Recent advances in nanotechnology have enabled transformative strategies for addressing the multifaceted challenges associated with gastrointestinal (GI) diseases. These disorders, encompassing inflammatory bowel diseases, colorectal cancer, and infections like Helicobacter pylori, often demand precise therapeutic delivery and reduced systemic toxicity—requirements that conventional treatments struggle to meet. Nanomedicine offers a paradigm shift by leveraging diverse nanocarriers such as liposomes, polymeric nanoparticles, dendrimers, exosomes, and inorganic platforms to enhance drug solubility, protect labile drugs, and achieve controlled and site-specific delivery. This review outlines the latest passive and active targeting strategies, including ligand-mediated approaches and stimuli-responsive release systems, which improve drug accumulation at disease sites. It also highlights oral delivery challenges posed by the gastrointestinal microenvironment and discusses engineering solutions such as surface modification and protective coatings. Furthermore, plant-derived and cell-derived vesicle-like nanoparticles are emerging as bioinspired delivery vectors offering biocompatibility and immune modulation. We synthesize current preclinical and clinical progress, emphasizing nanomedicines already under investigation or approved for GI conditions. Despite promising data, barriers such as scalable production, regulatory complexities, and long-term safety concerns remain. This review concludes by charting future directions that focus on personalized therapy, biosensing integration, and intelligent nanoplatforms. By dissecting the intersection of materials science, pharmacology, and gastroenterology, this work provides a roadmap for accelerating translational breakthroughs in GI-targeted nanotherapies.

Traditional herbal medicine, which utilizes herbal materials for complementary, alternative, and integrative therapies, has seen increasing application across diverse medical fields in recent decades, including the treatment of inflammatory bowel disease (IBD). To our knowledge, no bibliometric analyses have been conducted over the past 3 decades to evaluate the global research landscape of herbal medicine applications in IBD treatment. We performed a bibliometric analysis of scientific publications indexed in the Web of Science database in the past 3 decades (1990-2023), focusing on studies related to IBD treatments involving herbal medicines, including decoctions, formulas, herbal plants, and natural derivatives. By our analysis, China emerged as the most productive country in this field, with Nanjing University of Chinese Medicine contributing the highest number of publications. Hsiao Chung-Der was identified as the most prolific author, while Markus F. Neurath ranked as the most cited author. Journals such as Frontiers in Pharmacology, Journal of Ethnopharmacology, and Evidence-Based Complementary and Alternative Medicine were not only the top publishers but also the most frequently cited sources. Our analysis further revealed that the most widely used herbal decoctions and herbal plants exhibit shared molecular targets and signaling pathways with therapeutic potential against IBD. This study provides a systematic, visualized, and objective evaluation of research trends, offering insights to guide future investigations in this field.

Turning agricultural and food processing by-products into health-promoting ingredients is pivotal for developing sustainable food systems. This study developed an integrated multi-dimensional evaluation framework to assess whether the common pomelo peel by-product (Citrus grandis (L.) Osbeck, CGO) can serve as a functionally equivalent alternative to the rare Citrus grandis ‘Tomentosa’ (CGT) for functional food ingredient development. The framework combined comparative metabolomics and delayed luminescence profiling to characterize chemical and physical properties, alongside multi-parametric in vivo bioactivity and safety assessment in a diet-induced vertebrate model. Analyzes confirmed CGO and CGT as distinct chemotypes and physicotypes, with differential enrichment in bioactive pathways like phenylpropanoid biosynthesis. Crucially, both extracts demonstrated statistically equivalent efficacy in alleviating hepatic steatosis, oxidative stress, and inflammation in a high-cholesterol diet-induced zebrafish model, and modulated key genes related to lipid metabolism, antioxidant response, and inflammation. Safety assessment revealed CGO’s significantly wider safety margin. Data integration across dimensions demonstrates that despite compositional differences, the net bioactivity converges on similar beneficial outcomes for liver metabolic health. This work provides a validated strategy for transforming underutilized residues into a multi-target, dietary-relevant ingredient, offering a replicable framework for resource-efficient development of sustainable functional crops and food supply chains.

Artemisia annua L. is extensively cultivated for artemisinin, generating large amounts of aerial biomass, while its essential oil (AAO) remains underutilized. This study aims to evaluate the regenerative potential of AAO and to elucidate its mechanism, so that to support by-product valorization for wound healing and tissue repair applications. AAO was extracted from aerial parts and characterized by GC–MS, which identified 31 major constituents dominated by mono- and sesquiterpenes, with artemisia ketone as a representative abundant component. Regenerative efficacy was assessed in a zebrafish caudal fin amputation model and mechanistic insights were obtained by integrating network pharmacology with transcriptomics and experimental validation. AAO significantly accelerated fin regrowth and tissue restoration, whereas the glucocorticoid control (beclomethasone) impaired regeneration. Network pharmacology identified four core targets (HSD11B1, PA2G4, TJP1, SLC6A3) linked to inflammation–autophagy–regeneration processes. Transcriptomic profiling and in vivo validation showed that AAO timely attenuated early inflammatory responses, evidenced by reduced neutrophil accumulation and downregulation of pro-inflammatory genes, and dynamically regulated autophagy, characterized by early enhancement followed by restoration of homeostasis. Subsequently, AAO robustly activated pro-regenerative gene programs and promoted fin restoration. Overall, AAO exhibits dual anti-inflammatory and pro-regenerative activities mediated by spatiotemporal coordination of the inflammation–autophagy–regeneration cascade, supporting its development as a plant-derived functional ingredient and providing a feasible route to increase the economic value of Artemisia annua L. biomass streams.

Panax ginseng flowers, an annually renewable yet underutilized byproduct of ginseng cultivation, represent a promising raw material for functional foods that bridges traditional East Asian ethnobotanical practices with modern nutritional science. This review systematically summarizes the phytochemical constituents and pharmacological activities of ginseng flowers to evaluate their potential as health-oriented food ingredients. Published studies from recent decades were collected and analyzed. The major bioactive compounds identified include dammarane-type ginsenosides (protopanaxadiol and protopanaxatriol types), malonylated ginsenosides, polysaccharides, and volatile constituents. Ginseng flower exhibits a broad spectrum of bioactivities and health-promoting potential, including antioxidant, anti-inflammatory, immunomodulatory, anti-fatigue, hepatoprotective, and cardiovascular protective effects. In terms of food applications, ginseng flowers have been explored as functional ingredients in beverages and fermented foods, with preliminary studies confirming technical feasibility and initial consumer acceptance. However, several challenges limit their industrial application: thermal processing induces transformation or degradation of heat-sensitive ginsenosides; bitterness and astringency hinder consumer acceptance; bioactive variability depends on cultivar, growing conditions, and harvest stage; and high-quality clinical evidence remains insufficient. Ginseng flower holds significant potential as a sustainable functional food ingredient, and future research should focus on mild processing technologies, sensory optimization, and quality standardization to facilitate its evidence-based development.

Black ginseng, a functional food, is known for enhanced bioactivity, yet systems-level understanding of how its specific bioactive compounds modulate host physiology remains to be elucidated. This study employed an integrated multi-omics approach to map the systemic host responses by which processed black ginseng influences gut health. Through bioactivity-guided screening in a dextran sulfate sodium (DSS)-induced zebrafish model, nine-time steamed black ginseng extract (BG-9) exhibited optimal efficacy in inhibiting neutrophil infiltration and oxidative stress. Chemical profiling by HPLC revealed that rare ginsenosides Rk1, Rg3, and Rg5 were the predominant components in BG-9, collectively accounting for 56.87% of the total ginsenosides. Among them, Rk1 showed the most potent protective effects in vivo. Integrated transcriptomic and metabolomic analyses uncovered that Rk1 intervention significantly reversed DSS-induced metabolic disturbances, primarily by regulating glycine, serine, threonine, and cysteine-methionine metabolism pathways, alongside neuroactive ligand-receptor interactions. These findings provide a multi-omics map delineating that rare ginsenoside Rk1 serves as the primary bioactive constituent through which black ginseng induces systemic physiological changes that modulate gut homeostasis. This work bridges the gap between the consumption of black ginseng as a functional food and its health benefits, offering a systems biology perspective for its application in gut health promotion.

Rheum maximowiczii Losinsk. is a Central Asian rhubarb increasingly considered for cultivation, yet its industrial utilization is hindered by limited chemical and safety evidence. To evaluate its potential as a novel industrial crop, this study performed a multi-dimensional comparative assessment against the cultivated benchmark Rheum tanguticum. We integrated targeted quantification, metabolomics analysis, delayed luminescence (DL) phenotyping, and zebrafish embryo acute toxicity testing. Metabolomics revealed a distinct chemotype for R. maximowiczii, marked by significantly lower anthraquinones but a relatively enriched profile of phenolic acids like catechin and gallic acid, aligning with its traditional uses. DL, a rapid biophysical tool, effectively differentiated the species and correlated strongly with these phenolic compounds, suggesting its utility for quality screening. A pivotal and unexpected finding was the acute toxicity profile. R. maximowiczii exhibited a potent, ''switch-like'' lethality with an LC₅₀ over three times lower than that of R. tanguticum, despite its low anthraquinone content. This reveals a chemical-toxicity disconnect, suggesting that its safety assessment from conventional frameworks. Our findings provide the first foundational dataset for R. maximowiczii, establishing that its responsible industrialization requires a dedicated strategy focused on its unique chemistry, tailored safety evaluation, and the development of adapted rapid quality control technologies.

The search for novel therapeutics for prevalent liver diseases such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and drug-induced liver injury is constrained by the methodological gaps in conventional preclinical models, which struggle to balance physiological complexity with screening efficiency. This challenge is particularly acute for natural products, where elucidating multifaceted mechanisms and inherent toxicological risks is paramount for translation. The zebrafish (Danio rerio) model, with its unique attributes of optical transparency, genetic tractability, and high-throughput capability, has emerged as a transformative platform to address this bottleneck. This review synthesizes and critically evaluates the integral role of zebrafish in advancing natural product-based hepatology. We provide a systematic analysis of established protocols for modeling key liver pathologies—from diet-induced and ethanol-induced steatosis to chemical hepatotoxicity—and consolidate evidence on how these models have been leveraged to decipher protective mechanisms, including the regulation of lipid metabolism, oxidative stress, and inflammation. Crucially, we integrate the parallel and essential discourse on safety, highlighting how zebrafish models, especially transgenic lines, enable the real-time visualization and mechanistic interrogation of compound-induced hepatotoxicity. By confronting current limitations, such as interspecies metabolic differences and protocol variability, we outline a strategic roadmap for the field. This involves the integration of multi-omics, humanized genetics, and standardized approaches to enhance the predictive validity of zebrafish studies. Ultimately, this review articulates how the zebrafish serves as a unified in vivo system to accelerate the identification and mechanistic validation of plant-derived therapeutics while concurrently de-risking their development, thereby directly contributing to the pipeline for new treatment options in liver disease.

Background: Glucocorticoid-induced osteoporosis (GIOP) is marked by impaired osteogenesis and reduced bone formation. Isobavachin (IBA), a flavonoid from Psoralea corylifolia, shows multiple potentials in anti-inflammatory and bone metabolism regulations, but its effects against GIOP remain unclear. This study investigated the osteoprotective effects and potential mechanism of IBA using zebrafish GIOP model. Methods: osteoprotective effects of IBA was assessed by fluorescence imaging in a prednisolone-induced zebrafish model, following with osteogenic gene expressions measured by RT-qPCR. Potential targets and pathways of IBA was filtered and predicted by network pharmacology, molecular docking, and molecular dynamics (MD) simulations, and finally validated with a pharmacological rescue experiment using a PI3K-specific inhibitor. Results: IBA improved bone mineralization and upregulated osteogenesis-related genes. Network pharmacology identified the PI3K-Akt pathway as a key pathway, with ESR1, GSK3B, MTOR, and CCND1 as core targets. PI3K inhibition attenuated the osteoprotective effects of IBA and suppressed downstream osteogenic gene expression. Conclusions: IBA alleviates GIOP by modulating the ESR1-associated PI3K-Akt signaling pathway and may serve as a multi-target therapeutic candidate for osteoporosis.

As a major by-product of juice processing, pomegranate peel holds significant valorization potential in sustainable food industries. However, conventional complete carbonization for adsorbent production destroys its bioactivity. This study proposes an innovative strategy based on controlled thermal processing to convert pomegranate peel into a novel solid food ingredient with integrated antioxidant functionality. Effects of different temperatures and durations on the phenolic composition, in vitro antioxidant activity, and safety (benzo[a]pyrene content) of the processed material were systematically investigated. The results showed that processing at 200 °C for 10 min yielded the optimal antioxidant activity, strongly linked to punicalagin enrichment. Subsequently, delayed luminescence was introduced as a process analytical tool. The key parameter Y0 (representing initial photon intensity) exhibited strong correlations with both punicalagin content and antioxidant activity, indicating its potential as a rapid, non-destructive indicator to monitor the evolution of key functional components during thermal processing. This work establishes a scientific foundation for intelligently converting pomegranate peel into a value-added food ingredient via a synergistic approach including controlled heating, targeted phytochemical regulation, and exploration of a physical signal indicator. Subject to independent validation, this exploratory indicator holds promise for supporting quality assessment in similar thermal processing applications.

Ginseng has garnered significant global interest as a functional food and nutritional supplement. It is among the top-selling natural health products owing to its potent health advantages. The growth age of ginseng is vital in the production of functional foods as it directly influences its nutritional and economic worth, particularly for forest cultivated ginseng. However, determining the growth age of forest cultivated ginseng is consistently problematic. This study assessed four samples of forest cultivated ginseng of varying growth ages using delayed luminescence (DL) and high-performance liquid chromatography. The immunomodulatory effects of these ginsengs were evaluated in vivo utilizing a zebrafish tail fin amputation model. We determined that DL characteristics effectively differentiate forest cultivated ginseng samples aged 10 years or less from those aged 15 years or more. Moreover, the DL parameters and quality indicators in these ginsengs, including ginsenosides Rg1, Rb1, Re, and Rd, exhibited substantial correlation. Furthermore, 15-year-old ginseng had the most effective action in regulating neutrophils. Consequently, DL measurement can not only accurately determine the growth age of forest cultivated ginseng but may also serve as a promising tool for assessing its quality. This work introduced a novel DL technique, establishing a robust scientific basis for enhancing research on determining the growth age of forest cultivated ginseng.

BACKGROUND: The Huangqin decoction (HQD) is widely used in clinical practice and has significant therapeutic effects on inflammatory bowel disease (IBD). However, its active ingredients and mechanisms of action for IBD remain unknown. OBJECTIVE: This study aimed to elucidate the underlying mechanism of HQD through network pharmacology and molecular docking and to verify the effectiveness of the potential active components by preliminary experimental verification. METHODS: The principal components and related protein targets of HQD were retrieved through TCMSP and Uniprot database. The disease targets were obtained in GeneCards database. The intersection targets of drug and disease were imported into STRING 11.5 database to construct the protein-protein interaction (PPI) network. GO enrichment analysis and KEGG pathway enrichment analysis of intersection targets were performed using Metascape platform. AutoDock1.5.7 software was used to verify the molecular docking between core components and core targets. The DSS-induced zebrafish IBD model was used to approve the effects of selected core targets formononetin. RESULTS: A total of 170 active components, 192 related targets and 43 intersection targets of IBD were obtained, including 6 core components and 9 core targets. 1090 results were obtained from GO analysis, including 1001, 31 and 58 results from biological process (BP), cellular component (CC), and molecular function (MF) respectively. Enrichment analysis of the KEGG pathway yielded 139 results. The results of molecular docking confirmed that HQD could exert synergistic effects through multi-components, multi-targets and multi-pathways. Furthermore, formononetin has been demonstrated as a beneficial component through molecule docking screening, which effectively affected dextran sulfate sodium (DSS)-induced zebrafish intestinal increasing neutrophils numbers, changed zebrafish larvae intestine morphology, and provided new ideas and new methods for further research on the mechanism of HQD or corresponding active targets screening in the treatment of IBD. CONCLUSION: This study comprehensively illustrates the bioactive, potential targets, and molecular mechanism of HQD against IBD. It also provided a promising strategy to uncover the scientific basis and therapeutic mechanism of traditional Chinese medicine formulae in treating IBD.

Xiaoqinglong Decoction (XQLD) is a traditional oriental medicine. Modified- Xiaoqinglong Decoction (M-XQLD) was established by adding astragalus membranaceus and codonopsis pilosula on the basis of XQLD. M-XQLD has been shown to be effective in therapying asthma in clinical trials, but the mechanism of M-XQLD in asthma is currently unknown. Mice were sensitized by ovalbumin (OVA) to induce asthma. M-XQLD were administered by oral gavage. Label-free proteomics was conducted to identify the downstream target of M-XQLD. Histopathological assessment, multiple cytokine examination in bronchoalveolar lavage fluid (BALF) were conducted. In vitro, we isolated Naïve CD4 + T cells for analysis. OVA stimulation decreased the expression of StAR Related Lipid Transfer Domain Containing 13 (STARD13), while M-XQLD treatment increased it. STARD13 overexpression reduced the inflammatory cell infiltration and goblet cells. STARD13 overexpression reduced the levels of OVA-specific IgE, IL-4, and IL-5 in serum and BALF. STARD13 overexpression inhibited the expression of IL-1β, IL-17A, and IL-22, and reduced Th17 differentiation. STARD13 overexpression inhibited the RhoA/ROCK2, while knockdown of STARD13 resulted in continuous activation of RhoA. Furthermore, STARD13 overexpression decreased p38 phosphorylation level. SB203580 treatment further inhibited the RORC expression and p38 phosphorylation. More importantly, the therapeutic efficacy of M-XQLD in OVA-induced mice was significantly reduced by STARD13 knockdown. This study revealed that M-XQLD targets to STARD13, and highlighted that STARD13 alleviated asthma by reducing Th17 differentiation via inhibiting the RhoA/ROCK2/p38 signaling.

Autophagy plays a crucial role in the physiopathological mechanisms of diseases by regulating cellular functions and maintaining cellular homeostasis, which has garnered extensive attention from researchers worldwide. The holistic regulation and bidirectional regulation effects of acupuncture can modulate cellular autophagy, promoting or restoring the homeostasis of the body’s internal environment to achieve therapeutic outcomes. This paper systematically reviews the research progress on the use of acupuncture for treating various diseases via the autophagy pathway, summarizes signal pathways related to acupuncture regulating autophagy, and analyzes the deficiencies present in the existing research. The review results indicate that the mechanism of action of acupuncture on autophagy dysfunction is reflected in the changes in LC3, Beclin1, p53, and autophagy-associated (ATG) protein expression, and regulates signaling pathways and key proteins or genes. The regulatory effect of acupuncture on autophagy capacity is bidirectional: it inhibits the abnormal activation of autophagy to prevent exacerbation of injury and reduce apoptosis, while also activating or enhancing autophagy to promote the elimination of inflammation and reduce oxidative stress. Further analysis suggests that the mechanisms of acupuncture regulating autophagy are insufficiently explored. Future research should prioritize the development of more appropriate animal models, analyzing the accuracy of relevant pathways and the specificity of indicators, exploring the synergistic effects among targets and signaling pathways, clarifying the regulatory mechanisms of acupuncture at various stages of autophagy, and evaluating the efficacy of acupuncture in autophagy modulating. This paper offers valuable insights into the regulation of autophagy by acupuncture.

Neuroinflammation represents the central pathological process in neurological disorders. Effectively regulating neuroinflammation to restore immune homeostasis and alleviate neuronal damage has emerged as a critical strategy in the prevention and treatment of these diseases. In recent years, the role of acupuncture in neuroimmune regulation, along with its anti-inflammatory and analgesic effects, has attracted considerable attention. Its potential to modulate immune homeostasis and inflammatory responses through various targets and pathways has been gradually elucidated, offering new research directions for the regulation of neuroinflammation. A series of studies have emphasized that acupuncture has significant clinical applications by regulating the immunoinflammatory pathway mediated by the brain’s TRPV1 channel. This discovery not only enhances the scientific understanding of the mechanisms underlying acupuncture but also offers new potential targets for the prevention and treatment of neuroinflammation-related diseases. The immunomodulatory properties of brain TRPV1 channels in inflammation associated with the nervous system have been emphasized. Furthermore, this study explores the immunomodulatory benefits of acupuncture in treating neuroinflammation, focusing on the potential mechanisms of TRPV1 channels at the brain level, as well as the criteria for selecting acupoints, intensity, frequency, and other relevant parameters in these studies. A deeper understanding of the neuroimmune regulatory mechanisms mediated by brain TRPV1 channels may offer new strategies and approaches for developing treatments or preventing neuropathological diseases.

Ginsenosides, the vital bioactive components in the functional food ginseng, are widely celebrated for their ability to improve physiological states and boost energy levels. Recent studies have discovered that ginsenosides can enhance endurance and elevate exercise performance by modulating the gut microbial environment. However, there remains a lack of comprehensive, systematic, and synthesized methods to evaluate the overall efficacy of ginsenosides in enhancing exercise performance. In this study, we employed non-invasive ultra-weak photon emission (UPE) detection technology to characterize the pre- and post-exercise performance of mice administered ginsenosides, along with a co-metabolic analysis of their gut microbiota. The results demonstrated that ginsenosides can improve the exercise endurance of mice. Notably, the trends in UPE changes in the abdomens of young mice and the backs of old mice were consistent with the observed improvements in their exercise endurance. Furthermore, metabolites strongly associated with gut microbiota were enriched in pathways related to energy metabolism. The accumulation of these metabolites in mice may help explain the reason by which ginsenosides enhance exercise performance. Additionally, the UPE signals were closely linked with beneficial gut bacteria and metabolites such as lipids and organic acids. Changes in these microorganisms and metabolites (e.g., Tephrowatsin B, gamma-tocotrienol, Vamonolide) may contribute to improved physical fitness and enhanced exercise performance. Our research provides a robust scientific foundation for the efficient and holistic analysis of how ginsenosides intake enhance exercise performance, offering valuable insights for future studies and applications in this field.

Phellodendron amurense Rupr., a rare herb renowned for its medicinal and ecological significance, has remained genetically unexplored at the mitochondrial level until now. This study presents the first-ever systematic assembly and annotation of the complete mitochondrial genome of P. amurense, achieved through a hybrid strategy combining Illumina and Nanopore sequencing data. The mitochondrial genome spans 566,285 bp with a GC content of 45.51 %, structured into two circular molecules. Our comprehensive analysis identified 32 protein-coding genes (PCGs), 33 tRNA genes, and 3 rRNA genes, alongside 181 simple sequence repeats, 19 tandem repeats, and 310 dispersed repeats. Notably, multiple genome conformations were predicted due to repeat-mediated homologous recombination. Additionally, we assembled the chloroplast genome, identifying 21 mitochondrial plastid sequences that provide insights into organelle genome interactions. A total of 380 RNA-editing sites within the mitochondrial PCGs were predicted, enhancing our understanding of gene regulation and function. Phylogenetic analysis using mitochondrial PCGs from 30 species revealed evolutionary relationships, confirming the homology between P. amurense and Citrus species. This foundational study offers a valuable genetic resource for the Rutaceae family, facilitating further research into genetic evolution and molecular diversity in plant mitochondrial genomes.

Cardiovascular diseases (CVDs) are a major global health challenge, significantly impacting public health and healthcare systems. Ethnopharmacological remedies and botanical medicines are widely used for the prevention and treatment of CVDs due to their multi-component, multi-target properties. Understanding the mechanisms of these natural products is essential for developing safe and effective therapies. The zebrafish model, an emerging tool in experimental pharmacology, has been increasingly used to evaluate the pharmacological activities of natural products. This review focuses the use of zebrafish models to test the prevention and treatment effects of various CVDs, and to investigate the inhibition of hyperlipidemia, thrombosis, the progress of heart failure, and the promotion of angiogenesis and toxicity. Emphasizing its experimental advantages-including the transparency characteristics of the body, its applicability to the analysis of multiple samples, and its support for real-time monitoring-aims to reveal its potential value in combining traditional cognition with contemporary pharmacological testing capabilities. The literature summary provides strong evidence for the cognitive improvement of the zebrafish system in clarifying the efficacy of natural ingredients in the cardiovascular field.

ObjectiveType 2 diabetes mellitus (T2DM) over time predisposes to inflammatory responses and abnormalities in functional brain networks that damage learning, memory, or executive function. The hippocampus is a key region often reporting connectivity abnormalities in memory disorders. Here, we investigated peripheral inflammatory responses and resting-state functional connectivity (RSFC) changes characterized of hippocampal subregions in type 2 diabetes-associated cognitive decline (T2DACD).MethodsThe study included 16 patients with T2DM, 16 patients with T2DACD and 25 healthy controls (HCs). Subjects were assessed for cognitive performance, tested for the expression of inflammatory factors IL-6, IL-10 and TNF-α in peripheral serum, underwent resting-state functional magnetic resonance imaging scans, and analyzed for RSFC using the hippocampal subregions as seeds. We also calculated the correlation between cognitive performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis.ResultsT2DACD patients showed a decline in their ability to complete cognitive assessment scales and experimental paradigms, and T2DM did not show abnormal cognitive performance. IL-6 expression was increased in peripheral serum in both T2DACD and T2DM. Compared with HCs, T2DACD showed abnormalities RSFC of the left anterior hippocampus with left precentral gyrus and left angular gyrus. T2DM showed abnormalities RSFC of the left middle hippocampus with right medial frontal gyrus, right anterior and middle hippocampus with left precuneus, left anterior hippocampus with right precuneus and right posterior middle temporal gyrus. Compared with T2DM, T2DACD showed abnormalities RSFC of the left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response time (r=0.766, P=0.001). In the ROC analysis, the significantly altered RSFC values of T2DACD achieved significant performance.ConclusionsT2DACD showed a significant decrease in attentional inhibition and working memory, peripheral pro-inflammatory response increased, and abnormalities RSFC of the hippocampal subregions with default mode network and sensory-motor network. T2DM did not show a significant cognitive decline, but peripheral pro-inflammatory response increased and abnormalities RSFC of the hippocampus subregions occurred in the brain. In addition, the left precuneus may be a key brain region in the conversion of T2DM to T2DACD. The results of this study may provide a basis for the preliminary diagnosis of T2DACD.