This review synthesizes three decades of evidence regarding the role of cytochrome P450 enzymes (CYPs) in Parkinson's disease (PD), revealing their multifaceted roles beyond traditional pesticide metabolism. While CYP2D6 remains the most studied enzyme due to its association with PD risk in poor metabolizer phenotypes and its dual role in dopamine (DA) synthesis (directly via tyramine hydroxylation and indirectly through precursor demethylation), recent research has highlighted less-studied CYPs with critical pathological implications. Another focal enzyme, CYP2E1, mediates the bioactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to its neurotoxic metabolite, 1-methyl-4-phenylpyridinium, thereby inducing oxidative stress. It also partially contributes to DA oxidation, a process that generates multiple cytotoxic byproducts. These toxic products are implicated in two major pathological processes involved in the development of PD-oxidative stress and protein misfolding-which adversely affect dopaminergic neurons. Additionally, CYP3A4 converts acetaminophen to N-acetyl-p-benzoquinone imine in the substantia nigra, contributing to dopaminergic neuron loss. Emerging enzymes like CYP7B1 (which reduces midbrain DA neuron survival via 7α,26-dihydroxycholesterol) and CYP46A1 (inhibiting α-synuclein aggregation) further expand the involvement of the CYP network in PD. The CYP4 family has also emerged as regulators of fatty acid and eicosanoid metabolism, linking to neuroinflammation and oxidative stress. While CYP2D6 and CYP2E1 have dominated prior studies, this review underscores the broader impact of the CYP superfamily on PD pathogenesis through interconnected pathways involving xenobiotic detoxification, fatty acid homeostasis, cholesterol clearance, and neuroinflammation. By integrating these diverse mechanisms, this study establishes a multifactorial framework that connects CYP-mediated biochemical cascades to PD pathogenesis. SIGNIFICANCE STATEMENT: This article addresses the role of various Cytochrome P450 enzymes (CYPs) in Parkinson's disease (PD), covering both their biochemical functions and how genetic, epigenetic, and environmental factors influence PD progression. Recent findings on CYPs, particularly CYP2D6 and CYP2E1, and their involvement in PD pathogenesis through mechanisms such as pesticide metabolism, dopamine synthesis, and oxidative stress, are summarized. We also explore the contribution of lesser-studied CYPs, like CYP46A1 and CYP39A1, in cholesterol and fatty acid metabolism, presenting novel insights for therapeutic development. The review additionally touches on the influence of CYPs on disease biomarkers and therapeutic strategies, which may hold potential for both clinical application and personalized treatment of PD. Unlike prior reviews focused on CYP2D6 and CYP2E1, this work consolidates evidence for a broader CYP network in PD, highlighting novel therapeutic targets in cholesterol and fatty acid metabolism pathways.

Plant-derived powders and viscous extracts used in spices, herbal medicines, and foods typically require organic solvent extraction prior to chromatographic analysis, while centrifugation increases operational complexity. Herein, a magnetic particle-assisted solid-liquid separation (MPAS) strategy based on Fe₃O₄ nanoparticles is proposed for rapid, centrifugation-free pretreatment of plant samples. Efficient clarification was achieved using ~50 nm Fe₃O₄ nanoparticles at sample-to-particle mass ratios of 1:15 for powdered samples and 1:5 for viscous extracts, combined with 10 min ultrasonication. The resulting extract compositions were highly consistent with those obtained by conventional centrifugation in both GC-MS and LC-MS analyses, confirming the analytical reliability of MPAS. The method was further applied to monitor drying and heat-treatment processes of herbal medicines and spice powders, enabling dynamic profiling of active constituents and flavor compounds. Overall, MPAS offers a simple and effective centrifugation-free solution for the analysis and quality control of complex plant-derived products.

Fatty acids (FAs) are essential components of lipid metabolism and play crucial roles in biological systems. However, due to their low abundance and poor ionization efficiency, the detection of FAs in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) poses significant challenges, making the spatial distribution of these molecules in tissues difficult to analyze. We present a novel on-tissue derivatization strategy for FAs using N,N-diethylethylenediamine (DEEA) as the derivatization reagent, which converts the carboxyl group of FAs into a positively charged moiety via amidation, thereby improving their ionization efficiency in positive ion mode. By systematically optimizing experimental parameters including catalyst type, reaction time, and matrix concentration, combined with α-cyano-4-hydroxycinnamic acid (CHCA) matrix, in situ imaging of nine key FAs (palmitic acid, linoleic acid, eicosapentaenoic acid and docosahexaenoic acid, etc.) was successfully achieved in rat kidney tissues. The derivatization products were verified by ESI-Q-TOF-MS, confirming the reliability of the method. Furthermore, comparative analysis with the conventional derivatization reagent 2-picolylamine (PA) demonstrated that DEEA markedly enhanced the derivatization efficiency of FAs. This study employs DEEA as a derivatization reagent for MALDI imaging of FAs. This derivatization method effectively enhances the ionization efficiency of FAs in the positive ion mode of MALDI-TOF-MS, thereby providing a new and referable approach for the imaging of FAs in biological tissues.

IntroductionThe geographic origin of premium tobacco extracts fundamentally shapes their sensory profiles and commercial value, but authenticating these complex matrices remains a formidable analytical challenge. Conventional nontargeted analysis workflows typically rely on a minute fraction of structurally annotated metabolites, thereby discarding the vast majority of unannotated yet highly specific chemical markers. To address this limitation, this study introduces a geographic authentication framework utilizing machine learning models trained on characteristic ion feature (CIF) fingerprints.MethodsA large-scale dataset of 1,697 tobacco samples was analyzed using liquid chromatography-high resolution mass spectrometry coupled with a data-independent acquisition strategy. Rigorous statistical filtering was applied to isolate CIFs and strip away the shared background metabolome. To evaluate the samples, univariate thresholding based on pattern similarity (dot product) and marker intensity ratios (R score) was initially tested. To overcome the vulnerability of univariate methods to batch effects and overlapping chemical profiles, optimized multivariate machine learning models were also deployed. The models were evaluated under a strict Leave-One-Batch-Out cross-validation framework to ensure robust cross-batch generalization.ResultsStatistical filtering effectively stripped away over 90% of the shared background metabolome, isolating 47,543 CIFs for Zimbabwe tobacco and 3,646 CIFs for Yunnan tobacco. Univariate thresholding achieved a maximum balanced accuracy of 77.9% but proved too rigid. Under cross-validation, the multivariate Random Forest (RF) classifier demonstrated strong predictive performance, achieving a balanced accuracy of 74.6% for Zimbabwe tobacco and successfully detecting economically motivated adulteration across a wide dilution range (0–1,000 ppm). Conversely, both univariate and multivariate methods failed to achieve robust authentication for the Yunnan extracts. This underperformance was driven by severe intra-group heterogeneity stemming from diverse suppliers and heterogeneous processing treatments, which heavily diluted universal characteristic features.DiscussionUltimately, this hybrid strategy provides a scalable tool for the industrial verification of consistent premium extracts. Furthermore, the challenges encountered with the Yunnan samples underscore the necessity of cohort-specific modeling when dealing with highly diverse agricultural products that are subjected to varied processing treatments.

Neurological disorders such as neurodegenerative diseases (NDDs) and stroke have become a major global health burden. Evidences from several studies suggest that their pathogenesis is related to hypoxia. However, there are certain limitations and adverse effects associated with the current treatments for neurological disorders. Studies have shown that some natural products and their extracts—such as (−)-epigallocatechin-3-gallate, Centella asiatica, ginkgolides, quercetin, berberine, and curcumin, which are the focus of this paper, along with briefly mentioned resveratrol and compounded preparations—have some neuroprotective effects in hypoxia-induced neurological injury. Owing to their favorable safety profile and minimal adverse effects, they have attracted widespread attention. Moreover, their primary mechanisms of action possibly stem from oxidative stress inhibition, neuroinflammation attenuation, and neuronal apoptosis reduction, providing potential approaches for the prevention and treatment of neurological diseases. In this review, we searched the PubMed and Web of Science databases for relevant literature collected over the past 35 years. Overall, we summarized the neuroprotective effects of these natural products against hypoxia-related neurological injury, focusing on the molecular mechanisms and signaling pathways, thereby offering a theoretical basis for further research on the specific neuroprotective mechanisms and drug targets of their observed preventive and therapeutic effects on NDDs, primarily Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) in this review.

Rapid and sensitive detection of volatile compounds in complex matrices remains challenging due to limited ionization efficiency. Herein, we developed a novel hybrid ionization source by coaxially integrating low-temperature plasma with desorption electrospray ionization (LTP-DESI). The LTP-DESI hybrid source was equipped with a triple quadrupole mass spectrometer to analyze volatile aroma compounds. Under the LTP-DESI mode, volatile aroma compounds exhibited significant signal enhancements, with intensities increased by up to 2 orders of magnitude compared with DESI or LTP. This enhancement arises from a three-stage synergistic mechanism: (1) droplet and plasma-driven desorption, (2) primary ionization by both charged droplets and plasma species, and (3) synergistic ionization enhancement via plasma-droplet interaction. The spatial and temporal overlap of the charged droplet and plasma plume significantly promotes [M + H]+ generation through Penning ionization, proton transfer and charge exchange under atmospheric pressure. The quantitative and qualitative capability of the LTP-DESI-MS platform was validated through analyses of commercial perfumes and banana tissues, achieving recoveries of 75.3-108.5% with relative standard deviations of 2.7-17.1%. These results highlight the potential of the LTP-DESI system as a robust, practical technique for rapid ambient analysis of aromas in diverse complex samples.

Astringency is closely associated with polyphenols found in food and beverages. Given their importance to both the food industry and human health, accurate detection of polyphenols has become a focal point of research. In this study, a dual-mode probe was constructed for polyphenol detection by colorimetry alongside surface-enhanced Raman scattering (SERS). The probe is core-molecule-shell gold/4-MBA/silver nanorods (Au@M@Ag NRs). The silver shell on the surface of Au@M@Ag NRs can be etched by hydrogen peroxide (H2O2), resulting in a significant red-shift in UV absorption spectra and a marked decrease in SERS signal output from 4MBA. Upon introducing polyphenols with strong antioxidant properties, the etching process of the silver shell is inhibited, thereby protecting the shell-core ratio of Au@M@Ag NRs. This process can be readily monitored through both colorimetry and SERS analysis. In our work, harnessing the anti-etching effect exhibited by kaempferol, a type of polyphenol, our dual-mode sensor demonstrates superior detection limits (43.2 nM for colorimetry and 0.786 nM for SERS) compared to previously reported methods. We successfully distinguished five different polyphenols with varying antioxidant capacities: chlorogenic acid, epicatechin, epigallocatechin gallate, kaempferol, and tannic acid through linear discriminant analysis (LDA). This dual-mode sensor can decrease false-positive results while offering promising applications for determining and identifying polyphenols within complex food samples.

Nicotine's neuroactive properties and influence on brain metabolism are not widely explored, particularly in spatially resolved contexts. This technical note presents an in vivo solid-phase microextraction method coupled with UHPLC-TOF/MS to investigate the temporo-spatial distribution of nicotine-associated metabolites in rat brain regions. The coating material, a Palladium-doped covalent organic framework (I-TFBPT-COF@Pd), exhibited a large surface area, suitable pore diameter, and good biocompatibility. The metabolite distribution pattern spectra demonstrated SPME's superior adsorption performance, as evidenced by a broader and more uniform distribution of metabolites. Principal component analysis and orthogonal partial least-squares discriminant analysis indicated that nicotine exposure induced a profound alteration in the metabolite composition of the experimental samples. In addition, 46 differential metabolites and 7 key pathways in the hippocampus and striatum were identified, which revealed the range of nicotine's influence on various biochemical processes, including neurotransmitter synthesis, energy metabolism, and inflammation regulation. This method provides an effective way to study the potential neural effects of nicotine in the brain, surpassing traditional sampling techniques, and it has broad application prospects in biomedicine.

Sweetening compounds are commonly incorporated into food products to enhance their texture and flavor, thereby indicating product quality. 4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) is a sweet aromatic compound characterized by its pineapple-like baking scent. While it serves as a taste enhancer in various industries, including wine production and soy sauce manufacturing, HDMF also exhibits DNA-damaging activity in foods. In this study, a fluorescence detection method based on fluorescence resonance energy transfer (FRET) for the sensitive detection of HDMF was developed. Initially, gold nanoparticles were deposited onto the surface of Fe3O4 to create fluorescence-quenching materials. Subsequently, thiol-functionalized β-cyclodextrin (SH-β-CD) was modified to provide cavities that allow the fluorescent dye rhodamine 6G (R6G) to enter. The fluorescence of R6G remains quenched until HDMF is present because it will compete with R6G for binding sites within the SH-β-CD cavities through competitive host–guest recognition. Furthermore, the fluorescence intensity of R6G at 553 nm exhibited a strong linear correlation with the logarithmic value of HDMF concentration over a range from 5 × 10−7 M to 10−4 M. This rapid and sensitive fluorescence detection strategy rooted in FRET and competitive host–guest recognition demonstrated significant potential for detecting HDMF in food products.

Aldehyde compounds play an important role in daily and industrial supplies. Herein, a dual-mode detection strategy of aldehyde compounds has been constructed based on triangular silver nanoprisms (T-AgNPRs). Aldehyde compounds consume a part of Tollens' reagent at first, then, the remaining Tollens' reagent can etch TAgNPRs, accompanied by a changed UV absorbance peak and localized surface plasmon resonance (LSPR) signal. In this work, furfural in transformer lubricating oil and glucose in food were chosen as models to illustrate the application of the aldehyde compound detection method. In colorimetry analysis, the linear ranges of furfural and glucose detection were 10 nM to 100 mu M and 1 nM to 10 mu M, respectively. In DFM imaging, the linear range of furfural and glucose detection were 2 nM to 20 mu M and 20 pM to 2 mu M, respectively. Their detection limits in DFM imaging were calculated to be 1.82 nM and 13.18 pM, respectively. As a result, the dual-mode detection method combines the simplicity of colorimetry and sensitivity of DFM imaging, indicating the great potential of the aldehyde compound detection in daily and industrial supplies.

Olfactory dysfunction serves as a potential early diagnostic biomarker for Parkinson's disease (PD), providing essential evidence for investigating PD pathogenesis and developing neuroprotective strategies. Capsaicin (CAP) and nicotine (Nic), pungent flavor compounds derived from Solanaceae plants, exhibit anti-inflammatory properties. Epidemiological studies indicate that higher levels of chili pepper consumption and smoking are inversely associated with PD risk. However, the mechanisms of CAP and Nic against PD-related olfactory dysfunction remain unclear. In this study, we observed that CAP and Nic ameliorated olfactory dysfunction in MPTP intranasal-treated PD mice and alleviated dopaminergic damage in key brain regions including the olfactory bulb, anterior olfactory nucleus, striatum and substantia nigra. Both compounds suppressed microglial activation in these regions, downregulated IL-6 expression, and upregulated TGF-β protein levels. Furthermore, our findings demonstrated that CAP and Nic could effectively mitigate MPTP-induced olfactory deficits by attenuating neuroinflammation mediated through the cGAS/TBK1/STING and MAPK signaling.

Development of combined mass spectrometry ionization sources has enabled expansion of the application and scope of mass spectrometry. A novel hybrid ionization system combining vacuum ultraviolet (VUV) and atmospheric pressure chemical ionization (APCI) was constructed. Gaseous samples were self-aspirated into an ionization zone through a capillary by negative pressure, generated by high-speed airflow based on the Venturi effect. Compared with APCI mode alone, the signal-to-noise ratio (S/N) in APCI/VUV mode was increased by about 276-times. To increase the ionization efficiency further, correlated experimental conditions were optimized. Four types of volatile organic compounds (VOCs) were tested to evaluate the performance of the APCI/VUV ion source. Excellent linearity and limit of detection were achieved for compounds in mixed solutions. Quantitative analyses of four VOCs (toluene, cyclohexanone, styrene and ethylbenzene) using APCI/VUV-MS were done, and the relative standard deviations (RSDs) were 1.57%, 6.30%, 4.49% and 8.21%, respectively, indicating that the APCI/VUV ionization source had excellent reproducibility. Our results demonstrated that the developed method was promising for analyzing VOCs as well as being rapid, simple, and easy to operate. An atmospheric pressure chemical ionization/photoionization combined ionization source was built through the Venturi effect for introducing samples to detect volatile organic compounds.

Olfaction appeared much early than other senses for avoiding danger, seeking food and communication. Olfactory analysis is the key point in some industrial production processes and unique technological fields. Human olfaction plays an important role in real-time detection, olfactory assessment, threshold determination etc. Although, the demands for multiple objective analytical methods and precise quantitative analysis could boost the development of sensor-based instrumental olfaction, the research of human olfactory detection is the source and foundation of the artificial olfaction and electronic nose. This review summarizes the analytical applications of human olfaction and also presents the promising techniques for olfactory analysis. In addition, the combination of olfaction and analytical instruments is systemically discussed. Finally, the bionic sensors based on human olfaction are also reviewed in this work. With better understanding of analytical techniques of human olfaction, new methods of olfactory analysis could be discovered, enlightening the methodology of sensory analysis and the development of artificial olfaction.

The interaction mechanisms between vanillin and olfactory receptors were studied by computational chemistry approaches. Results showed that 10 receptors exhibited different affinities for vanillin (-4.992∼-6.518 kcal/mol). Residues Arg286 (81%, OR2G2), His154 (78%, OR10G4; 62%, OR10G7), His104 (72%, OR10G4), Gly203 (57%, OR1L3), Val182 (58%, OR2J2), and Glu182 (51%, OR5AC2) with high frequencies particularly contributed to vanillin recognition. Hydrogen bonding coupled with hydrophobic interactions were the key forces of binding, and the hydroxyl group of vanillin was essential for its stability in olfactory receptors. Odorants 2,6-dimethoxy-4-methylphenol (2#), vanillyl alcohol (9#), 1-(5-methyl-2-thienyl)ethan-1-one (29#), and 3-acetylpyridine (37#) were identified as vanillin analogs based on comparative molecular field analysis, among them, 9# matched well (0.80∼0.91, overall similarity) with the molecular fields of the nine template ligands. Sensory analysis showed that the addition of 2#, 9#, and 37# effectively increased the correct detection probability of vanillin at low concentrations and decreased the vanillin detection threshold. The obtained results contribute to better understanding of vanillin perception and screening of its analogs.

Menthol is a monocyclic monoterpene with a distinct flavor that is frequently utilized in a variety of food and medicinal items. In this study, a sensitive method based on quartz crystal microbalance (QCM) with gold nanoparticles amplification was developed. A gold chip was initially modified with mono(6-mercapto-6-deoxy)-beta-cyclodextrin (SH-beta-CD) through Au-S affinity binding. When menthol is absent, the host-guest interaction brings ferrocene (Fc) labeled-ssDNA (Fc-ssDNA) to enter the SH-beta-CD cavity. The hybridization between Au nanoparticles functionalized-ssDNA (AuNPs-ssDNA) and Fc-ssDNA produces a significant frequency shift. However, in the presence of menthol, the inclusion competition between Fc and menthol reduces AuNPs-ssDNA modification on the chip surface. In this case, the change of QCM frequency is greatly reduced by menthol. Thus, menthol determination is accomplished by measuring the change in QCM frequency with a linear range from 10-8 M to 10-2 M and a limit of detection of 7.81 nM, which is superior to previously reported results. The method has also been applied in real samples such as mint and essential oil with satisfactory results.

Developing a high-sensitive platform for furfuryl mercaptan (FFT) detection is significant but remains challenging. Herein, Au/Ag core-shell nanorods@metal-organic frameworks (Au/Ag@MIL(Fe)) hybrids were constructed through electrostatic interaction, which combined the abundant "hot spots" regions caused by Au/Ag NRs and the great enrichment ability of porous MIL(Fe) and amplified the Raman signal greatly, achieving high sensitivity in FFT solution and volatile gas detection. The enhancement factor (EF) of the Au/Ag@MIL(Fe) substrates reaches 3.96 x 107. The linear detection ranges of FFT solution and gas were 10-3 - 10- 8 M and 102 -105 ppb, respectively. The LODs were as low as 4.94 x 10-9 M for solution detection and 77.6 ppb for gas detection and were comparable to HPLC-MS methods. Meanwhile, the Au/Ag@MIL(Fe) hybrids demonstrated favorable reproducibility, stability, selectivity, and successful application for FFT detection in coffee, with a recovery rate from 92.3 % to 108.0 %. The proposed quantitative strategy has significant potential in real food sample analysis.

Competitive release is an important release pattern of β-cyclodextrin (β-CD) inclusion complexes. Releasing flavor by absorbing harmful molecules is an ideal situation. Thus, two inclusion complexes, phenethyl alcohol β-CD inclusion (PACD) and phenol β-CD inclusion (PNCD), were prepared and their combining capacity was studied. The binding constant of PNCD was over 9 times more than PACD. PN could accelerate the release of PACD by entering the empty β-CD, revealing competitive release effect. However, we noticed that weak-combining molecules also induced competitive release effect. PACD and PNCD were treated with several different competitors, demonstrating that the release behavior of β-CD inclusion complexes could be controlled by changing competitors. However, the process lasted much longer for “weak” molecules to exchange “strong” ones. The mechanism of competitive release of β-CD inclusion complexes was conforming to chemical equilibrium theory. The release rate could be adjusted by changing the competitors with different concentration and different combining capacity. Moreover, solid inclusion complexes could interact with gaseous competitors, revealing competitive release effect. Competitive release effect could achieve the release of flavor while absorbing harmful molecules. Also, combining capacity or solvent condition was not the determination of competitive release effect, but also an adjustment strategy for molecule release, largely expanding the application of β-CD inclusion complexes.

Diacetyl is an important food additive with rich creamy flavor whose excessive intake may cause various diseases. Herein, for the first time, we designed a dual-mode method for diacetyl detection based on colorimetry and surface-enhanced Raman scattering (SERS) technology. Diacetyl exhibited excellent oxidase-like catalytic activity under light-mediated condition, facilitating the oxidation of colorless 3,3’,5,5’-tetramethylbenzidine (TMB) to blue ox-TMB for colorimetric detection. Notably, diacetyl could control the oxidation process of TMB by simply adjusting light irradiation, unlike traditional enzymatic reactions that required terminators to stop the reaction. Interestingly, ox-TMB was an ideal Raman marker for SERS analysis. Then, a three-dimensional flower-like zinc oxide/silver (ZnO/Ag) for sensitive SERS detection was prepared, which exhibited outstanding SERS effect with a high enhancement factor of 1.89×108 due to effective charge transfer and synergistic effect between ZnO and Ag. Based on these, SERS method was constructed to indirectly detect diacetyl, which has not been reported due to low Raman activity of diacetyl. The linear ranges of colorimetry and SERS were 0.5-60 μM and 10-9-10-5 M respectively, with detection limits of 0.41 μM and 0.73 nM. Obviously, the dual-mode strategy combined the simplicity and practicality of colorimetry and the high sensitivity of SERS, offering great potential applications in practical samples.

Long-chain esters (LCEs) are known to affect aroma perception, but the mechanism of their effects remains unclear. In this study, ethyl palmitate (EP), an important LCE in Osmanthus fragrans flower absolute (OFFA), was selected as a target to identify its role and mechanism. The release characteristics of 10 aroma compounds from OFFA with and without EP were obtained by headspace gas chromatography mass spectrometry (HS-GC/MS) and olfactometry evaluation, respectively. The results show that EP changes the release behaviors of volatile compounds in solution, increases their olfactory detection thresholds (ODTs), and reduces the equilibrium headspace concentrations. According to Whitman’s two-film model, EP was found to change the partition coefficients and mass transfer coefficients of the compounds between the liquid and gas phases. This indicates that EP plays an important role in the scent formation of a flavor product and that it is very valuable for the style design of the flavor product.

The main pathological mechanisms of Alzheimer's Disease (AD) are extracellular senile plaques caused by β-amyloid (Aβ) deposition and intracellular neurofibrillary tangles derived from hyperphosphorylated Tau protein (p-Tau). However, it is difficult to obtain a good curative effect because of the poor brain bioavailability of drugs, which is attributed to the blood-brain barrier (BBB) restriction and complicated brain conditions. Herein, HM-DK was proposed for synergistic therapy of AD by using hollow mesoporous manganese dioxide (HM) as a carrier to deliver an Aβ-inhibiting peptide and a Dp-peptide inhibitor of Tau-related fibril formation synergistically. Inspired by 4T1 cancer cells promoting BBB penetration during brain metastasis, a prospective biomimetic nanocarrier (HM-DK@CM) encapsulated by 4T1 cell membranes was designed. After crossing the BBB, HM-DK@CM inhibited Aβ aggregation and prevented Tau phosphorylation simultaneously. Moreover, by taking advantage of the catalase-like activity of HM, HM-DK@CM relieved oxidative stress and altered the microenvironment associated with the development of AD. Compared with the single therapeutic drug, HM-DK@CM restored nerve damage and improved AD mice's learning and memory abilities by decreasing Aβ oligomer, p-Tau protein, and inflammation through various pathways for synergistic therapy, which has broad prospects for the effective treatment of AD.