JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
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2019
·Vol. 100
·期 3
·986-994
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IF 2.422
Jing Wang,Jiang Zhao,Yong Yan,Dong Liu,Chengtao Wang,Hao Wang
BACKGROUND Controlling the blood glucose level is an effective method to reduce type 2 diabetes and prevent diabetes-related complications. Ursolic acid is a plant extract that can reduce postprandial hyperglycemia effectively. This study aimed to explore the inhibitory effect and interaction mechanism of ursolic acid against α-amylase and α-glucosidase. RESULTS In this study, the effect of ursolic acid on glycosidase was studied in vitro , in vivo , and in silico . The half-maximal inhibitory concentration (IC 50 ) of ursolic acid on α-amylase and α-glucosidase was 0.482 ± 0.12 mg mL −1 and 0.213 ± 0.042 mg mL −1 , respectively. The results of enzymatic kinetics showed that ursolic acid inhibited α-amylase and α-glucosidase activity in a non-competitive manner. The fluorescence spectrum showed that the combination of ursolic acid and glycosidase caused the intrinsic fluorescence quenching of glycosidase. The observation of starch granules revealed that the activity of α-amylase was inhibited and the hydrolysis of starch granules was prevented in the presence of ursolic acid. Molecular docking results showed that ursolic acid bound to the inactive site of α-amylase and α-glucosidase through the formation of ursolic acid–glucosidase complex. Ursolic acid interacted with α-amylase and α-glucosidase mainly through hydrogen bonding. The postprandial hypoglycemic effect of ursolic acid in C57BL/6J mice showed that the high concentration of ursolic acid could quickly reduce postprandial blood glucose level. CONCLUSION Ursolic acid can be considered as a natural ingredient in functional foods to control postprandial blood glucose levels and prevent diabetes by delaying the digestion of starch in foods. © 2019 Society of Chemical Industry
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2014
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IF 3.107
Guang Yang,Tan Yang,Wendian Zhang,Miao Lu,Xiang Ma,Guangya Xiang
The antitumor efficacy of ursolic acid (UA) was limited by poor hydrophilicity and low bioavailability. To overcome this issue, UA was encapsulated in liposomes modified with folate conjugates for better solubility and bioavailability. This novel agent was prepared by a thin-film dispersion method and characterized by mean diameter, zeta potential, and entrapment efficiency (160.1 nm, −21.2 mV, and 88.9%, respectively). In vitro, cellular uptake efficiency, cytotoxicity, apoptosis, and cell cycle analyses were performed to show that folate-receptor (FR) positive cells endocytose more FR-targeted liposome (FTL-UA) than nontargeted PEGylated liposome (PL-UA) and that FTL-UA induced more cytotoxicity and higher apoptosis than PL-UA. Pharmacokinetic assessments showed advantages of systemic bioavailability of FTL-UA (AUC = 218.32 mg/L·h, t1/2 = 7.61 h) over free UA (AUC = 36.88 mg/L·h, t1/2 = 0.78 h). In vivo, FTL-UA showed significantly higher human epidermoid carcinoma (KB) inhibition in Balb/c nu/nu mice compared to PL-UA or free UA. The results indicate the great potential of FTL-UA against KB tumor.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2017
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IF 3.671
Huafang Ding,Xing Hu,Ximing Xu,Guowen Zhang,Deming Gong
Glycemic control which can be efficaciously regulated by inhibiting α-glucosidase activity is an effective therapy for diabetes mellitus. This work is to investigate the kinetics and inhibition mechanism of oleanolic acid and ursolic acid on α-glucosidase. Oleanolic acid and ursolic acid exhibited potent inhibitory activities with IC 50 values of (6.35 ± 0.02) × 10 −6 and (1.69 ± 0.03) × 10 −5 mol L −1 respectively in a reversible and non-competitive manner. Both of them binding to α-glucosidase induced the conformational change and intrinsic fluorescence quenching of α-glucosidase. The binding constants of oleanolic acid and ursolic acid with α-glucosidase at 298 K were (2.04 ± 0.02) × 10 3 and (1.87 ± 0.02) × 10 3 L mol −1 , respectively. Docking results showed that oleanolic acid and ursolic acid bound in different allosteric sites of cavity 2 and cavity 4 on α-glucosidase, respectively, which triggered allosteric regulation to perturb conformational dynamics of α-glucosidase, eventually leading to a decrease of catalytic activity of the enzyme. The substrate was not catalyzed by α-glucosidase to generate further products due to formation of a nonreactive ternary complex of oleanolic acid– or ursolic acid–α-glucosidase–substrate. The combination of oleanolic acid and ursolic acid displayed a significant synergistic inhibition on α-glucosidase.
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FOOD CHEMISTRY
·
2026
·
IF 9.8
Liang Liu,Huaiyu Zhang,Junjie Wang,Yueli Zhou,Dayuan Chen,Ya Yang,Jing Li,Haotian Ma,Zhao-Jun Wei
Ursolic acid (UA) possesses antifungal activity against A. alternata , however, its poor solubility poses a challenge for practical application. We prepared UA nanoemulsions consisting of ethyl oleate, Cremophor EL, and Transcutol HP. The particle size of the UA nanoemulsions ranged from 20.53 to 27.88 nm. Electron microscopy revealed a nearly spherical structure. Fourier-transform infrared analysis proved that UA was successfully encapsulated, and the encapsulation efficiency ranged from 82 to 84%. UA nanoemulsions showed stable characteristics for 15 days of storage. The minimum inhibitory concentration of UA nanoemulsions against A. alternata was 0.8 mg/mL. UA nanoemulsions suppressed hyphal growth, reduced the spore yield and germination rate, and shortened the length of germ tubes in A. alternata . In vivo experiments confirmed that UA nanoemulsions could inhibit the goji berries and apple fruits infected by A. alternata . Collectively, these results demonstrate that UA nanoemulsion shows strong antifungal potential for postharvest rot control.
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MOLECULAR NUTRITION & FOOD RESEARCH
·
2017
·Vol. 61
·期 12
·1700332
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IF 4.323
Xiaoyao Ma,Yuan Zhang,Zengyong Wang,Yunbing Shen,Man Zhang,Quandeng Nie,Yuanyuan Hou,Gang Bai
Scope Ursolic acid (UA) is a pentacyclicterpenoid carboxylic acid that is present in a wide variety of plant foods. There are many beneficial health effects that are attributed to the properties of UA. However, the specific cellular targets of UA and the mechanism underlying downstream signal transduction processes linked to the anti-inflammation pathway have not been thoroughly elucidated to date. Methods and results Chemical biology strategies such as target fishing, click reaction synthesis of a UA probe and molecular imaging were used to identify potential target proteins of UA. Cysteinyl aspartate specific proteinase 3 (CASP3) and its downstream signaling pathway were verified as potential targets by molecular docking, intracellular enzyme activity evaluation and accurate pathway analysis. The results indicated that UA acted on CASP3, ERK1 and JNK2 targets, alleviated inflammation-associated downstream multiple signal transduction factors, including ERK1, NF-κB and STAT3, and exhibited anti-inflammation activities. Conclusion As a natural dietary supplement, UA demonstrated anti-inflammation activity via inhibition of CASP3 and shows the potential to improve the therapy effect of several inflammation-associated diseases.
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Parasites & Vectors
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2018
·Vol. 11
·期 1
·1-9
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IF 3.163
Yin Jianhai,Liu Congshan,Shen Yujuan,Zhang Haobing,Cao Jianping
Background Cystic echinococcosis is a global public health problem; however, the drugs (albendazole and mebendazole) currently recommended by WHO for its treatment, have limited efficacy. Therefore, novel drugs are required to provide more choices for the treatment of this disease. Methods The anthelmintic effects of ursolic acid (UA) were tested on Echinococcus granulosus protoscoleces, germinal cells and metacestodes in vitro. The in vivo efficacy of UA was investigated in mice following secondary infection with E. granulosus . Furthermore, the corresponding ultrastructural damage induced by UA was evaluated by electron microscopy. Results In vitro, 45.95 ± 5.30% of protoscoleces were killed by UA at 40 μg/ml, while the growth of more than 90% of germinal cells was inhibited by UA at 10 to 40 μg/ml. The same effect was observed in metacestodes 7 days after treatment with UA at 10, 20 and 40 μg/ml, and more than 50% of metacestodes showed loss of integrity at the end of the experiment. In vivo, metacestode weight was significantly reduced following oral administration of UA at 200 and 100 mg/kg (39.5 and 38.3%, respectively). Additionally, ultrastructural damage, such as alternations in germinal cell morphology and formation of vacuoles and lipid granules were observed in parasites treated with UA in vitro, while detachment of the germinal layer from the laminated layer was also seen in metacestodes in vivo. Conclusions UA was demonstrated to exert parasiticidal activity against E. granulosus in vitro and in vivo, thus implicating UA as a potential anti-echinococcosis agent.
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Biomedical Materials
·
2024
·Vol. 19
·期 3
·035013
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IF 3.9
Jieqiong Ding,Jie Tan,Xiaohang Peng,Liyuan Cheng,Weiling Huang,Binhua Luo
A novel biodegradable amphiphilic triblock copolymer, polyphosphate, polyethylene glycol, and polylactic acid (PAEEP-PEG-PLLA), was synthesized by twice ring-opening polymerization and triphenylphosphine (TPP) was grafted onto the block copolymer to synthesize a carrier material TPP-PAEEP-PEG-PLLA, which was identified by 1H-nuclear magnetic resonance (1H-NMR) spectroscopy. The TPP-PAEEP-PEG-PLLA nanoparticles encapsulated with ursolic acid (UA) were prepared by the emulsion-solvent evaporation method and characterized by dynamic light scattering. The mitochondrial targeting ability of fluorescently labeled nanoparticles was evaluated by laser confocal microscopy. The average particle size and surface charge of the UA -loaded nanoparticle solution were 180.07 ± 1.67 nm and +15.57 ± 1.33 mV, respectively. The biocompatibility of nanoparticles was briefly evaluated by erythrocyte hemolysis assay. In vitro cell proliferation assay and scratch migration assay were performed to compare the difference in anti-tumor effect between UA and UA nanoparticles. The results showed that TPP-modified triblock copolymers had good mitochondrial targeting and improved the low bioavailability of UA, and UA nanoparticles exhibited more pronounced anti-tumor capabilities. In summary, the results suggested that our UA nanoparticles were a promising drug-targeted delivery system for the treatment of tumors.
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EUROPEAN JOURNAL OF NUTRITION
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2021
·Vol. 61
·期 1
·115-126
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IF 5.619
Yan Xin,Liu Xiaoyun,Wang Yu,Ren Xueyang,Ma Jiamu,Song Ruolan,Wang Xiuhuan,Dong Ying,Fan Qiqi,Wei Jing,Yu Axiang,Sui Hong,She Gaimei
Purpose Alcoholic liver disease (ALD) is a major health issue globally. In addition to pharmacotherapy, dietary support is also regarded as reliable strategy for ALD management. As a widely distributed natural constituent within edible plants, the present study aims to investigate the hepatoprotective effects of ursolic acid (UA) against ALD and also to deepen insights into the underlying targets and mechanisms comprehensively. Methods The hepatoprotective activity of UA against chronic alcohol-induced liver injury was investigated on Lieber–DeCarli liquid diet-based mouse model. In-depth RNA-seq transcriptomics and TMT-based proteomics analyses were conducted in parallel. Data integration as well as bioinformatics analysis were also performed to unravel the targets and mechanisms associated with the hepatoprotective activity of UA intake against alcoholic liver injury comprehensively. Results The serum biomarkers and pathological characteristics indicated the hepatoprotective effects of UA intake on alcoholic liver injury. 567 target genes and 377 target proteins related to the hepatoprotective activity of UA were identified in transcriptomics and proteomics analysis respectively, most of which were associated with function of cellular process, cell part and binding. After data integration, 56 co-regulated targets, including ADH4, CYP450 enzymes, NQO1, apolipoproteins, glutathione–S–transferase, etc. which were consistently modulated on both mRNA and protein levels were identified. These co-regulated targets were found to be correlated with 70 KEGG pathways led by carcinogenesis, retinol metabolism and CYP450 metabolism pathways. Conclusion UA intake ameliorated chronic alcohol-induced liver injury. Given the role of the co-regulated targets in ALD and the bioinformatics analysis results, CYP450-, glutathione and redox homeostasis-dependent antioxidation, promotion of lipid transport, and restoration of ethanol metabolic capacity are the potentially underlying mechanisms. This information will further deepen our insights into the hepatoprotective effects of UA-rich edible plants, and provide us valuable instruction for ALD management.
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Nanomaterials
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2022
·Vol. 12
·期 17
·2933
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IF 5.719
Hongyu Lv,Meng Zhao,Yiran Li,Kun Li,Shaojuan Chen,Wenwen Zhao,Shaohua Wu,Yantao Han
The design and development of novel dressing materials are urgently required for the treatment of chronic wounds caused by diabetic ulcers in clinics. In this study, ursolic acid (UA) extracted from Chinese herbal plants was encapsulated into electrospun nanofibers made from a blend of chitosan (CS) and polyvinyl alcohol (PVA) to generate innovative CS-PVA-UA dressings for diabetic wound treatment. The as-prepared CS-PVA-UA nanofiber mats exhibited randomly aligned fiber morphology with the mean fiber diameters in the range of 100–200 nm, possessing great morphological resemblance to the collagen fibrils which exist in the native skin extracellular matrix (ECM). In addition, the CS-PVA-UA nanofiber mats were found to possess good surface hydrophilicity and wettability, and sustained UA release behavior. The in vitro biological tests showed that the high concentration of UA could lead to slight cytotoxicity. It was also found that the CS-PVA-UA nanofiber dressings could significantly reduce the M1 phenotypic transition of macrophages that was even stimulated by lipopolysaccharide (LPS) and could effectively restore the M2 polarization of macrophages to shorten the inflammatory period. Moreover, the appropriate introduction of UA into CS-PVA nanofibers decreased the release levels of TNF-α and IL-6 inflammatory factors, and suppressed oxidative stress responses by reducing the generation of reactive oxygen species (ROS) as well. The results from mouse hepatic hemorrhage displayed that CS-PVA-UA nanofiber dressing possessed excellent hemostatic performance. The in vivo animal experiments displayed that the CS-PVA-UA nanofiber dressing could improve the closure rate, and also promote the revascularization and re-epithelization, as well as the deposition and remodeling of collagen matrix and the regeneration of hair follicles for diabetic wounds. Specifically, the mean contraction rate of diabetic wounds using CS-PVA-UA nanofiber dressing could reach 99.8% after 18 days of treatment. In summary, our present study offers a promising nanofibrous dressing candidate with multiple biological functions, including anti-inflammation, antioxidation, pro-angiogenesis, and hemostasis functions, for the treatment of hard-to-heal diabetic wounds.Keywords:electrospinning;bioactive nanofibers;ursolic acid;wound dressing;diabetic wound
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MOLECULES
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2022
·Vol. 27
·期 4
·1282
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IF 4.927
Li Zong,Guorong Cheng,Jingwu Zhao,Xiaoyu Zhuang,Zhong Zheng,Zhiqiang Liu,Fengrui Song
The cause of death in most breast cancer patients is disease metastasis and the occurrence of multidrug resistance (MDR). Ornithine decarboxylase (ODC), which is involved into multiple pathways, is closely related to carcinogenesis and development. Ursolic acid (UA), a natural triterpenoid compound, has been shown to reverse the MDR characteristics of tumor cells. However, the effect of UA on the invasion and metastasis of tumor cells with MDR is not known. Therefore, we investigated the effects of UA on invasion and metastasis, ODC-related polyamine metabolism, and MAPK-Erk-VEGF/MMP-9 signaling pathways in a doxorubicin-resistant breast cancer cell (MCF-7/ADR) model. The obtained results showed that UA significantly inhibited the adhesion and migration of MCF-7/ADR cells, and had higher affinities with key active cavity residues of ODC compared to the known inhibitor di-fluoro-methyl-ornithine (DFMO). UA could downregulate ODC, phosphorylated Erk (P-Erk), VEGF, and matrix metalloproteinase-9 (MMP-9) activity. Meanwhile, UA significantly reduced the content of metabolites of the polyamine metabolism. Furthermore, UA increased the intracellular accumulation of Dox in MCF-7/ADR cells. Taken together, UA can inhibit against tumor progression during the treatment of breast cancer with Dox, and possibly modulate the Erk-VEGF/MMP-9 signaling pathways and polyamine metabolism by targeting ODC to exert these effects.Keywords:ursolic acid;metastasis;multidrug resistance;polyamine metabolism;ornithine decarboxylase
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Advanced Healthcare Materials
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2026
·
IF 11
Jiahui Wang,Wanxin Hou,Xiuxiu Qiu,Yu Zhang,Li Tao,Yukun Chen,Beibei Hong,Lei Zhou,Hegen Li,Zhanxia Zhang
Lung cancer metastasis is the primary cause of patient mortality, underscoring an urgent need for highly effective and low-toxicity therapies. Ursolic acid (UA), a natural triterpenoid, possesses potent antitumor activity, yet its clinical translation has been hindered by poor water solubility, low bioavailability, and nonspecific distribution. To overcome these limitations, we developed a UA-loaded iron-based metal–organic framework (MOF) nanomedicine, termed Ursolic Acid-loaded Iron-MOF (UA@MOF). Harnessing the high surface area and tunable porosity of MOFs, this system enables efficient UA encapsulation and promotes tumor-targeted delivery through the enhanced permeability and retention (EPR) effect. Once internalized, UA suppresses the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) signaling pathway, while iron ions released from the MOF induce ferroptosis in tumor cells via Fenton reactions. Together, these dual mechanisms act synergistically to inhibit tumor growth and metastasis. This work presents a novel strategy to improve the delivery and efficacy of natural antitumor agents, offering promising potential for the treatment of metastatic lung cancer.
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Pharmaceuticals
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2026
·Vol. 19
·期 5
·726
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IF 5.7
Huiyue Shen,Zhaolan Ni,Haibo Guo,Xiaofeng Liu,Yaru Zhao,Xuan He,Yinghan Liu,Yan Zhao,Hongbo Teng
Background : Ursolic acid (UA) is a natural pentacyclic triterpenoid with notable antitumor activity, yet its poor water solubility and insufficient targeting restrict clinical translation. Methods : Forty novel ursolic acid-phosphine derivatives bearing seven distinct lipophilic cationic moieties were synthesized via C28 modification and structurally characterized by 1 H NMR and 13 C NMR. Their antitumor activities in PC3-M cells were evaluated via in vitro assays. Mechanistic investigations were performed using transcriptomic analysis and Western blot. Molecular docking was performed to predict the binding profile of Compound 25 with FGFR1. In vivo antitumor efficacy and biosafety were assessed in RM-1 xenograft models in C57BL/6 mice. Results : Compound 25 (bearing a tris(3,5-dimethylphenyl)phosphine group at the C28 position with an alkyl chain length of five methylene units) exhibited the most potent activity against PC3-M cells, dose-dependently inhibiting proliferation, migration, and invasion and inducing apoptosis. It triggered mitochondrial apoptosis via ROS accumulation and disrupted cytoskeletal homeostasis by suppressing the FGFR1/KRAS/RAC1/PIP4K2 axis. Molecular docking results suggested its strong binding affinity and specificity. In vivo studies confirmed its significant antitumor effect and favorable safety. Conclusions : These results highlight the potential of Compound 25 as a promising lead compound and provide valuable insights for further medicinal chemistry optimization and the development of novel anticancer drugs derived from ursolic acid.
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