FOOD CHEMISTRY
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2024
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IF 8.5
Minghao Yuan,Yan Wan,Yulu Wang,Sihui Li,Jiamei Tang,Xue Liang,Xin Tan,Sirui Yi,Xiaohang Wei,Xiaohong Li,Li Guo,Yiping Guo
Oleanolic acid (OA) is a food-derived bioactive component with antidiabetic activity, but its water solubility and oral bioavailability are notably restricted. In this study, to overcome these limitations, ursodeoxycholic acid-modified chitosan oligosaccharide (UCOS) was synthesized to encapsulate OA in self-assembled nanomicelles (UCOS-OA). The encapsulation efficiency and drug loading of UCOS-OA were 86 % and 11 %, respectively. UCOS-OA exhibited enhanced gastrointestinal stability and prolonged intestinal retention time when compared with free OA, resulting in a 10.6-fold increase in oral bioavailability. The enhanced antidiabetic activity of UCOS-OA was confirmed in the type 2 diabetes mellitus mice model, as it significantly improved glycolipid metabolism disorders and mitigated liver injury. Furthermore, UCOS-OA ameliorated the dysbiosis of gut microbiota and fecal metabolites. In conclusion, UCOS serves as an effective polymeric carrier for encapsulating OA, thereby improving its bioavailability and antidiabetic activity. This work provides valuable insights for the advancement of oral delivery systems for bioactive compounds.
研究领域:
药剂学
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代谢病学
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生物材料学
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DOI
PubMed
高影响因子
Drug Design Development and Therapy
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2025
·
IF 5.1
Zhiqi Shi,Qing Wang,Qing Li,Fan Jia,Weifeng Xu
Purpose: Major depressive disorder (MDD) is a global health concern. Studies have demonstrated that oleanolic acid (OA) has a regulatory effect on MDD. However, OA is poorly soluble, has low oral bioavailability, and faces challenges in crossing the blood-brain barrier. In this study, building upon a previous formulation of OA cubic liquid crystal nanoparticles (OA-LCNP), we combined nanoparticles with a thermosensitive gel for nasal administration and investigated the pharmacological effects of OA-LCNP thermosensitive gel (OANG) on depression. This study aimed to evaluate the effects of OANG on depression symptoms in rats.Methods: OANG was prepared using Poloxamer F127 and F68 as the gel matrix, and the ratios of F127 and F68 were investigated. The pharmacokinetics of OANG was studied in rats, and OA content was determined using liquid chromatography-mass spectrometry (LC-MS). The pharmacological effects of OANG on depression were evaluated in chronic unpredictable mild stress (CUMS) model rats.Results: The phase transition temperature of the gel was 34°C, and the release of OA from OANG was slow according to the Higuchi kinetic equation. The AUC0-t of brain tissue after nasal OANG administration was 1.21 times that observed after intravenous administration. Additionally, the brain-targeting efficiency and nasal-brain direct transfer were 29.91% and 9.44% higher, respectively, than those observed after intravenous administration, indicating the brain-targeting capability of the OANG delivery system. Network pharmacological analysis revealed that the anti-depressant effects may be linked to neuroactive ligand-receptor interactions, the PPAR signaling pathway, and efferocytosis signaling pathways. Experimental results from CUMS rats showed that the gel significantly affected interleukin (IL)-4, IL-6, acetylcholinesterase, acetylcholine, 5-hydroxytryptamine, and brain-derived neurotrophic factor, and improved depression-like behavior in rats, as measured by sucrose preference, forced swimming, and box shuttle tests.Conclusion: The OANG nasal drug delivery system has specific brain-targeting properties and exerts anti-depressant effects.
研究领域:
药剂学
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神经科学
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药物递送系统
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DOI
PubMed
高影响因子
JOURNAL OF LIPOSOME RESEARCH
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2025
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IF 4.3
Amna Naz,Sadia Haider,Malik Ihsan Ullah Khan,Rabia Khokhar,Mavra Rubab,Muhammad Farooq,Attia Afzal,Muhammad Sarfraz
This study addresses the limitations of traditional cancer therapies—such as high toxicity and non-selectivity—by developing a novel nanoparticulate system co-loaded with plant-derived compounds, apigenin (APG) and oleanolic acid (OA). These naturally occurring phytochemicals are known for their anticancer properties but face clinical challenges due to poor solubility and limited efficacy. The Apigenin and Oleanolic Acid Nanoparticulate System (AONS) was refined and optimized using the Box-Behnken statistical design approach, resulting in nanoparticles with a mean diameter of 169 nm and size homogeneity. A validated HPLC technique was employed to simultaneously quantify both apigenin and oleanolic acid in the developed formulation as well as in various biological matrices. In vitro drug release was enhanced at acidic pH (5.5), mimicking the tumor microenvironment. AONS showed strong physicochemical stability under refrigerated storage. Cytotoxicity tests on HepG2, MDA-MB-231, and U87 glioma cells demonstrated significantly improved anticancer activity compared to control, free drugs, or individual nanoformulations. Cellular uptake studies confirmed efficient internalization in U87 cells, and ELISA results indicated apoptosis via activation of the p53 pathway. Biodistribution analysis revealed prolonged systemic drug retention with AONS (up to 72 hours), surpassing the short circulation time of free drugs. Notably, LC-MS data confirmed that the nanoparticle system could cross the blood-brain barrier, highlighting its therapeutic potential for treating brain cancers.
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高影响因子
FOOD RESEARCH INTERNATIONAL
·
2026
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IF 8.8
Quanrun He,Zhiyuan Zhen,Yong Zhu,Daniel Granato,Judyta Cielecka-Piontek,Jihang Chen
Carrier-free oleanolic acid nanoparticles (OA-NM) formed via anti-solvent exchange. • OA-NM self-assembly was driven by hydrogen bonding and hydrophobic interactions. • OA-NM was internalized mainly via clathrin-mediated endocytosis. • OA-NM improved lipid metabolism and insulin resistance in 3 T3-L1 adipocytes. • OA-NM exert stronger anti-inflammatory effects in RAW264.7 macrophages. Oleanolic acid (OA) is a plant-derived pentacyclic triterpenoid with anti-obesity and anti-inflammatory activities, but its poor solubility limits bioavailability. In this study, self-assembled OA nanoparticles (OA-NM) were prepared via an anti-solvent method to enhance dispersibility and efficacy. OA-NM exhibited uniform spherical morphology (~228 nm), good stability, and supramolecular reorganization driven mainly by hydrophobic interactions and hydrogen bonding. Its cellular uptake occurred primarily via clathrin-mediated endocytosis. Compared with free OA, OA-NM showed lower cytotoxicity and enhanced bioactivity. In 3 T3-L1 adipocytes, OA-NM reduced lipid accumulation, suppressed adipogenic gene expression, improved mitochondrial function, and restored insulin signaling. In LPS-stimulated RAW264.7 macrophages, OA-NM inhibited M1 polarization, promoted M2 transition, and suppressed NF-κB-mediated inflammation. Overall, self-assembly significantly improves the functional performance of OA, highlighting OA-NM as a promising strategy to enhance the utilization of hydrophobic dietary bioactives for metabolic health applications. Download: Download high-res image (205KB) Download: Download full-size image
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高影响因子
MICROCHEMICAL JOURNAL
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2025
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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.
研究领域:
植物化学
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分析化学
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DOI
高影响因子
KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
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2021
·Vol. 37
·期 6
·505-512
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IF 2.744
Xiao-Kai Zhang,Qi-Wen Wang,Ya-Juan Xu,Hong-Mei Sun,Lei Wang,Li-Xin Zhang
Multidrug resistance (MDR) of chemotherapy is one of the significant concerns in cancer therapy. Here in our study, cisplatin (DDP) and oleanolic acid (OA) were co-loaded in mesoporous silica nanoparticles (Nsi) to construct DDP/OA-Nsi and solve the DDP-resistance in lung cancer therapy. The cytotoxicity and apoptosis assays demonstrated that in DDP-resistant A549/DDP cells, the cytotoxicity of DDP/OA-Nsi was significantly higher than that of free DDP or DDP single delivery system (DDP-Nsi). The intracellular drug accumulation study revealed that the intracellular DDP concentration in the DDP/OA-Nsi group was also higher than that in free DDP and DDP-Nsi groups. In the A549/DDP xenograft tumor model, DDP/OA-Nsi showed the best anticancer effect. In summary, DDP/OA-Nsi was a promising drug delivery system to solve MDR in lung cancer therapy.
研究领域:
药理学
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肿瘤学
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纳米技术
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2020
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IF 7.182
Xia Chen,Shiwei Niu,David H. Bremner,Xuejing Zhang,Hongmei Zhang,Yanyan Zhang,Shude Li,Li-Min Zhu
Nanocomposites as “stevedores” for co-delivery of multidrugs hold great promise in addressing the drawbacks of traditional cancer chemotherapy. In this work, our strategy presents a new avenue for the stepwise release of two co-delivered agents into the tumor cells. The hybrid nanocomposite consists of a pH-responsive chitosan (CS), a thermosensitive poly( N -vinylcaprolactam) (PNVCL) and a functionalized cell-penetrating peptide (H6R6). Doxorubicin (DOX) and oleanolic acid (OA) are loaded into the nanocomposite (H6R6-CS-g-PNVCL). The system displayed a suitable size (∼190 nm), a high DOX loading (13.2 %) and OA loading efficiency (7.3 %). The tumor microenvironment triggered the nanocomposite to be selectively retained in tumor cells, then releasing the drugs. Both in vitro and in vivo studies showed a significant enhancement in antitumor activity of the co-delivered system in comparison to mono-delivery. This approach which relies on redox, pH and temperature effects utilizing co-delivery nanosystems may be beneficial for future applications in cancer chemotherapy.
研究领域:
药理学
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纳米技术
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肿瘤学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2015
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IF 2.532
Pan Chen,Jingjie Li,Xiaomei Fan,Hang Zeng,Rongrong Deng,Dongshun Li,Min Huang,Huichang Bi
Obstructive cholestasis is characterized by impairment of hepatic canalicular bile efflux and there are no clinically effective drugs to cure except surgeries. Previously we revealed that oleanolic acid (OA) protected against lithocholic acid (LCA)-induced intrahepatic cholestasis in mice. Cholestasis caused by LCA is characterized by segmental bile duct obstruction, whether OA possesses the beneficial effect on completed obstructive cholestasis induced by bile duct ligation (BDL) remains unknown. In this study, we demonstrated that BDL-induced mice liver pathological change, and increase in serum levels of ALT, AST and ALP were all significantly reduced by OA (20 mg/kg, i.p.). Meanwhile, OA also lowered total bilirubin and total bile acids levels in serum, as well as total bile acids level in liver, in contrast, urinary total bile acids output was remarkably up-regulated by OA. Gene expression analysis showed that OA caused significant increased mRNA expression of MRP3 and MRP4 located at hepatic basolateral membrane , and restoration of MRP2 and BSEP located at hepatic cannalicular membrane. Furthermore, significant NRF2 protein accumulation in nucleus was also observed in OA treated mice. In mice primary cultured hepatocytes, the effects of OA on MRP2, MRP3 and MRP4 expression were directly proved to be mediated via NRF2 activation, and BSEP downregulation induced by OA was in part due to FXR antagonism. Luciferase assay performed in Hep G2 cells also illustrated that OA was a partial FXR antagonist. Taken together, we conclude that OA attenuates obstructive cholestasis in BDL mice, possibly via activation of NRF2-MRPs and FXR antagonism.
研究领域:
肝病学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Drug Design Development and Therapy
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2025
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IF 5.1
Guojiang Tian,Fan Dong,Ai Fu,Shanglei Lai,Jundi Yu,Jingjing Ni,Qinchao Ding,Yueping Jin
Purpose Oleanolic acid (OA), a naturally occurring pentacyclic triterpenoid, has been reported to possess anti-inflammatory and barrier-protective properties. However, its molecular mechanism in the context of ulcerative colitis (UC) remains unclear.Methods In this study, we evaluated the therapeutic potential of OA (25 and 50 mg/kg/day) in a dextran sulfate sodium (DSS)-induced acute colitis model in C57BL/6 mice.Results Oral administration of OA significantly alleviated clinical symptoms of colitis, including weight loss, colon shortening, increased disease activity index (DAI), and histopathological injury. Additionally, OA demonstrated potent anti-inflammatory effects by suppressing the production of pro-inflammatory cytokines and promoting anti-inflammatory cytokines. It also restored redox homeostasis by enhancing antioxidant defenses and reducing lipid peroxidation. OA also restored intestinal barrier integrity, as evidenced by increased tight junction protein expression and decreased intestinal permeability. Mechanistically, OA was found to inhibit the activation of the NF-κB signaling pathway, as evidenced by reduced phosphorylation of IKKα/β and p65, and decreased degradation of IκBα. A key finding was that OA restored the expression of PPARγ, a known negative regulator of NF-κB. OA promoted the accumulation of peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor essential for maintaining intestinal epithelial homeostasis and anti-inflammatory signaling. OA inhibited the ubiquitin-mediated proteasomal degradation of PPARγ, thereby stabilizing its protein levels in colonic tissue. Pharmacological inhibition of PPARγ with GW9662 abolished the protective effects of OA on intestinal inflammation and epithelial barrier function, confirming that PPARγ activation is required for OA-mediated protection.Conclusion These findings identify a previously unrecognized mechanism whereby OA protects against colitis through post-translational stabilization of PPARγ. Our study not only highlights the therapeutic value of OA as a potential intervention for UC but also provides mechanistic insight into the regulation of nuclear receptor homeostasis during intestinal inflammation.
研究领域:
药理学
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免疫学
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胃肠病学
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分子生物学
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天然产物研究
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Yujie Xiao,Xianda Liu,Ziyue Ling,Shifan Chen,Ran Wei,Weifeng Zhao,Changsheng Zhao
Low-density lipoprotein apheresis (LDL-a) mainly aims to eliminate circulating low-density lipoprotein (LDL) in patients with atherosclerosis, but seldom alleviates the inflammatory responses that drive disease progression. Since the LDL provides more binding sites for acrylated β-cyclodextrin (AβCD) than oleanolic acid (OA), we propose that LDL could displace AβCD-bound OA, enabling LDL-responsive OA release and simultaneous LDL clearance. Herein, a dual-responsive LDL microsphere adsorbent with inflammation-regulating capability is successfully developed. By combining AβCD with the thermo-responsive poly(N-acryloylglycinamide) (PNAGA), the microspheres enable OA release triggered by both elevated LDL concentrations and temperature. The preloaded OA helps reduce nonspecific interactions between the microspheres and other serum proteins, without compromising the intrinsic LDL adsorption capacity of the microspheres. In normal saline, the elevated LDL concentration and temperature both trigger the release of OA from the microspheres, reflecting their dual-responsive behavior. In plasma, the LDL adsorption capacity of the microspheres reaches 76.9 mg/g. Under dynamic whole blood conditions, this value further increases to 184.6 mg/g. To elucidate the underlying mechanism, the isothermal titration calorimetry (ITC) results reveal that the binding constant (Ka) between AβCD and LDL is significantly higher than that between AβCD and OA. Moreover, the lower Gibbs free energy (ΔG) of AβCD-LDL indicates a more stable interaction. The anti-inflammatory potential of the microspheres is verified through co-incubation with RAW 264.7 macrophages, followed by qualitative immunofluorescence staining and quantitative ELISA analysis of inflammatory cytokines. Subsequently, the in vivo LDL clearance efficacy and biosafety of OA/NDSCD microspheres are validated using the rat hyperlipidemic model. This study demonstrates that the dual-responsive microspheres effectively integrate LDL removal and inflammation modulation, offering a promising approach to atherosclerosis.
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高影响因子
Bioengineering-Basel
·
2026
·Vol. 13
·期 8
·908
·
IF 4.4
Dandan Zhang,Zhigang Zhang,Dingxing Huang,Zhuoran Sun,Jiamin Huang,Chi Zhang,Qingyang Zeng,Qiling Liu,Wenzhuo Chen
Osteoarthritis is an irreversible degenerative joint disease driven by sustained NF-κB-mediated inflammatory responses, and conventional intra-articular hyaluronic acid or small-molecule NF-κB inhibitors cannot achieve targeted on-demand treatment due to poor solubility, rapid clearance and lack of lesion microenvironment responsiveness. OA with inherent anti-chondrolytic activity can self-assemble into nanocarriers in water, yet it lacks stimuli-responsive capacity. Herein, we rationally designed and synthesized an OA-Der by covalently conjugating o-phenylenediamine fragments to the OA backbone.1H NMR and HRESI-MS spectra fully verified the accurate chemical structures of intermediate and final OA-Der. Blank OA-Der micelles exhibited uniform spherical core–shell nanostructures (50–150 nm) under TEM and AFM, while pathological high NO triggered complete disassembly of micellar assemblies. We further co-assembled OA-Der with NF-κB inhibitor BAY 11-7082 to construct NO-responsive BAY@OA-Der supramolecular micelles. In vitro experiments using human C28/I2 chondrocytes with LPS-induced inflammatory injury demonstrated that BAY@OA-Der significantly improved cell viability and reduced apoptotic chondrocyte proportion. At mRNA and protein levels, the supramolecular micelle formulation remarkably suppressed NF-κB p65 phosphorylation, downregulated cartilage-degrading ADAMTS5, and upregulated ACAN compared with free BAY or blank OA-Der. Collectively, this natural bioactive self-assembled NO-responsive delivery platform achieves synergistic anti-inflammatory and matrix-protective effects by precisely releasing drugs at NO-overexpressed osteoarthritis inflammatory sites and offers an in vitro design strategy for osteoarthritis responsive delivery systems.
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高影响因子
FOOD CHEMISTRY
·
2018
·
IF 4.946
Pujun Xie,Lixin Huang,Caihong Zhang,Yejun Deng,Xiaojie Wang,Jiang Cheng
Three techniques of ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE) and solvent extraction (SE) were used for enhancing the hydroxytyrosol (HT), maslinic acid (MA) and oleanolic acid (OA) extraction from olive pomace, being evaluated and compared through process parameters, kinetics and thermodynamics, plus greenness assessment analysis. Results showed that UAE yielded the maximum compounds due to a strong cavitation effect and the strongest mass and heat transfer efficiency involving the kinetic constants ( h , C e and K ) and thermodynamic parameters (△H, △S and △G). Additionally, the optimal extraction conditions were acquired: ethanol concentration of 90%, extraction temperature of 50 °C, extraction time of 5 min, liquid to solid ratio of 30 mL/g, ultrasound intensity of 135.6 W/cm 2 , and ultrasound frequency of 60 kHz. UAE was confirmed as an effective and greener technique with the lowest E factor, energy consumption and carbon emission during the extraction process of bioactive compounds from olive pomace.
研究领域:
食品科学
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环境科学
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植物化学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）