OBJECTIVE: To explore the mechanism of Dihuang Yinzi (DHYZ) in the treatment of Alzheimer's disease (AD) by integrating metabolomics and experimental verification. METHODS: Forty-eight male APP/PS1 mice were divided into model, high- (DHYZ-H), medium- (DHYZ-M), and low-dose DHYZ (DHYZ-L) groups (12 mice per group) according to a random number table. Mice in DHYZ groups were gavaged with DHYZ 6.34, 12.68, and 25.35 g/(kg·d), respectively. Twelve C57BL/6 mice were gavaged with distilled water as the blank group. Metabolomics was used to analyze differential metabolites in the brains of mice. Morris water maze test was used to detect the memory abilities of mice. The hematoxylin-eosin staining and transmission electron microscopy were used to observe the general morphology and ultrastructure of neurons. The enzyme-linked immunosorbent assay was used to detect the levels of superoxide dismutase (SOD), reactive oxygen species (ROS), and amyloid β -protein 1-42 (A β_1-42). The real-time quantitative polymerase chain reaction was used to detect the mRNA expressions of density-regulated protein 1 (DRP1), fission 1 (FIS1), mitofusin-1 (MFN1), and optic atrophy protein 1 (OPA1). Western blot was used to detect the protein expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response binding protein (CREB), brain-derived neurotrophic factor (BDNF), synapsin 1 (SYN1), synaptophysin (SYP), and postsynaptic density protein 95 (PSD95). RESULTS: A total of 82 differential metabolites were identified in the brains of APP/PS1 mice, among which 7 differential metabolites could be regulated by DHYZ. After DHYZ intervention, the memory abilities of mice significantly increased (P<0.05 or P<0.01), the number of synapses and neurons in the hippocampus increased, and the mitochondrial morphology and structure were relatively intact. The DHYZ groups exhibited a significant reduction in hippocampal ROS and A β_1-42 levels, along with a significant elevation in SOD level (P<0.05 or P<0.01). The mRNA expressions of DRP1 and FIS1 were reduced, while the mRNA expressions of MFN1 and OPA1 were increased after DHYZ treatment (P<0.05 or P<0.01). The cAMP/PKA/CREB-BDNF pathway was activated, and the expressions of SYN1, SYP and PSD95 proteins were significantly increased in the DHYZ-H group (P<0.05 or P<0.01). CONCLUSIONS DHYZ could improve mitochondrial dynamics and synaptic plasticity in APP/PS1 mice, inhibit oxidative stress, and thereby enhancing learning and memory abilities in APP/PS1 mice. Its mechanism might be related to activation of the cAMP/PKA/CREB-BDNF signaling pathway.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Male ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Brain/drug effects* ; Metabolomics ; Mice, Inbred C57BL ; Neuronal Plasticity/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Cyclic AMP/metabolism* ; Reactive Oxygen Species/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Mice, Transgenic ; Mice ; Amyloid beta-Peptides/metabolism* ; Signal Transduction/drug effects* ; Alzheimer Disease/drug therapy* ; Superoxide Dismutase/metabolism*

Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans ; Peptides/therapeutic use* ; Structure-Activity Relationship ; Functional Food ; Diabetes Mellitus, Type 2/drug therapy* ; Biological Availability ; Alzheimer Disease/drug therapy* ; Inflammatory Bowel Diseases/drug therapy* ; Hypertension/drug therapy* ; Liver Diseases/drug therapy* ; Bioactive Peptides, Dietary

OBJECTIVES: To investigate the active components and possible mechanisms of n-butanol fraction of Periploca forrestii Schltr. ethanol extract for treating Alzheimer's disease (AD). METHODS: The active components of n-butanol fraction of Periploca forrestii Schltr. ethanol extract were analyzed using UPLC-QE-MS technique. In a SD rat model of AD induced by treatment with AlCl₃ and D-gal, the therapeutic effects of low, moderate and high doses of the n-butanol fraction, saline, and donepezil hydrochloride were evaluated using ELISA, HE and Nissl staining, immunohistochemistry and Western blotting. The therapeutic mechanisms of the n-butanol fraction were explored using network pharmacology and molecular docking. RESULTS: Seventeen active components were identified from the n-butanol fraction of Periploca forrestii Schltr. ethanol extract, including phenylpropanoids, flavonoids, anthraquinones, triterpenoids, steroids, and volatile oils. In the rat models of AD, treatment with the n-butanol fraction significantly lowed AChE content in the hippocampus, increased the contents of ACh, SOD, CAT, and GSH-Px, enhanced the expressions of neuronal apoptotic factors Bcl-2, PI3K, Akt, p-PI3K, and p-Akt, and reduced the expressions of Bax and caspase-3 proteins. The treatment also dose-dependently up-regulated hippocampal expressions of Nrf-2, HO-1 and BDNF and down-regulated Keap-1, Aβ and Tau expressions. Bioinformatics analysis identified 14 key intersected targets (including TNF, AKT1 and ESR1) between the n-butanol fraction and AD. CONCLUSIONS The therapeutic effect of n-butanol fraction of Periploca forrestii Schltr. ethanol extract in AD mice is mediated by its multiple active components that regulate multiple targets and pathways.
Animals ; Rats, Sprague-Dawley ; Rats ; 1-Butanol/chemistry* ; Plant Extracts/pharmacology* ; Periploca/chemistry* ; Ethanol/chemistry* ; Alzheimer Disease/drug therapy* ; Male ; Molecular Docking Simulation ; Apoptosis/drug effects*

Alzheimer's disease (AD) is regarded as a neurodegenerative disease, and it has been proposed that AD may be a systemic disease. Studies have reported associations between non-neurological diseases and AD. The correlations between AD pathology and systemic (non-neurological) pathological changes are intricate, and the mechanisms underlying these correlations and their causality are unclear. In this article, we review the association between AD and disorders of other systems. In addition, we summarize the possible mechanisms associated with AD and disorders of other systems, mainly from the perspective of AD pathology. Regarding the relationship between AD and systemic pathological changes, we aim to provide a new outlook on the early warning signs and treatment of AD, such as establishing a diagnostic and screening system based on more accessible peripheral samples.
Alzheimer Disease/therapy* ; Humans ; Brain/pathology*

Accurate prediction of drug-target interactions (DTIs) plays a pivotal role in drug discovery, facilitating optimization of lead compounds, drug repurposing and elucidation of drug side effects. However, traditional DTI prediction methods are often limited by incomplete biological data and insufficient representation of protein features. In this study, we proposed KG-CNNDTI, a novel knowledge graph-enhanced framework for DTI prediction, which integrates heterogeneous biological information to improve model generalizability and predictive performance. The proposed model utilized protein embeddings derived from a biomedical knowledge graph via the Node2Vec algorithm, which were further enriched with contextualized sequence representations obtained from ProteinBERT. For compound representation, multiple molecular fingerprint schemes alongside the Uni-Mol pre-trained model were evaluated. The fused representations served as inputs to both classical machine learning models and a convolutional neural network-based predictor. Experimental evaluations across benchmark datasets demonstrated that KG-CNNDTI achieved superior performance compared to state-of-the-art methods, particularly in terms of Precision, Recall, F1-Score and area under the precision-recall curve (AUPR). Ablation analysis highlighted the substantial contribution of knowledge graph-derived features. Moreover, KG-CNNDTI was employed for virtual screening of natural products against Alzheimer's disease, resulting in 40 candidate compounds. 5 were supported by literature evidence, among which 3 were further validated in vitro assays.
Alzheimer Disease/drug therapy* ; Biological Products/therapeutic use* ; Humans ; Neural Networks, Computer ; Machine Learning ; Drug Discovery/methods* ; Algorithms ; Drug Evaluation, Preclinical/methods*

Monoclonal antibodies targeting β-amyloid (Aβ)(represented by Lecanemab) have been approved in the United States, Japan and China for the treatment of mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild AD dementia, and AD treatment has moved towards the era of disease modifying therapy (DMT). In view of the lack of use experience with DMT in China, this article presents recommendations for Aβ-based DMT clinical practice based on its clinical evidence, as well as its existing usage experience and research regarding AD. These recommendations include the mechanism of action, patient selection, standardized use, effectiveness, and safety monitoring, intending to help guide the rational use in real-world clinical practice.
Humans ; Alzheimer Disease/drug therapy* ; Amyloid beta-Peptides

As population aging aggravates,the prevalence of dementia is increasing,seriously impacting the daily lives of patients.Sensory stimulation therapy has emerged as a safe and effective non-pharmacological intervention for individuals with dementia.Consequently,exploring non-pharmacological treatments for Alzheimer's disease is crucial.By a review of the relevant literature,this paper provides an overview of sensory stimulation therapy in terms of the concept,applications,and effects on dementia,aiming to promote the broader implementation of this therapy in the care of individuals with dementia.
Humans ; Alzheimer Disease/therapy*

This paper explores the research progress of acupuncture for the prevention and treatment of Alzheimer's disease (AD) based on the "kidney-governor vessel-brain" axis. According to the fundamental pathogenesis of AD in traditional Chinese medicine (TCM), which attributes to kidney deficiency, marrow depletion, and impaired mental faculties, as well as the governor vessel's connection between the kidney and brain, the concept of the "kidney-governor vessel-brain" axis is proposed. The theoretical basis of the "kidney-governor vessel-brain" axis is analyzed based on the meridian pathway and physiological functions of the governor vessel, as well as the interdependent and mutually reinforcing relationships among the kidney, governor vessel, and brain. The relationship between AD and the "kidney-governor vessel-brain" axis is elucidated from both traditional medical theories and modern biological perspectives. Integrating clinical and mechanistic research on AD prevention and treatment based on this axis, it is suggested that the "kidney-governor vessel-brain" axis provides valuable insights and references for future research on AD prevention and treatment.
Humans ; Alzheimer Disease/physiopathology* ; Acupuncture Therapy ; Kidney/blood supply* ; Brain/blood supply* ; Meridians ; Blood Vessels/physiopathology*

This article reports 2 cases of urinary retention in Alzheimer's disease with agitation treated by acupuncture. Based on patients' clinical symptoms, the etiology and pathogenesis were determined, and acupuncture was applied to Baihui (GV20), Sishencong (EX-HN1), Shenting (GV24), and bilateral Ciliao (BL32), Zhongliao (BL33), Fengchi (GB20), Taiyang (EX-HN5), etc. to regulate the mind and promote water metabolism. The positive and negative electrodes of the SDZ-Ⅴ type electroacupuncture device were attached to ipsilateral Ciliao (BL32), Zhongliao (BL33) respectively, with continuous wave, at the frequency of 15 Hz, and the current of 3 to 10 mA, depending on patients' tolerance. The needles were retained for 20 min. The treatment was delivered once every other day, 3 interventions a week and 12 interventions as 1 course. Both patients reported the micturition desire after 1 intervention with acupuncture and the catheter was removed on the same day. The urination was ameliorated without dysuresia after 1-2 courses of treatment, and the agitated behavior was alleviated. It can be the reference for the clinical treatment of urinary retention in patients with Alzheimer's disease with agitation.
Humans ; Alzheimer Disease/psychology* ; Acupuncture Therapy ; Urinary Retention/etiology* ; Male ; Female ; Aged ; Acupuncture Points ; Psychomotor Agitation/complications*

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People