Isolation, structure, biological activity and application progress of ginseng polysaccharides from the Araliaceae family.

Phytopolysaccharides are a class of natural macromolecules with a range of biological activities. Ginseng, red ginseng, American ginseng, and Panax notoginseng are all members of the Araliaceae family. They are known to contain a variety of medicinal properties and are typically rich in a wide range of medicinal values. Polysaccharides represent is one of the principal active ingredients in the aforementioned plants. However, there is a paucity of detailed reports on the separation methods, structural characteristics and comparison of various pharmacological effects of these polysaccharides. This paper presents a review of the latest research reports on ginseng, red ginseng, American ginseng and ginseng polysaccharides. The differences in extraction, separation, purification, structural characterization, and pharmacological activities of the four polysaccharides are compared and clarified. Upon examination of the current research literature, it becomes evident that the extraction and separation processes of the four polysaccharides are highly similar. Modern pharmacological studies have corroborated the multiple biological activities of these polysaccharides. These activities encompass a range of beneficial effects, including antioxidant stress injury, fatigue reduction, tumor inhibition, depression alleviation, regulation of intestinal flora, immunomodulation, diabetes management, central nervous system protection, anti-aging, and improvement of skin health. This paper presents a review of studies on the extraction, purification, characterization, and bioactivities of four natural plant ginseng polysaccharides. Furthermore, the review presents the most recent research findings on their pharmacological activities. The information provides a theoretical basis for the future application of natural plant polysaccharides and offers a new perspective for the in-depth development of the medicinal value of ginseng in the clinical practice of traditional Chinese medicine.

Network Pharmacology and Transcriptomics to Explore the Pharmacological Mechanisms of 20(S)-Protopanaxatriol in the Treatment of Depression.

Depression is one of the most common psychological disorders nowadays. Studies have shown that 20(S)-protopanaxatriol (PPT) can effectively improve depressive symptoms in mice. However, its mechanism needs to be further explored. In this study, we used an integrated approach combining network pharmacology and transcriptomics to explore the potential mechanisms of PPT for depression. First, the potential targets and pathways of PPT treatment of depression were screened through network pharmacology. Secondly, the BMKCloud platform was used to obtain brain tissue transcription data of chronic unpredictable mild stress (CUMS) model mice and screen PPT-altered differential expression genes (DEGs). Gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed using network pharmacology and transcriptomics. Finally, the above results were verified by molecular docking, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR). In this study, we demonstrated that PPT improved depression-like behavior and brain histopathological changes in CUMS mice, downregulated nitric oxide (NO) and interleukin-6 (IL-6) levels, and elevated serum levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) after PPT treatment compared to the CUMS group. Eighty-seven potential targets and 350 DEGs were identified by network pharmacology and transcriptomics. Comprehensive analysis showed that transthyretin (TTR), klotho (KL), FOS, and the phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling pathway were closely associated with the therapeutic effects of PPT. Molecular docking results showed that PPT had a high affinity for PI3K, AKT, TTR, KL, and FOS targets. Gene and protein level results showed that PPT could increase the expression of PI3K, phosphorylation of PI3K (p-PI3K), AKT, phosphorylation of AKT (p-AKT), TTR, and KL and inhibit the expression level of FOS in the brain tissue of depressed mice. Our data suggest that PPT may achieve the treatment of depression by inhibiting the expression of FOS, enhancing the expression of TTR and KL, and modulating the PI3K-AKT signaling pathway.

Binding activity and specificity of tail fiber protein 35Q for Salmonella pullorum.

Salmonella, a prevalent pathogen with significant implications for the poultry industry and food safety, presents a global public health concern. The rise in antibiotic resistance has exacerbated the challenge of prevention. Accurate and sensitive detection methods are essential in combating Salmonella infections. Bacteriophages, viruses capable of targeting and destroying bacteria, leverage their host specificity for accurate microbial detection. Notably, the tail fiber protein of bacteriophages plays a crucial role in recognizing specific hosts, making it a valuable tool for targeted microbial detection. This study focused on the tail fiber protein 35Q of Salmonella pullorum (SP) bacteriophage YSP2, identified through protein sequencing and genome analysis. Bioinformatics analysis revealed similarities between 35Q and other Salmonella bacteriophage tail fiber proteins. The protein was successfully expressed and purified using an Escherichia coli expression system, and its binding activity and specificity were confirmed. ELISA assays and adsorption experiments demonstrated that 35Q interacts with the outer membrane protein (OMP) receptor on bacterial surfaces. This investigation provides valuable insights for targeted Salmonella detection, informs the development of specific therapeutics, and enhances our understanding of the interaction between Salmonella bacteriophages and their hosts.

Study on the intervention effect of HCH integrated SMG health management model on community high-risk group of cardiovascular disease.

Objective: This study aimed to evaluate the integration of the Hospital-Community-Home (HCH) model with the Self-Mutual-Group (SMG) health management model for high-risk populations with cardiovascular disease in the Yuhua community of Shijiazhuang city. The study focused on implementing care interventions (HCH, SMG) with a specific emphasis on SMG to promote beneficial views/behaviors, enhance self-efficacy/agency, and address detrimental determinants of health, ultimately leading to durable changes and healthier lifestyles. Comparing the HCH model with the combined SMG model helps to comprehensively assess the strengths and weaknesses of different health management approaches. This comparison contributes to theoretical innovation and practical development in the field of health management, as well as improving patients' health outcomes and quality of life. Methods: This study employed a quasi-experimental design. Using stratified sampling, individuals who underwent health examinations in Community A and Community B from Shijiazhuang city between May 2023 and August 2023 were randomly selected. After informing the participants about the study and obtaining informed consent via telephone, high-risk patients with cardiovascular disease were screened based on their medical examination reports. Data on lifestyle behaviors, self-efficacy, medical responses, quality of life, and readmission rates were collected and compared before and after the intervention. Results: A total of 526 eligible participants were included, with 241 in the control group and 285 in the study group. After the intervention, there was no significant change in the proportions of smokers, alcohol consumers, and individuals engaging in leisure exercises in the control group. However, in the study group, the proportions of smokers and alcohol consumers significantly decreased, while the proportion of individuals engaging in leisure exercises significantly increased. After the intervention, both the study group and the control group showed significant increases in scores on the General Self-Efficacy Scale-Schwarzer (GSES) and the Seattle Angina Questionnaire (SAQ), with the study group scoring significantly higher than the control group. Avoidance and surrender scores significantly increased after the intervention, with the study group scoring significantly lower than the control group. Confrontation scores significantly increased after the intervention, with the study group scoring significantly higher than the control group. During the follow-up period, the study group had a significantly lower readmission rate than the control group. Conclusion: The integration of HCH with SMG health management model can significantly improve lifestyle behaviors, optimize medical responses, enhance self-efficacy and quality of life, and significantly reduce readmission rates among high-risk populations with cardiovascular disease.

Choline Phosphate-Grafted Nanozymes as Universal Extracellular Vesicle Probes for Bladder Cancer Detection.

Urinary extracellular vesicles (uEVs) are regarded as highly promising liquid-biopsy biomarkers for the early diagnosis and prognosis of bladder cancer (BC). However, detection of uEVs remains technically challenging owing to their huge heterogeneity and ultralow abundance in real samples. We herein present a choline phosphate-grafted platinum nanozyme (Pt@CP) that acts as a universal EV probe for the construction of a high-throughput and high-sensitivity immunoassay, which allowed multiplex profiling of uEV protein markers for BC detection. With the Pt@CP-based immunoassays, three uEV protein markers (MUC-1, CCDC25, and GLUT1) were identified for BC, by which the BC cases (n = 48), cystitis patients (n = 27), and healthy donors (n = 24) were discriminated with high clinical sensitivity and specificity (area under curve = 98.3%). For the BC cases (n = 9) after surgery, the Pt@CP-based immunoassay could report the postoperative residual tumor that cannot be observed by cystoscopy, which is clinically significant for assessing BC recurrence. This work provides generally high sensitivity for EV detection, facilitating the discovery and clinical use of EV-based biomarkers.

CD3ζ-Mediated Signaling Protects Retinal Ganglion Cells in Glutamate Excitotoxicity of the Retina.

Excessive levels of glutamate activity could potentially damage and kill neurons. Glutamate excitotoxicity is thought to play a critical role in many CNS and retinal diseases. Accordingly, glutamate excitotoxicity has been used as a model to study neuronal diseases. Immune proteins, such as major histocompatibility complex (MHC) class I molecules and their receptors, play important roles in many neuronal diseases, while T-cell receptors (TCR) are the primary receptors of MHCI. We previously showed that a critical component of TCR, CD3ζ, is expressed by mouse retinal ganglion cells (RGCs). The mutation of CD3ζ or MHCI molecules compromises the development of RGC structure and function. In this study, we investigated whether CD3ζ-mediated molecular signaling regulates RGC death in glutamate excitotoxicity. We show that mutation of CD3ζ significantly increased RGC survival in NMDA-induced excitotoxicity. In addition, we found that several downstream molecules of TCR, including Src (proto-oncogene tyrosine-protein kinase) family kinases (SFKs) and spleen tyrosine kinase (Syk), are expressed by RGCs. Selective inhibition of an SFK member, Hck, or Syk members, Syk or Zap70, significantly increased RGC survival in NMDA-induced excitotoxicity. These results provide direct evidence to reveal the underlying molecular mechanisms that control RGC death under disease conditions.

Oral Administration of Deer Bone Collagen Peptide Can Enhance the Skin Hydration Ability and Antioxidant Ability of Aging Mice Induced by D-Gal, and Regulate the Synthesis and Degradation of Collagen.

Skin problems caused by aging have attracted much attention, and marine collagen peptides have been proved to improve these problems, while mammalian collagen peptides are rarely reported. In this study, fermented deer bone collagen peptide (FCP) and non-fermented deer bone collagen peptide (NCP) were extracted from fermented and non-fermented deer bone, respectively, and their peptide sequences and differential proteins were analyzed using LC-MS/MS technology. After they were applied to aging mice induced with D-gal, the skin hydration ability, antioxidant ability, collagen synthesis, and degradation ability of the mice were studied. The results show that FCP and NCP are mainly peptides that constitute type Ⅰ collagen, and their peptide segments are different. In vivo experiments show that FCP and NCP can improve the richness of collagen fibers in the skin of aging mice; improve the hydration ability of skin; promote the activity of antioxidant-related enzymes; and also show that through the TGF-ß and MAPK pathways, the synthesis and degradation of collagen in skin are regulated. These results show that deer bone collagen peptide can improve skin problems caused by aging, promote skin hydration and antioxidant capacity of aging mice, and regulate collagen synthesis and degradation through the MAPK pathway.

Paeoniflorin alleviates depression by inhibiting the activation of NLRP3 inflammasome via promoting mitochondrial autophagy.

Depression ranks among the most common neuropsychiatric disorders globally. Current studies examining the roles of inflammation and mitochondrial autophagy in the antidepressant efficacy of paeoniflorin (PF) are sparse. This study aimed to elucidate PF's antidepressant mechanism by promoting autophagy and inhibiting NLRP3 inflammasome activation using chronic unpredictable mild stimulation (CUMS)-induced C57BL/6 mouse models in vivo and corticosterone (CORT)-induced HT22 cell models in vitro. Results demonstrated that PF enhanced the viability of HT22 cells following CORT exposure, restored mitochondrial membrane potential (MMP), reduced reactive oxygen species accumulation, increased LC3 fluorescence intensity, and suppressed inflammatory cytokine secretion and inflammation activation. Additionally, PF ameliorated depressive behaviors induced by CUMS and improved damage in hippocampal neurons. It also reduced the expression of NLRP3, ASC, Caspase-1, IL-1ß, and the assembly of the NLRP3 inflammasome. Moreover, PF upregulated the expression of autophagy-related proteins in the hippocampus, facilitating the clearance of damaged mitochondria and enhancing autophagy. The role of autophagy in PF's antidepressant effects was further confirmed through the use of the autophagy inhibitor 3-methyladenine (3-MA), which reduced the efficacy of PF. In conclusion, PF effectively improved depressive behaviors in CUMS-induced mice and reduced NLRP3-mediated inflammation both in vivo and in vitro, likely via the induction of autophagy.

Polypeptide-PNP2 in Corn Cervi Pantotrichum Ameliorates Cognitive Impairment in Alzheimer's Disease Mice by Inhibiting Microglial Cell Activation.

We isolated a polypeptide PNP2 from Corn Cervi Pantotrichum and investigated its effect and mechanism on cognitive impairment in Alzheimer's disease (AD) mice. Morris water maze was used to assess the degree of cognitive impairment in mice. Histopathological changes were detected by H&E staining; the expressions of inflammatory cytokines were assayed by ELISA. Western blotting was employed to detect the protein expressions. PNP2 could improve cognitive impairment, central inflammatory response, and NLRP3 signaling in AD mice. In vitro experiments revealed that PNP2 could suppress the inflammatory response of microglial cells and reduce the activation of NLRP3 in microglial cells, while MCC950 could antagonize the effects of PNP2. Polypeptide component PNP2 in Corn Cervi Pantotrichum can ameliorate central nervous inflammation and cognitive impairment in AD mice by suppressing NLRP3 signaling.

Analysis of the mechanism of fibrauretine alleviating Alzheimer's disease based on transcriptomics and proteomics.

The dried rattan stem of the Fibraurea Recisa Pierre plant contains the active ingredient known as fibrauretine (FN). Although it greatly affects Alzheimer's disease (AD), the mechanism of their effects still remains unclear. Proteomics and transcriptomics analysis methods were used in this study to determine the mechanism of FN in the treatment of AD. AD model is used through bilateral hippocampal injection of Aß1-40. After successful modeling, FN was given for 30 days. The results showed that FN could improve the cognitive dysfunction of AD model rats, reduce the expression of Aß and P-Tau, increase the content of acetylcholine and reduce the activity of acetylcholinesterase. The Kyoto Encyclopedia of Genes and Genomes enriched differentially expressed genes and proteins are involved in signaling pathways including metabolic pathway, AD, pathway in cancer, PI3K-AKT signaling pathway, and cAMP signaling pathway. Transcriptomics and proteomics sequencing resulted in 19 differentially expressed genes and proteins. Finally, in contrast to the model group, after FN treatment, the protein expressions and genes associated with the PI3K-AKT pathway were significantly improved in RT-qPCR and Western blot and assays. This is consistent with the findings of transcriptomic and proteomic analyses. Our study found that, FN may improve some symptoms of AD model rats through PI3K-AKT signaling pathway.

Unlocking the potential of biochar: an iron-phosphorus-based composite modified adsorbent for adsorption of Pb(II) and Cd(II) in aqueous environments and response surface optimization of adsorption conditions.

In this work, iron-phosphorus based composite biochar (FPBC) was prepared by modification with potassium phosphate and iron oxides for the removal of heavy metal ions from single and mixed heavy metal (Pb and Cd) solutions. FTIR and XPS characterization experiments showed that the novel modified biochar had a greater number of surface functional groups compared to the pristine biochar. The maximum adsorption capacities of FPBC for Pb(II) and Cd(II) were 211.66 mg·g-1 and 94.08 mg·g-1 at 293 K. The adsorption of Pb(II) and Cd(II) by FPBC followed the proposed two-step adsorption kinetic model and the Freundlich isothermal adsorption model, suggesting that the mechanism of adsorption of Pb(II) and Cd(II) by FPBC involved chemical adsorption of multiple layers. Mechanistic studies showed that the introduction of -PO4 and -PO3 chemisorbed with Pb(II) and Cd(II), and the introduction of -Fe-O increased the ion exchange with Pb(II) and Cd(II) during the adsorption process and produced precipitates such as Pb3Fe(PO4)3 and Cd5Fe2(P2O7)4. Additionally, the abundant -OH and -COOH groups also participated in the removal of Pb(II) and Cd(II). In addition, FPBC demonstrated strong selective adsorption of Pb(II) in mixed heavy metal solutions. The Response Surface Methodology(RSM) analysis determined the optimal adsorption conditions for FPBC as pH 5.31, temperature 26.01 °C, and Pb(II) concentration 306.30 mg·L-1 for Pb(II). Similarly, the optimal adsorption conditions for Cd(II) were found to be pH 5.66, temperature 39.34 °C, and Cd(II) concentration 267.68 mg·L-1. Therefore, FPBC has the potential for application as a composite-modified adsorbent for the adsorption of multiple heavy metal ions.

Temporomandibular Joint Disorder: An integrated study of the pathophysiology, neural mechanisms, and therapeutic strategies.

OBJECTIVE: The study aims to investigate Temporomandibular Joint Disorder (TMJD) through a interdisciplinary lens, integrating insights from neuroscience, dentistry, and psychology to dissect its complex pathophysiology and neural mechanisms. It focuses on exploring the neurobiological underpinnings of TMJD, emphasizing the role of pain perception, modulation, and the impact of neurophysiological changes on the disorder. DESIGN: This is a comprehensive narrative review of the literature. RESULTS: Research findings pinpoint altered pain perception and modulation processes as central neural mechanisms contributing to TMJD, highlighting the importance of personalized treatment approaches due to the disorder's complexity and patient variability. The study recognizes advances in neuroscience offering new treatment avenues, such as neuromodulation and biofeedback, which provide non-invasive and personalized options. However, it also addresses the challenges in TMJD research, such as the multifaceted nature of the disorder and the need for more comprehensive, interdisciplinary strategies in research and clinical practice. CONCLUSIONS: TMJD is a multifaceted disorder requiring an interdisciplinary approach for effective management. The study stresses the crucial role of neuroscience in understanding and treating TMJD, facilitating the development of innovative treatment strategies. It emphasizes the need for further research, advocating an integrated approach that combines neuroscience, dentistry, and psychology to address TMJD's complexities comprehensively and improve patient care, thereby enhancing the quality of life for affected individuals.

PM2.5 exposure promotes the progression of acute kidney injury by activating NLRP3-mediated macrophage inflammatory response.

AIM: We reveal the mechanism of action whereby ambient PM2.5 promotes kidney injury. METHODS: Using C57BL/6 mice, the effects of PM2.5 exposure on the acute kidney injury (AKI) were investigated, including renal function changes, expression of inflammatory cytokines, histopathological changes, as well as activation of nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3（NLRP3）. The effects of PM2.5 on renal injury after NLRP3 inhibition were explored using NLRP3 inhibitor (MCC950) and NLRP3 knockout mice. The effects of PM2.5 on the inflammatory response of renal macrophages were investigated at the cellular level. RESULTS: PM2.5 exposure could promote kidney injury, NLRP3 activation and inflammatory response in mice. After using MCC950 and NLRP3 knockout mice, the effects of PM2.5 and the kidney injury could be inhibited. The cellular-level results also suggested that MCC950 could inhibit the effects of PM2.5. CONCLUSION: PM2.5 can promote the progression of AKI and aggravate tissue inflammation through NLRP3, which is an important environmental toxicological mechanism of PM2.5.

Establishment of a real-time fluorescent quantitative PCR detection method and phylogenetic analysis of BoAHV-1.

BACKGROUND: Infectious bovine rhinotracheitis (IBR), caused by Bovine alphaherpesvirus-1 (BoAHV-1), is an acute, highly contagious disease primarily characterized by respiratory tract lesions in infected cattle. Due to its severe pathological damage and extensive transmission, it results in significant economic losses in the cattle industry. Accurate detection of BoAHV-1 is of paramount importance. In this study, we developed a real-time fluorescent quantitative PCR detection method for detecting BoAHV-1 infections. Utilizing this method, we tested clinical samples and successfully identified and isolated a strain of BoAHV-1.1 from positive samples. Subsequently, we conducted a genetic evolution analysis on the isolate strain's gC, TK, gG, gD, and gE genes. RESULTS: The study developed a real-time quantitative PCR detection method using SYBR Green II, achieving a detection limit of 7.8 × 101 DNA copies/µL. Specificity and repeatability analyses demonstrated no cross-reactivity with other related pathogens, highlighting excellent repeatability. Using this method, 15 out of 86 clinical nasal swab samples from cattle were found to be positive (17.44%), which was higher than the results obtained from conventional PCR detection (13.95%, 12/86). The homology analysis and phylogenetic tree analysis of the gC, TK, gG, gD, and gE genes of the isolated strain indicate that the JL5 strain shares high homology with the BoAHV-1.1 reference strains. Amino acid sequence analysis revealed that gC, gE, and gG each had two amino acid mutations, while the TK gene had one synonymous mutation and one H to Y mutation, with no amino acid mutations observed in the gD gene. Phylogenetic tree analysis indicated that the JL5 strain belongs to the BoAHV-1.1 genotype and is closely related to American strains such as C33, C14, and C28. CONCLUSIONS: The established real-time fluorescent quantitative PCR detection method exhibits good repeatability, specificity, and sensitivity. Furthermore, genetic evolution analysis of the isolated BoAHV-1 JL-5 strain indicates that it belongs to the BoAHV-1.1 subtype. These findings provide a foundation and data for the detection, prevention, and control Infectious Bovine Rhinotracheitis.

The Structure of Hypersexuality and Its Relation to Impulsivity.

Among the multiple controversies surrounding hypersexuality is the important issue of whether it constitutes a univocal construct. Although an initial study supported its homogeneity, more resent research has identified two separate subcomponents-problematic sexuality and sexual drive. The present survey study addressed this issue in a sample that included both in-person tested college students (n = 69) and online respondents (n = 339). A factor analysis of scales attempting to capture the indicators of each subcomponent of hypersexuality yielded two correlated, but separate factors. Whereas Problematic Sexuality (PS) comprised scales measuring sexual compulsivity, using sex as a coping mechanism, and the negative consequences of sexual behavior, Sexual Drive (SD) was defined by frequent sexual activity, preoccupation with sexual fantasies, a predilection for impersonal sexual behavior, and facile sexual arousal. These two subcomponents of hypersexuality were found to covary with different types of impulsivity, further supporting their discrimination and providing external validation for their differentiation. Contrary to a priori hypotheses, however, PS correlated highly with Callous/Manipulative/Risk-Taking as well as with a predicted Affective Instability/Behavioral Disinhibition factor, suggesting that PS may constitute an equifinality of separate developmental trajectories for those high on both subtypes of hypersexuality.

Sortilin-Mediated Inhibition of TREK1/2 Channels in Primary Sensory Neurons Promotes Prediabetic Neuropathic Pain.

Neuropathic pain can occur during the prediabetic stage, even in the absence of hyperglycemia. The presence of prediabetic neuropathic pain (PDNP) poses challenges to the management of individuals with prediabetes. However, the mechanisms underlying this pain remain unclear. This study aims to investigate the underlying mechanism and identify potential therapeutic targets of PDNP. A prediabetic animal model induced by a high-energy diet exhibits both mechanical allodynia and thermal hyperalgesia. Furthermore, hyperexcitability and decreased potassium currents are observed in the dorsal root ganglion (DRG) neurons of these rats. TREK1 and TREK2 channels, which belong to the two-pore-domain K+ channel (K2P) family and play an important role in controlling cellular excitability, are downregulated in DRG neurons. Moreover, this alteration is modulated by Sortilin, a molecular partner that modulates the expression of TREK1. The overexpression of Sortilin negatively affects the expression of TREK1 and TREK2, leading to increased neuronal excitability in the DRG and enhanced peripheral pain sensitivity in rats. Moreover, the downregulation of Sortilin or activation of TREK1 and TREK2 channels by genetic or pharmacological approaches can alleviate PDNP. Therefore, targeting the Sortilin-mediated TREK1/2 pathway may provide a therapeutic approach for ameliorating PDNP.

Palmatine improves cognitive dysfunction in Alzheimer's disease model rats through autophagy pathway and regulation of gut microbiota.

Alzheimer's disease (AD) is a primary degenerative encephalopathy that first appeared as a decline in memory and learning skills. Over time, the condition's severity grew. Palmatine (Pal) alleviates Alzheimer's disease symptoms, which has neuroprotective benefits. Numerous investigations have demonstrated a close relationship among AD and gut structure changes. The aim of the research was investigating whether the improvement of Pal on AD is linked to regulating gut flora and autophagy. First, we used Aß1-40 to induce apoptosis in HT22 cells. After Pal treatment, apoptosis can be improved. Then, We used bilateral intracranial hippocampal injection of Aß1-40 for establishing the AD model, after treatment with Pal, the morris water maze experiment and eight-arm maze test demonstrated that Pal enhanced the AD rats' capacity for learning and memory, HE staining illustrated that Pal improved the morphological abnormalities of brain cells and gut tissue damage. Pal reduced the death of hippocampus neurons, as shown by Nissl staining. Pal substantially reduced Tau hyperphosphorylation and Aß accumulation in the brain, according to immunohistochemical labelling. Pal improved the expression of LC3, Beclin 1, AMPK, and suppressed the expression of mTOR and P62, as validated by RT-qPCR and immunofluorescence labelling. This suggests that Pal's treatment of AD may be associated with the control of the AMPK/mTOR autophagy signalling system. 16S rRNA sequencing and short-chain fatty acids (SCFAs) content detection analysis illustrated that Pal has the potential to enhance the content of SCFAs, reverse the alterations in gut microorganisms. It has been showed by the study that Pal could improve AD by activating autophagy signaling pathway and improving gut barrier changes.