JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
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IF 4.5
Haigang Li,Jiaxuan Liu,Lei Zhang,Xinru Zhu,Jing Jiang,Zhaohui Ge,Yifei Zuo,Xiangzhu Chen,Chun Zhang
This study aims to achieve co-delivery of paeoniflorin (PF) and butyric acid (BA) to the colon through Eudragit S100 (EUS100)-coated halloysite nanotube/o-butyryl chitosan microspheres (EUS100-HNT-BUCHNPs). O-butyrylated chitosan (BUCH) was prepared by the acylation reaction of chitosan (CH) and butyric anhydride with methane sulfonic acid as a catalyst. PF-loaded halloysite nanotube/o-butyrylated chitosan microspheres (HNT-BUCHNPs) were prepared by emulsion crosslinking with glutaraldehyde as the crosslinking agent and then coated with EUS100 using the emulsion solvent evaporation method. X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy results indicated the presence of EUS100 coating on the surface of HNT-BUCHNPs. In vitro release studies demonstrated that the EUS100 coating effectively prevented the release of PF and BA at pH 1.2, while the halloysite nanotube slowed down PF release at pH 6.8. Sequential release experiments in different pH media showed lower release of PF and BA at pH 1.2 and pH 6.8, and higher release at pH 7.4, reaching approximately 80 % and 85 %, respectively. Gastrointestinal tract retention studies in mice confirmed that EUS100-HNT-BUCHNPs reduced the release of PF and BA in the upper digestive tract, facilitating delivery to the colon. In vivo and in vitro results indicated efficient transport of PF and BA to the colon, suggesting the potential of EUS100-HNT-BUCHNPs as colon-targeted carriers for PF and BA.
研究领域:
药剂学
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生物医学工程
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产品关联
DOI
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2022
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IF 4.52
Yipeng Gu,Kai Chen,Bingwen Xi,Jun Xie,Xuwen Bing
Paeonol (2′-hydroxy-4′-methoxyacetophenone) is a phenol that exhibits antioxidant and anti-inflammatory capabilities. In this study, the underlying mechanism of paeonol against LPS-induced oxidative stress and inflammatory responses in gibel carp was investigated. Three hundred healthy gibel carp were divided into five groups ( n = 9), intraperitoneally injected with LPS and thereafter treated with paeonol (16 mg/kg and 64 mg/kg). Fish were anesthetized with MS-222 (100 mg/L), and samples were collected at 72 h to investigate plasma biochemical indexes, liver histopathology , antioxidant enzymatic activity , and TLR receptor-related gene expression. Fish injected with LPS (20 mg/kg) exhibited significantly increased plasma aminotransferase (ALT), aminotransferase (AST), lactate dehydrogenase (LDH), glucose (GLU), diamine oxidase (DAO), and alkaline phosphatase (ALP) levels ( P < 0.05). In addition, LPS challenge significantly enhanced myeloperoxidase (MPO) and malondialdehyde (MDA) contents, whereas those of catalase (CAT) and glutathione peroxidase (GSH-Px) decreased ( P < 0.05). However, treatment with paeonol attenuated these LPS-induced changes ( P < 0.05). The mRNA expression of TLR4 , TIRAP , MyD88 , TRAF6 , NF-κB, TNF-α, IL-1β, and IL-8, which were activated by LPS challenge ( P < 0.05), were downregulated by paeonol. Additionally, histopathological examination demonstrated that paeonol alleviates LPS-induced hepatic tissue lesions in fish. Taken together, the results suggest that paeonol mitigates LPS-induced liver oxidative stress and inflammation in gibel carp.
研究领域:
水产养殖学
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免疫学
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药理学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Musen Lin,Yue Wang,Yan Zhao,Xiaohan Zhai,Yan Hu,Qinrong Luan,Li Lv,Zhecheng Wang,Jihong Yao
Background Acetaminophen-induced hepatotoxicity remains a clinical challenge with limited targeted therapeutic options. While recent advances have identified blood‒biliary barrier disruption as a critical pathogenic mechanism, effective interventions preserving this barrier are notably lacking. Albiflorin, a key bioactive constituent of Paeonia lactiflora Pall ., exhibits unique bile acid modulation along with antioxidant and anti-inflammatory activities, suggesting its potential efficacy in preventing acetaminophen-induced liver injury. However, its specific role and underlying mechanisms in alleviating acetaminophen-induced hepatotoxicity remain unclear. Objective This study's objective was to examine the pharmacological effects and primary molecular mechanisms of albiflorin in alleviating acetaminophen-induced liver injury. Methods An acetaminophen-induced liver injury mouse model was created using a 300 mg/kg dose of acetaminophen. The hepatoprotective effects of albiflorin were assessed through histological and biochemical analyses. Blood‒biliary barrier integrity was evaluated via Evans blue dye tests, immunofluorescence, and bile acid assays. Transcriptomic analysis, gene overexpression and interference techniques, and ChIP‒qPCR were employed to explore the molecular mechanisms underlying the protective effects of albiflorin. Results Albiflorin significantly reduced acetaminophen-induced liver injury, as evidenced by improved biochemical profiles and hepatocyte morphology. It also prevented increases in blood‒biliary barrier permeability and bile acid levels. RNA sequencing identified 3,184 differentially expressed genes, revealing critical pathways involved in maintaining blood‒biliary barrier integrity. AF reversed the acetaminophen-induced changes in the expression of genes related to the blood‒biliary barrier, particularly occludin, claudin 5, ABCG5, and ABCG8. Albiflorin protected the blood‒biliary barrier and mitigated acetaminophen-induced liver injury by enhancing ATF3 protein stability, with ATF3 identified as a critical mediator of these protective effects. Conclusion This study provides pioneering evidence that albiflorin protects against acetaminophen-induced liver injury by interacting with ATF3 to regulate blood–biliary barrier proteins and maintain the integrity of the blood–biliary barrier. These findings deepen our understanding of the role of the blood‒biliary barrier in liver diseases and suggest a therapeutic strategy for drug overdose-induced liver injury.
研究领域:
药理学
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肝脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
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2025
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IF 10.2
Xintao Jia,Zixuan Dou,Ying Zhang,Changxiang Yu,Mengru Yang,Haonan Xie,Yun Lin,Zhidong Liu
Diabetic foot ulcers (DFUs), a severe and common complication of diabetes, present significant treatment challenges due to the limitations of conventional dressings, such as poor mechanical properties, bioactivity, and limited functionality, which hinder fast and effective wound healing. To address these issues, we developed a novel natural amino acid-based hydrogel loaded with paeoniflorin (PF@PNMA1) and comprehensively evaluated its properties and functions. The nanogel particles (NGs) were synthesized via emulsion polymerization using N-isopropylacrylamide (NIPAM), methacrylic acid (MAA), and chemically modified arginine (MArg). The poly(NIPAM-co-MAA) (PNM) and poly(NIPAM-co-MAA-co-MArg) (PNMA) gels were prepared by functionalizing the NGs with glycidyl methacrylate (GMA). The different concentrations of amino acids were added to explore the optimal mechanical properties of the gel. Through the rheological measurement, we found that PNMA1 gel has good ductile properties with a critical strain up to about 63 %. At the same time, we also verified its antibacterial activity and found that the viability of bacteria decreased to 47.46 % after 3 h. Preliminary tests using network pharmacology and molecular docking confirmed the therapeutic potential of PF for DFUs. The PF@PNMA1 gel demonstrated excellent biocompatibility, and in vivo experiments revealed its effectiveness in promoting angiogenesis and wound healing. After 10 days, the wound healing rate was 25.6 % higher than that of the control group. The PF@PNMA1 shows great potential as an effective therapy for DFUs treatment.
研究领域:
生物材料学
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药理学
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医学工程
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2025
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IF 4.8
Xiaoqing Shen,Jing Lian,Chao Zhang,Yixiang Miu,Yuan Zhang,Ji Shi,Nan Xu,Tianzhu Jia
Introduction: Kidney Yang Deficiency (KYD) is a metabolic disorder associated with kidney damage. Its slow progression means that causative factors and effective therapeutic agents remain unclear. Extensive evidence links KYD to gut microbiome metabolic diseases and the Hypothalamic-Pituitary-Thyroid (HPT) axis. Cistanche deserticola (CD) is a commonly used traditional Chinese medicine for treating KYD. However, the precise interactions between gut microbiota and KYD, as well as the mechanisms of raw and processed CD total glycosides (CDG) in modulating KYD, require further investigation. This study aims to evaluate the effects and mechanisms of CDG in a KYD rat model using 16S rRNA gene sequencing and fecal metabolomics.Methods: CDG was extracted from both raw and processed CD and analyzed via HPLC. Propylthiouracil-induced KYD rats were used to assess pharmacological effects, including serum levels of T3, T4, TSH, TRH, FFA, LPL, and NO; organ indices of the spleen, kidney, and thymus; blood cAMP/cGMP levels; and liver levels of glycogen, SDH, Ca2+-ATPase, and Na+-K+-ATPase. Immunohistochemistry was also performed.Results: Fecal non-targeted metabolomics identified 98 metabolites associated with KYD, while 16S rRNA sequencing revealed 13 key intestinal microbiotas linked to KYD. CDG therapy effectively alleviated KYD symptoms by modulating the gut microbiota, improving metabolic and microbial imbalances in KYD. RG/WG significantly improves KYD rats mainly through the relationship between the intestinal microbiota and arachidonic acid metabolism. The key bacterial genera lleibacterium and Streptococcus observed in the changes of intestinal flora and fecal metabolite content were significantly negatively correlated with phosphatidylcholine and phosphatidylethanolamine.Discussion: This integrative approach of gut microbiome and fecal metabolomics not only provides a scientific basis for CDG’s preventive effects on KYD via the HPT axis but also elucidates the potential mechanisms underlying CDG’s action against KYD.
研究领域:
中医药学
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药理学
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微生物学
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分子生物学
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代谢组学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
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2024
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IF 2.3
Huafeng Yang,Hui Liu,Yuan Zheng,Bo Li,Shujing Wang,Jun Zhang,Jiandong Wang
Cornus officinalis total glycosides (COTG) derived from the traditional Chinese medicine Cornus officinalis, is a natural immunosuppressant and has been extensively studied in immunomodulation and immunosuppression. This study aimed to explore the effects of COTG on granulomatous lobular mastitis (GLM) and its associated mechanisms. Compared to the model group, COTG effectively ameliorated histopathological damage to breast tissue, reduced mammary gland suppuration, and enhanced the blood-milk barrier. Additionally, COTG treatment reduced the total number of T cells and B cells in GLM rats, significantly improving clinical indicators such as P-selectin, E-selectin, and intercellular cell adhesion molecule-1. We also observed downregulation of CD28 and B7 expression levels, an upregulation of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) expression, and a significant decrease in inflammatory marker levels in the COTG group. COTG exerts an anti-inflammatory effect in GLM by stimulating CTLA-4, inhibiting the B7-CD28 signaling pathway affecting T cell activation, and promoting the blood-milk barrier. These findings suggest that COTG could be a promising therapeutic option for managing GLM, potentially improving patient outcomes by modulating immune responses and reinforcing the blood-milk barrier.
研究领域:
药理学
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免疫学
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病理学
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中医药
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产品关联
DOI
PubMed
高影响因子
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