Nanoparticle delivery systems have good application prospects in the field of precision therapy, but the preparation process of nanomaterial has problems such as short in vivo circulation time, easy recognition, and clearance by the immune system in the body. In recent years, biomimetic nanoparticle delivery systems mediated by natural cell membranes have become a research hotspot to address these issues. The natural membrane biomimetic nanoparticle delivery system cleverly integrates the advantages of natural biofilm "autologous" and "artificial" functional carriers by using endogenous cell membranes to modify the surface of nanocarriers, endowing them with characteristics such as tumor targeting, low immunogenicity, and long blood circulation. Currently, biomimetic nanoparticle delivery systems have been used in the treatment of malignant tumors, cardiovascular diseases, bacterial infections, and other diseases. This paper analyzes the development status and current research hotspots of natural cell membrane camouflaged biomimetic nanoparticle delivery systems mainly reviews the latest research progress of red blood cell membrane camouflaged biomimetic nanoparticle delivery systems in the field of disease treatment in recent years. It focuses on exploring the advantages, future development prospects, and limitations of biomimetic nanoparticle delivery systems based on red blood cell membrane camouflage in improving drug delivery, to provide a reference for the in-depth research and development of this system.

OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

Objective To investigate the effects of raddeanin A(RA)on the proliferation and apoptosis of HCT116 cells and on the β-catenin/c-Myc pathway.Methods Human colon cancer HCT116 cells were divided into four groups:Control group,experimental-L group,experimental-M group and experimental-H group.Experimental-L,experimental-M,experimental-H groups were treated with 5,10 and 20 μmol·L-1raddeanin A,and the control group was given the same amount of normal saline,respectively.The inhibitory effect of RA on the proliferation of HCT116 cells of colon cancer was detected by cell counting kit-8(CCK-8)method.Cell nucleus morphology change was observed with the fluorescence;the apoptosis rate was detected by flow cytometry;and the expression of related proteins of β-catenin/c-Myc signaling pathway was detected by western blot.Results After 48 h,the cell inhibitory rates of the control group,experimental-L,experimental-M,experimental-H groups were 0,(19.15±0.65)％,(35.11±0.40)％and(49.93±1.13)％,respectively;the cell apoptosis rates were(0.16±0.18)％,(9.26±0.42)％,(17.87±2.54)％and(38.10±2.70)％,respectively;the protein expression levels of β-catenin were 0.74±0.03,0.69±0.01,0.33±0.02 and 0.16±0.04,respectively;the protein expression levels of c-Myc were 0.89±0.01,0.54±0.03,0.29±0.03 and 0.13±0.04,respectively;the protein expression levels of Cyclin D1 were 0.84±0.04,0.66±0.01,0.48±0.06 and 0.21±0.03,respectively;the expression levels of Cleaved-Caspase3 protein were 0.19±0.03,0.26±0.04,0.45±0.04 and 0.78±0.01,respectively.The above indicators in the experimental-L,experimental-M,experimental-H groups showed statistically significant differences compared to those of control group(all P＜0.05).Conclusion RA can inhibit the proliferation of HCT116 cells and induce apoptosis,which may be related to the inhibition of β-catenin/c-Myc signaling pathway.

This study used kidney metabolomics to investigate the underlying mechanisms of Guilingji (GLJ) on mild cognitive impairment (MCI) rats. The rats were randomly divided into 6 groups (n = 8), i.e., control group, model group, positive drug (Ginkgo biloba tablet, donepezil) group, GLJ group (low and high dose group). The MCI rat model was replicated using subcutaneous injection of D-galactose into the back of the neck along with a semi-high-fat diet for a total of 8 weeks, and drug was administered from the 5th week for 4 weeks. The kidney function and renal pathological changes of each group of rats were tested. And LC-MS based kidney metabolomics coupled with multivariate data analysis were conducted to explore the potential biomarkers, and corresponding metabolic pathways were then determined. After administration of GLJ, the level of urea nitrogen was decreased compared with those of the model group, and the abnormalities of morphology in kidney tissues were improved. The positive drugs (ginkgo biloba tablet and donepezil) had no significant modulating effect on renal function indexes. Ginkgo biloba tablet can lessen the pathological injury of kidney tissue, and donepezil had no improvement on renal histopathology. A total of 23 MCI related differential metabolites were identified in kidney, and 17 metabolites were signifcantly restored by GLJ compared with those of the model group. Additionally, we found that the cysteine and methionine metabolism, nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism were significantly involved in the regulatory effect of GLJ. The results illuminate the "cong shen zhi nao" mechanism of GLJ, and also provide a research basis for the clinical use of GLJ for the treatment of MCI. The animal experiment of this study was approved by the Ethics Committee of Shanxi University (approval number: 2020DW121).

To explore the absorption mechanism of APS-Ⅱ in vivo by establishing M cell model. First, Astragalus polysaccharides (APS) was divided into two different molecular weight polysaccharides APS-I ( > 2 000 kDa) and APS-II (10 kDa) by ultrafiltration, and APS-II (10 kDa) was prepared and fluorescently labeled. Meanwhile, M cell model was constructed by Caco-2 cells and Raji cells. The M cell model was treated with transport inhibitors to explore the transport of APS-Ⅱ on M cells. The results show that FITC has been successfully labeled to the end of APS-Ⅱ, and the M cell model was successfully constructed, which found that APS-Ⅱ could be transported by M cells, and four transport inhibitors of 5-(N-ethyl-N-isopropyl) amiloride (EIPA), genistein, dynasore and nocodazole indicated that APS-II may enter cells through clathrin and caveolin-mediated endocytosis.

Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).

Diabetic retinopathy (DR) is a diabetic ocular complication that can lead to poor vision and blindness. This experiment aimed to investigate the ameliorative effect and its mechanism of Panax notoginseng saponins (PNS) eye drops on streptozotocin (STZ)-induced non-proliferative diabetic retinopathy (NPDR) in rats. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine (No. PZSHUTCM 211115004). Diabetes mellitus was induced by a single intraperitoneal injection of STZ into rats. Two months later, PNS solution was dropped binocular twice per day at 6 h intervals at dose of 20, 40, and 80 mg·kg^-1 continuously for 1 month. The morphological structure and activation of microglia of the retina were observed by hematoxylin-eosin staining and immunohistochemical assay. The disruption of the blood-retina barrier (BRB) was conducted by the Evans blue dye leakage assay. The number of acellular capillaries in the retina was assessed by digesting and hematoxylin-eosin staining assay. The number of retinal leukocyte adhesion was observed by fluorescein isothiocyanate-coupled concanavalin A lectin labeling assay. The serum expression of inflammatory factors was measured using enzyme-linked immunosorbent assay. Western blot experiments were used to detect the expression of relevant proteins in retinal tissue and transcriptional activation of nuclear factor kappa-B (NF-κB). The results revealed that PNS eye drops significantly increased the thickness of the retina, decreased the number of acellular capillaries, and up-regulated the expression of the tight junction proteins claudin-1 and occludin, thereby alleviating BRB damage. In addition, PNS eye drops were also able to significantly reduce leukocyte adhesion and microglia activation, the expression of inflammatory factors in serum, and the nuclear translocation of retinal p65 proteins, effectively inhibiting the occurrence of retinal inflammation. The above results showed that PNS eye drops played a role in improving NPDR by inhibiting the activation of the NF-κB signaling pathway and reducing inflammation.

The effect of different concentrations of glycyrrhizic acid (GA) and Zn²⁺ on the self-assembly of metal complexes was investigated by forming metal complexes, and the properties and assembly mechanisms of the formed carrier-free supramolecular hydrogel were characterised. Scanning electron microscopy (SEM) and zeta potential were used to characterise the microscopic morphology and stability of the GA-Zn complex hydrogel, which had spherical-like particles of about 1 μm with good stability; the rheometer was used to detect its materialistic properties, which showed excellent stability, self-healing property and reversibility; through in vitro bacterial inhibition, it was found that the GA-Zn carrier-free supramolecular hydrogel has enhanced bacterial inhibition function after assembly. The hydrogel was also found to possess both anti-inflammatory and antioxidant efficacy when evaluated using LPS and H₂O₂ induced RAW 264.7 cell damage models, respectively. The above results suggest that GA-Zn hydrogel not only has good materialistic properties, but also possesses good antibacterial, anti-inflammatory and antioxidant activities, which has the value of clinical research as a carrier-free multi-functional antimicrobial dressing, and the present study provides a reference for the discovery of novel biomedical materials from active molecules of natural traditional Chinese medicine.

italic>Astragalus polysaccharides are the most immunoregulatory active and abundant substances in Astragalus, with anti-tumor, anti-viral, and immune-promoting biological activities. They have been widely used in clinical practice. Previous studies have found that Astragalus polysaccharides are mainly composed of two different polysaccharides, APS-I (>2 000 kDa) and APS-Ⅱ (10 kDa), with APS-Ⅱ (10 kDa) being the most active component of Astragalus polysaccharides. We used α-1,4-glucan endo-hydrolysis enzyme to degrade APS-Ⅱ into oligosaccharides, and screened the immune activity of oligosaccharides in vitro. We found that the overall immune activity of 2-9 oligosaccharides was low, while the immune activity of 10-14 oligosaccharides was strong, and the activity was better than that of untreated APS-Ⅱ. To investigate the key structural features of APS-Ⅱ oligosaccharides that play a role in immune activity, we used MALDI-TOF-MS biochemical mass spectrometry and high-resolution mass spectrometry instrument ESI-Q Exactive-MS to analyze the APS enzymatic oligosaccharides. By comparing, we found that 10-14 oligosaccharides contain 1→4 and 1→6 branched structures with coexisting linkages, suggesting that 1→4 and 1→6 linkages in branched structures are key structural features that play a role in the immune activity of APS-Ⅱ, laying a theoretical foundation for the structure-activity relationship of Astragalus polysaccharides and oligosaccharides.

In this paper, the antitussive and expectorant activity of platycodin D (PD) were studied by constructing a mouse cough induced by concentrated ammonia water and a mouse trachea phenol red excretion model. The mechanism of antitussive and expectorant effect of PD was studied by metabolomics. The animal experiment was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (approval number: JZLLSC-20220739). Then mice were randomly divided into the normal, model, positive drug, PD low-dose, PD medium-dose and PD high-dose group. The antitussive and expectorant effects of PD were evaluated using a cough mouse model induced by concentrated ammonia water and a mouse tracheal phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of mouse lung tissue, and multivariate statistical analysis method of orthogonal partial least squares discriminant analysis (OPLS-DA) was used for metabolites profile analysis. The differential metabolites were screened by variable projected importance value (VIP) and t-test results. Pathways for enrichment of differentiated metabolites were analyzed using the MetaboAnalyst platform. The comparative method was applied to analyze the differences in mechanisms of PD, Deapio-platycodin D (DPD) and total platycosides fraction. The results showed that PD at different concentrations could significantly prolong (P < 0.05) the incubation period of cough mice induced by ammonia water, reduce the coughs frequency, and significantly increase (P < 0.05) the amount of phenol red excretion in phenol red excretion model mice. PD could regulate 6 metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism, phenylalanine metabolism, glycerophospholipid metabolism, and tyrosine metabolism to exert antitussive effect. It could also regulate 8 metabolic pathways of linoleic acid metabolism, glyoxylic acid and dicarboxylic acid metabolism, glycerol phospholipid metabolism, citric acid cycle and arachidonic acid metabolism to exert an expectorant effect. However, only linoleic acid metabolism and glycerophospholipid metabolism could be regulated by the PD, total platycosides fraction and DPD, which may be ascribed to the structural difference of the platycosides and the interaction between platycosides and the intestinal microbiota. Functional analysis showed that these metabolic pathways are closely related to the regulatory mechanisms of anti-inflammatory response, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and cell apoptosis. This study shows that PD possesses good antitussive and expectorant activities. In addition, the mechanism difference of PD, total platycosides fraction and DPD imply that the apiose in PD and the interaction between PD and intestinal microbiota could exert an important effect on the antitussive and expectorant mechanism of the platycosides.