Gliomas present a formidable challenge in oncology due to their immunosuppressive tumor microenvironment and the restricted delivery of therapeutics across the blood-brain barrier. Here, we report a novel hybrid nanoplatform (HEV) for synergistic chemo-immunotherapy, constructed by integrating honeysuckle-derived vesicle-like nanoparticles (HDVN) with paclitaxel (PTX)-loaded liposomes via PEG-mediated fusion. HDVN, extracted from Lonicera japonica Flos using sucrose gradient ultracentrifugation, measured 104 ± 2.1 nm in diameter and carried functional miRNAs, including miRNA2911, capable of modulating tumor-associated macrophage (TAM) polarization through the JNK and p38 MAPK pathway. The resulting HEV achieved an encapsulation efficiency of 86.58 ± 0.06% and were administered intranasally to exploit nasal-to-brain (N2B) delivery and enhanced permeability effects. In vitro, HEV exhibited potent cytotoxicity against C6 glioma cells (IC50: 3.93 µg/mL) and promoted M1 polarization of TAM, upregulating CD80, CD86, and MHC-II while suppressing CD206. In vivo, HEV significantly inhibited tumor growth in C6 glioma-bearing mice, extending median survival from 21 to 66 days, with reduced systemic toxicity compared to free paclitaxel. miRNA sequencing and KEGG pathway analysis confirmed the cross-kingdom immunomodulatory function of HDVN, contributing to the synergistic therapeutic effect. This study establishes HDVN and HEV as a pioneering nanoplatform for targeted chemo-immunotherapy in glioma, offering a promising strategy with potential for clinical translation.

Objective Euphorbia Semen (ES) and Euphorbia Semen Pulveratum (ESP) could spontaneously form Euphorbia Semen microemulsion (ESM) and Euphorbia Semen Pulveratum microemulsion (ESPM) in aqueous solution. However, the differences in the absorption and distribution of ESM and ESPM in vivo have not yet been evaluated. This study focused on exploring the differences of pharmacokinetic characteristics and in vivo gastrointestinal distribution of ESM and ESPM. Methods ESM and ESPM were prepared and preliminarily characterized using ES and ESP as model drugs, respectively, without any addition of carriers and excipients. Meanwhile, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analytical method for the simultaneous determination of six diterpenoid esters (Euphorbia factors L1, L2, L3, L7a, L7b, L8) in rat plasma was developed and validated for the first time, as well as innovatively applied to investigate the pharmacokinetic characteristics of ESM and ESPM in rat plasma following oral administration. Furthermore, the gastrointestinal tract distribution of ESM and ESPM was examined by the small animal in vivo imaging. Results This established UPLC-MS/MS method exhibited good specificity, linearity, accuracy, precision, stability, matrix effect and extraction recovery, and innovatively applied to pharmacokinetics of six diterpenoid esters of ESM and ESPM in rat plasma. Pharmacokinetic and in vivo imaging results displayed that time to maximum concentration (Tmax), half-life of elimination (t1/2), mean residence time (MRT), and area under the concentration–time curve (AUC) of Euphorbia factors L1, L2, L3, L7a, L7b, L8 were increased (P < 0.05, 0.01), maximum concentration (Cmax) and clearance (CLz/F) were decreased (P < 0.05, 0.01) in ESPM compared with ESM, and both ESM and ESPM mainly accumulated in the stomach and colon within 12 h of oral administration. The above results suggested that compared with ESM, ESPM showed a slowed rate of absorption and elimination in vivo, a prolonged mean residence time in vivo, resulting in a better accumulation in the stomach and colon, thus increasing absorption and bioavailability in vivo and demonstrating a slow-release effect. Conclusion This study demonstrated for the first time that the pharmacokinetic characteristics and gastrointestinal distribution of the six active diterpenoid esters in ESM and ESPM differed in vivo, which might be related to changes in multicomponent interactions and their effects on the absorption and distribution of diterpenoid esters. This research will lay scientific support for further analyzing pharmacodynamic basis of ESPM and promoting its in-depth development, application and clinical transformation.

The incidence rate of cognitive dysfunction (CD) urgently requires the development of safe and effective dietary supplements to prevent and treat this disease. Polygonatum cyrtonema Hua (PS) is a traditional Chinese herb that can be used as both food and a medicine, and is known to improve memory and nourish the nerves. However, there has been limited research on the commonly used wine-processed form of PS (WPS) in clinical practice; consequently, we know little about the pharmacological effects of WPS and the mechanisms involved. In this study, we investigated the homogeneous polysaccharides extracted from PS (SP3) and WPS (JP3) and investigated the effects of JP3 on the CD and the brain-gut axis in chronic unpredictable mild stress (CUMS) mice. SP3 and JP3 showed significant differences in terms of molecular weight, monosaccharide content, and surface morphology. Mechanistic studies showed that JP3 affected the brain-gut axis by regulating the gut microbiota and the intestinal barrier, and improved lesions and oxidative stress in the hippocampus, thus alleviating cognitive impairment. JP3 was able to increase probiotics such as Lactobacillus murinus, improve hippocampal lesions, and oxidative stress levels. Compared with inulin, JP3 better promotes the proliferation of Lactobacillus murinus and the production of butyric acid and isobutyric acid. The results suggest that WPS homogeneous polysaccharides can regulate intestinal microbiota and improve cognitive level, which is a potential functional product for the prevention of CD.

BACKGROUNDS:Plant-derived exosome-like nanovesicles (PELNVs) are nanoscale vesicles with lipid bilayer as the basic framework, which include nucleic acids, encapsulate various proteins, and other bioactive substances. They have recently become promising preparations for disease treatment and intercellular signaling. Studies have shown that Chinese medicine-derived exosome-like nanovesicles (CMELNVs) have great potential in solving a variety of human health diseases. However this also brings to light several challenges, such as diverse sources, complex ingredients, unclear mechanisms of action, and no uniform standards for the isolation and identification of CMELNVs. OBJECTIVES:The present work systematically reviewes and synthesizes the studies on the isolation, characterization, pharmacology, and toxicology of CMELNVs. This review seeks to clarify the functions and potential mechanisms of PELNVs in disease treatment, emphasizing the importance of incorporating PELNVs into drug delivery platforms. MATERIAL AND METHOD:The PRISMA guidelines were followed in the following sequence: researching literature, organizing retrieved documents, abstracting relevant information, assessing study quality and bias, synthesizing data, and preparing a comprehensive report. A comprehensive survey was conducted on multiple databases including PubMed, Web of Science, CNKI and Wanfang Data. Keywords used in the search include "Chinese medicine", "application of fresh medicine", "exosomes", "plant exosomes", "biomedical applications", "vesicle, disease" AND "natural extracts". Comprehensive research and compilation of literature up to May 2025 were conducted. RESULTS:Reports showed that the CMELNVs have demonstrate unique and favorable therapeutic effects in various diseases. This review provides an exhaustive overview of the biological composition, isolation and identification methods, pharmacological actions, mechanisms and safety of CMELNVs, highlighting the current challenges and potential future research directions for CMELNVs to inspire new ideas and methodologies for the study on establishing quality standards for CMELNVs.

Given the limited efficacy and notable side effects associated with conventional skin wound repair therapies, there is an urgent need to develop novel bioactive therapeutic strategies. As a novel type of bioactive nanovesicle formulation, plant-derived exosomes (PDEs) have demonstrated potential for multidimensional regulation in skin wound treatment. PDEs are characterized by low immunogenicity, high biocompatibility, and the ability of trans-barrier delivery. They accelerate skin tissue repair through multiple mechanisms such as regulating inflammatory response, promoting angiogenesis, and inducing cell proliferation and migration. Current reports on the role of PDEs in skin wound repair and their associated mechanisms are limited, highlighting their novelty and the need for in-depth exploration. The purpose of this review is to provide an overview of the biological properties, extraction and characterization methods, biological functions of PDEs and their mechanisms of action, and applications in skin wound repair. At the end, the future potentials and challenges of PDEs in skin wound repair are summarized to provide theoretical support for precise wound repair therapy based on PDEs.

Polygonatum cyrtonema Hua (PC) is a traditional Chinese medicine with a long history of use as pharmaceuticals or functional foods. Wine steaming is the main processing method of PC, which changes the structure of polysaccharides and oligosaccharides in PC and enhances biological activities. This study investigated the structural characterization of raw and wine-steamed PC oligosaccharides and the differences in the immunomodulatory effects using cyclophosphamide (CTX)-induced immunosuppression rat model. The oligosaccharides content and molecular weight of PC after wine steaming decreased, the proportion of oligosaccharides in total sugars and the reducing sugars content increased, and the monosaccharides composition of oligosaccharides changed. The raw Polygonatum cyrtonema Hua oligosaccharides (PCCO) and the wine-steamed Polygonatum cyrtonema Hua oligosaccharides (PCWO) exerted regulatory effects on organ index, immunoglobulin G (IgG), complement 3 (C3) spleen and colon tissue morphology, hematopoietic function of immunosuppressive rats treated by cyclophosphamide (CTX). Both PCCO and PCWO significantly regulated and improved the diversity and abundance of gut microbiota in immunosuppressed rats and increased the content of short-chain fatty acids (SCFAs) in the feces of rats, and the regulating effect of PCWO was better than PCCO. Differential microbiota analysis showed that PCWO could promote the proliferation of Bifidobacterium, Bacteroides, Oscillibacter, Roseburia, and Alistipes. In summary, the difference in the structural characteristics of PC oligosaccharides might be the reason for immune enhancement. This study could provide a theoretical basis for clarifying the scientific connotation of wine steaming to enhance the efficacy of PC, and promote the application of wine-steamed PC as an immunomodulator in pharmaceuticals or functional foods.

Malignant ascites effusion (MAE) is a common complication of advanced malignant tumors with limited treatments. Euphorbia lathyris (EL) has a long history of application in patients with edema and ascites. Herein, we reported for the first time a mode in which EL and EL Pulveratum (PEL) spontaneously formed natural microemulsions (ELM and PELM) without the addition of any carriers and excipients, and found that the protein and phospholipid contained in them encapsulated fatty oil and diterpenoid esters through non-covalent interactions. The denaturation and degradation of protein in PELM resulted in stronger binding of diterpenoid esters to the hydrophobic region of protein, which facilitated the sustained and slow release of diterpenoid esters and improved their bioavailability in vivo, thereby retaining the efficacy of preventing MAE while alleviating the irritation of intestinal mucosa. The mechanism by which PELM retained efficacy might be related to increased feces moisture and urine volume, and decreased expression of AVPR2, cAMP, PKA and AQP3 in MAE mice. And its mechanism of reducing intestinal mucosal irritation was related to decreased cell apoptosis, amelioration of oxidative stress, elevation of mitochondrial membrane potential, and up-regulation of Occludin and Claudin-1 expression in IEC-6 cells. This nano-adjuvant-free natural microemulsions may be a promising therapeutic strategy in the field of phytochemistry for promoting the application of natural and efficient nano-aggregates spontaneously formed by medicinal plants in MAE, and provide a new perspective for advancing the development of the fusion of Chinese herbal medicine and nanomedicine and its clinical translation.

The plant Dipsacus asperoides C. Y. Cheng et T. M. A., has been traditionally utilized as a medicinal plant in China due to its roots known as “Dipsaci Radix”. It is suggested that Dipsaci Radix exhibits antihyperglycemic, hypolipidemic, and antioxidant properties, along with down-regulating effects on advanced glycation end-products (AGEs) formation. However, there are currently no reliable reports on the effective components derived from Dipsaci Radix for anti-diabetes. In this study, the methanol extract and its corresponding ethyl acetate (EA) fraction of Dipsaci Radix were investigated as potential natural sources of antidiabetic agents and antioxidants by in vivo methods. The existence of phenolic components in extract and fraction enhances their antioxidant and antidiabetic properties. This is evidenced by the fact that all isolated phenolic compounds exhibited such properties, with half of them (Compound 2, 4, 5, 8, 10) displaying multidirectional inhibitory effects. Quality evaluation of these active components using high performance liquid chromatography-ultraviolet (HPLC-UV) technology combined with grey relational analysis provides further information regarding the spectrum-effect relationship between active components and their activities. Among them, the presence of the active ingredient “5-O-caffeoylquinic acid” significantly contributes to the antidiabetic and antioxidant properties of Dipsaci Radix. This holds promising applications in traditional health products and cosmeceuticals.

The plant Dipsacus asperoides C. Y. Cheng et T. M. A., has been traditionally utilized as a medicinal plant in China due to its roots known as “Dipsaci Radix”. It is suggested that Dipsaci Radix exhibits antihyperglycemic, hypolipidemic, and antioxidant properties, along with down-regulating effects on advanced glycation end-products (AGEs) formation. However, there are currently no reliable reports on the effective components derived from Dipsaci Radix for anti-diabetes. In this study, the methanol extract and its corresponding ethyl acetate (EA) fraction of Dipsaci Radix were investigated as potential natural sources of antidiabetic agents and antioxidants by in vivo methods. The existence of phenolic components in extract and fraction enhances their antioxidant and antidiabetic properties. This is evidenced by the fact that all isolated phenolic compounds exhibited such properties, with half of them (Compound 2, 4, 5, 8, 10) displaying multidirectional inhibitory effects. Quality evaluation of these active components using high performance liquid chromatography-ultraviolet (HPLC-UV) technology combined with grey relational analysis provides further information regarding the spectrum-effect relationship between active components and their activities. Among them, the presence of the active ingredient “5-O-caffeoylquinic acid” significantly contributes to the antidiabetic and antioxidant properties of Dipsaci Radix. This holds promising applications in traditional health products and cosmeceuticals.

Mori Fructus (MF) is the dried fruit of Morus alba L., which is a dual-purpose resource for medicine and food. As one of the main active components of MF, polysaccharides exhibit many biological activities such as immunomodulation, hypoglycaemia effects, liver protection, and regulation of the intestinal flora. In recent years, the extraction and purification methods, structure, biological activity, and structure-activity relationship of Mori Fructus polysaccharides (MFP) have attracted extensive attention. MFP composed of repetitive disaccharide fragments of 1,4-linked u03B1-GalpA and 1,2-linked u03B1-Rhap. Structural information such as extraction yield, molecular weight (Mw), and monosaccharide composition of MFP differs based on the extraction process used. In addition, the Mw, monosaccharide composition, and chemical modification of MFP are closely related to its biological activity. Currently, the research of MFP is still in the primary stage, and further exploration is required to fully reveal their structure and biological functions. This paper systematically reviews the research progress of extraction, purification, structural characterization, and biological activities of MFP, deeply analyzes their structure-activity relationship and product application status, and discusses some existing problems in order to provide support for the further development and utilization of MFP.

Euphorbia lathyris L. (EL) is a traditional poisonous herbal medicine used to treat dropsy, ascites, amenorrhea, anuria and constipation. Processing to reduce toxicity of EL is essential for its safe and effective application. However, there is little known regarding the molecular mechanism of reducing toxicity after EL processing. This research aimed to screen the differential markers for EL and PEL, explore the differential mechanisms of inflammatory injury induced by EL and processed EL (PEL) to expound the mechanism of alleviating toxicity after EL processing. The results showed that 15 potential biomarkers, mainly belonging to diterpenoids, were screened to distinguish EL from PEL. EL promoted the expressions of TLR4, NLRP3, NF-κB p65, IL-1β and TNF-α, increased lipid rafts abundance and promoted TLR4 positioning to lipid rafts. Meanwhile, EL decreased LXRα and ABCA1 expression, and reduced cholesterol efflux. In contrast to EL, the effects of PEL on these indicators were markedly weakened. In addition, Euphorbia factors L1, L2, and L3 affected LXRα, ABCA1, TLR4, NLRP3, NF-κB p65, TNF-α and IL-1β expression, influenced cholesterol efflux and lipid rafts abundance, and interfered with the colocalization of TLR4 and lipid rafts. The inflammatory injury caused by processed EL was significantly weaker than that caused by crude EL, and reduction of Euphorbia factors L1, L2, and L3 as well as attenuation of inflammatory injury participated in processing-based detoxification of EL. Our results provide valuable insights into the attenuated mechanism of EL processing and will guide future research on the processing mechanism of toxic traditional Chinese medicine.

通过分析药事管理学教学"五育"融合现状,结合课程教学目标,明确全方位、全过程教育理念,探求药事管理学"五育"的融合点,分析教学内容、方式与"五育"融合的策略,以培养出德智体美劳全面发展的药事管理专业人才.