Drug Design Development and Therapy
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2025
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IF 5.1
Yijing Zhou,Chengli Lou,Xiuqin Xu,Bo Feng,Xiaoping Fan,Xiangjing Wang
Purpose Ursolic acid (UA) improves diabetic nephropathy (DN), but its regulatory mechanism requires further verification.Methods The bioactive component-target network of UA in DN was determined using a network pharmacology approach. DN mice (STZ-diabetic C57BL/6 mice, n = 8/group, 4 weeks) were treated with UA (25 mg/kg and 100 mg/kg) and the JAK agonist RO8191 (2 mg/kg). The DN cell model (high glucose-injured NRK-52E cells) was treated with UA (10 and 50 µM) and RO8191 (2 μM) for 24 h. The molecular mechanisms by which UA acts were further verified in vivo and in vitro.Results UA treatment ameliorated the general state of the DN mouse model, as characterized by the attenuation of weight loss and downregulation of fasting blood glucose (FBG) and fasting serum insulin (FINS) levels (all P < 0.05). Renal pathological changes and impaired renal function (increased levels of Scr, BUN, and UAER) were also improved by UA treatment (all P < 0.05). In vitro, UA increased the viability of DN cells in vitro (P < 0.001). Concurrently, UA remarkably downregulated the levels of ROS, SOD, and iron and up-regulated the levels of MDA, GPX4, and SLC7A11 (all P < 0.05) in vivo and in vitro. Mechanistically, activation of the JAK2-STAT3 pathway with the agonist RO8191 significantly reduced UA’s anti-ferroptosis and anti-oxidative effects of UA.Conclusion UA protected against DN by blocking JAK2/STAT3-mediated ferroptosis.
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Food Packaging and Shelf Life
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2025
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IF 10.6
Fengyan Liang,Jinwen Geng,Ziming Yang,Wanqi Cen,Miaoyu Zhao,Xunting Huang,Changbin Wei,Puwang Li,Kaidong Liu
Amphiphilic chitosan (DA-CS-AG) was synthesized and incorporated with ursolic acid (UA) to develop an active coating film. Characterization techniques confirmed the preparation of DA-CS-AG, and UA was successfully entrapped in the active coating films. With the weight ratios of UA to DA-CS-AG increasing from 1:20, 2:20–4:20, the coating films exhibited increased thickness, improved water resistance, higher tensile strength, and enhanced antioxidant and antibacterial properties. As the UA/DA-CS-AG weight ratio increased from 1:20–2:20, the films ’ UV-shielding capability, water vapor barrier properties, and elastic properties increased. However, these properties deteriorated when the weight ratio increased to 4:20. Preservation experiments of papaya fruits demonstrated that UA/DA-CS-AG-2 coating films delayed the ripening of papaya at 25 º C for 16 days based on appearance, color changes, quality indexes, and sensory evaluation. In conclusion, these active coating films can serve as packaging materials for fruits and vegetables.
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PHYTOMEDICINE
·
2026
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IF 11.3
Wen-Biao Zu,Zhao-Jie Wang,Dong-Mei Tang,Qin-Yu Lu,Yan-Yan Zhu,Zhong-Shun Zhou,Mei-Zhen Wei,Xiao-Dong Luo
Background Fungal diseases affect over one billion individuals worldwide and represent a significant public health concern. Oral candidiasis (OC) is a common fungal infection primarily caused by Candida albicans. Eriocapitella rivularis is a traditional medicinal herb for the treatment of oral fungal infections. Purpose This study aimed to identify potent antifungal compounds from E. rivularis and elucidate their underlying mechanisms of action. Methods Bio-guided isolation combined with network pharmacology was used to identify anti- C. albicans compounds from E. rivularis , followed by metabolomics analysis to explore potential regulatory pathways. Antifungal activity and synergistic efficacy were evaluated using broth microdilution, checkerboard, and time-kill assays. Biofilm inhibition was assessed through quantitative and biochemical analyses. Reverse transcription quantitative polymerase chain reaction was performed to elucidate molecular mechanisms. An in vivo murine OC model was employed to verify efficacy. Results Prosapogenin CP4 disrupted the fungal cell wall, targeted ergosterol to induce plasma membrane permeabilization, inactivated mitochondrial function, and inhibited hyphal growth, potentially through interference with ABC transporters, modulation of cAMP export, and induction of metabolic disorders. Prosapogenin CP4 and ursolic acid exhibited a synergistic inhibitory effect against fluconazole-resistant C. albicans (FICI = 0.375) with low resistance. This combination regulated genes in the Ras/cAMP/PKA signalling pathway, significantly inhibited biofilm formation and reduced fungal burden, inflammatory responses, and fungal colonisation in murine oral tissues, with efficacy comparable or superior to that of nystatin. Conclusion The finding presents a synergistic phytomedicine strategy using two triterpenoids from E. rivularis as a promising therapeutic approach for OC, particularly biofilm-associated infections.
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CARBOHYDRATE POLYMERS
·
2024
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IF 10.7
Yufan Guo,Xiuru Yang,Yihong Zhang,Fazhen Luo,Juan Yang,Xupeng Zhang,Jinxia Mi,Yan Xie
Cancer multidrug resistance (MDR) dramatically hindered the efficiency of standard chemotherapy. Mitochondria are highly involved in the occurrence and development of MDR; thus, inducing its malfunction will be an appealing strategy to treat MDR tumors. In this paper, a natural polysaccharides-based nanoplatform (TDTD@UA/HA micelles) with cell and mitochondria dual-targeting ability was facilely fabricated to co-deliver ursolic acid (UA) and doxorubicin (DOX) for combinatorial MDR therapy. TDTD@UA/HA micelles featured a spherical morphology, narrow size distribution (∼140 nm), as well as favorable drug co-loading capacity (DOX: 8.41 %, UA : 9.06 %). After hyaluronic acid (HA)-mediated endocytosis , the lysosomal hyaluronidase promoted the degradation of HA layer and then the positive triphenylphosphine groups were exposed, which significantly enhanced the mitochondria-accumulation of nano micelles . Subsequently, DOX and UA were specifically released into mitochondria under the trigger of endogenous reactive oxygen species (ROS), followed by severe mitochondrial destruction through generating ROS, exhausting mitochondrial membrane potential, and blocking energy supply, etc. ; ultimately contributing to the susceptibility restoration of MCF-7/ADR cells to chemotherapeutic agents. Importantly, TDTD@UA/HA micelles performed potent anticancer efficacy without distinct toxicity on the MDR tumor-bearing nude mice model. Overall, the versatile nanomedicine represented a new therapeutic paradigm and held great promise in overcoming MDR-related cancer.
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Arabian Journal of Chemistry
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2024
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IF 5.3
Zhiwen Qi,Pujun Xie,Zhihong Wang,Hao Zhou,Ran Tao,Sergey A. Popov,Guliang Yang,Elvira E. Shults,Chengzhang Wang
Excessive oxidation can lead to inflammation and affect health. Studies have shown that ursolic acid (UA) and gallic acid are widely employed in medicine and cosmetics owing to their obvious antioxidant and anti-inflammatory properties. In this study, a series of 16 novel UA hybrids tethered via 1,2,3-triazole to the modified gallate moieties were synthesized via CuAAC 1,3-cycloaddition reactions. In vitro , all derivatives were proved to be effective in antioxidation and anti-inflammation activities. Interestingly, compound 20 significantly inhibited the expression of pro-inflammatory cytokines including mRNA of inducible nitric oxide synthase (iNOS) ( p < 0.05) and cyclooxygenase-2 (COX-2) ( p < 0.01) in lipopolysaccharide (LPS)-induced RAW264.7 cells in a dose-dependent manner. The inhibitory effect of compound 20 on pro-inflammatory cytokines was closely associated with suppression of the LPS-activated PI 3 K/Akt signal pathway. Compound 20 significantly alleviated inflammation in the gastrointestinal tract of zebrafish in vivo . In addition, compound 20 showed good biosafety in cytotoxicity evaluation. This study provides a novel reference for the development of treatments for health problems related to anti-oxidation and anti-inflammation properties.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2021
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IF 5.279
Xin Yan,Xueyang Ren,Xiaoyun Liu,Yu Wang,Jiamu Ma,Ruolan Song,Xiuhuan Wang,Ying Dong,Qiqi Fan,Jing Wei,Axiang Yu,Gaimei She
Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut–liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. A fecal microbiota transplantation study indicated that liver injury as well as ileum oxidative stress and gut barrier dysfunction of recipient mice were partly ameliorated as a result of microbiome remodeling. These results suggest that dietary UA alleviates ALD through GLA homeostasis modulation. Gut microbiome manipulation contributes to the hepatoprotective activity and GLA modulating effect of UA.
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PHYTOMEDICINE
·
2022
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IF 6.656
Xiaoyao Ma,Yongping Bai,Kaixin Liu,Yiman Han,Jinling Zhang,Yuteng Liu,Xiaotao Hou,Erwei Hao,Yuanyuan Hou,Gang Bai
Background In hypercholesteremia , the concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are enhanced in serum, which is strongly associated with an increased risk of developing atherosclerosis . Ursolic acid (UA), a pentacyclic terpenoid carboxylic acid , was found to alleviate hypercholesterolemia and hypercholesterolemia-induced cardiovascular disease. However, the specific targets and molecular mechanisms related to the effects of UA in reducing cholesterol have not been elucidated. Purpose In this study, we aimed to illustrate the target of UA in the treatment of hypercholesterolemia and to reveal its underlying molecular mechanism. Methods Nontargeted metabolomics was conducted to analyze the metabolites and related pathways that UA affected in vivo . The main lipid metabolism targets of UA were analyzed by target fishing and fluorescence colocalization in mouse liver. Molecular docking , in-gel fluorescence scan and thermal shift were assessed to further investigate the binding site of the UA metabolite with HMGCS1 . C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks to induce hypercholesteremia. Liver tissues were used to verify the cholesterol-lowering molecular mechanism of UA by targeted metabolomics, serum was used to detect biochemical indices, and the entire aorta was used to analyze the formation of atherosclerotic lesions. Results Our results showed that hydroxy‑3-methylglutaryl coenzyme A synthetase 1 (HMGCS1) was the primary lipid metabolism target protein of UA. The UA metabolite epoxy-modified UA irreversibly bonds with the thiol of Cys-129 in HMGCS1, which inhibits the catalytic activity of HMGCS1 and reduces the generation of precursors in cholesterol biosynthesis in vivo . The contents of TC and LDL-C in serum and the formation of the atherosclerotic area in the entire aorta were markedly reduced with UA treatment in Diet-induced hypercholesteremia mice. Conclusion UA inhibits the catalytic activity of HMGCS1, reduces the generation of downstream metabolites in the process of cholesterol biosynthesis and alleviates Diet-induced hypercholesteremia via irreversible binding with HMGCS1 in vivo . It is the first time to clarify the irreversible inhibition mechanism of UA against HMGCS1. This paper provides an increased understanding of UA, particularly regarding the molecular mechanism of the cholesterol-lowering effect, and demonstrates the potential of UA as a novel therapeutic for the treatment of hypercholesteremia.
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DYES AND PIGMENTS
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2023
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IF 4.5
Shibing Chen,Minqian Zhu,Xiangfei Xu,Hongyu Guo,Fafu Yang
The macrocycles with the features of large cavity, optical property and CPL response to guest simultaneously are rarely reported but very attractive based on their potential application. Herein, a macrocycle ( BiCDB-MC ) with dynamically racemic feature, inwardly directed functional groups, a large hollow with size of 1.3 nm and fluorescent property was designed and synthesized. BiCDB-MC was found to have two equally chiral conformations and was dynamically racemic in solution based on their rapidly interconvertion via macrocycle flipping. It was interesting that BiCDB-MC exhibited a selective turn-on CPL response with g lum = 0.00248 toward ursolic acid since one of the stable chiral conformations could form a more stable inclusion complex. This kind of turn-on CPL emission for dynamical-racemic macrocycle with CPL recognition for complicated natural chiral compound was described for the first time.
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Foods
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2023
·Vol. 12
·期 2
·310
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IF 5.2
Haiyan Li,Yugang Liu,Shiyin Guo,Meng Shi,Si Qin,Chaoxi Zeng
Extracting ursolic acid (UA) from plant resources using organic solvents is incompatible with food applications. To address this, in this study, 15 edible hydrophobic deep eutectic solvents (HDESs) were prepared to extract UA from apple peel, the extraction conditions were optimized, and the optimization strategies were compared. It was found that the solubility of UA in the HDESs can be 9 times higher than the traditional solvent such as ethanol. The response surface optimization concluded that temperature had the greatest effect on the extraction and the optimized test conditions obtained as follows: temperature of 49 °C, time of 32 min, solid–liquid ratio of 1:16.5 g/mL, respectively. Comparing the response surface methodology (RSM) and artificial neural networks (ANN), it was concluded that ANN has more accurate prediction ability than RSM. Overall, the HDESs are more effective and environmentally friendly than conventional organic solvents to extract UA. The results of this study will facilitate the further exploration of HDES in various food and pharmaceutical applications.Keywords:apple peel;ultrasonic-assisted extraction;response surface methodology;artificial neural network
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JOURNAL OF CHROMATOGRAPHY A
·
2020
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IF 4.049
Chaoyue Wang,Xiang Wang,Shanshan Zhao,Guanglei Zuo,Min Xu,Shengqiang Tong
Two structural isomeric pentacyclic triterpenes, oleanolic acid and ursolic acid, were considered as the models for the quality control of many traditional Chinese herbal medicines and they have been proved to own important pharmacological activities. In the present work, liquid chromatographic and liquid-liquid chromatographic separation with high peak resolution of structural isomeric oleanolic acid and ursolic acid using hydroxypropyl-β-cyclodextrin as mobile phase additive was successfully achieved, respectively. A high peak resolution, R S =8.143, was achieved for the two structural isomeric compounds by conventional reverse phase high performance liquid chromatography, which was greatly improved compared with the published values. Meanwhile, a biphasic solvent system composed of n- hexane-ethyl acetate-0.1 mol/L hydroxypropyl-β-cyclodextrin (9:1:10, v/v) was selected for liquid-liquid chromatography, which provided a high peak resolution, R S = 6.573, for analytical apparatus and R s = 8.500 for semi-preparative apparatus after optimization by liquid-liquid extractions. Two elution modes including reverse phase mode and normal phase mode were investigated for preparative separation of two acids from crude exact of Eriobotrya japonica Thunb. Furthermore, the inclusion complex between each of the two structural isomers and hydroxypropyl-β-cyclodextrin were also investigated for high performance liquid chromatography and liquid-liquid chromatography, respectively, in which formation constants were determined for oleanolic acid and ursolic acid.
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RSC Advances
·
2019
·Vol. 9
·期 66
·38860-38866
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IF 3.049
Chaoyue Wang,Xiang Wang,Shanshan Zhao,Wenyu Sun,Shengqiang Tong
In this work, pH-zone-refining countercurrent chromatography was investigated in the preparative separation of two bioactive components, oleanolic acid and ursolic acid, from three different natural products, Aralia chinensis, apple peels and Eriobotrya japonica Thunb. Oleanolic acid and ursolic acid are structurally isomeric pentacyclic triterpene acids that are widely distributed in many natural products. However, it was difficult to separate these components with high purity by conventional methods. A biphasic solvent system composed of n-hexane–dichloromethane–methanol–water (7 : 3 : 2 : 8, v/v) was selected, in which an optimized concentration of 10 mmol L−1 trifluoroacetic acid was added in the upper phase as the retainer and 10 mmol L−1 ammonia (with 25–28% NH3) was added in the aqueous phase as the eluter. Consequently, 38.56 mg of oleanolic acid with 99.01% purity was separated from 100 mg of the crude extract of Aralia chinensis, while 65.6 mg of a mixture of ursolic acid (90.98%) and oleanolic acid (6.51%) and 46.6 mg of a mixture of ursolic acid (74.35%) and oleanolic acid (23.61%) were separated from 100 mg of the crude extract of apple peels and 100 mg of the crude extract of Eriobotrya japonica Thunb., respectively, by pH-zone-refining countercurrent chromatography using the above selected biphasic solvent system. The results showed that pH-zone-refining countercurrent chromatography is an efficient method for the preparative separation of pentacyclic triterpene acids from natural products.
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Journal of Analytical Methods in Chemistry
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2017
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IF 1.801
Chang Xu,Yiyi Liao,Chunyan Fang,Makoto Tsunoda,Yingxia Zhang,Yanting Song,Shiming Deng
In this paper, a novel method of QuEChERS-based extraction coupled with high-performance liquid chromatography has been developed for the simultaneous determination of ursolic acid (UA) and oleanolic acid (OA) in guava leaves. The QuEChERS-based extraction parameters, including the amount of added salt, vortex-assisted extraction time, and absorbent amount, and the chromatographic conditions were investigated for the analysis of UA and OA in guava leaves. Under the optimized conditions, the method showed good linearity over a range of 1–320 μg mL−1, with correlation coefficients above 0.999. The limits of detection of UA and OA were 0.18 and 0.36 μg mL−1, respectively. The intraday and interday precision were below 1.95 and 2.55%, respectively. The accuracies of the UA and OA determinations ranged from 97.4 to 111.4%. The contents of UA and OA in the guava leaf samples were 2.50 and 0.73 mg g−1, respectively. These results demonstrate that the developed method is applicable to the simultaneous determination of UA and OA in guava leaves.
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