MOLECULES
·
2019
·Vol. 24
·期 20
·3732
·
IF 3.06
Li Ji,Zhonghui Qiao,Xin Zhang,Xiaolei Cheng,Weiyang Wang,Fan Zhang,Yifa Zhou,Ye Yuan
Monosialotetrahexosylganglioside (GM1) has good activity on brain diseases and was developed to be a drug applied in clinics for neurological disorders and nerve injury. It is difficult to isolate GM1 in industry scale from the brains directly. In this work, a simple and highly efficient method with high yield was developed for the isolation, conversion, and purification of GM1 from a pig brain. Gangliosides (GLS) were first extracted by supercritical CO2(SCE). The optimum extraction time of GLS by SCE was 4 h, and the ratio of entrainer to acetone powder from the pig brain was 3:1 (v/w). GM1 was then prepared from GLS by immobilized sialidase and purified by reverse-phase silica gel. Sodium alginate embedding was used for the immobilization of sialidase. Under the optimized method, the yield of high-purity GM1 was around 0.056%. This method has the potential to be applied in the production of GM1 in the industry.Keywords:ganglioside;GM1;supercritical CO2extraction;immobilization;sialidase;purification
研究领域:
生物化学
·
药物开发
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2018
·
IF 4.432
Kun Wang,Chuan Yu,Yang Liu,Wendiao Zhang,Yanan Sun,Yong Chen
Atherosclerosis remains one of the leading causes of morbidity and mortality globally. Recently, reconstituted high-density lipoprotein (rHDL), the synthetic form of endogenous plasma HDL, has been utilized as a therapeutic delivery system for statins, a class of lipid-lowering drugs, to treat atherosclerosis. Accumulating evidence suggests that ganglioside GM1 modification can induce an increased stability, a prolonged circulation time, and a decreased reticuloendothelial system uptake of liposomes. Therefore, we hypothesized that GM1 modification probably has similar effects on statin-loaded rHDL and finally enhances its inhibitory effect on atherogenesis. To test this hypothesis, we prepared GM1-modified lovastatin (LT)-loaded rHDL (LT-GM1-rHDL), as well as LT-loaded rHDL (LT-rHDL) and LT-loaded nanostructured lipid carriers (LT-NLC) for comparison, via thin film dispersion followed by physicochemical characterization, in vitro LT release assay, and in vitro cellular experiments. Subsequently, the pharmacokinetic behavior, tissue distribution, and in vivo antiatherosclerotic effect of all LT-loaded nanocarriers were evaluated by using ApoE–/– mice fed with a high-fat diet. We found that LT-GM1-rHDL has a more efficient LT sustained-release, a longer circulation time, a lower liver uptake, a better atherosclerotic plaque targeting efficiency, and a stronger inhibitory effect on atherogenesis compared with LT-NLC and LT-rHDL. The data verified our hypothesis that GM1 modification of statin-loaded rHDL can induce an enhanced inhibitory effect on atherogenesis and imply that statin-GM1-rHDL can potentially be recruited as a promising drug delivery system for the treatment of atherosclerosis.
研究领域:
药学
·
心血管疾病
·
药物递送系统
·
脂质代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2024
·
IF 7
Yanjun Liu,Yuhe Zhu,Xiaoxu Wang,Yiyang Li,Shuaiqi Yang,Hongyan Li,Bo Dong,Zhigao Wang,Yu Song,Jie Xu,Changhu Xue
The neurotoxin β -methylamino- L -alanine (BMAA) produced by cyanobacteria is widely present in foods and dietary supplements, posing a significant threat to human health. Ganglioside GM1 (GM1) has demonstrated potential for treating neurodegenerative diseases; however, its ability to prevent BMAA-induced neurotoxicity remains uncertain. In this study, zebrafish embryos were treated with Ganglioside GM1 to investigate its neuroprotective effects against BMAA exposure and the underlying mechanisms. Exposure to BMAA (400 μM) resulted in increased malformation rate and heart rates in zebrafish embryos at 72 h post-fertilization, along with the decreased survival rates. Conversely, GM1 intervention rescued BMAA-induced movement disorders and brain cell apoptosis, and oxidative stress was alleviated. In addition, GM1 inhibited the neurotoxic effects of BMAA in zebrafish embryos, as indicated by the up-regulation of genes related to neuron development (gpx1a, bdnf, ngfb, and islet-1) and the down-regulations of neurodegeneration-related genes (cdk5, gfap, and nptxr). GM1 treatment restored 261 differentially expressed genes (DEGs) identified through RNA sequencing, with the most enriched DEGs related to the mitogen-activated protein kinase (MAPK) signaling pathway ( P < 0.05, 47 genes). GM1 modulated MAPK-targeted gene expression at the mRNA level. These findings suggest that GM1 alleviates BMAA-induced neurotoxicity in the early-life stage of zebrafish embryos. The neuroprotective mechanism may involve the MAPK pathway, offering new insights into lipid signaling for the prevention of neurotoxic hazards to biological health.
研究领域:
神经科学
·
毒理学
·
分子生物学
·
发育生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Zhenhua Li,Xiaoqin Wang,Xiaoli Deng,Jiansen Song,Tong Yang,Yujie Liao,Guiping Gong,Linjuan Huang,Yu Lu,Zhongfu Wang
Glycosphingolipids (GSLs) in human milk regulate the immune system, support intestinal maturation, and prevent gut pathogens. The structural complexity and low abundance of GSLs limits their systematic analysis. Here, we coupled the use of monosialoganglioside 1–2-amino-N-(2-aminoethyl) benzamide (GM1-AEAB) derivatives as internal standards with HILIC-MS/MS to qualitatively and quantitatively compare GSLs in human, bovine, and goat milk. One neutral glycosphingolipid (GB) and 33 gangliosides were found in human milk, of which 22 were newly detected and three were fucosylated. Five GB and 26 gangliosides were identified in bovine milk , of which 21 were newly discovered. Four GB and 33 gangliosides were detected in goat milk, 23 of them newly reported. GM1 was the main GSL in human milk; whereas disialoganglioside 3 (GD3) and monosialogangloside 3 (GM3) were dominant in bovine and goat milk, respectively; N -acetylneuraminic acid (Neu5Ac) was detected in >88 % of GSLs in bovine and goat milk. N -hydroxyacetylneuraminic acid (Neu5Gc)-modified GSLs were 3.5 times more abundant in goat than in bovine milk; whereas GSLs modified with both Neu5Ac and Neu5Gc were 3 times more abundant in bovine than in goat milk. Given the health benefits of different GSLs, these results will facilitate the development of custom-designed human milk-based infant formula.
研究领域:
营养学
·
生物化学
·
代谢组学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Siqing Zhu,Yu Zhang,Chang Li,Zhiqing Deng,Ying Yin,Zhufeng Dong,Lei Kuang,Chuanming Li,Xiaoye Hu,Tieying Yin,Yazhou Wang
Aging is a critical factor in the onset and progression of neurodegenerative diseases and cognitive decline, with aging-related neuroinflammation and cellular senescence being major contributors. In the aging brain, the cerebral vascular endothelium overexpresses vascular cell adhesion molecule 1 (VCAM1), activating microglia and leading to neuroinflammation and cognitive impairment. Quercetin, a natural neuroprotective agent widely used for treating neurodegenerative diseases, their therapeutic efficacy, however, is limited by its poor water solubility and inability to penetrate the blood-brain barrier (BBB). To address these challenges, we developed a multifunctional micellar platform (Anti-VCAM1-GM1@Q) to improve age-related neurodegenerative diseases. The micelles incorporate anti-VCAM1 antibodies to target cerebral vascular endothelial cells and block VCAM1. Additionally, monosialoganglioside (GM1) was utilized to deliver quercetin due to its biparental properties, high BBB permeability, and neuroprotective effects. Anti-VCAM1-GM1@Q micelles demonstrated strong anti-aging properties. They improved quercetin's bioavailability, effectively penetrated the BBB, targeted cerebral vascular endothelial cells, and reduced neuroinflammation. In animal models, these micelles provided effective neuroprotection, improved memory function and age-related cognitive impairment, and mitigated age-related neurodegeneration. Notably, this system exhibited remarkable treatment efficacy and high safety, indicating substantial potential for clinical translational applications.
研究领域:
神经科学
·
药理学
·
衰老研究
·
纳米技术
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
·
2017
·Vol. 292
·期 12
·4789-4800
·
IF 4.125
Yun-Bin Han,Liu-Qing Chen,Zhuo Li,Yu-Meng Tan,Yan Feng,Guang-Yu Yang
Endoglycoceramidases (EGCases) specifically hydrolyze the glycosidic linkage between the oligosaccharide and the ceramide moieties of various glycosphingolipids, and they have received substantial attention in the emerging field of glycosphingolipidology. However, the mechanism regulating the strict substrate specificity of these GH5 glycosidases has not been identified. In this study, we report a novel EGCase I from Rhodococcus equi 103S (103S_EGCase I) with remarkably broad substrate specificity. Based on phylogenetic analyses, the enzyme may represent a new subfamily of GH5 glycosidases. The X-ray crystal structures of 103S_EGCase I alone and in complex with its substrates monosialodihexosylganglioside (GM3) and monosialotetrahexosylganglioside (GM1) enabled us to identify several structural features that may account for its broad specificity. Compared with EGCase II from Rhodococcus sp. M-777 (M777_EGCase II), which possesses strict substrate specificity, 103S_EGCase I possesses a longer α7-helix and a shorter loop 4, which forms a larger substrate-binding pocket that could accommodate more extended oligosaccharides. In addition, loop 2 and loop 8 of the enzyme adopt a more open conformation, which also enlarges the oligosaccharide-binding cavity. Based on this knowledge, a rationally designed experiment was performed to examine the substrate specificity of EGCase II. The truncation of loop 4 in M777_EGCase II increased its activity toward GM1 (163%). Remarkably, the S63G mutant of M777_EGCase II showed a broader substrate spectra and significantly increased activity toward bulky substrates (up to >1370-fold for fucosyl-GM1). Collectively, the results presented here reveal the exquisite substrate recognition mechanism of EGCases and provide an opportunity for further engineering of these enzymes.
研究领域:
生物化学
·
结构生物学
·
酶学
·
糖鞘脂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomedical Optics Express
·
2018
·Vol. 9
·期 10
·4850-4862
·
IF 3.482
Chao Zhang,Wei Feng,Elena Vodovozova,Daria Tretiakova,Ivan Boldyrevd,Yusha Li,Jurgen Kürths,Tingting Yu,Oxana Semyachkina-Glushkovskaya,Dan Zhu
The photodynamic (PD) effect has been reported to be efficient for the opening of the blood-brain barrier (BBB), which provides a new informative platform for developing perspective strategies towards brain disease therapy and drug delivery. However, this method is usually performed via craniotomy due to high scattering of the turbid skull. In this work, we employed a newly-developed optical clearing skull window for investigating non-invasive PD-induced BBB opening to high weight molecules and 100-nm fluid-phase liposomes containing ganglioside GM1. The results demonstrated that the BBB permeability to the Evans blue albumin complex is related to laser doses. By in vivo two-photon imaging and ex vivo confocal imaging with specific markers of the BBB, we noticed PD-related extravasation of rhodamine-dextran and liposomes from the vessels into the brain parenchyma. The PD induced an increase in oxidative stress associated with mild hypoxia and changes in the expression of tight junction (CLND-5 and ZO-1) and adherens junction (VE-cadherin) proteins, which might be one of the mechanisms underlying the PD-related BBB opening for liposomes. Our experiments indicate that optical clearing skull window will be a promising tool for non-invasive PD-related BBB opening for high weight molecules and liposomes that provides a novel useful tool for brain drug delivery and treatment of brain diseases.
研究领域:
神经科学
·
药理学
·
生物医学工程
·
光学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）