International Journal of Nanomedicine
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2022
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IF 7.033
Wei Shang,Xin Zhao,Fan Yang,Dongyi Wang,Le Lu,Zihan Xu,Zhiming Zhao,Hui Cai,Junyi Shen
Background: Compared with traditional drugs, nanomaterial drugs have the benefits of improving the solubility, bioavailability, and absorption rate of insoluble drugs. Nanoporous complexes can increase the efficiency with which drugs can penetrate the blood-brain barrier and reach target organs. Ginsenoside Rg1 is an effective drug that promotes angiogenesis. Ginsenoside Rg1 composite nanoparticles were employed to induce the expression of several key epigenetic enzymes and then activate the VEGF and Notch pathways after the onset of ischemic brain lesions. Methods: We constructed nanoparticles to fully encapsulate the therapeutic drug (ginsenoside Rg1), which can be transferred into brain tissue via the receptor-mediated transfer of drug-encapsulated nanoparticles. Evaluation of the therapeutic effect of ginsenoside Rg1 complex nanovesicles (CNV) was performed by in vitro and in vivo experiments. Real-time polymerase chain reaction (RT- PCR), Western blot, immunohistochemistry staining (IHC), and Co-immunoprecipitation (co-IP) were employed to screen for epigenetic enzymes with an up-regulated expression post ginsenoside Rg1-CNV intervention. RNA sequencing, shRNA knockdown, and chromatin Immunoprecipitation (ChIP) sequencing were performed to detect the target genes of ginsenoside Rg1-CNV that regulate angiogenesis. Then, bioinformatic analysis was performed to investigate the mechanism of action of epigenetic modifying enzymes in regulating target genes. Results: The average of the synthesized ginsenoside Rg1-CNV was 203.78±6.83 nm, the polydispersion index was 0.135±0.007, and the Zeta potential was 23.13±1.65 mV. Through in vivo and in vitro experiments, we found that it promotes the proliferation, migration, and tubular formation of brain microvascular endothelial cells (BMECs). Meanwhile, the intervention of ginsenoside Rg1-CNV promoted the demethylation of H3K27me3 within the promoter region of VEGF-A and Jagged1 genes and reduced the H3K27me3 modification within this region. Conclusion: The ginsenoside Rg1 nanoparticles may be an available blood-brain barrier penetrating agent for ischemic stroke.
研究领域:
药理学
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神经科学
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分子生物学
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表观遗传学
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高影响因子
Experimental and Therapeutic Medicine
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2023
·Vol. 27
·期 1
·1-13
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IF 2.7
Qiankun Quan,Xinxin Ma,Ming Li,Xi Li,Haifeng Yuan
β‑Amyloid peptide (Aβ) deposition in the brain is an important pathological change in Alzheimer's disease (AD). Insulin‑degrading enzyme (IDE), which is regulated transcriptionally by peroxisome proliferator‑activated receptor γ (PPARγ), is able to proteolyze Aβ. One of the members of the MAPK family, ERK, is able to mediate the phosphorylation of PPARγ at Ser112, thereby inhibiting its transcriptional activity. Ginsenoside Rg1 is one of the active ingredients in the natural medicine ginseng and has inhibitory effects on Aβ production. The present study was designed to investigate whether ginsenoside Rg1 is able to affect the regulation of PPARγ based on the expression of its target gene, IDE, and whether it is able to promote Aβ degradation via inhibition of the ERK/PPARγ phosphorylation pathway. In the present study, primary cultured rat hippocampal neurons were treated with Aβ1‑42, ginsenoside Rg1 and the ERK inhibitor PD98059, and subsequently TUNEL staining was used to detect the level of neuronal apoptosis. ELISA was subsequently employed to detect the intra‑ and extracellular Aβ1‑42 levels, immunofluorescence staining and western blotting were used to detect the translocation of ERK from the cytoplasm to the nucleus, immunofluorescence double staining was used to detect the co‑expression of ERK and PPARγ, and finally, western blotting was used to detect the phosphorylation of PPARγ at Ser112 and IDE expression. The results demonstrated that ginsenoside Rg1 or PD98059 were able to inhibit primary cultured hippocampal neuron apoptosis induced by Aβ1‑42 treatment, reduce the levels of intra‑ and extraneuronal Aβ1‑42 and inhibit the translocation of ERK from the cytoplasm to the nucleus. Furthermore, administration of ginsenoside Rg1 or PD98059 resulted in attenuated co‑expression of ERK and PPARγ, inhibition of phosphorylation of PPARγ at Ser112 mediated by ERK and an increase in IDE expression. In addition, the effects when PD98059 to inhibit ERK followed by treatment with ginsenoside Rg1 were found to be more pronounced than those when using PD98059 alone. In conclusion, ginsenoside Rg1 was demonstrated to exert neuroprotective effects on AD via inhibition of the ERK/PPARγ phosphorylation pathway, which led to an increase in IDE expression, the promotion of Aβ degradation and the decrease of neuronal apoptosis. These results could provide a theoretical basis for the clinical application of ginsenoside Rg1 in AD.
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高影响因子
INDUSTRIAL CROPS AND PRODUCTS
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2023
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IF 5.9
Na Li,Huan Xia,Shiyuan Liu,Junjiang Teng,Yanbin Jiang
In order to improve the activity and reusability of β-xylosidase, the β-xylosidase mutant S160N-R333H (R333H) which could convert notoginsenoside R1 to ginsenoside Rg1 and xylose was immobilized on the metal-organic framework (MOF) UiO-66-NH 2 . The physical and biochemical properties of immobilized β-xylosidase ( [email protected] 2 ) were studied in detail. The results showed improved performances, i.e. the high immobilization yield of 93% and recovery activity of 192.8%, better stability under acidic or trypsin-containing conditions, the higher activity in the reaction containing ions , and the improved catalytic efficiency (was 1.37-fold than that of free R333H). Importantly, the ginsenoside Rg1 yields remained more than 80% after six recycles in McIlvaine buffer and pure water. The UiO-66-NH 2 could catalyze xylose dehydration to produce furfural and the yield reached 69%. Thus this study provides a promising method for production of bioactive or platform chemicals via continuous conversion of xyloylated substrates using nanocatalyst synthesized by β-xylosidase and MOF.
研究领域:
生物技术
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酶工程
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化学工程
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药学
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高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2026
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IF 8
Rucui Yu,Yan Zhang,Ruiying Wu,Jingwei Xu
Objective Mitochondrial dysfunction and dysregulated cell death are key drivers of diabetic kidney disease (DKD) progression. This study aimed to construct CD44-targeted chitosan (Cs) nanoparticles encapsulating ginsenoside Rg1 (CD44-Cs@Rg1) for targeted delivery, and to evaluate their ability to regulate autophagy, pyroptosis, and mitochondrial function in DKD. Methods CD44-Cs@Rg1 nanoparticles were synthesized using a covalent modification strategy. Their targeting uptake, effects on GSDMD-mediated pyroptosis, autophagic flux, and energy metabolism were systematically evaluated in renal tubular epithelial cells under high-glucose (HG) conditions and in DKD mouse models. Mitochondrial function was assessed by Western blotting, immunostaining, MitoSOX, JC-1, and ATP assays. Transcriptomic profiling and pharmacological interventions were applied to elucidate the involvement of the AMPK/mTOR signaling axis. Results CD44-Cs@Rg1 nanoparticles were efficiently internalized by renal tubular epithelial cells, significantly reducing pyroptosis while restoring autophagic flux through AMPK activation and mTOR inhibition. These effects improved mitochondrial membrane potential, reduced reactive oxygen species accumulation, and enhanced ATP production. In vivo , CD44-Cs@Rg1 treatment markedly ameliorated renal dysfunction and histopathological injury in DKD mice. Transcriptomic and protein-level analyses consistently revealed enrichment of pathways related to AMPK signaling, autophagy, and energy metabolism. Conclusion CD44-targeted Cs nanoparticles enable precise delivery of ginsenoside Rg1 to renal tubular cells in DKD, restoring mitochondrial homeostasis and regulating autophagy–pyroptosis balance via the AMPK/mTOR axis. This nanotherapeutic platform demonstrates strong translational potential for DKD treatment.
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高影响因子
FOOD RESEARCH INTERNATIONAL
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2023
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IF 8.1
Xianqiang Chen,Xinyu Chu,Xue Li,Fuliang Cao,Qirong Guo,Jiahong Wang
Molecular interaction forces regulate the interfacial properties of oil-in-water emulsion and play a key role in the rheology and stability of the emulsion in the food industry. In this study, the effects of non-thermal plasma (NTP) treatment on the structural and functional properties of whey protein isolate (WPI) and its binding interaction with ginsenoside Rg 1 (GR 1 ) were investigated. The results based on surface hydrophobicity, infrared spectroscopy and fluorescence spectroscopy test showed that the NTP treatment induced the unfolding of the structure of WPI and promoted the binding affinity between WPI and GR 1 . By comparing with untreated WPI (an α-helix content of 19.63 % and a β-sheet content of 31.66 %), there was a greater decrease in α-helix content and an increase in β-sheet content of WPI in N 20 -WPI (α-helix = 9.63 %, β-sheet = 39.63 %) and N 20 -WPI-GR 1 (α-helix = 4.98 %, β-sheet = 48.66 %) groups. Importantly, the NTP treatment increased the interfacial adsorption and antioxidant capacity of the WPI-GR1 complexes, which contributed to the improvement of the rheological properties and oxidation stability of the emulsion. As a result, the NTP treatment could markedly improve the rheological and antioxidative properties of the WPI-GR 1 complexes and the NTP-treated WPI-GR 1 emulsions was more stable than that untreated. The present research indicated that NTP-treated formation of protein-saponin complexes could enhance the functional properties of the proteins, thus expanding their application as functional ingradients in nutritionally fortified food.
研究领域:
食品科学
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化学工程
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生物技术
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PubMed
高影响因子
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