ACTA PHARMACOLOGICA SINICA
·
2020
·Vol. 42
·期 7
·1101-1110
·
IF 5.064
Ma Xiao-yao,Zhang Man,Fang Ge,Cheng Chuan-jing,Wang Mu-kuo,Han Yi-man,Hou Xiao-tao,Hao Er-wei,Hou Yuan-yuan,Bai Gang
Alcoholic liver disease (ALD) is one of the pathogenic factors of chronic liver disease with the highest clinical morbidity worldwide. Ursolic acid (UA), a pentacyclic terpenoid carboxylic acid, has shown many health benefits including antioxidative, anti-inflammatory, anticancer, and hepatoprotective activities. We previously found that UA was metabolized in vivo into epoxy-modified UA containing an epoxy electrophilic group and had the potential to react with nucleophilic groups. In this study we prepared an alkynyl-modified UA (AM-UA) probe for tracing and capturing the target protein of UA from liver in mice, then investigated the mode by which UA bound to its target in vivo. By conducting proteome identification and bioinformatics analysis, we identified caspase-3 (CASP3) as the primary target protein of UA associated with liver protection. Molecule docking analysis showed that the epoxy group of the UA metabolite reacted with Cys-163 of CASP3, forming a covalent bond with CASP3. The binding mode of the UA metabolites (UA, CM-UA, and EM-UA) was verified by biochemical evaluation, demonstrating that the epoxy group produced by metabolism played an important role in the inhibition of CASP3. In alcohol-treated HepG2 cells, pretreatment with the UA metabolite (10 μM) irreversibly inhibited CASP3 activities, and subsequently decreased the cleavage of PARP and cell apoptosis. Finally, pre-administration of UA (20–80 mg· kg −1 per day, ig, for 1 week) dose-dependently alleviated alcohol-induced liver injury in mice mainly via the inhibition of CASP3. In conclusion, this study demonstrates that UA is a valuable lead compound for the treatment of ALD.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 19
·14771
·
IF 5.6
Pan Lei,Zhiyang Li,Qiuwei Hua,Ping Song,Lun Gao,Long Zhou,Qiang Cai
The neuroinflammatory response after intracerebral hemorrhage (ICH) causes a large amount of neuronal loss, and inhibiting the inflammatory response can improve the prognosis. In previous laboratory studies and clinical trials, ursolic acid (UA) inhibited the inflammatory response, but whether it can be administered to inhibit the neuroinflammatory response after cerebral hemorrhage is unknown. The aim of this study was to investigate the effects of ursolic acid after cerebral hemorrhage. Online databases were used to obtain potential therapeutic targets of ursolic acid for the treatment of cerebral hemorrhage, and possible mechanisms were analyzed by KEGG, GO, and molecular docking. A rat model of cerebral hemorrhage was established using collagenase, and an in vitro cerebral hemorrhage model was constructed by adding hemin to BV2 cell culture medium. Enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), immunofluorescence, TUNEL staining, and calcein/PI staining were used to investigate the degree of microglial M1 polarization, changes in the levels of inflammatory factors, activation of the NF-κB pathway, and changes in the indicators of cellular death after ursolic acid treatment. In addition, phorbol 12-myristate 13-acetate (PMA) was used to activate the NF-κB pathway to verify that ursolic acid exerts its anti-neuroinflammatory effects by regulating the NF-κB/NLRP3/GSDMD pathway. Network pharmacology and bioinformatics analyses revealed that ursolic acid may exert its therapeutic effects on cerebral hemorrhage through multiple pathways. Together, in vivo and in vitro experiments showed that ursolic acid inhibited microglial M1 polarization and significantly reduced the levels of p-NF-κB, GSDMD-N, cleaved caspase-1, TNF-α, IL-6, and IL-1β, which were significantly inhibited by the use of PMA. Ursolic acid inhibits microglial pyroptosis via the NF-κB/NLRP3/GSDMD pathway to alleviate neuroinflammatory responses after cerebral hemorrhage.Keywords:ursolic acid;neuroinflammation;cerebral hemorrhage;microglial;pyroptosis
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2023
·
IF 4.1
Ying Wang,Xiaodan Wu,Guansong Shao,Tao Wang,Zihan Wang,Bingyang Qin,Jingru Zhao,Zhiguo Liu,Yujie Fu
In this article, thermosensitive molecularly imprinted polymer and composite aerogel were combined for the first time to create an intelligent temperature-responsive aerogel reactor to effectively enrich ursolic acid (UA). Because aerogel carrier had a higher specific surface area and higher porosity compared to other carriers, the ursolic acid molecularly imprinted intelligent temperature responsive aerogel reactor (ITR&AR(G570)&UA-MIP) demonstrated a higher adsorption capacity for UA. More notably, ITR&AR(G570)&UA-MIP have the extraordinary capacity to spontaneously adsorb-desorb target molecule UA by regulating the reaction temperature. The ratio of the target molecule UA to the functional monomer and crosslinker in the grafting process and external influences had a major impact on how ITR&AR(G570)&UA-MIP were prepared overall. When the molar ratio of UA to 4-VP was 1:8, the weight ratio between ITR&AR(G570)&UA-MIP and EGDMA/DVB was 1:2:10, the reaction temperature was 60 °C, and the ambient pH = 6, the material showed the best adsorption capacity, reaching a peak of about 70 mg g −1 . After researching the appropriate synthesis conditions, ITR&AR(G570)&UA-MIP were applied to lingonberry (Vaccinium Vitis-Idaea L .) berry extracts in this work. The outcomes show that this technique provides a new, intelligent, temperature-controlled adsorption material for the solid-phase extraction of triterpenoid acids in natural products, with good specific adsorption performance for the target molecule UA.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2023
·
IF 8.8
Ruiling Liu,Liping Zhang,Shangyue Xiao,Hangjun Chen,Yanchao Han,Ben Niu,Weijie Wu,Haiyan Gao
Cuticular wax has been reported to play an essential role in resisting pathogens in various fruits. This study investigated the antifungal ability of the components in blueberry cuticular wax. We showed that the cuticular wax of blueberry inhibited the growth of Botrytis cinerea and ursolic acid (UA) was the key antifungal compound. UA inhibited B. cinerea growth in vitro and in vivo . Furthermore, UA increased extracellular conductivity and cellular leakage in B. cinerea , deformed the mycelial morphology, and destroyed cell ultrastructure. We also demonstrated that UA stimulated the accumulation of reactive oxygen species (ROS) and inactivated ROS scavenging enzymes. These results indicate that UA may exert antifungal effects against B. cinerea by disrupting cell membrane integrity. Thus, UA has significant potential as an agent for the control of gray mold in blueberry.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2017
·Vol. 28
·期 7
·075102
·
IF 3.44
Wenming Cheng,Fatima Zohra Dahmani,Juan Zhang,Hui Xiong,Yuanyuan Wu,Lifang Yin,Jianping Zhou,Jing Yao
Heparin, a potential blood anti-coagulant, is also known for its binding ability to several angiogenic factors through electrostatic interactions due to its polyanionic character. However, the clinical application of heparin for cancer treatment is limited by several drawbacks, such as unsatisfactory therapeutic effects and severe anticoagulant activity that could induce hemorrhaging. Herein, low molecular weight heparin (LMWH) was conjugated to ursolic acid (UA), which is also an angiogenesis inhibitor, by binding the amine group of aminoethyl–UA (UA–NH2) with the carboxylic groups of LMWH. The resulting LMWH–UA conjugate as an amphiphilic twin drug showed reduced anticoagulant activity and could also self-assemble into nanomicelles with a mean particle size ranging from 200–250 nm. An in vitro endothelial tubular formation assay and an in vivo Matrigel plug assay were performed to verify the anti-angiogenic potential of LMWH–UA. Meanwhile, the in vivo antitumor effect of LMWH–UA was also evaluated using a B16F10 mouse melanoma model. LMWH–UA nanomicelles were shown to inhibit angiogenesis both in vitro and in vivo. In addition, the i.v. administration of LMWH–UA to the B16F10 tumor-bearing mice resulted in a significant inhibition of tumor growth as compared to the free drug solutions. These findings demonstrate the therapeutic potential of LMWH–UA as a new therapeutic remedy for cancer therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2022
·
IF 5.518
Jie-Ping Fan,Feng-Hui Tao,Xue-Hong Zhang,Tian-Tao Yuan,Chun-Fang Xie,Hui-Ping Chen,Hai-Long Peng
Low-molecular-weight supramolecular hydrogels (LMWSHs) are widely used in biomedical area and soft materials with desirable stimuli-responsiveness and self-healing abilities. Natural product hydrogelators (NPHGs) based LMWSHs can be synergistically used as drug matrix due to the low toxicity, good biocompatibility, biodegradability and biological activity from hydrogelator. Usually NPHGs based LMWSHs are obtained in organic reagents or following complex modifications. This work introduces a pentacyclic triterpene acid, ursolic acid , derivatives based LMWSH that formed in aqueous solution following simple preparation of 1-ethyl-3-methylimidazolium ursolic salt ([EMIM][UA]). Surprisingly, the gelator [EMIM][UA] based LMWSH showed unusual heating-induced irreversible transparent-turbid transitions in sol state at the gelator concentration lower than the minimum gelation concentration (MGC), but self-assembled to form LMWSH upon cooling like a conventional low-molecular-weight gelator (LMWG) at the gelator concentration higher than MGC. Rarely observed in the LMWSH system, a large number of crystallites were formed in both sol and gel state by increasing temperature, which was analogous to lower critical solution temperature (LCST) phase behavior in polymer systems. Moreover, the formed LMWSH displayed enormous viscoelasticity as chewing gum at room temperature with a porous honeycomb structure based supramolecular network. The good stability and injectability of the formed LMWSH, together with the in vitro drug releasing ability, demonstrated the potential of the formed LMWSH to be the drug delivery system for sustained drug releasing.
✓ 已验证
DOI
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2025
·
IF 4.9
Meiling She,Tianbai Li,Lingli Zhou,Zihao Deng,Minna Huang,Yan Yan,Meng Zhang,Yajun Yang,Dongtao Wang
Background Sarcopenia significantly impairs quality of life, especially in diabetic patients, where effective treatment options remain limited. The IL-17a-related gut-muscle axis suggests a potential role of the gut microbiota in the development of sarcopenia. Ursolic acid (UA) has shown promise as an anti-sarcopenic agent. Nevertheless, the relationship between UA and the IL-17a-related gut-muscle axis remains unclear. Methods In this research, sarcopenia model was established using streptozotocin in vivo and in vitro with TNF-α-managed C2C12 myotubes. Results UA significantly altered the gut microbiota, notably increasing observed OTUs and the Shannon index of sarcopenic mice. Specifically, UA effectively mitigated the decrease of Bacteroides thetaiotaomicron and restored the total level of short-chain fatty acids, particularly reducing propionic acid and increasing isovaleric acid. Additionally, UA markedly improved muscle quality and function, as evidenced by increased body weight, grip strength, and muscle weight, as well as significantly decreased expression of Atrogin-1 and MuRF-1. Moreover, RNA sequencing results clearly indicated that UA suppressed the IL-17 signaling pathway in sarcopenic mice. Furthermore, UA alleviated oxidative stress and apoptosis in sarcopenic mice. Notably, UA inhibited the IL-17a pathway in sarcopenic mice by suppressing the heightened expression of the proteins. In vitro experiments further confirmed that UA inhibited TNF-α-induced myotube atrophy, reduced Atrogin-1 and MuRF-1 expression, and strongly suggested that IL-17a may be a key target of UA in combating myotube atrophy. Conclusions The study emphasizes the importance of UA in alleviating sarcopenia, possibly through the IL-17a-related gut-muscle axis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 5
·2335-2350
·
IF 3.925
Wen-Yan Wang,Zi-Hui Yang,A-Liang Li,Qing-Song Liu,Yue Sun,Wen Gu
A series of novel 2-amino-4-aryl-pyrimidine derivatives of ursolic acid were designed, synthesized, and evaluated for their anticancer activities against four cancer cell lines (MCF-7, HeLa, HepG2, and A549) and a human hepatocyte cell line (LO2) via MTT assay. Among these derivatives, compound 7b exhibited potent cytotoxic activity against MCF-7 and HeLa cells with IC50 values of 0.48 ± 0.11 and 0.74 ± 0.13 μM, respectively, and substantially lower cytotoxicity to LO2 cells. Further cellular mechanism studies in MCF-7 cells elucidated that compound 7b could inhibit cell migration, induce cell cycle arrest at S phase and trigger mitochondrial-related apoptosis by increasing the generation of intracellular ROS and decreasing the mitochondrial membrane potential (MMP), which was associated with upregulation of the protein expression level of Bax and downregulation the level of Bcl-2 and the activation of caspase cascade. Western blot analyses also revealed that compound 7b could simultaneously suppress RAS/Raf/MEK/ERK and PI3K/AKT/mTOR signaling pathways, which could be responsible for the induction of apoptosis. Molecular docking study revealed that MEK1 kinase could be one of the possible targets of the title compounds. These results offered a promising scaffold for the investigation of novel targeted anticancer agents.
✓ 已验证
DOI
高影响因子
Materials Today Bio
·
2026
·
IF 11
Zhen-Zhen Wang,Lihua Cao,Zhenzhu Zhao,Mengke Zhao,Yanyan Lu,Yanhui Zhu,Weijie Xie,Ping Li,Siqi Liu,Xuejiao Li,Kang Yang,Xiaobo Sun
TLR4 activation and the cascade of neutrophil extracellular trap (NET) formation exacerbate excessive inflammation and organ damage in the pathogenesis of acute lung injury (ALI), yet effective pharmacological interventions remain unavailable. Nanoaggregates derived from natural products offer promising avenue by leveraging synergistic anti-inflammatory effects. In this study, we surprisingly discovered that leonurine and ursolic acid spontaneously self-assemble into nanoparticles (LUNP) through non-covalent interactions, achieving a drug loading capacity of 100%. The LUNP platform exhibits superior biophysical properties, including enhanced mucus penetration, pH-responsive drug release, improved cellular uptake, and prolonged retention within inflamed lung tissue. Mechanistically, LUNP ameliorates ALI by dampening TLR4/MyD88/NF-κB-driven inflammatory activation, thereby remodeling the microenvironment to limit NOX4-PAD4-mediated NET formation. Notably, inhalational LUNP exhibits outstanding biosafety with minimal off-target distribution. Overall, this work introduces a synergistic self-assembled nanoplatform for precise pulmonary intervention in ALI, showcasing its ability to safely and effectively orchestrate the coordinated modulation of multiple pathological pathways. In summary, by inhibiting both TLR4 activation and NET formation, the synergistic LUNP platform offers an efficient, safe, and easily accessible therapeutic strategy for ALI, providing a promising solution for clinical translation.
✓ 已验证
DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Shu-zhen Xiao,Jie Wang,Jia Liu,Yin Wu,Chang-Zhao Wang,Zhong-ping Yin,Xin-chen Shangguan,Da-yong Peng
A novel fluorescent labeling reagent 4-(2-(9-ethyl-9H-carbazol-3-yl)-1H-phenanthro[9,10-d] imidazol-1-yl) butyl-4-methylbenzene sulfonate (CPIOTs) was designed, synthesized and applied in this study for the determination of triterpene acids using high-performance liquid chromatography with a fluorescence detector (HPLC-FLD). The derivatives of CPIOTs demonstrated exceptional stability and fluorescence properties, with maximum excitation and emission wavelengths at 311 nm and 398 nm, respectively. Calibration curves under optimized conditions displayed outstanding linear responses, as evidenced by correlation coefficients (R 2 ) exceeding0.9996. The detection and quantification limits were in the range of 0.098–0.160 ng/ml and 0.354–0.528 ng/ml, respectively. Therefore, CPIOTs proved to be a successful tool for detecting trace levels of oleanolic acid (OA) and ursolic acid (UA) in loquat leaves samples.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2017
·
IF 3.154
Guirong Zheng,Yiling Shen,Ruirui Zhao,Fan Chen,Ying Zhang,Aixiao Xu,Jingwei Shao
A targeting drug delivery system (TDDS) can selectively deliver antitumor drugs to cancerous parts to improve its anticancer efficacy. Hence, a targeted drug delivery system (UA/siVEGF@MSN-FA) coloading ursolic acid (UA) and vascular endothelial growth factor (VEGF) targeted siRNA (siVEGF) based on mesoporous silica (MSN) nanocarrier modified by a folic acid (FA) molecule was designed and synthesized. The MSN-FA nanoparticles were investigated for shape, diameter, and zeta potential and and by infrared (IR) spectroscopy. FR-overexpressing HeLa cells and FR-negative HepG2 cell lines were used to evaluate the in vitro cellular uptake and the cytotoxicity of MSN-FA nanoparticles. The morphology of HeLa cells transfected with siVEGF@MSN-FA was observed using fluorescence microscopy. Our findings demonstrated that UA@MSN-FA nanoparticles were near-spherical, and the particle size was about 209 ± 9.21 nm. The MSN-FA nanocarrier not only could enhance the in vitro transfection efficiency and the stability of siVEGF but also could further improve the targeted anticancer efficacy of UA and siVEGF via the active targeting property of FA. Overall, the MSN-FA drug delivery system could serve as an excellent material in biomedical applications.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2015
·
IF 3.35
Yu Gao,Zhihong Li,Xiaodong Xie,Chaoqun Wang,Jiali You,Fan Mo,Biyu Jin,Jianzhong Chen,Jingwei Shao,Haijun Chen,Lee Jia
The anticancer efficacy of ursolic acid (UA) was limited by poor water solubility, non-specific tumor distribution, and low bioavailability. To overcome this problem, polyamidoamine (PAMAM) conjugated with UA and folic acid (FA) as novel dendrimeric prodrugs were designed and successfully synthesized by a concise one-pot synthetic approach. Both FA and UA were covalently conjugated to the surface of PAMAM through acid-labile ester bonds and the covalently linked UA could be hydrolysed either in acidic (pH 5.4) or in neutral (pH 7.4) PBS solution. The cellular uptake study indicated that the presence of FA enhanced uptake of the dendrimeric prodrugs in folate receptor (FR) over-expressing Hela cells. The enhanced cellular uptake could be due to the electrostatic absorptive endocytosis and FR-mediated endocytosis. In contrast, for HepG2 cells, a FR-negative cell line, FA conjugation on the surface of the dendrimer showed no effect on the cellular uptake. In MTT assay and cell cycle analysis, FA-modified dendrimeric prodrugs showed significantly enhanced toxicity than non-FA-modified ones in Hela cells. These results suggested that FA-modified dendrimeric UA prodrugs have the potential for targeted delivery of UA into cancer cells to improve its anti-tumor efficacy.
✓ 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）