ACS Applied Nano Materials
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2022
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IF 6.14
Kaijia Zhang,Jian Dong,Jun Lu,Lan Li,Huan Liang,Jing Jin,Peng Wang,Xiaolian Sun,Qing Jiang
Bone fracture is a huge medical and sociological problem. Among various therapeutic drugs, icaritin (ICA), as a novel natural osteoinductive agent, has attracted considerable attention due to its remarkable osteogenic effect, but it still has some drawbacks such as poor bone targeting and a rapid plasma clearance rate. Recently, iron oxide nanoparticles (IONPs) show increasingly potential as drug delivery vehicles to overcome these limitations. In this study, porous hollow iron oxide nanoparticles (PHNPs) were synthesized via thermal decomposition and controllable oxidation methods and ICA was incorporated during the hydrophilic phase transfer process. The preosteoblastic MC3T3-E1 cell line was used to evaluate their osteogenic effect, and the results demonstrated that ICA-incorporated PHNPs displayed superior biocompatibility and pronounced alkaline phosphatase activity and expression of osteogenic-related genes and proteins in a synergistic manner. Mechanistic investigations demonstrated that the MEK/ERK/p90RSK signaling pathway might provide a potential explanation for ICA-incorporated PHNP-mediated osteogenic differentiation. Furthermore, hyaluronic acid–cholesterol (HA–CHOL) was used to establish nanoclusters (ICA-PHNP-NCs) for in vivo bone regeneration assessment using a murine femur fracture as a model. The results showed that ICA-PHNP-NCs efficiently accumulated at the fracture site in the presence of a static magnetic field and accelerated fracture repair rapidly and effectively. For the first time, the dual application of osteogenic agents transport and ICA delivery using the ICA-PHNP-NC formulation was achieved against bone fracture, providing a new treatment strategy for diseases related to fractures.
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高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2025
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IF 3.1
Song Wang,Xinnan Chang,Jing Li,Zuoqiao Shi,Guowen Li
Herbal pairs are combinations of two relatively fixed herbs that are frequently used in clinical practice to achieve specific therapeutic effect. Epimedium and Astragalus are frequently used together in clinical settings. However, there is a lack of an in-depth understanding of the active components of these herbs in vivo . In this study, a method based on ultra-high-performance liquid chromatography coupled to high resolution mass spectrometry together with diagnostic fragment ions (DFIs) mass defect filtering (MDF) was developed to systematically screen and identify the chemical ingredients presenting in Epimedium-Astragalus granule pair (EAGP) and the absorbed components and their metabolites in rat plasma following oral administration. Using accurate mass determination, mass defect filtering and diagnostic fragment ion screening strategies, a total of eighty-five ingredients were identified in EAGP. By comparing the total ion chromatograms obtained from dosed rat plasma, blank rat plasma and EAGP solution, a total of forty-six compounds were detected in dosed rat plasma, including twenty-five prototypes and twenty-one metabolites. Among these, seventeen parent compounds were derived from Epimedium and eight were from Astragalus. These metabolites were associated with ononin (M1, M2, M9 M10 and M17), calycosin-7- O - β -D-glucoside (M6, M7, M8 and M13), icariin (M3, M4, M5, M11, M14, M15, M18, M19, M20 and M21) and methylnissolin (M12). The metabolic pathways included hydroxylation, demethylation, deglycosylation and glucuronidation. This study elucidated the potential pharmacologically active components of EAGP and provided essential data for the further study on its pharmacological materials basis and mechanism of action.
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Jiaojiao Ding,Tiexiang Gao,Songlin Liu,Zhezhe Li,Baifei Hu,Junping Zhen,Xiaowei Yao,Hongtao Liu,Haiming Hu
Epimedin C, an anti-cardiovascular disease natural compound derived from Herba Epimedii , exhibits low oral bioavailability, with its metabolism closely related to the gut microbiota. In this study, we investigated the roles of intestinal bacteria in the catabolism of epimedin C. We discovered that a strain of Parabacteroides distasonis QZH 1201 ( P. distasonis ) from human fecal samples can convert epimedin C to 2”-O-rhamnosylicariside II and baohuoside I. More importantly, we identified an α-L-rhamnosidase enzyme from P. distasonis (PdRha), which plays a crucial role in this process by efficiently transforming epimedin C into icariside I. PdRha showed optimal activity at pH 6 and a temperature of 50 °C. Under the condition that the final concentration of epimedin C was 0.5 mM, its conversion efficiency reached 78.72 %. Additionally, we investigated the substrate profile of PdRha and discovered that it can hydrolyze rutin, naringin, and icariin, releasing isoquercitrin, prunin, and icariside I. Molecular docking was performed to gain insights into the enzymatic mechanism. This study provides valuable insights into how a common intestinal symbiotic bacterium processes an important natural flavonoid.
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Anyi Wu,Junping Zhou,Yinan Xue,Yun Liu,Jidong Shen,Xin Gao,Zhiqiang Liu,Yuguo Zheng
Icaritin (ICT) shows various pharmacological activities and is used as an anti-hepatocellular carcinoma drug. While most of the studies focused on constructing yeast chassis cells for ICT production to replace the ICT extraction of Epimedium species, an efficient multi-enzyme system was first constructed here in the prokaryote Escherichia coli , for the successful biotransformation from naringenin (NAR) and prenol to ICT. The plant-derived flavonoid 3-hydroxylase (F3H) and flavonol synthase (FLS) were screened, and then fused together with protein linkers to efficiently catalyze the conversion of NAR to kaempferol (KAE). The isopentenol utilization (IU) pathway was subsequently introduced to increase dimethylallyl diphosphate (DMAPP) supply, along with catalytic activity improvement of prenyltransferase (PT) using N -terminal truncations and active site pocket engineering. Furthermore, by screening O -methytransferases (OMT) from different sources, EpOMT 4 from Epimedium pseudowushanense was selected for the ICT production. With the combination of these strategies, 80.8 ± 3.6 mg/L ICT could be produced from NAR and prenol in the recombinant E. coli , from the original 0 % degree of conversion. The systematic engineering of multi-enzyme system for ICT biosynthesis has laid the foundation for the large-scale ICT production using the industrially important E. coli chassis cell.
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Jiali Tang,Yanlu Chen,Hao Lai,Qi Zeng,Yu Li,Junqi Feng,Ningjing Lin,Ronghua Jin,Junjie Liu,Tao Luo,Zixuan Liang
Tumor hypoxia remains a formidable barrier to the efficacy of conventional cancer therapies, promoting therapeutic resistance and fostering immunosuppressive microenvironments. To overcome these challenges, a novel ImmunoSonogen Nanoplatform was engineered, seamlessly integrating ultrasound-triggered oxygen generation, immunomodulation, and targeted drug delivery for enhanced treatment of colon cancer. This platform incorporated barium titanate (BTO), a piezoelectric oxygen generator, encapsulated within mesoporous silica nanoparticles (MSNs), loaded with the bioactive flavonoid icaritin (ICT), and functionalized with hyaluronic acid (HA) for precise tumor targeting. Under ultrasound (US) irradiation, BTO generated oxygen and reactive oxygen species (ROS), mitigated tumor hypoxia and amplifying ICT-induced cytotoxicity and immunogenic cell death (ICD). The HA modification ensured selective nanoparticle accumulation within tumor tissues, thereby minimizing off-target effects and systemic toxicity. In vitro and in vivo studies revealed that the ImmunoSonogen Nanoplatform not only robustly suppressed tumor growth but also triggered potent antitumor immune responses through the upregulation of pro-inflammatory cytokines and the recruitment of immune cells. Additionally, ICT-mediated activation of key oncogenic pathways synergized with ROS-induced oxidative stress to dismantle tumor survival mechanisms. This integrated approach, combining oxygenation, immunomodulation, and sonodynamic activation, offered an innovative solution to counteract hypoxia-driven cancer progression. The promising therapeutic outcomes and favorable safety profile underscored the potential of the ImmunoSonogen Nanoplatform for clinical translation, advancing the future of cancer therapy.
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高影响因子
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