查找使用阿拉丁产品的科研文献

Dual-template molecularly imprinted polymers based on dopamine-modified porous cellulose for simultaneous enrichment of oleanolic acid and ursolic acid from lingonberries

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.

The novel nanocomplexes containing deoxycholic acid-grafted chitosan and oleanolic acid displays the hepatoprotective effect against CCl4-induced liver injury in vivo

Chao Xin,Shuang Liu,Hang Qu,Zhenyu Wang

Chemical liver injury threatens seriously human health, along with the shortage of efficiency and low-toxicity drugs. Herein, the novel oral nanocomplexes composed of deoxycholic acid-grafted chitosan and oleanolic acid were constructed to reverse the CCl 4 -induced acute liver damage in mice. Results indicated core-shell nanocomplexes, maintained by the hydrophobic interaction between deoxycholic acid and oleanolic acid, could be dissociated in the intestine. Notably, the nanocomplexes possessed superior hepatoprotective effect in vivo , possibly due to the synergistic effect between grafted chitosan and oleanolic acid. Mechanism investigations suggested that nanocomplexes reversed CCl 4 -induced liver injury through improving hepatic antioxidant capacity via NrF2/Keap1 pathway and regulating inflammation response via NF-κB signaling pathway. The novel oral nanocomplexes represent an effective strategy for chemical liver injury therapy.

Oleanolic acid and ursolic acid as potential inhibitors of human salivary α-amylase: insights from in vitro assays and in silico simulations

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

Synthesis and evaluation of the cancer cell growth inhibitory activity of the ionic derivatives of oleanolic acid and ursolic acid with improved solubility

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.

Soy protein/chitosan-based microsphere as Stable Biocompatible Vehicles of Oleanolic Acid: An Emerging Alternative Enabling the Quality Maintenance of Minimally Processed Produce

Sunan Gao,Mingyi Yang,Zisheng Luo,Zhaojun Ban,Ya Pan,Mengyun Tu,Quan Ma,Xingyu Lin,Yanqun Xu,Li Li

In this work, the soy protein/chitosan-based microsphere (SCM), as a stable biocompatible vehicle of oleanolic acid (OA), was constructed for the first time under acidic conditions, and OA was firstly used for quality maintenance of minimally processed products. The effect of soybean protein isolate/chitosan ratio, particle concentration and oil fraction on emulsion stability was studied. Additionally, the interfacial characteristics of SCM with and without loading OA were determined by cryo-SEM. Results demonstrated that the encapsulation efficiency of SCM embedded with 0.15% OA (SCM-OA 0.15% ) rated up to 87.53% ± 2.23%, and SCM-OA showed smaller particle size, greater stability, and better liquid-state behavior, as well as the enhanced antibacterial and antioxidant properties in comparison to the control and SCM group. The minimally processed apples were used to evaluate the potential application of SCM-OA delivery system and it was evident that SCM-OA contributed to reducing weight loss, maintaining total phenol content and inhibiting color browning of minimally process apples. These findings shed new light on the emerging biocompatible vehicles of plant-derived bioactive substance.

Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo

Yuling Luo,Zhongbing Liu,Xiaoqin Zhang,Juan Huang,Xin Yu,Jinwei Li,Dan Xiong,Xiaoduan Sun,Zhirong Zhong

Encapsulation of oleanolic acid into cyclodextrin metal-organic frameworks by co-crystallization: Preparation, structure characterization and its effect on a zebrafish larva NAFLD model

Meng Li,Dongxia Hu,Dian Zhang,Guangya Xu,Di Wu,Chengcheng Gao,Linghan Meng,Xiao Feng,Weiwei Cheng,Zhenjiong Wang,Yuling Yang,Xiaozhi Tang

Oleanolic acid (OA) is a common pentacyclic triterpenoid and has been used to relieve metabolic-related diseases. However, its low water solubility severely limits its clinical application. In this study, OA was encapsulated by a cyclodextrin metal–organic framework material (CD-MOF) using the co-crystallization method to obtain the OA and CD-MOF inclusion complex (OA@CD-MOF). The OA@CD-MOF was characterized using scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis, which proved that OA was successfully loaded into the CD-MOF. Molecular docking data revealed that OA tends to occupy the cyclodextrin dimolecular cavity outside the CD-MOF. The formation of OA@CD-MOF significantly increased the apparent water solubility of OA to 269.27 ± 19.40 μg/mL. Further zebrafish experiments showed that the OA@CD-MOF exhibited better anti-steatosis, anti-lipid accumulation, and anti-oxidative stress activities than OA. Overall, this study presents a promising approach for delivering OA, enhancing its bioavailability in vivo and mitigating metabolic-related diseases such as non-alcoholic fatty liver disease.

Oleanolic Acid Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by Inhibiting Ferroptosis through Targeting PTGS2 as a Key Molecular Node and Activating the AMPK/ACC Signaling Pathway

Wei Ye,Lei Wang,Ye Fan,Li Ma,Zaohong Chen,Jinmeng Zhang,Rong Zeng,Xiang Liu

Metabolic dysfunction-associated steatotic liver disease (MASLD) progression closely involves ferroptosis. Using high-fat diet-challenged mice and free fatty acid (FFA)-treated HepG2 cells, we demonstrate that oleanolic acid (OA) ameliorates MASLD and suppresses ferroptosis─an effect validated by the ferroptosis activator Erastin. Supported by network pharmacology, mechanistic analyses reveal that OA exerts synergistic efficacy via a dual-axis network. First, molecular docking, cellular thermal shift assay (CETSA), and molecular dynamics (MD) simulations confirm that OA directly binds PTGS2, mitigating lipid peroxidation and inflammatory mediator release. Second, OA activates the AMPK/ACC metabolic signaling pathway, inhibiting ACC through phosphorylation to correct lipid metabolism disorders, and its antiferroptotic effect can be blocked by AMPK inhibitors. This study first elucidates OA’s therapeutic mechanism against MASLD via “metabolic correction + oxidative inhibition,” outlining a novel strategy for targeting hepatic ferroptosis.

The Protective Effect of Boschnikia rossica Extract on Free Radical-Induced Oxidative Damage of Biomolecules and Establishment of a Method for Determining the Content of Oleanolic Acid

Zhuohao Zhao,Mingjie Jia,Yuning An,Yihong Bao,Yuncai Zhao

Oxidative stress-induced damage to biomolecules such as proteins, lipids, and DNA is closely related to chronic diseases. Developing efficient, low-toxicity, and multi-target natural antioxidants has become an important research direction in food and medicine. This study established a detection method for oleanolic acid (OA) content inBoschnikia rossicaextract (BRE). It systematically evaluated the in vitro antioxidant activity and protective effect ofBoschnikia rossicaextract on oxidative damage of biomolecules. Firstly, the detection method based on RP-HPLC has improved the problem of low separation efficiency and high interference in detecting OA inBoschnikia rossica. The optimal analysis conditions were obtained by optimizing the chromatographic conditions: the chromatographic column was Agilent TC-C18(250 mm × 4.6 mm, 5 μm); the mobile phase was methanol/0.4% phosphoric acid aqueous solution (85/15,v/v), pH 2.14; the column temperature was 20 °C; the flow rate was 1.2 mL/min; and the detection wavelength was 220 nm. Under these conditions, the linear relationship of OA was good within the concentration range of 100–800 mg/L, with a recovery rate of 98.88–101.46% and RSD less than 2%. The content of OA was 0.358 mg/g. Next, the in vitro antioxidant effect of BRE was tested, and it was found that BRE had reasonable scavenging rates against ABTS, DPPH, and hydroxyl radicals, with IC50values of 224.32 mg/L, 58.43 mg/L, and 432.21 mg/L, respectively. In addition, BRE had significant inhibitory effects on protein oxidative degradation, carbonylation modification, lipid oxidation, and DNA oxidative damage induced by different free radicals. Finally, BRE can be a natural alternative to synthetic antioxidants and has important application value in delaying food oxidation and developing anti-aging functional foods.

Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/d-α-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment

Hao Wu,Qingxiang Zhong,Rongling Zhong,Houcai Huang,Zhi Xia,Zhongcheng Ke,Zhenhai Zhang,Jie Song,Xiaobin Jia

Oleanolic acid (OA) is a triterpenoid found in various fruits and vegetables and used in traditional Chinese medicine. OA plays a crucial role in the treatment of several cancers, but poor water solubility, low permeability, and significant efflux have limited its widespread clinical use. Vitamin E-d-α-tocopheryl polyethylene glycol succinate (vitamin E-TPGS) and Pluronic P105 were used to improve the solubility and permeability and to decrease the efflux of OA. OA-loaded mixed micelles were prepared by ethanol thin-film hydration. The physicochemical properties of the micelles, including zeta potential, morphology, particle size, solubility, drug loading, and drug entrapment efficiency were characterized. OA release from micelles was slower than that from the free drug system. OA uptake by A549 non-small-cell lung cancer (NSCLC) cells was enhanced by the micelles. A tumor model was established by injecting A549 cells into nude mice. In vivo imaging showed that OA-micelles could accumulate in the tumors of nude mice. Additionally, smaller tumor size and increased expression of pro-apoptotic proteins were observed in OA-micelle-treated mice, indicating that OA-micelles are more effective than free OA in treating cancer. In vitro experiments were performed using two NSCLC cell lines (A549 and PC-9). Cytotoxicity evaluations showed that the half-maximal inhibitory concentrations of free OA and OA-micelles were 36.8±4.8 and 20.9±3.7 μM, respectively, in A549 cells and 82.7±7.8 and 56.7±4.7 μM, respectively, in PC-9 cells. Apoptosis assays revealed that the apoptotic rate of OA-micelle-treated A549 and PC-9 cells was higher than that of cells treated with the same concentration of free OA. Wound healing and transwell assays showed that migration and invasion were significantly suppressed in OA-micelle-treated cells. Immunofluorescence and Western blot analyses confirmed that the epithelial–mesenchymal transition was reversed in OA-micelle-treated cells. Mixed micelles are a promising nano-drug delivery system for lung cancer treatment.

Low Dose of Oleanolic Acid Protects against Lithocholic Acid–Induced Cholestasis in Mice: Potential Involvement of Nuclear Factor-E2-Related Factor 2-Mediated Upregulation of Multidrug Resistance-Associated Proteins

Pan Chen,Hang Zeng,Yongtao Wang,Xiaomei Fan,Chenshu Xu,Rongrong Deng,Xunian Zhou,Huichang Bi,Min Huang

Oleanolic acid (OA) is a natural triterpenoid and has been demonstrated to protect against varieties of hepatotoxicants. Recently, however, OA at high doses was reported to produce apparent cholestasis in mice. In this study, we characterized the protective effect of OA at low doses against lithocholic acid (LCA)–induced cholestasis in mice and explored further mechanisms. OA cotreatment (5, 10, and 20 mg/kg, i.p.) significantly improved mouse survival rate, attenuated liver necrosis, and decreased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase; more importantly, serum total bile acids and bilirubin, as well as hepatic total bile acids were also remarkably reduced. Gene and protein expression analysis showed that hepatic expression of multidrug resistance-associated protein 2 (Mrp2), Mrp3, and Mrp4 was significantly increased by OA cotreatment, whereas other bile acid metabolism- and transport-related genes, including Na+/taurocholate cotransporter, organic anion transporter 1b2, bile salt export pump, multidrug resistance protein 3, Cyp3a11, Cyp2b10, Sulfotransferase 2a1 (Sult2a1), and UDP-glucuronosyltransferase 1a1 (Ugt1a1), were only slightly changed. OA also caused increased nuclear factor-E2–related factor (Nrf2) mRNA expression and nuclear protein accumulation, whereas nuclear receptors farnesoid X receptor (FXR), pregnane X receptor (PXR), and constitutive androstane receptor were not significantly influenced by OA. Luciferase (Luc) assays performed in HepG2 cells illustrated that OA was a strong Nrf2 agonist with moderate PXR and weak FXR agonism. Finally, in mouse primary cultured hepatocytes, OA dose- and time-dependently induced expression of Mrp2, Mrp3, and Mrp4; however, this upregulation was abrogated when Nrf2 was silenced. In conclusion, OA produces a protective effect against LCA-induced hepatotoxicity and cholestasis, possibly due to Nrf2-mediated upregulation of Mrp2, Mrp3, and Mrp4.