CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Chun Song,Xu Qin,Siqi Jin,Ming Wu,Yanyang Wang,Jing Yu,Na Peng
The mitochondrial targeting UT was synthesized by modifying ursolic acid (UA) with TPP-NH 2 . • A CaO 2 -based nanosystem loaded UT and surface coated with hyaluronic acid (HA) was successfully constructed for selective accumulation in hepatocellular carcinoma (HCC). • The combination of Ca 2+ overload and mitochondrion localized UT effectively promotes cancer cell apoptosis via induced mitochondrial dysfunction. • CUTP@HA significantly reduced the IC 50 for Hepa 1–6 cells to 14.6 μmol·L −1 and suppressed orthotopic liver tumor growth by 93.65%. Mitochondria not only act as the central regulator in cell apoptosis, but also highly determine the death of cancerous cells. The triggering of endoplasmic reticulum (ER) stress and mitochondrial dysfunction pose as potential strategies for advanced hepatocellular carcinoma (HCC) therapies of chemotherapeutic agents. Herein, we firstly reported the synthesis of mitochondrial targeted ursolic acid (UT) by modification of ursolic acid with [2-(triphenylphosphonio)ethyl]amine bromide (TPP-NH 2 ). Then, UT was loaded during the preparation of CaO 2 via crosslinking of Ca 2+ with dendritic polyacrylic acid in H 2 O 2 , and finally surface-coated with tumor-targeting hyaluronic acid (HA), termed CUTP@HA. CUTP@HA selectively accumulated in HCC and was destructed in the acidic tumor environment, which provoked the generation of abundant exogenous Ca 2+ , H 2 O 2 , and O 2 in situ. They effectively trigger calcium influx to jointly stimulate ER stress, and synergized with mitochondria-located UT to enhance Ca 2+ overload-induced mitochondrial dysfunction in cancer therapy, ultimately promoting cell apoptosis. Consequently, the amplified Ca 2+ overload-induced mitochondrial dysfunction’ methodology remarkably reduced the IC 50 of CUTP@HA for Hepa 1–6 cells to 14.6 μmol·L −1 , thereby suppressing orthotopic liver tumor growth by 93.65%. CUTP@HA provides perspectives on the modification and enhanced antitumor efficacy of active Chinese novel herbal chemotherapeutic ingredients. Synergism of Ca 2+ overload with mitochondria-targeted ursolic acid to enhance hepatocellular carcinoma therapy via endoplasmic reticulum stress and mitochondrial dysfunction. Download: Download high-res image (134KB) Download: Download full-size image
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高影响因子
REACTIVE & FUNCTIONAL POLYMERS
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2026
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IF 5.4
Linan Sun,Maoyu Zhang,Ming Qu,Chengdong Nie,Tao Wang,Jingru Zhao,Zhen Zhou,Yujie Fu
Ursolic acid (UA) and oleanolic acid (OA) are among the most commonly utilized natural products for liver protection and anti-hepatitis applications, and are also prevalent ingredients in skincare formulations. In this study, cellulose-based molecularly imprinted polymers (MCC/PDA-OA/UA-MIPs) were synthesized using surface molecular imprinting technology, wherein OA and UA bimodal template molecules were incorporated onto the surface of polydopamine-modified cellulose microspheres. The MCC/PDA-OA/UA-MIPs exhibited specific recognition ability towards OA and UA via the complementary imprinted cavities, thereby achieving simultaneous enrichment of both compounds. Characterization and adsorption evaluations revealed that the MCC/PDA-OA/UA-MIPs possessed a uniform shape, good stability, and selective adsorption properties; the maximum adsorption capacities for UA and OA reached 48.26 ± 1.97 mg g −1 and 38.06 ± 1.55 mg g −1 , respectively. The enrichment efficiencies of OA and UA from lingonberry crude extract reached 62.12% and 68.46%. Overall, the MCC/PDA-OA/UA-MIPs developed in this work feature high enrichment efficiency and enhanced sustainability, providing a feasible alternative strategy for the targeted extraction of natural products.
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Biomaterials Advances
·
2026
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IF 6.7
Jun Che,Ai Yang,Feng Mo,Yaqin Gao,Yunshu Li,Yuting Cui,Feihong Zhuo,Yun Hong,Yiheng Zhang,Tianyi Chen,Fei Qin,Gaohong LYU,Zhipeng Chen,Liu Xu
GelMA hydrogelco-loaded anti-caries/odontogenic components (Gel/UFN) was developed. • Gel/UFN was designed to achieve prolonged release over 55 days. • Gel/UFN upregulates odontogenesis-related genes and regenerative mineralization. • Gel/UFN promotes angiogenesis and enables the regeneration of dentin in vivo . Dental caries is a prevalent bacterial infectious disease, yet current clinical treatments remain limited because conventional restorative materials provide only mechanical filling and fail to induce dental tissue regeneration. Herein, we developed a composite gelatin methacryloyl (GelMA) hydrogel system (Gel/UFN) co-loaded with three active components from traditional Chinese medicine, including ursolic acid (UA), ferulic acid (FA) and naringin (Nar), to remodel the carious microenvironment and promote dentin remineralization and vascularized pulp–dentin-like tissue formation. Gel/UFN showed excellent biocompatibility and favorable physicochemical and mechanical properties for dental applications, supporting adhesion and proliferation of human dental pulp stem cells (hDPSCs). Functionally, Gel/UFN significantly inhibited Streptococcus mutans ( S. mutans ) growth and biofilm formation, downregulated inflammatory cytokine expression and promoted the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs). More importantly, Gel/UFN upregulated odontogenesis-related genes in hDPSCs, thereby enhancing odontogenic differentiation, alkaline phosphatase activity, collagen maturation and regenerative mineralization. In vivo , Gel/UFN exhibited slow degradation and sustained drug release for over 55 days. After implantation of Gel/UFN-filled dentin discs into nude mice, H&E staining demonstrated the formation of vascular structures, dentin-like mineralized tissue and cell-rich pulp-like tissue. Western blot analysis further revealed increased expression of the odontogenesis-related proteins RUNX2, DSPP, DMP1, and COL1A1 in the Gel/UFN group, providing additional protein-level evidence of its pro-odontogenic effects in vivo . These newly formed tissues were observed to cover exposed dentinal tubules on the surface of dentin disc using scanning electron microscopy (SEM). Micro-CT further confirmed that dental tissue induced by Gel/UFN exhibited a higher remineralization density at the defect site, supporting enhanced dentin remineralization. Overall, Gel/UFN may serve as a promising bioactive hydrogel platform for dentin repair and vascularized pulp–dentin-like tissue formation through antibacterial, anti-inflammatory, pro-angiogenic and pro-differentiation effects. Download: Download high-res image (213KB) Download: Download full-size image
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2023
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IF 5.6
Zhehuan Wang,Huiru Zhang,Caihong Qi,Hui Guo,Xiangyue Jiao,Jia Yan,Yifei Wang,Qiangsheng Li,Mingming Zhao,Xinhao Guo,Baoluo Wan,Xiaotian Li
Background Ursolic acid (UA) is a triterpenoid compound found in natural plants. It has been reported to have anti-inflammatory, antioxidant, and immunomodulatory properties. However, its role in atopic dermatitis (AD) is unknown. This study aimed to evaluate the therapeutic effect of UA in AD mice and explore the underlying mechanisms. Methods Balb/c mice were treated with 2, 4-dinitrochlorobenzene (DNCB) to induce AD-like lesions. During modeling and medication administration, dermatitis scores and ear thickness were measured. Subsequently, histopathological changes, levels of T helper cytokines, and oxidative stress markers levels were evaluated. Immunohistochemistry staining was used to assess changes in the expression of the nuclear factor of kappa B (NF-κB) and NF erythroid 2-related factor 2 (Nrf2). Furthermore, CCK8 assay, reactive oxygen species (ROS) assay, real-time PCR, and western blotting were employed to evaluate the effects of UA on ROS levels, inflammatory mediator production, and the NF-κB and Nrf2 pathways in TNF-α/IFN-γ-stimulated HaCaT cells. Results The results showed that UA significantly reduced dermatitis score and ear thickness, effectively inhibited skin proliferation and mast cell infiltration in AD mice, and decreased the expression level of T helper cytokines. Meanwhile, UA improved oxidative stress in AD mice by regulating lipid peroxidation and increasing the activity of antioxidant enzymes. In addition, UA inhibited ROS accumulation and chemokine secretion in TNF-α/IFN-γ-stimulated HaCaT cells. It might exert anti-dermatitis effects by inhibiting the TLR4/NF-κB pathway and activating the Nrf2/HO-1 pathway. Conclusion Taken together, our results suggest that UA may have potential therapeutic effects on AD and could be further studied as a promising drug for AD treatment.
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PubMed
高影响因子
RSC Advances
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2018
·Vol. 8
·期 29
·15906-15914
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IF 2.936
Zhaokun Yan,Qingtang Wang,Xiaolong Liu,Jun Peng,Qin Li,Ming Wu,Jiumao Lin
Ursolic acid (UA) has shown great potential in cancer therapy but their efficacy is seriously compromised by poor water-solubility and limited cellular uptake. In this paper, cationic nanomicelles self-assembled from Pluronic F127 with the cationic polymer of C18-polyethylenimine (C18-PEI) as a functional component are fabricated as delivery vehicles of Chinese herbal medicine active components of ursolic acid (UA) for colorectal cancer treatment. The inhibition effects of this drug loaded cationic nanomicelles (named as FUP) on cell viability and cell colony formation were more significant than the free UA, due to their cationic surface which can increase UA uptake by colorectal cancer cells. Cell cycle analysis showed that this inhibition effect was mediated by a cell cycle arrest at the G1 checkpoint, and the cell death induced by these nanomicelles occurred via apoptosis, which was detected by annexin V antibody and propidium iodide staining. Further western blot analysis demonstrated the apoptosis mechanism was associated with the regulation of Fas/FasL and activation of caspase-8 and caspase-3. Therefore, our cationic nanomicelles can potentially be used to enhance the therapeutic effect of UA for colorectal cancer treatment.
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高影响因子
JOURNAL OF MOLECULAR MODELING
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2017
·Vol. 23
·期 8
·1-11
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IF 1.425
Sun Jiachen,Dong Shengjie,Wu Yueting,Zhao Hui,Li Xia,Gao Wenyuan
It is known that inhibiting α-amylase, an important enzyme in digestion of starch and glycogen, is a useful strategy for treating disorders in carbohydrate uptake. Two natural components distributed in many fruits and plants, oleanolic acid and ursolic acid, are endowed with important pharmacological activities and wide therapeutic possibilities. Until now, only a tiny fraction of their applications have been identified and exploited. Our in vitro inhibition studies demonstrated that oleanolic acid and ursolic acid non-competitively inhibit the activity and function of human salivary α-amylase. The molecular simulations revealed that oleanolic acid and ursolic acid interact with amino acid residues within the binding pocket of human salivary α-amylase, among which the side chain of Arg195 and Asp 197 was supposed to be important in imparting the inhibitory activity of triterpenoids. The present work will provide meaningful information for future development of functional drugs for the treatment of disorders in carbohydrate metabolism.
This work is valuable for providing a deeper insight into the interaction mechanism of oleanolic acid and ursolic acid with α-amylase
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高影响因子
PHYTOMEDICINE
·
2024
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IF 6.7
Yiren Yang,Pengyu Liu,Yue Jin,Huilin Zhu,Miao Wang,Xiaowen Jiang,Huiyuan Gao
Background Conventional chemotherapy medications are inadequate for managing the primary or acquired drug resistance, high toxicity, and adverse effects of colorectal cancer (CRC) treatment. Ursolic acid (UA) and Solasodine (Sol) are natural compounds found in a wide variety of traditional medicinal plants, as well as in many fruits and vegetables, such as Actinidia arguta (Sieb. & Zucc) Planch and Solanum nigrum L.. These compounds exhibit significant anti-tumor activity. Recent investigations have demonstrated that a combination strategy using natural products exhibits greater potential in CRC treatment compared to a single-drug strategy. Purpose This study aimed to elucidate the potential of UA-Sol synergy against CRC and to investigate the mechanism of action involved in inducing apoptosis and inhibiting metastasis through the AKT1/ERK1/2-GSK-3 β - β -catenin axis. Methods The optimal ratio of UA-Sol and its synergistic effects were explored using an MTT assay combined with the technique of Chou Talalay. The effects of UA-Sol on the apoptosis, autophagy, and metastasis of CRC cells were assessed using Annexin V-FITC/PI, TUNEL, Immunofluorescence, Wound healing, Transwell migration, and western blotting. The core mechanism of action of UA-Sol against CRC was investigated employing network pharmacology prediction combined with CETSA and plasmid transfection. Finally, in vivo validation was conducted using mouse xenograft tumor and lung metastasis models. Results The combination of UA and Sol synergistically inhibited CRC cell viability at a molar ratio of 6:24. UA-Sol induced the expression of pro-apoptotic and autophagy genes such as Bax/Bcl-2 and LC3, ultimately leading to apoptosis and autophagy in CRC cells in vitro . In addition, this combination inhibited MMP-9 and promoted the expression of the adhesion protein E-cadherin, thereby inhibiting CRC cell metastasis. Mechanistically, UA-Sol regulated the expression of a downstream protein GSK-3 β by targeting AKT1 and ERK1/2 inhibition. This induced a cross-talk between the MAPK cascade pathway and the PI3K/AKT pathway, thereby inhibiting the nuclear translocation of β -catenin and participating in the regulation of CRC cell processes. Conclusion UA-Sol inhibited the AKT1/ERK1/2-GSK-3 β - β -catenin axis to induce apoptosis, autophagy and anti-metastasis by targeting AKT1 and ERK1/2 inhibition. This dual-target drug combination strategy provides promising insights into the development of novel, safe, and efficient drugs for the treatment of CRC.
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高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
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2020
·Vol. 137
·期 36
·49081
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IF 2.52
Huan Yu,Haiyan Liu,Xiaoya Pang,Miaomiao Zhang,Hongyuan Yan,Ligai Bai
In this study, a composite poly(functional graphene oxide- co - N -isopropylacrylamide- co -trimethylolpropane triacrylate- co -ethylene dimethacrylate) (poly(f-GO- co -NIPAAm- co -TMPTA- co -EDMA)) monolith was prepared, in which f-GO was added. The obtained monolith was characterized by nitrogen adsorption–desorption isotherm and scanning electron microscopy. The monolith exhibited a homogeneous and continuous structure, good permeability, and large surface area. The composite monolith was used as solid-phase extraction absorbent in conjunction with high-performance liquid chromatography for enrichment of ursolic acid. The calibration equation was y = 73.3980 x + 0.2555, and the linear regression coefficient was 0.9987; The calibration curve was ranged from 1 to 700 μg ml −1 ; The limit of detection and limit of quantification values were 0.3 and 1.0 μg ml −1 , respectively; The intraday and interday precisions were less than 2.6 and 7.4%, respectively. The recovery was in the range of 84.44–111.76%. Moreover, the adsorption amount of ursolic acid on the composite monolith was compared with the monolith without f-GO added and silica gel-C18 adsorbent. The results showed that the composite monolithic column was feasible to be used as an online SPE absorbent, which exhibiting low back pressure, good permeability, and high adsorption capacity. In addition, this method provided the possibility to extract and analyze trace components from medicinal plants.
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高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Cheng Peng,Shiqi Kang,Meijun Jiang,Mingxi Yang,Xu Gong
Background The formation of adhesion after tendon injury represents a major obstacle to tendon repair, and currently there is no effective anti-adhesion method in clinical practice. Oxidative stress, inflammation, and fibrosis can occur in tendon injury and these factors can lead to tendon adhesion. Antioxidant carbon dots and ursolic acid (UA) both possess antioxidant and anti-inflammatory properties. In this experiment, we have for the first time created RCDs/UA@Lipo-HAMA using red fluorescent carbon dots and UA co-encapsulated liposomes composite hyaluronic acid methacryloyl hydrogel. We found that RCDs/UA@Lipo-HAMA could better attenuate adhesion formation and enhance tendon healing in tendon injury.Materials and Methods RCDs/UA@Lipo-HAMA were prepared and characterized. In vitro experiments on cellular oxidative stress and fibrosis were performed. Reactive oxygen species (ROS), and immunofluorescent staining of collagens type I (COL I), collagens type III (COL III), and α-smooth muscle actin (α-SMA) were used to evaluate anti-oxidative and anti-fibrotic abilities. In vivo models of Achilles tendon injury repair (ATI) and flexor digitorum profundus tendon injury repair (FDPI) were established. The major organs and blood biochemical indicators of rats were tested to determine the toxicity of RCDs/UA@Lipo-HAMA. Biomechanical testing, motor function analysis, immunofluorescence, and immunohistochemical staining were performed to assess the tendon adhesion and repair after tendon injury.Results In vitro, the RCDs/UA@Lipo group scavenged excessive ROS, stabilized the mitochondrial membrane potential (ΔΨm), and reduced the expression of COL I, COL III, and α-SMA. In vivo, assessment results showed that the RCDs/UA@Lipo-HAMA group improved collagen arrangement and biomechanical properties, reduced tendon adhesion, and promoted motor function after tendon injury. Additionally, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the RCDs/UA@Lipo-HAMA group increased; the levels of cluster of differentiation 68 (CD68), inducible Nitric Oxide Synthase (iNOS), COL III, α-SMA, Vimentin, and matrix metallopeptidase 2 (MMP2) decreased.Conclusion In this study, the RCDs/UA@Lipo-HAMA alleviated tendon adhesion formation and enhanced tendon healing by attenuating oxidative stress, inflammation, and fibrosis. This study provided a novel therapeutic approach for the clinical treatment of tendon injury.
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2018
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IF 3.997
Xin Ji,Qiao Tang,Peng Pang,Jianping Wu,Thomas Brett Kirk,Jiake Xu,Dong Ma,Wei Xue
Antitumor efficacy of ursolic acid (UA) is seriously limited due to its low hydrophilicity and needy bioavailability. To overcome these obstacles, chemosensitive polyspermine (CPSP) conjugated with UA and folic acid (FA) as a novel targeted prodrug was designed and successfully synthesized in this investigation. This prodrug not only showed high aqueous solubility, GSH-triggered degradation and good biocompatibility, but also exhibited better inhibition effect on the tumor cells proliferation in comparison with free UA. FA-CPSP-UA could down-regulate the generation of GSH and manifest excellent ability in enhancing antitumor efficacy. In addition, FA-CPSP-UA could inhibit the expression of MMP-9, which led to restricting MCF-7 cells migration. Taken together, the results indicated that FA-CPSP-UA, as a carrier, can efficiently deliver UA to folate receptor positive cancer cells and improve tumor therapy of UA by Chemosensitive effect.
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高影响因子
JOURNAL OF MOLECULAR LIQUIDS
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2021
·
IF 6.165
Jie-Ping Fan,Xiao-Hui Lai,Xue-Hong Zhang,Lu Yang,Tian-Tao Yuan,Hui-Ping Chen,Xianrui Liang
Formation of ionic derivatives from drugs provided a simple tool to tune physical properties including water solubility and biological activity of the drugs. Oleanolic acid (OA) and ursolic acid (UA) are two ubiquitous isomeric triterpene phytochemicals with many pharmacological effects . But the poor water solubility greatly limits their clinical application. In order to improve the solubility of OA and UA, this research exploited a non-covalent synthetic approach to prepare a series of novel ionic derivatives of OA and UA by a simple acid-base neutralization method for converting them into simple organic salts. The OA/UA based ionic derivatives were characterized by HRMS , FTIR, NMR, XRPD , and TGA-DSC, their solubilities and apparent 1-octanol/water partition coefficients were measured under different conditions. The solubility of the ionic derivatives turned out to be higher than that of OA/UA under most of experiment conditions, which indicated our aim to improve the solubility was attained. The apparent 1 - octanol/water partition coefficients indicated that the ionic derivatives of OA/UA had higher hydrophilicity than OA/UA under most of the experiment conditions. Moreover, the human hepatoma cell lines (HepG2) growth inhibitory activity of the derivatives was also evaluated by MTT assay . The results suggested that UA based ionic derivatives exhibited significantly lower IC 50 values than OA based ionic derivatives under the same conditions, indicating stronger inhibitory effect on the growth of HepG2 cells.
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高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2016
·
IF 3.773
Tao Li,Xiufen Chen,Yajun Liu,Lulu Fan,Liqing Lin,Yu Xu,Sijia Chen,Jingwei Shao
Ursolic acid (UA) as a nature product exhibits good anti-cancer activity, low toxicity, and good liver protection features. However, the low-solubility and poor bioavailability restrict its further clinical application. To overcome this problem, a pH-sensitive prodrug delivery system (UA@MSN-UA) that incorporated acid-sensitive linkage between drug and silica-based mesoporous nanosphere (MSN) was successfully designed and synthesized. The physicochemical properties of the UA@MSN-UA nanoparticles were investigated for shape, particle size, zeta potential , nitrogen adsorption-desorption and infrared (IR) spectroscopy. The nanoparticles were further evaluated for in vitro cytotoxicity, including proliferation inhibition, cell cycle distribution and apoptotic effects against human hepatocellular carcinoma HepG2 cells. The TEM image showed that the size of synthesized MSN nanoparticle was a near-spherical shape with ~ 100 nm diameter. In vitro cytotoxicity testing demonstrated that UA@MSN-UA nanoparticles prodrug exhibited higher proliferation inhibition, cell cycle arrest at the G2/M phase and significantly caused the early and late apoptosis in HepG2 cells, which would be contributed to high loading capacity, high cellular uptake and sustained release of UA. Overall, the UA-modified MSN prodrug delivery system can be a promising drug carrier for improving the bioavailability of UA, and further enhance its anti-cancer efficacy.
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高影响因子
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