Developmental toxicity assay of xanthatin in zebrafish embryos.

Xanthatin (XAN), a xanthanolide sesquiterpene lactone, isolated from Chinese herb, Xanthium strumarium L, has various pharmacological activities, such as antitumor activity and anti-inflammatory. However, little is known about its potential toxicity and the mechanism. Here, zebrafish model was used to study the developmental toxicity in vivo. Our results indicated that xanthatin increased the mortality and led to the morphological abnormalities including pericardial edema, yolk sac edema, curved body shape and hatching delay. Furthermore, xanthatin damaged the normal structure and/or function of heart, liver, immune and nervous system. ROS elevation and much more apoptosis cells were observed after xanthatin exposure. Gene expression results showed that oxidative stress-related genes nrf2 was inhibited, while oxidative stress-related genes (keap1 and nqo1) and apoptotic genes (caspase3, caspase9 and p53) were increased after xanthatin exposure. Mitophagy related genes pink1 and parkin, and wnt pathway (ß-catenin, wnt8a and wnt11) were significantly increased after xanthatin exposure. Taken together, our finding indicated that xanthatin induced developmental toxicity, and the ROS elevation, apoptosis activation, dysregulation of mitophagy and wnt pathways were involved in the toxicity caused by xanthatin.

Lacticaseibacillus rhamnosus HF01 fermented yogurt alleviated high-fat diet-induced obesity and hepatic steatosis via the gut microbiota-butyric acid-hepatic lipid metabolism axis.

The objective of this study was to investigate the anti-obesity effects and underlying mechanism of Lacticaseibacillus rhamnosus HF01 fermented yogurt (HF01-Y). Herein, obesity was induced in mice through a high-fat diet and the changes in the gut microbiota were evaluated using 16S rRNA gene sequencing, combined with the expression levels of the liver AMPK signaling pathway to analyze the potential relationship between HF01-Y-mediated gut microbiota and obesity. The results showed that supplementation with HF01-Y improved obesity-related phenotypes in mice, including reduced body weight, improved serum lipid profiles, and decreased hepatic lipid droplet formation. In addition, HF01-Y altered the composition of the gut microbiota in obese mice, significantly upregulated norank_f__Muribaculaceae, unclassified_c__Clostridia, Blautia, unclassified_o__Bacteroidales, and Rikenellaceae_RC9_gut_group, while downregulating unclassified_f__Desulfovibrionaceae, Colidextribacter, and unclassified_f__Oscillospiraceae. These alterations led to an increase of the cecum butyric acid content, which in turn indirectly promoted the activation of the AMPK signaling pathway, subsequently, inhibited fat synthesis, and promoted fatty acid oxidation related gene expression. Therefore, HF01-Y was likely to alleviate hepatic fat and relieve obesity by modulating the gut microbiota-butyric acid-hepatic lipid metabolism axis, ultimately promoting host health.

Anti-Tumor Activity and Mechanism of Silibinin Based on Network Pharmacology and Experimental Verification.

Silibinin is a flavonoid compound extracted from the seeds of Silybum marianum (L.) Gaertn. It has the functions of liver protection, blood-lipid reduction and anti-tumor effects. However, the potential molecular mechanism of silibinin against tumors is still unknown. This study aimed to assess the anti-tumor effects of silibinin in adenoid cystic carcinoma (ACC2) cells and Balb/c nude mice, and explore its potential mechanism based on network pharmacology prediction and experimental verification. A total of 347 targets interacting with silibinin were collected, and 75 targets related to the tumor growth process for silibinin were filtrated. Based on the PPI analysis, CASP3, SRC, ESR1, JAK2, PRKACA, HSPA8 and CAT showed stronger interactions with other factors and may be the key targets of silibinin for treating tumors. The predicted target proteins according to network pharmacology were verified using Western blot analysis in ACC2 cells and Balb/c nude mice. In the pharmacological experiment, silibinin was revealed to significantly inhibit viability, proliferation, migration and induce the apoptosis of ACC2 cells in vitro, as well as inhibit the growth and development of tumor tissue in vivo. Western blot analysis showed that silibinin affected the expression of proteins associated with cell proliferation, migration and apoptosis, such as MMP3, JNK, PPARα and JAK. The possible molecular mechanism involved in cancer pathways, PI3K-Akt signaling pathway and viral carcinogenesis pathway via the inhibition of CASP3, MMP3, SRC, MAPK10 and CDK6 and the activation of PPARα and JAK. Overall, our results provided insight into the pharmacological mechanisms of silibinin in the treatment of tumors. These results offer a support for the anti-tumor uses of silibinin.

Examining the wound healing potential of curcumin-infused electrospun nanofibers from polyglutamic acid and gum arabic.

Advancements in medicine have led to continuous enhancements and innovations in wound dressing materials, making them pivotal in medical care. We used natural biological macromolecules, γ-polyglutamic acid and gum arabic as primary raw materials to create nanofibers laden with curcumin by blending electrostatic spinning technology in the current investigation. These nanofibers were meticulously characterized using fluorescence microscopy, scanning electron microscopy, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Our comprehensive analyses confirmed the successful encapsulation of curcumin within the nanofiber carrier and it has uniform diameter, good water absorption and mechanical properties. Subsequently, we evaluated the antimicrobial effects of these curcumin-loaded nanofibers against Staphylococcus aureus through an oscillating flask method. We created a mouse model with acute full-thickness skin defects to further investigate the wound healing potential. We conducted various biochemical assays to elucidate the mechanism of action. The results revealed that curcumin nanofibers profoundly impacted wound healing. They bolstered the expression of TGF-ß1 and VEGF and reduced the expression of inflammatory factors, leading to an accelerated re-epithelialization process, enhanced wound contraction, and increased regeneration of new blood vessels and hair follicles. Furthermore, these nanofibers positively influenced the proportion of three different collagen types. This comprehensive study underscores the remarkable potential of curcumin-loaded nanofibers to facilitate wound healing and lays a robust experimental foundation for developing innovative, natural product-based wound dressings.

Whey Protein Peptide Pro-Glu-Trp Ameliorates Hyperuricemia by Enhancing Intestinal Uric Acid Excretion, Modulating the Gut Microbiota, and Protecting the Intestinal Barrier in Rats.

Hyperuricemia (HUA) is a metabolic disorder characterized by an increase in the concentrations of uric acid (UA) in the bloodstream, intricately linked to the onset and progression of numerous chronic diseases. The tripeptide Pro-Glu-Trp (PEW) was identified as a xanthine oxidase (XOD) inhibitory peptide derived from whey protein, which was previously shown to mitigate HUA by suppressing UA synthesis and enhancing renal UA excretion. However, the effects of PEW on the intestinal UA excretion pathway remain unclear. This study investigated the impact of PEW on alleviating HUA in rats from the perspective of intestinal UA transport, gut microbiota, and intestinal barrier. The results indicated that PEW inhibited the XOD activity in the serum, jejunum, and ileum, ameliorated intestinal morphology changes and oxidative stress, and upregulated the expression of ABCG2 and GLUT9 in the small intestine. PEW reversed gut microbiota dysbiosis by decreasing the abundance of harmful bacteria (e.g., Bacteroides, Alloprevotella, and Desulfovibrio) and increasing the abundance of beneficial microbes (e.g., Muribaculaceae, Lactobacillus, and Ruminococcus) and elevated the concentration of short-chain fatty acids. PEW upregulated the expression of occludin and ZO-1 and decreased serum IL-1ß, IL-6, and TNF-α levels. Our findings suggested that PEW supplementation ameliorated HUA by enhancing intestinal UA excretion, modulating the gut microbiota, and restoring the intestinal barrier function.

Active compounds from Calendula officinalis flowers act via PI3K and ERK signaling pathways to offer neuroprotective effects against Parkinson's disease.

Calendula officinalis flowers, associated with diverse biological effects, could be utilized as functional food ingredients to play a crucial role in human health. In this study, we examined the anti-PD activity of C. officinalis flower extracts and investigated their bioactive compounds and molecular mechanisms based on LC-MS/MS assay, bioinformatic exploration and in vitro treatment of SH-SY5Y cells. C. officinalis extracts exhibited significant positive effects on the length and fluorescence density of the dopaminergic neuron region in zebrafish larvae. At 10 µg/mL, the extract restored the length to 96.54% and fluorescence density to 87.77% of the control values, which was equivalent to the effect of a positive drug, indicating the extract's powerful potential to alleviate PD symptoms. Five active compounds, including chlorogenic acid, 3,4-dicaffeoylquinic acid (DA), rutin, isorhamnetin 3-O-glucoside (IG) and calenduloside E (CE) were identified in extracts by LC-QTOF-MS/MS. Hsp90α, PI3K and ERK were revealed as core targets of DA, IG and CE in relation to anti-PD activity. The compounds docked deeply within the pocket region of Hsp90α protein, and their binding energies (∆G b) were -6.93 kcal/mol (DA), -6.51 kcal/mol (IG) and -3.03 kcal/mol (CE), respectively. Subsequently, they concurrently activated the PI3K/Akt signaling pathway and inhibited the ERK signaling pathway, thereby preventing neuronal death and alleviating neuronal degeneration. These compounds from C. officinalis could be potent nutraceutical agents with protective properties that may shield dopaminergic neurons against the damage caused by PD. Our findings provide a basis for utilizing the C. officinalis flowers in functional foods.

Synergistic effects of MFG-E8 and whey protein on mitigating d-galactose-induced sarcopenia through PI3K/AKT/PGC-1α and MAPK/ERK signaling pathways.

Milk fat globule epidermal growth factor 8 (MFG-E8) and whey protein have emerged as promising bionutrient supplements for enhancing skeletal muscle mass and function. In the present study, aging-related sarcopenia rat model was employed to elucidate the effects of the combined administration of MFG-E8 and whey protein on the catabolism and anabolism of gastrocnemius protein. Combined intervention led to notable enhancements in the antioxidative stress status and mitochondrial biogenesis capacity of gastrocnemius muscle fibers in the aging rats, concomitant with a significant inhibition of lipid accumulation. Moreover, the synergistic effect of MFG-E8 and whey protein was found to exert modulatory effects on key signaling pathways, including PI3K/Akt/PGC-1α pathway and MAPK/ERK signaling pathways in the gastrocnemius muscle of the aging rats. Specifically, this combined intervention was observed to promote mitochondrial biogenesis and regulate the expression of protein anabolism and catabolism-related regulators, thereby facilitating the alleviation of mitochondrial oxidative stress and enhancing biogenesis in gastrocnemius tissues. The findings of our study provide compelling evidence for the potential of MFG-E8 as a promising dietary supplement with antisarcopenic properties to ameliorate muscle protein metabolism disorders and mitigate mitochondrial-mediated myoblast apoptosis induced by oxidative stress.

Limosilactobacillus fermentum HF06-derived paraprobiotic and postbiotic alleviate intestinal barrier damage and gut microbiota disruption in mice with ulcerative colitis.

BACKGROUND: Paraprobiotics and postbiotics have shown potential in the treatment of ulcerative colitis (UC). However, their in vivo application is still in its infancy and their mechanisms of action are not well understood. RESULTS: Here, we investigated the mitigation effects of Limosilactobacillus fermentum HF06-derived paraprobiotic (6-PA) and postbiotic (6-PS) on dextran sulfate sodium induced UC and the potential mechanisms. Results indicated that the administration of 6-PA and 6-PS resulted in the inhibition of weight loss and colon shortening in mice with UC. Furthermore, they led to a significant reduction in both fecal moisture content and the levels of proinflammatory cytokines and oxidative stress in the intestine of the mice. 6-PA and 6-PS treatment strengthened the intestinal mucosal barrier by dramatically upregulating the levels of zonula occludens-1 and occludin proteins. In addition, 6-PA and 6-PS restored intestinal dysbiosis by regulating abundances of certain bacteria, such as Bifidobacterium, Faecalibaculum, Muribaculaceae, Corynebacterium, Escherichia-Shigella and Clostridium_sensu_stricto_1, and regulated the level of short-chain fatty acids. CONCLUSION: These findings illustrated for the first time that L. fermentum HF06-derived paraprobiotic and postbiotic enhanced the intestinal barrier function, and restored gut microbiota alterations. © 2023 Society of Chemical Industry.

Developmental toxicity induced by chelerythrine in zebrafish embryos via activating oxidative stress and apoptosis pathways.

Chelerythrine (CHE), a natural benzophenanthridine alkaloid, possesses various biological and pharmacological activities, such as antimicrobial, antitumor and anti-inflammatory effects. However, its adverse side effect has not been fully elucidated. Therefore, this study was designed to investigate the developmental toxicity of CHE in zebrafish. We found that CHE could lead to a notably increase of the mortality and malformation rate, while lead to reduction of the hatching rate and body length. CHE also could affect the normal developing processes of the heart, liver and phagocytes in zebrafish. Furthermore, the reactive oxygen species (ROS) and apoptosis levels were notably increased. In addition, the mRNA expressions of genes (bax, caspase-9, p53, SOD1, KEAP1, TNF-α, STAT3 and NF-κB) were significantly increased, while the bcl2 and nrf2 were notably inhibited by CHE. These results indicated that the elevation of ROS and apoptosis were involved in the developmental toxicity induced by CHE. In conclusion, CHE exhibits a developmental toxicity in zebrafish, which helps to understand the potential toxic effect of CHE.

Whey protein peptides PEW and LLW synergistically ameliorate hyperuricemia and modulate gut microbiota in potassium oxonate and hypoxanthine-induced hyperuricemic rats.

Pro-Glu-Trp (PEW) and Leu-Leu-Trp (LLW) are peptides derived from whey protein digestive products; both peptides exhibit xanthine oxidase inhibitory activity in vitro. However, it remains unclear whether these peptides can alleviate hyperuricemia (HUA) in vivo. In this study, we investigated the roles of PEW and LLW, both individually and in combination, in alleviating HUA induced by potassium oxonate and hypoxanthine. Together, PEW and LLW exhibited synergistic effects in reducing the serum levels of uric acid (UA), creatinine, and blood urea nitrogen, as well as increasing the fractional excretion of UA. The combined treatment with PEW and LLW inhibited UA synthesis, promoted UA excretion, and restored renal oxidative stress and mitochondrial damage. Moreover, the combined treatment alleviated dysbiosis of the gut microbiota, characterized by increased helpful microbial abundance, decreased harmful bacterial abundance, and increased production of short-chain fatty acids. Taken together, these results indicate that the combination of PEW and LLW mitigate HUA and kidney injury by rebalancing UA synthesis and excretion, modulating gut microbiota composition, and improving oxidative stress.

Covalent modification of (+)-catechin to improve the physicochemical, rheological, and oxidative stability properties of rice bran protein emulsion.

The aim of this study is the effects of (+)-catechin (CC) covalent cross-linking (CCCI) (0.05-0.25 %, w/v) on the physicochemical properties, rheological properties, and oxidative stability of rice bran protein (RBP) emulsion. Analysis of particle size, ζ-potential, circular dichroism, fluorescence spectroscopy, surface hydrophobicity, and emulsifying properties demonstrated that a concentration of 0.15 % (w/v) CCCI facilitated protein structure unfolding, resulting in reduced particle size, enhanced electrostatic repulsion, and improved emulsion stability. Moreover, the covalent complexes of RBP-0.15 %CC (w/v) exhibited increased viscosity and shear stress, reflected by the highest G' and G″ values, ultimately enhancing the oxidative stability. Furthermore, analysis using atomic force microscopy and confocal laser scanning microscopy revealed that the RBP-0.15 %CC complexes exhibited the smallest particle size (164 nm) and displayed greater homogeneity. An increase in CC concentration to 0.25 % (w/v) resulted in a higher emulsion aggregation. The emulsions stabilized by CCCI exhibited superior rheological properties and enhanced oxidation stability compared to the control. In conclusion, an appropriate amount of CC can enhance the rheology and oxidation stability of the RBP emulsion, while CCCI treatment holds potential for expanding the utility of RBP in various applications.

Preparation, structural properties, and in vitro and in vivo activities of peptides against dipeptidyl peptidase IV (DPP-IV) and α-glucosidase: a general review.

Diabetes is one of the fastest-growing and most widespread diseases worldwide. Approximately 90% of diabetic patients have type 2 diabetes. In 2019, there were about 463 million diabetic patients worldwide. Inhibiting the dipeptidyl peptidase IV (DPP-IV) and α-glucosidase activity is an effective strategy for the treatment of type 2 diabetes. Currently, various anti-diabetic bioactive peptides have been isolated and identified. This review summarizes the preparation methods, structure-effect relationships, molecular binding sites, and effectiveness validation of DPP-IV and α-glucosidase inhibitory peptides in cellular and animal models. The analysis of peptides shows that the DPP-IV inhibitory peptides, containing 2-8 amino acids and having proline, leucine, and valine at their N-terminal and C-terminal, are the highly active peptides. The more active α-glucosidase inhibitory peptides contain 2-9 amino acids and have valine, isoleucine, and proline at the N-terminal and proline, alanine, and serine at the C-terminal.

Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice.

Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.

Influence of storage time on protein composition and simulated digestion of UHT milk and centrifugation presterilized UHT milk in vitro.

The centrifugation presterilizing UHT (C-UHT) sterilization method removes 90% of the microorganism and somatic cells from raw milk using high-speed centrifugation following UHT treatment. This study aimed to study the changes in protein composition and plasmin in the UHT and C-UHT milk. The digestive characteristics, composition, and peptide spectrum of milk protein sterilized with the 2 technologies were studied using a dynamic digestive system of a simulated human stomach. The Pierce bicinchoninic acid assay, laser scanning confocal microscope, liquid chromatography-tandem mass spectrometry, and AA analysis were used to study the digestive fluid at different time points of gastric digestion in vitro. The results demonstrated that C-UHT milk had considerably higher protein degradation than UHT milk. Different processes resulted during the cleavage of milk proteins at different sites during digestion, resulting in different derived peptides. The results showed there was no significant effect of UHT and C-UHT on the peptide spectrum of milk proteins, but C-UHT could release relatively more bioactive peptides and free AA.

Tandem mass tag-based quantitative proteomics analysis reveals the effects of the α-lactalbumin peptides GINY and DQW on lipid deposition and oxidative stress in HepG2 cells.

The objective of this study was to investigate the mechanism by which the α-lactalbumin peptides Gly-Ile-Asn-Tyr (GINY) and Asp-Gln-Trp (DQW) ameliorate free fatty acid-induced lipid deposition in HepG2 cells. The results show that GINY and DQW reduced triglyceride, total cholesterol, and free fatty acid levels significantly in free fatty acid-treated HepG2 cells. Based on proteomic analysis, GINY and DQW alleviated lipid deposition and oxidative stress mainly through the peroxisome proliferator-activated receptor (PPAR) pathway, fatty acid metabolism, oxidative phosphorylation, and response to oxidative stress. In vitro experiments confirmed that GINY and DQW upregulated the mRNA and protein expression of fatty acid ß-oxidation-related and oxidative stress-related genes, and downregulated the mRNA and protein expression of lipogenesis-related genes by activating peroxisome proliferator-activated receptor α (PPARα). Meanwhile, GINY and DQW reduced free fatty acid-induced lipid droplet accumulation and reactive oxygen species generation, and enhanced the mitochondrial membrane potential and ATP levels. Furthermore, GINY and DQW enhanced carnitine palmitoyl-transferase 1a (CPT-1a) and superoxide dismutase activities, and diminished acetyl-coenzyme A carboxylase 1 (ACC1) and fatty acid synthase (FASN) activities in a PPARα-dependent manner. Interestingly, GW6471 (a PPARα inhibitor) weakened the effects of GINY and DQW on the PPARα pathway. Hence, our findings suggest that GINY and DQW have the potential to alleviate nonalcoholic fatty liver disease by activating the PPARα pathway.

Current findings support the potential use of bioactive peptides in enhancing zinc absorption in humans.

More than two billion people around the world are affected by zinc deficiency, mainly due to the inadequate intake and absorption of zinc. Based on recent research findings, the bioactive peptides could potentially be used to combat zinc deficiency particularly due to their Zinc chelating ability. The main aim of this review was to present current findings, supporting the potential use of bioactive peptides based on their ability to enhance zinc absorption. In-vivo, in-vitro, and ex-vivo studies have demonstrated that zinc chelating peptides can enhance the retention, transportation, and absorption of zinc. Comparative studies on zinc bioavailability from protein hydrolysates and zinc salts have demonstrated that the protein hydrolysates-zinc complexes are more bioavailable than the zinc salts. Data from the structure-function relationship of zinc chelating peptides suggest that the zinc chelating capacities of peptides increase in the following order; the position of zinc chelator > zinc chelator strength > abundance of zinc chelators > net charge > molecular weight. In addition, the transport mechanism of peptide-zinc complex is hypothesized, and the potential use of bioactive peptides based on their safety and taste and limitations to their commercialization are also discussed.

Identification, inhibitory mechanism and transepithelial transport of xanthine oxidase inhibitory peptides from whey protein after simulated gastrointestinal digestion and intestinal absorption.

In the present study, xanthine oxidase (XO) inhibitory peptides were identified from peptides that survived in whey protein isolate (WPI) simulated gastrointestinal digestion and passed through the Caco-2 cell monolayer, and their inhibitory mechanism and transepithelial transport were investigated. After in silico screening and activity validation, PEW and LLW showed the highest XO inhibitory activity with 50 % inhibitory concentrations (IC50) of 3.46 ± 0.22 and 3.02 ± 0.17 mM, respectively. Molecular docking, molecular dynamics simulation, and circular dichroism (CD) results revealed that these two peptides could interact with the residues in the XO active cavity via hydrogen bonds and hydrophobic forces to form a more stable protein-ligand complex, thus affecting the binding of the substrate to XO. Furthermore, PEW and LLW were transported across Caco-2 cell monolayers intact through the paracellular route and peptide transporter 1 (PepT1), and tight junction proteins zonula occludens 1 (ZO-1) and occludin were not disrupted by PEW and LLW. This study suggests that PEW and LLW potentially regulate XO activity in vivo to exert antihyperuricemia effects.

Neurotoxicity of sanguinarine via inhibiting mitophagy and activating apoptosis in zebrafish and PC12 cells.

Sanguinarine, a plant-derived phytoalexin, displays various biological activities, such as insecticidal, antimicrobial, anti-inflammatory, anti-angiogenesis and antitumor effects. But its potential neurotoxicity and the underlying mechanisms has rarely been investigated. Therefore, we aimed to assess the neurotoxicity of sanguinarine using zebrafish model and PC12 cells in this study. The results showed that sanguinarine induced the reduction of the length of dopamine neurons and inhibited the blood vessel in the head area of the zebrafish. Further studies demonstrated that the behavioral phenotype of the larval zebrafish was changed by sanguinarine. In addition, there were more apoptotic cells in the larval zebrafish head area. The mRNA expression levels of ß-syn, th, pink1 and parkin, closely related to the nervous function, were changed after sanguinarine treatment. The in vitro studies show that notably increases of ROS and apoptosis levels in PC12 cells were observed after sanguinarine treatment. Moreover, the protein expression of Caspase3, Parp, Bax, Bcl2, α-Syn, Th, PINK1 and Parkin were also altered by sanguinarine. Our data indicated that the inhibition of mitophagy, ROS elevation and apoptosis were involved in the neurotoxicity of sanguinarine. These findings will be useful to understand the toxicity induced by sanguinarine.

Potential of food-derived bioactive peptides in alleviation and prevention of Alzheimer's disease.

Memory and cognitive impairment are the principal clinical symptoms of Alzheimer's disease (AD). Cholinergic deficiency, amyloid-beta (Aß) toxicity, tau protein hyperphosphorylation, synaptic dysfunction, oxidative stress, and neuroinflammation can all exacerbate the development of AD. With the increased number of AD patients and the frequency of AD complications, people are more inclined to select hydrolyzed proteins or bioactive peptides derived from natural foods as intervention agents to combat this type of neurological disease. Currently, our lack of understanding of the complex pathological mechanisms of the disease has led to a high failure rate in the generation of anti-AD food-derived peptides. Accordingly, this review describes the specific regulatory mechanisms of food-derived bioactive peptides on AD-related therapeutic targets over the past decade and highlights the pathogenesis of AD, potential food sources of anti-AD bioactive peptides, methods for evaluating memory efficacy, and regulatory pathways of food-derived bioactive peptides against AD disease.