased since 1990 globally and is still heaviest in developed regions. Females accounted predominantly for the burden than males. Timely measures are needed to against high BMI.

Alkali-Driven Photoinduced N-Dealkylation of Aryl Tertiary Amines and Amides.

By extending the photoinduced oxidative mechanism of aryl tertiary amines proposed earlier to an alkaline environment based on the prediction of quantum mechanics computations and the validation of meticulous experiments, we discovered a photoinduced oxidative N-dealkylation method for both aryl tertiary amines and amides. The dealkylation was achieved in an alkaline environment under mild conditions accompanied by excellent functional group tolerance.

Inflammatory microenvironment in gastric premalignant lesions: implication and application.

Gastric precancerous lesions (GPL) are a major health concern worldwide due to their potential to progress to gastric cancer (GC). Understanding the mechanism underlying the transformation from GPL to GC can provide a fresh insight for the early detection of GC. Although chronic inflammation is prevalent in the GPL, how the inflammatory microenvironment monitored the progression of GPL-to-GC are still elusive. Inflammation has been recognized as a key player in the progression of GPL. This review aims to provide an overview of the inflammatory microenvironment in GPL and its implications for disease progression and potential therapeutic applications. We discuss the involvement of inflammation in the progression of GPL, highlighting Helicobacter pylori (H. pylori) as a mediator for inflammatory microenvironment and a key driver to GC progression. We explore the role of immune cells in mediating the progression of GPL, and focus on the regulation of inflammatory molecules in this disease. Furthermore, we discuss the potential of targeting inflammatory pathways for GPL. There are currently no specific drugs for GPL treatment, but traditional Chinese Medicine (TCM) and natural antioxidants, known as antioxidant and anti-inflammatory properties, exhibit promising effects in suppressing or reversing the progression of GPL. Finally, the challenges and future perspectives in the field are proposed. Overall, this review highlights the central role of the inflammatory microenvironment in the progression of GPL, paving the way for innovative therapeutic approaches in the future.

Corrigendum: Systems pharmacology approach to investigate the mechanism of Kai-Xin-San in Alzheimer's disease.

[This corrects the article DOI: 10.3389/fphar.2020.00381.].

Multifunctional Gomisin B enhances cognitive function in APP/PS1 transgenic mice by regulating Aß clearance and neuronal apoptosis.

This study aimed to investigate the potential effects of Gomisin B, a natural compound known for its inhibition of CYP3A4, on cognitive dysfunction in APP/PS1 transgenic mice with Alzheimer's disease (AD). Additionally, the study explored the combined effects of Gomisin B and Osthole (OST). The research involved male wild-type (WT) mice and 7-month-old APP/PS1 transgenic AD mice. The assessment of behavioral changes included the use of the open field test (OFT) and the Morris water maze (MWM). OST levels in brain tissue were quantified using LC-MS/MS, while levels of oxidative stress were measured through an assay kit. Neuronal apoptosis was studied using Nissl staining, RT-qPCR, and immunofluorescence. Amyloid plaque clearance was assessed using thioflavine-S (Th-S) staining, RT-qPCR, and ELISA. The results of the study revealed that Gomisin B led to a significant improvement in cognitive dysfunction in APP/PS1 mice. Moreover, the simultaneous administration of OST and Gomisin B demonstrated enhanced therapeutic effects. These effects were attributed to the inhibition of ß-site APP-Cleaving Enzyme 1 (BACE1) and oxidative stress by Gomisin B, along with its anti-apoptotic properties. The combined use of OST and Gomisin B exhibited a synergistic impact, resulting in more pronounced anti-oxidant and anti-apoptotic effects. In summary, this study pioneers the exploration of Gomisin B's multifunctional anti-AD properties in APP/PS1 mice. The findings provide a solid groundwork for the development of anti-Alzheimer's drugs based on natural active ingredients.

Identification of immune-associated signatures and potential therapeutic targets for pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) comprises a heterogeneous group of diseases with diverse aetiologies. It is characterized by increased pulmonary arterial pressure and right ventricular (RV) failure without specific drugs for treatment. Emerging evidence suggests that inflammation and autoimmune disorders are common features across all PAH phenotypes. This provides a novel idea to explore the characteristics of immunological disorders in PAH and identify immune-related genes or biomarkers for specific anti-remodelling regimens. In this study, we integrated three gene expression profiles and performed Gene Ontology (GO) and KEGG pathway analysis. CIBERSORT was utilized to estimate the abundance of tissue-infiltrating immune cells in PAH. The PPI network and machine learning were constructed to identify immune-related hub genes and then evaluate the relationship between hub genes and differential immune cells using ImmucellAI. Additionally, we implemented molecular docking to screen potential small-molecule compounds based on the obtained genes. Our findings demonstrated the density and distribution of infiltrating CD4 T cells in PAH and identified four immune-related genes (ROCK2, ATHL1, HSP90AA1 and ACTR2) as potential targets. We also listed 20 promising molecules, including TDI01953, pemetrexed acid and radotinib, for PAH treatment. These results provide a promising avenue for further research into immunological disorders in PAH and potential novel therapeutic targets.

Wogonin inhibits oxidative stress and vascular calcification via modulation of heme oxygenase-1.

Vascular calcification (VC) is highly prevalent and increases the morbidity and mortality of cardiovascular diseases. However, the underlying mechanism remains unclear and there is no effective treatment so far. Interestingly, using systems pharmacology approach, we have predicted that Wogonin (Wog) exhibited potential activity against VC. Then we validated the effect of Wog on VC using human and rat vascular smooth muscle cells (VSMCs), rat arterial rings and vitamin D3-overloaded mouse models. Our results showed that Wog dose-dependently inhibited calcification of VSMCs and rat arterial rings. Consistently, alizarin red staining and calcium content assay confirmed that Wog inhibited aortic calcification in vitamin D3-overloaded mice. Moreover, by constructing the protein regulating network of Wog in suppressing VC, we found heme oxygenase-1 (HMOX-1) was regulated by Wog. Additionally, pathway enrichment analysis revealed that inhibition of reactive oxygen species (ROS) pathway participated in the inhibitory role of Wog in VC and HMOX-1 was also involved in this process. Notably, our study revealed that Wog treatment promoted HMOX-1 expression, and reduced ROS levels in VSMCs. Interestingly, both inhibition of HMOX-1 by ZnPP9 and knockdown of HMOX-1 by siRNA independently eliminated the inhibitory effect of Wog on VC. Finally, administration of Wog suppressed aortic calcification in vitamin D3-overloaded mice and this effect was counteracted by ZnPP9,suggesting the crucial role of HMOX-1 in the inhibitory effect of Wog on VC. Collectively, this study combines systems pharmacology-based strategy and experiments to identify the therapeutic potential of Wog for VC via upregulating HMOX-1 and reducing oxidative stress.

Modulating endoplasmic reticulum stress in APP/PS1 mice by Gomisin B and Osthole in Bushen-Yizhi formula: Synergistic effects and therapeutic implications for Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with no effective cure. Targeting endoplasmic reticulum (ER) stress pathway may offer a novel approach to ameliorate cognitive deficits in AD. Bushen-Yizhi formula (BSYZ), a traditional Chinese medicine (TCM) prescription, has shown potential benefits for AD. To facilitate the development of new therapeutic agents for AD, it is important to identify the active components and the underlying mechanisms of BSYZ against AD. PURPOSE: The aim of this study was to systematically screen the active components of BSYZ that could improve learning and memory impairment in AD by modulating ER stress pathway. METHODS: A drug-target (D-T) network was constructed to analyze the herbal components of BSYZ. Network proximity method was used to identify the potential anti-AD components that targeted ER stress and evaluate their synergistic effects. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties and the literature evidence were considered to select promising candidates for further validation. The selected components were tested in vitro using an AD cell model (APPswe-SH-SY5Y). In vivo anti-AD effects of the components were assessed in APP/PS1 double-transgenic mice. RESULTS: 58 potential anti-AD components targeting ER stress were detected by network proximity analysis, and 13 out of them were selected based on ADMET properties and literature evidence. In vitro experiments confirmed that 5 components, namely gomisin B, ß-Carotene, imperatorin, chrysophanol, and osthole (OST), exhibited anti-AD effects on the APPswe-SH-SY5Y model. Moreover, network proximity analysis suggested that OST and Gomisin B might have synergistic effects on modulating ER stress. In vivo experiments demonstrated that OST, Gomisin B, OST+Gomisin B, and BSYZ all improved learning and memory function in APP/PS1 mice. Gomisin B and OST also restored cellular morphology and tissue structure in APP/PS1 mice. Thioflavine-S (Th-S) staining revealed that they reduced amyloid plaque deposition in the brain tissue of AD model mice. The qPCR results indicated that BSYZ, OST, and Gomisin B differentially regulated IRE1α, PERK, EIF2α, DDIT3, and Caspase 12 expression levels, while the OST and Gomisin B co-administration group showed better efficacy. This trend was further confirmed by immunofluorescence experiments. CONCLUSION: This study identified the active components of BSYZ that could ameliorate learning and memory impairment in AD by targeting ER stress pathway. OST and Gomisin B exhibited synergistic effects on modulating ER stress and reducing amyloid plaque deposition in vivo. Overall, our study elucidated the molecular mechanisms of BSYZ and its active components in attenuating AD symptoms which suggested the therapeutic potential of TCM for AD.