International Journal of Nanomedicine
·
2023
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IF 8
Muhammad Waseem Khan,Pengxuan Zhao,Asifullah Khan,Faisal Raza,Shahid Masood Raza,Muhammad Sarfraz,Yan Chen,Minsi Li,Tan Yang,Xiang Ma,Guangya Xiang
Background: Cisplatin (CDDP), a widely used chemotherapeutic agent against hepatocellular carcinoma (HCC), faces severe resistance and hepatotoxicity problems which can be alleviated through combination therapy.Purpose: The objective of this study was to develop a pH-dependent calcium carbonate nano-delivery system for the combination therapy of CDDP with oleanolic acid (OA).Methods: A microemulsion method was employed to generate lipid coated cisplatin/oleanolic acid calcium carbonate nanoparticles (CDDP/OA-LCC NPs), and the loading concentration of CDDP and OA was measured by atomic absorption spectroscopy and HPLC respectively.Transmission electron microscopy (TEM) was used to examine the nanoparticles morphology while its pH dependent release characteristics were investigated through in vitro release study. Cellular uptake was examined through a fluorescence microscopy. Apoptotic assays and western blot analysis were conducted to explore the synergistic apoptotic effect of OA on CDDP against HCC cells. The hepatoprotective of OA for CDDP was evaluated through H&E staining.Results: TEM analysis revealed nanoparticles spherical shape with an average particle size of 206±15 nm, and the overall entrapment efficiency was 63.70%±3.9%. In vitro drug release study confirmed the pH-dependent property of the formulation, with the maximum CDDP release of 70%±4.6% at pH 5.5, in contrast to 28%±4.1% CDDP release at pH 7.4. Annexin V-FITC/PI assay and cell cycle analysis confirmed that CDDP and OA synergistically promoted greater HepG2 cells apoptosis for the CDDP/OA-LCC NPs as compared to their individual free drug solutions and NPs-treated groups. Western blot analysis also proved that CDDP/OA-LCC NPs induced the apoptosis by enhancing the proapoptotic protein expressions through downregulating P13K/AKT/mTOR pathway and upregulating p53 proapoptotic pathway. OA helped CDDP to overcome the resistance by downregulating the expression of proteins like XIAP, Bcl-2 via NF-κB pathway. OA also significantly alleviated CDDP-induced hepatotoxicity as evident from the decreased alanine transaminase, aspartate transaminase levels and histochemical evaluation. The possible mechanism may be related to the Nrf-2 induction via its antioxidant mechanism to maintain the redox balance and reduction in CYP2E1 activity which can lead to ROS-mediated oxidative stress.Conclusion: These results suggest that CDDP/OA-LCC NPs have promising applications for co-delivering CDDP and OA to synergize their anti-tumor activity against HCC and to utilize OA’s protective effect against CDDP-induced hepatotoxicity.
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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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL SCIENCES
·
2023
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IF 1.6
Zhang Miaomiao,Wei Xuanwen,Bai Ligai,Liu Haiyan
In present work, a method for enrichment, purification, and content determination of oleanolic acid (OA) in medicinal plants was established based on on-line solid phase extraction (SPE). A metal organic frameworks–porous organic polymer monolith (MOF–POPM) was prepared with functionalized UiO-66-(OH) 2 as monomer and was used as SPE column for online enrichment and purification of OA. The ratio of adsorbent, enriching and eluting solvent, mobile phase pH, and flow rate had been systematically investigated. Under the optimum conditions, the linear range of OA was 0.59–2500 μg/mL with r = 0.9996. The limit of detection (LOD) was 0.18 μg/mL and the limit of quantification (LOQ) was 0.59 μg/mL. The intra-day relative standard deviations (RSDs) and inter-day RSDs of retention time and peak area were less than 0.3% and 1.3%, respectively. The average recoveries of OA in medicinal plants samples ranged from 87.7 to 104.6%. The results demonstrated that the online system was reliable and accurate for enrichment, purification, and content determination of OA in medicinal plants. Graphical abstract
研究领域:
分析化学
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药学
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材料科学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2022
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IF 4.46
Lin Leilei,Qiu Wenke,Luo Yuyuan,Lin Sihang,Sun Xue,Chen Weiqiang,Ye Lianbao,Wang Ying,Li Yan,Li Ming
Liver fibrosis has the potential to progress into liver cirrhosis , liver failure, and even death. Hepatic stellate cells (HSCs) activation play a central role in liver fibrosis, and persistently damaged hepatocytes secrete soluble factors that activate transdifferentiation of HSCs into myofibroblasts. Our previous studies indicated that fine particulate matter (PM2.5) can activate HSCs by stimulating hepatocytes to secrete TGF-β1. However, whether PM2.5 activates HSCs by regulating oxidative stress in hepatocytes remains uncertain. Oleanolic acid (OA) has been widely used in the clinic for hepatoprotection in Chinese medicine. In the present study, OA-loaded nanoparticles (OA-NP) with high solubility were used to attenuate the activation of HSCs induced by PM2.5-treated hepatocytes, and further studies were performed to explore the mechanism in which OA-NP plays a vital part. Our results showed that consistently PM2.5 treatment induced oxidative stress in hepatocytes. Moreover, the activation of HSCs induced by PM2.5-treated hepatocytes was reversed by antioxidant N -acetylcysteine treatment. Hence, PM2.5 may participate in the activation of HSCs by regulating oxidative stress in hepatocytes. Using a co-cultivation system, our results proved pretreatment with OA-NP significantly attenuates the activation of HSCs induced by PM2.5-exposed hepatocytes. In addition, the TGF-β1 expression and oxidative stress in hepatocytes with PM2.5 treated were reduced by the incubation with OA-NP. These observations demonstrated that OA-NP protects against the activation of HSCs by decreasing the TGF-β1 level and oxidative stress in PM2.5-exposed hepatocytes.
研究领域:
药理学
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毒理学
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细胞生物学
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环境健康
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DOI
PubMed
高影响因子
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.
研究领域:
分析化学
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植物化学
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药物分析
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
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IF 5.3
Minghao Yuan,Yulu Wang,Yan Wan,Sihui Li,Jiamei Tang,Xue Liang,Bin Zeng,Meifeng Li,Xiaohang Wei,Xiaohong Li,Li Guo,Yiping Guo
Liposomes have demonstrated great potential for drug delivery and diabetes treatment. However, hydrolysis by enzymes and emulsification by endogenous bile salts make liposomes unstable in the gastrointestinal tract. In this study, sodium tauroursodeoxycholate (TUDCNa)-based multifunctional bilosomes were designed to address the deficiencies of conventional liposomes. In the designed bilosomes, cholesterol was replaced by TUDCNa, which served as both a membrane stabilizer and an antidiabetic drug. Oleanolic acid (OA) was encapsulated in both conventional liposomes (OA-Ch-Lip) and bilosomes (OA-Tu-Bil) to compare their properties. Firstly, OA-Tu-Bil exhibited similar encapsulation efficiency and drug loading compared to OA-Ch-Lip, but with a smaller particle size. Secondly, OA-Tu-Bil showed better stability than OA-Ch-Lip. Thirdly, bilosomes exhibited prolonged intestinal retention time and improved permeability and oral bioavailability. Fourthly, in type 2 diabetes mellitus (T2DM) mice model, TUDCNa synergized with OA to exhibit the strongest therapeutic effect. In conclusion, TUDCNa have demonstrated the ability to substitute cholesterol in conventional liposomes, it provided a new approach for oral delivery of hypoglycemic drugs, and offered an innovative strategy for combination therapy.
研究领域:
药学
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药物递送系统
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糖尿病治疗
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
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IF 9.8
Ying Han,Xuening Yang,Shiyao Fu,Chuqiang Que,Zuxin Zhang,Xiaoting Wang,Jing Wang,Xin Yang
Proanthocyanidin B2 (Pac B2) exhibits potent antioxidant properties but suffers from poor stability in vivo , limiting its applications in food and medicine. This study developed composite nanoparticles (NPs) utilizing abietic acid (AA) and oleanolic acid (OA) as carriers, significantly enhancing Pac B2's stability. The OA/AA-Pac B2 NPs, prepared via solvent co-precipitation, were spherical with an average diameter of 164.18 nm and an encapsulation efficiency of 43.26 %, demonstrating improved thermal stability. Analytical techniques such as infrared spectroscopy, ultraviolet spectroscopy, and molecular dynamics revealed interactions such as hydrogen bonding and hydrophobicity between AA and Pac B2. The NPs facilitated sustained release of Pac B2 in simulated gastric and intestinal fluids over 2 h at 37 °C. In vitro tests demonstrated enhanced bioavailability and absorption efficiency of OA/AA-Pac B2 NPs compared with free Pac B2, validating the effectiveness of the co -assembly strategy in improving polyphenols' stability and bioavailability.
研究领域:
食品科学
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药物化学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Talanta Open
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2025
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IF 3.7
Amna Naz,Sadia Haider,Mavra Rana,Neelum Malik,Attia Afzal,Muhammad Farooq,Muhammad Sarfraz
Oleanolic acid (OA) and apigenin (APG) demonstrate a wide range of pharmacological effects, including antioxidant, anti-inflammatory, antiviral, antidiabetic, hepatoprotective, and cardioprotective activities. Both compounds show anticancer potential and have been used individually to treat various cancer types, creating a rationale for their combined use. However, quantifying both drugs in quality and plasma samples presents challenges due to differences in their physicochemical properties and absorption wavelengths (OA: 210-215 nm, APG: 212, 269, and 337 nm). We developed and validated a novel High-Performance Liquid Chromatography UV detection (HPLC-UV) method to address this problem. Using a C18 column (4.6 mm x 250 mm, packing L1, 5 µm particle size) and a mobile phase of acetonitrile: methanol: tetrahydrofuran: water (60:20:8:12, v/v) with a detection wavelength of 215 nm. The method achieved retention times of 4.7 and 10 minutes for OA and APG in quality samples, and 4.9 and 9.8 minutes in plasma samples, respectively. The plasma sample was prepared by simple protein precipitation step. All validation parameters, including sensitivity, selectivity, precision, accuracy, robustness, and stability, met the required criteria. The validated HPLC-UV bioanalytical method was effectively applied in quantification, stability, and pharmacokinetic studies of co-loaded nanoformulations of OA and APG with particle size 163 nm and entrapment efficiency up to 93 %, establishing it as a promising analytical technique for detecting these anticancer agents in complex matrices such as blood, plasma, and polymeric systems.
研究领域:
药理学
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分析化学
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肿瘤学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Tingting Zhang,Siyan Liu,Shenlin Liu,Pengtao Zhao,Chaoqun Zhang,Xiaoyu Wang,Yonghong Meng,Yalong Lu
Hyperuricemia (HUA) is a globally prevalent metabolic disorder characterized by an imbalance in uric acid (UA) production and excretion. In this study, we found that oleanolic acid (OA), a natural pentacyclic triterpene, effectively reduced HUA and associated kidney injury in C57BL/6J mice. A 12-week OA treatment significantly and dose-dependently reduced UA and creatinine levels in serum and urine while suppressing hepatic xanthine oxidase activity in HUA mice. Mechanistic analysis revealed that OA modulates the expression of urate transporters including ABCG2, GLUT9, and URAT1 in the kidney and small intestine. Furthermore, OA restored gut microbiota imbalances, increased short-chain fatty acid production, and enhanced the expressions of intestinal tight junction proteins in HUA mice, thereby improving gut barrier integrity in HUA mice. Consequently, fecal microbiota transplantation (FMT) was employed to illustrate the major mediating role of gut microbiota in OA’s alleviation of HUA in mice. Recipient HUA mice transplanted with feces from OA-treated HUA mice exhibited significantly lower blood and urinary UA levels, reduced kidney inflammation, and improved gut microbiota balance compared to those receiving feces from untreated HUA mice (p < 0.05). Additionally, FMT normalized urate transporter expression and reinforced intestinal tight junctions in recipient mice. These findings underscore that OA mitigates HUA primarily by modulating gut microbiota, regulating urate transporter expression, and reinforcing gut barrier integrity, offering novel insights into its preventive potential for managing HUA and related complications.
研究领域:
医学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
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.
研究领域:
中药学
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分析化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yujie Pan,Xiankang Xu,Weixue Zhao,Fang Tian,Yanrong Zhao,Tingting Zhang,Hui Yang,Jianzhong Han,Weilin Liu
Oleanolic acid (OA) is a terpenoid compound with anti-inflammatory and antioxidant effects, while its low stability and bioavailability limit the wide application. In this study, OA was incorporated into liposomes (OA-LIP), chitosan (CHI) coated liposomes (CHI-OA-LIP), and CHI-polygalacturonic acid (PGA)-double-layered (PGA-CHI-OA-LIP). The in vitro semi-dynamic digestion, cell absorption and pre-protective function for the liver-injured mouse of liposomes were evaluated. Compared to OA-LIP (91.96 ± 0.45 %), the polysaccharides double-layered OA-LIP, PGA-CHI-OA-LIP (99.84 ± 0.22 %), significantly improved the encapsulation efficiency of OA and exhibited higher stability during storage at room temperature and at 4 °C. In the in vitro semi-dynamic digestion and Caco-2 cell model, compared to free OA (6.22 ± 1.17 %, 6.56 ± 2.35 μg/mL), PGA-CHI-OA-LIP increased the bioavailability and cell absorption rate to 45.78 ± 0.71 % and 27.62 ± 1.69 μg/mL, respectively. Furthermore, it can improve the antioxidant capacity of Caco-2 cells, up-regulate the level of transportable terpene-related genes. In the mouse liver injury model, PGA-CHI-OA-LIP effectively reduced the activities of AST (aspartate aminotransferase) and ALT (alanine aminotransferase), decreased inflammatory factors, and thus effectively alleviated the infiltration and necrosis of liver cells. This study provided a promising avenue to improve the bioavailability of sensitive functional molecules and to develop versatile formula to repair liver damage.
研究领域:
药剂学
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生物化学
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肝脏病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2018
·Vol. 41
·期 17
·3496-3502
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IF 2.415
Chunxia Lu,Zonggui Tang,Changbin Liu,Xiaomei Ma
Surface molecularly imprinted polymers were successfully prepared by a novel two-step precipitation polymerization method. The first-step allowed the formation of 4-vinylpyridine divinylbenzene and trimethylolpropane trimethacrylate copolymeric microspheres. In the second-step precipitation polymerization, microspheres were modified with a molecularly imprinting layer of oleanolic acid as template, methacrylic acid as functional monomer, and divinylbenzene/ethylene glycol dimethacrylate as cross-linker. The obtained polymers had an average diameter of 4.43 μm and a polydispersity index of 1.011; adsorption equilibrium was achieved within 40 min, with adsorption capacity reaching 27.4 mg/g. Subsequently, the polymers were successfully applied as the adsorbents of molecularly imprinted solid-phase extraction to separate and purify the oleanolic acid from grape pomace. The content of oleanolic acid in the grape pomace extract was enhanced from 13.4 to 93.2% after using the molecularly imprinted solid-phase extraction process. This work provides an efficient way for effective oleanolic acid separation and enrichment from complex matrices, which is especially valuable in industrial production.
研究领域:
化学工程
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分离技术
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天然产物化学
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产品关联
DOI
PubMed
高影响因子
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.
研究领域:
植物化学
·
分离科学
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天然药物化学
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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）