This study predicted the quality markers of Cordyceps militaris in improving respiratory diseases by employing high performance liquid chromatography(HPLC) fingerprint, chemometric analysis, and network pharmacology and preliminarily validated them through anti-inflammatory activity evaluation in vitro, providing reference for quality control of C. militaris. HPLC was used to establish fingerprints of fifteen batches of C. militaris, and chemometric analysis was performed to preliminarily screen out differential components. A "component-target-pathway" network was constructed utilizing network pharmacology to further predict quality markers of C. militaris in improvement of respiratory diseases. The inflammatory model of the BEAS-2B cell was induced by lipopolysaccharide, and the levels of inflammatory factors interleukin(IL)-6, IL-1β, and tumor necrosis factor(TNF)-α were detected by quantitative real-time polymerase chain reaction(PCR) to verify the activity of quality markers. Their content was determined by HPLC. In the fingerprints of the fifteen batches of C. militaris, eight common peaks were calibrated, and five main components were identified with similarities between 0.893 and 0.996. Five differential compounds were preliminarily screened through chemometric analysis. Seven efficacy related ingredients were predicted by network pharmacology. Based on the "five principles" characteristics of TCM quality markers, four functional components, namely uridine, guanosine, adenosine, and cordycepin, were ultimately selected as quality markers of C. militaris for improving respiratory diseases. Furthermore, the quality markers were found to significantly inhibit the expression of IL-6, IL-1β, and TNF-α, exerting anti-inflammatory effects in in vitro experiments. Their average content was 0.198%, 0.142%, 0.258%, and 0.116%, respectively. This study comprehensively utilized HPLC fingerprint, chemometrics, network pharmacology, and activity evaluation to predict the quality markers of C. militaris in improving respiratory diseases. The study provides references for improving the quality evaluation standard system of C. militaris and lays a foundation for exploring its mechanism in treating respiratory diseases.

Pantothenic acid (PA), or vitamin B5, can be synthesized by gut commensals, but the contribution of microbial PA to metabolic health remains unclear. Here, we find that microbial PA supply is reduced in individuals with metabolic syndrome (MetS) and is associated with impaired gut barrier function and disease severity. Tracing microbial PA identifies Bacteroides fragilis as a key contributor, with panC required for PA biosynthesis, as confirmed by isotope tracing, bacterial culture, and germ-free colonization. In MetS models, colonization with wild-type, but not ΔpanC B. fragilis, restores PA, preserves gut barrier integrity, reduces endotoxemia, and improves metabolic dysfunction. Mechanistically, microbial PA requires host pantothenate kinase activity, as silencing pantothenate kinase 2/3 (PANK2/3) in colonic organoids and in vivo reduces coenzyme A (CoA)/acetyl-CoA metabolism, suppresses Krüppel-like factor 4 (KLF4)-associated differentiation programs, and blunts the protective effects of microbial PA. Finally, a plant-derived polysaccharide enriches PA-producing Bacteroides and restores colonic PA, highlighting a strategy for colonic homeostasis and metabolic health.

As an important barrier tissue, the intestinal mucosa is responsible for regulating immunity, absorbing nutrients, and maintaining microbial homeostasis. Structural damage or functional impairment of the mucosa not only leads to a series of mucosa-related diseases but also may cause pathological changes in extramucosal organs. Given the central role of mucosal dysfunction in the onset and progression of various diseases, effectively regulating mucosal function and improving drug delivery efficiency are critical for improving clinical outcomes in gastroenterology. This article systematically reviews the structural characteristics and main functions of the intestinal mucosa, and analyzes the manifestations and underlying mechanisms of mucosal dysfunction. Based on this, we summarize recent advances in barrier enhancement, precise tissue and cell-level targeting, and microenvironment-responsive delivery strategies, and further elaborate on the latest progress in bio-inspired nanosystems for the treatment of gastrointestinal diseases. Finally, this article discusses the clinical trial progress, current challenges, and future development prospects of artificial intelligence optimization technology in the regulation of intestinal mucosa and drug delivery, aiming to provide theoretical basis and research references for in-depth studies on the regulation of intestinal mucosa function and the clinical application of related delivery systems.

The incidence of respiratory diseases is increasing worldwide and imposes a significant health burden. Due to the complex etiology and diverse inducements of these diseases, existing therapies often struggle to control disease progression and reduce recurrence rates. Therefore, the medical community continues to explore novel strategies derived from natural medicines. As a precious traditional fungus, Cordyceps has long been used for nourishing the lungs in Asia. Extensive reports demonstrate that Cordyceps exhibits considerable potential in the treatment of respiratory diseases. This review seeks to comprehensively summarize the biologically active ingredients and underlying mechanisms of Cordyceps in the treatment of respiratory diseases. The aim is to offer valuable insights for future development of Cordyceps. The literature search is conducted in PubMed, Web of Science, Science Direct, and CNKI for publications from 2007 to 2025. The keywords include "Cordyceps", "respiratory diseases", "chronic obstructive pulmonary disease", "pulmonary fibrosis", "pneumonia", "cordycepin", "polysaccharide", "ergosterol", and other related terms. Both Chinese and English terms are used for the CNKI database. Literature consisting of original research and reviews on Cordyceps active ingredients for respiratory diseases is included. Non-respiratory system research, non-peer-reviewed literature, and repetitive literature are excluded. After eligibility screening, 194 studies are included in the final analyses. Nucleosides, polysaccharide and sterols emerge as the principal ingredients in Cordyceps, which exhibit significant function against respiratory diseases. The mechanisms mainly involve alleviating oxidative stress, inhibiting inflammatory reaction, modulating immune response and others. Up to now, Cordyceps does not show obvious toxic side effects in preclinical and clinical studies. Cordyceps is a promising fungal source. This review comprehensively analyzed the biologically active ingredients and elucidated the underlying mechanisms of Cordyceps in the treatment of respiratory diseases. The paper would provide evidence for clinical use of Cordyceps and lay a foundation for its future development.

Atractylodes macrocephala Koidz, is a traditional Chinese herb widely recognized for its dual application in both dietary and medicinal contexts, primarily due to its spleen-strengthening properties. In this study, we isolated a novel water-soluble glycan from this herb, designated as XGM, and aimed to further enhance its potential for development and utilization. To achieve this objective, we elucidated its precise structural characteristics and demonstrated its immunomodulatory effects in a murine model. Structural analysis of XGM, conducted through methylation analysis and nuclear magnetic resonance (NMR) spectroscopy, revealed that it is a homogeneous xyloglucomannan with an average molecular weight of 5.5 kDa. The linear backbone of XGM consisted of α-1,4-D-Glcp and α-1,4,6-D-Glcp residues, with branches comprising terminal β-D-Manp and β-D-Xylp units that were linked to the C-6 position of the α-1,4,6-D-Glcp residues. Oral administration of XGM in mice effectively alleviated cyclophosphamide (CTX)-induced immunosuppression, as indicated by elevated serum levels of TNF-α, IL-10, IgG, and IgM, as well as the normalization of CD4+/CD8+ T cell and Treg cell ratios. Mechanistically, XGM was found to enhance the abundance of beneficial gut microbiota, such as Lactobacillus species, and to restore tryptophan metabolism, a key pathway in intestinal immunity. These findings suggest that XGM exerts its immunomodulatory effects through the regulation of the gut microbiota-metabolite axis, thereby offering novel insights into the spleen-strengthening properties of A. macrocephala and the functional mechanisms of XGM.

OBJECTIVE:This research aimed to evaluate the beneficial impact of Cordyceps militaris (CM) on chronic obstructive pulmonary disease (COPD) and methodically clarify its underlying processes. METHODS:The fingerprint analysis and content determination of CM were carried out by HPLC. The effect of CM on COPD was evaluated by a COPD mouse model. Potential targets were further explored by combining metabolomics with network pharmacology. The binding capacity between the active ingredients of CM and potential targets was assessed by molecular docking. KEY FINDINGS:A total of five nucleosides in CM were identified, including uridine, guanosine, adenosine, cordycepin, and N6-(2-hydroxyethyl) adenosine. CM significantly improved lung function and ameliorated the pathological changes in COPD. Subsequently, eight shared differentially expressed metabolites were significantly altered following CM intervention via non-targeted metabolomics analysis, with the linoleic acid metabolic pathway enriched. Next, two potential targets involving IDH1 and CYP19A1 were identified by the metabolite-reaction-enzyme-gene network. Finally, molecular docking results further corroborated strong binding affinities between the six active ingredients and the two potential targets. CONCLUSIONS:This study suggested that CM could ameliorate COPD by modulating linoleic acid metabolism and influencing IDH1 and CYP19A1, which would provide a scientific basis for the treatment of COPD with CM.

Extracellular vesicles (EVs) are crucial for facilitating intercellular communication, promoting cell migration, and orchestrating the immune response. Recently, EVs can diagnose and treat tumors. EVs can be measured as biomarkers to provide information about the type of disease and therapeutic efficacy. Furthermore, EVs with lower immunogenicity and better biocompatibility are natural carriers of chemicals and gene drugs. Herein, we review the molecular composition, biogenesis, and separation methods of EVs. We also highlight the important role of EVs from different origins as biomarkers and drug delivery systems in tumor therapy. Finally, we provide deep insights into how EVs play a role in reversing the immunosuppressive microenvironment.

ETHNOPHARMACOLOGICAL RELEVANCE:Chronic obstructive pulmonary disease (COPD) is a global health challenge with the high morbidity and mortality. Cordyceps militaris (CM) is a medicinal fungus that has been widely used in Asia for centuries. It has the effects of tonifying the lung and kidney, replenishing essence, resolving phlegm, and stopping bleeding. CM has been used clinically for alleviating COPD in China. However, the potential mechanism of CM in treating COPD remains indistinct. PURPOSE:This article aimed to evaluate the efficacy and investigate the underlying mechanism of CM in treatment of COPD. METHODS:The ingredients in CM were identified by LC Q/TOF-MS. The effect of CM in COPD was evaluated. Untargeted metabolomics assay and 16S rDNA sequencing were employed to examine the changes in metabolites and gut microbiota in COPD mice. Gut microbiota ablation experiment and quantification of short chain fatty acids (SCFAs) were integrated to elucidate the systematic mechanism of CM in treatment of COPD. RESULTS:A total of 22 ingredients were identified in CM. CM alleviated COPD significantly by improving lung function and inhibiting pulmonary inflammation. Subsequently, 11 differential metabolites regulated by CM were mainly associated with amino acid metabolism. CM ameliorated the dysbiosis of intestinal microbiota in COPD mice, which contributed to the treatment of COPD. Moreover, CM increased the contents of SCFAs, including acetate, propionate, butyrate and isobutyrate. Spearman correlation indicated a close relationship among pulmonary function, differential metabolites, and gut microbiota. CONCLUSIONS:This study revealed that CM alleviated COPD by regulating amino acid metabolism, ameliorating the imbalance of gut microbiota and increasing the SCFAs. These findings not only establish a foundation for the research of CM but also provide a basis for new treatment strategies of COPD.

Personalized in situ tumor vaccine (PISTV), an attractive type of cancer immunotherapy, promotes a potent T cell anti-cancer immune response in multiple malignancies. Nevertheless, the limited cancer elimination efficacy of PISTV was exhibited in glioblastoma (GBM). Herein, an intranasal hybrid vesicle is designed based on ginseng-derived nanoparticles (GDNPs) fusing with liposomes, encapsulating shikosin (SKN), muscone, and MAN-CpG ODN (mCpG) to enable personalized in situ tumor vaccination for amplifying anti-GBM immune response. Following intranasal administration, the hybrid vesicles penetrated the nasal mucosal barrier and circumvented the blood-brain-barrier via the olfactory bulbar pathway. Subsequently, these nano-vaccines reached the tumor site, attributed to ginsenoside Rg3 in GDNPs. SKN-mediated whole tumor cell lysis served as a tumor-antigen pool to combine with immune adjuvant mCpG, resulting in the personalized in situ tumor vaccination, then recruiting dendritic cells (DCs) and promoting DCs maturation. Afterwards, DCs antigen presentation was enhanced to mobilize T cells, differentiating into cytotoxic T lymphocytes, thus inducing adaptive anti-tumor immunity. Furthermore, the GDNPs-mediated tumor-associated macrophages repolarization combines with SKN-blocked glycolytic pathway to reverse the immunosuppressive TME from “cold” into “hot”, thereby inducing innate immunity. We developed a nanoplatform that can deliver immunogenic cell death activators and Toll-like receptor agonists to antigen-capturing cells, synchronously conveying glycolysis inhibitors and TAM repolarization inducers to TME. This work demonstrated its robust capacity to activate innate and adaptive immune responses in distal metastasis, rechallenge, and humanized patient-derived xenograft tumor-bearing mice, providing a promising pathway for immunotherapeutic sensitization of GBM.

Neoantigen (nAg) vaccines can induce anti-tumor specific immunity, and tumor killing promotes further antigen diffusion, which is expected to improve prognosis. However, the mutation of cancer cells under the selective pressure of vaccines and the immunosuppressive tumor microenvironment make the therapeutic effect unsatisfactory. Here, we develop a nanovaccine (nAg-MRDE/Mn) that can deliver nAg and induce in situ cancer vaccination to synergistically promote a personalized immune response, enhance antigen diffusion, and improve the microenvironment by modulating immunosuppressive cells and activating the innate immune response. Experiments show that nAgs are presented by dendritic cells and expressed by T cells, which cooperate with in situ vaccination to stimulate specific immunity. Cells involved in immunosuppression, such as M2 macrophages and regulatory T cells, are down-regulated, while M1 macrophages and natural killer cells are increased. In addition, the hydrogel loaded with chemokines and nAg-MRDE/Mn inhibits postoperative tumor recurrence, and the combination of nAg-MRDE/Mn and αPD-1 improves the therapeutic effect of αPD-1. This study validates the clinical potential of this strategy and provides ideas for improving neoantigen vaccines.

In spite of noteworthy breakthroughs in clinical treatments, immune checkpoint blockade (ICB) therapy is often hindered by T lymphocyte dysfunction in the immunosuppressive microenvironment of glioblastoma (GBM). Herein, GBM-derived exosomes (GBM-Exos) co-encapsulate ferroptosis inducer arsenic trioxide (ATO) and NIR photosensitizer IR780, modified with superparamagnetic iron oxide nanoparticle (SPION), to construct homologous magnetic targeted immune vesicles (Sp-Exo/AI) for reinvigorating anti-tumor immunity. SPION modified GBM-Exos display capacities of tumor accumulation and blood-brain barrier penetration. Notably, reactive oxygen species metabolism is disturbed by ferroptosis activation augmented photodynamic therapy (PDT), hence triggering tumor cell lysis and mitochondrial damage to reshape tumor microenvironment (TME) and transform GBM from immune "cold" to "hot". Accordingly, the tumor specific T lymphocytes function and phenotype transformation of macrophages were promoted to stimulate robust innate and adaptive immunities. Significantly, the remarkable ferroptosis activation augmented PDT combining with programmed death-1 antibody actives long-term immune memory and inhibits distal tumor metastasis. Superior anti-tumor effect of Sp-Exo/AI in the recurrence model, breast cancer model and patient-derived model were observed as well. Altogether, the presented homologous magnetic targeted immune vesicles exhibit substantial potential for amplifying immune response in "cold" tumors like GBM through revising immunosuppressive TME.

Aconiti Lateralis Radix Praeparata (Fuzi) is a traditional Chinese medicine (TCM) widely used in treating cancer. Our formerly investigations confirmed the anti-lung cancer efficacy of Fuzi, but systematic analysis of the ingredients of Fuzi absorbed into serum and the corresponding molecular mechanism in treating lung cancer remained unknown. In this work, UPLC-Q-TOF-MS was applied to detect the ingredients of Fuzi in rat serum. Next, the possible targets and key pathways of the components absorbed into serum of Fuzi were predicted by network pharmacology. Then, the binding activity of components and potential targets were performed by molecular docking. Afterwards, the proliferation, mitochondrial membrane potential (MMP), apoptosis and reactive oxygen species (ROS) of lung cancer cells after treatment with Fuzi-containing serum were determined by MTT assay, JC-1 fluorescent probe, Annexin V-FITC/PI double staining and DCFH-DA respectively. Finally, the predicted target was further validated with qRT-PCR. In total, identification of 20 components of Fuzi derived from rat serum were achieved. The prediction of network pharmacology indicated that these compounds might exert their therapeutic effects by modulating mTOR. The findings from molecular docking proved that fuziline, songorine, napelline and hypaconitine exhibited binding potential with the mTOR. Cancer cell experiments revealed that the Fuzi-containing serum inhibited cell proliferation, induced apoptosis, reduced MMP and increased ROS. Additionally, Fuzi-containing serum significantly reduced the mRNA expression of mTOR. This study revealed that fuziline, songorine, napelline and hypaconitine were the main ingredients of Fuzi absorbed into serum. Furthermore, Fuzi-containing serum demonstrated inhibitory effects on the proliferation of lung cancer cells and induced the apoptosis. Combined with the results of network pharmacology, molecular docking and biological verification, Fuzi-containing serum might exert its anti-lung cancer effect by inhibiting mTOR. This study would provide a deeper understanding of Fuzi in treating lung cancer and offer a scientific reference for its clinical utilization.

Computer-aided drug design (CADD) provides unique benefits for discovering and optimizing lead compounds. Aconiti Lateralis Radix Praeparata (Fuzi in Chinese) is a traditional herbal medicine widely used in China and other Asian countries. This study employed virtual screening, molecular dynamics simulations, and experimental validation to identify activators of pyruvate kinase M2 (PKM2) from Fuzi alkaloids. The process involved molecular docking and ADME analyses, which led to the selection of 17 alkaloids for further investigation. The results from microscale thermophoresis showed that 14 alkaloids exhibited strong binding affinities to the PKM2 protein. The kinase activity assays showed that mesaconine, benzoylaconine, and hypaconitine were effective in activating the PKM2 recombinant protein. Western blotting, glutaraldehyde cross-linking assay and immunofluorescence experiments revealed that hypaconitine inhibited PKM2 phosphorylation, obstructed its nuclear translocation, increased the tetrameric form, and accordingly decreased the dimeric form. The stability of the hypaconitine-PKM2 complex was confirmed through molecular dynamics simulations. This study is the first to report that hypaconitine activated PKM2 significantly, which would provide references for the clinical use of Fuzi and lay foundation for the discovery of PKM2 activators.

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

Xingnaojing injection (XNJ), is the first-line Chinese medicine injection approved for treating ischemic stroke (IS). XNJ can attenuate the inflammatory responses and oxidative stress, thus reversing neuronal damage of IS. This study aims to prepare the biomimetic nanoparticles (Bo-GEVs/XNJM) of nasal administration for IS treatment. The grapefruit extracellular vesicles (GEVs) loaded with microemulsions sourced from Xingnaojing injection (XNJM) are modified with borneol (Bo) to bypass the blood-brain barrier (BBB). Bo-GEVs/XNJM has the property of brain-targeting, and in vivo and in vitro experiments have validated that it has positive effects in reducing apoptosis, inhibiting oxidative stress, anti-inflammation, protecting mitochondrial function, and protecting the BBB. In summary, Bo-GEVs/XNJM has good neuroprotective effects, and provides an interventional method for the treatment of ischemic stroke.

Immune checkpoint blockade (ICB) has achieved unprecedented progress in tumor immunotherapy by blocking specific immune checkpoint molecules. However, the high biodistribution of the drug prevents it from specifically targeting tumor tissues, leading to immune-related adverse events. Biomimetic nanodrug delivery systems (BNDSs) readily applicable to ICB therapy have been widely developed at the preclinical stage to avoid immune-related adverse events. By exploiting or mimicking complex biological structures, the constructed BNDS as a novel drug delivery system has good biocompatibility and certain tumor-targeting properties. Herein, the latest findings regarding the aforementioned therapies associated with ICB therapy are highlighted. Simultaneously, prospective bioinspired engineering strategies can be designed to overcome the four-level barriers to drug entry into lesion sites. In future clinical translation, BNDS-based ICB combination therapy represents a promising avenue for cancer treatment.

Extracellular vesicles (EVs), natural nano-vesicles carrying multiple bioactive molecules, have been broadly applied in brain diseases due to their excellent biocompatibility, low immunogenicity, and superior physicochemical properties. However, owing to the complexity of the blood-brain barrier (BBB) and brain diseases, and under the common oral and injectable drug delivery, EVs still have poor brain delivery and retention capabilities, and cannot achieve clinical therapeutic effects. Intranasal (IN) delivery may be a potential way to address this issue. IN delivery can bypass the body circulation and BBB, and enter the brain directly through the nasal mucosa, which offers the advantages of painless, non-invasive, and repeated administration. Herein, we discuss recent developments in the therapy of brain diseases with IN-delivered EVs. We outline the basic properties of EVs and summarize the effects of EVs on the brain. We then discuss the mechanistic pathways and advantages of IN delivery of EVs and review studies that combine EVs with IN delivery for the treatment of brain diseases. Finally, we briefly outline the challenges and prospects for IN-delivered EVs and suggest possible recommendations to facilitate the clinical translation and development of IN-delivered EVs.

Background: Non-small cell lung cancer (NSCLC) is a highly prevalent and fatal form of lung cancer. In China, Aconiti Lateralis Radix Praeparata (Fuzi in Chinese), derived from the lateral root of Aconitum carmichaeli Debx. (Ranunculaceae, Aconitum), is extensively prescribed to treat cancer in traditional medicine and clinical practice. However, the precise mechanism by which Fuzi treats NSCLC remains unknown. Purpose: This article aims to assess the efficacy of Fuzi against NSCLC and elucidate its underlying mechanism. Methods: Marker ingredients of Fuzi decoction were quantified using UPLC-TSQ-MS. The effectiveness of Fuzi on NSCLC was evaluated using a xenograft mouse model. Subsequently, a comprehensive approach involving network pharmacology, serum metabolomics, and 16S rDNA sequencing was employed to investigate the antiNSCLC mechanism of Fuzi. Results: Pharmacological evaluation revealed significant tumour growth inhibition by Fuzi, accompanied by minimal toxicity. Network pharmacology identified 29 active Fuzi compounds influencing HIF-1, PI3K/Akt signalling, and central carbon metabolism in NSCLC. Integrating untargeted serum metabolomics highlighted 30 differential metabolites enriched in aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate metabolism, and the tricarboxylic acid (TCA) cycle. Targeted serum metabolomics confirmed elevated glucose content and reduced levels of pyruvate, lactate, citrate, alpha-ketoglutarate, succinate, fumarate, and malate following Fuzi administration. Furthermore, 16S rDNA sequencing assay showed that Fuzi ameliorated the dysbiosis after tumorigenesis, decreased the abundance of Proteobacteria, and increased that of Firmicutes and Bacteriodetes. PICRUSt analysis revealed that Fuzi modulated the pentose phosphate pathway of the gut microbiota. Spearman correlation showed that Proteobacteria and Escherichia_Shigella accelerated the TCA cycle, whereas Bacteroidota, Bacteroides, and Lachnospiraceae_NK4A136_group suppressed the TCA cycle. Conclusions: This study firstly introduces a novel NSCLC mechanism involving Fuzi, encompassing energy metabolism and intestinal flora. It clarifies the pivotal role of the gut microbiota in treating NSCLC and modulating the TCA cycle. Moreover, these findings offer valuable insights for clinical practices and future research of Fuzi against NSCLC.

Ischemic stroke (IS), accounting for 87 % of stroke incidences, constitutes a paramount health challenge owing to neurological impairments and irreversible tissue damage arising from cerebral ischemia. Chief among therapeutic obstacles are the restrictive penetration of the blood-brain barrier (BBB) and insufficient targeting precision, hindering the accumulation of drugs in ischemic brain areas. Motivated by the remarkable capabilities of natural membrane-based delivery vehicles in achieving targeted delivery and traversing the BBB, thanks to their biocompatible architecture and bioactive components, numerous membrane-engineered systems such as cells, cell membranes and extracellular vesicles have emerged as promising platforms to augment IS treatment efficacy with the help of nanotechnology. This review consolidates the primary pathological manifestations following IS, elucidates the unique functionalities of natural membrane drug delivery systems (DDSs) with nanotechnology, as well as delineates the structural characteristics of various natural membranes alongside rational design strategies employed. The review illuminates both the potential and challenges encountered when employing natural membrane DDSs in IS drug therapy, offering fresh perspectives and insights for devising efficacious and practical delivery systems tailored to IS intervention.

Aconiti Lateralis Radix Praeparata (Fuzi in Chinese) is widely used in the clinical treatment of tumors. This study aims to explore the active fractions and underlying mechanisms of Fuzi in the treatment of non-small cell lung cancer (NSCLC). Fuzi alkaloids (FZA) is prepared and found to inhibit the growth of NSCLC both in vitro and in vivo significantly. A total of 53 alkaloids are identified in FZA by UPLC-Q-TOF-MS. Proteomics experiment show that 238 differentially expressed proteins regulated by FZA are involved in amino acid anabolism, pyrimidine metabolism and PI3K/Akt-mTOR signaling pathway. Metabolomics analyses identify 32 significant differential metabolites which are mainly involved in amino acid metabolism, TCA cycle and other pathways. Multi-omics research combined with molecular biological assays suggest that FZA might regulate glycolysis through PI3K/Akt-mTOR pathway to treat NSCLC. The study lays a foundation for the anti-cancer investigation of Fuzi and provides a possible scientific basis for its clinical application.