EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2014
·
IF 3.432
Ke-Guang Cheng,Chun-Hua Su,Lin-Dong Yang,Jun Liu,Zhen-Feng Chen
Five dimeric oleanolic acids linked at C-28 by 1,6-hexanediamine, or built around the carbon chains of varying lengths between two carboxyl groups were synthesized, to investigate the effect of internal spacer length and species upon the stereochemical features and anti-tumor activity of the resultant bis-oleanolic acids. The IC 50 values of these dimeric compounds for cytotoxicity evaluation in vitro against Hep-G2, A549, BGC-823, MCF-7 and PC-3 tumor cell lines, were mainly under 10.0 μM. This result was much better than the inhibition of proliferation against tested tumor cell lines of the monomer oleanolic acid and the commercial anticancer drug 5-fluorouracil. The cytotoxicity selectivity detection revealed that dimer 11c exhibited low cytotoxicity towards normal human liver cell HL-7702. A combination of fluorescence staining observation and flow cytometric analysis indicated that 11c could induce Hep-G2 cell apoptosis . Molecular mechanism studies suggested that 11c induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by finally activating effector caspase-3/9 to trigger cell apoptosis. Further studies revealed that 11c caused cell cycle arrest at G1 phase in Hep-G2 cells. Taken together, these results suggest that 11c may be a potential candidate for further cancer research.
研究领域:
药理学
·
肿瘤学
·
有机化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2021
·
IF 9.229
Jie-Ping Fan,Hui Zhong,Xue-Hong Zhang,Tian-Tao Yuan,Hui-Ping Chen,Hai-Long Peng
The natural-product-based low-molecular-weight supramolecular hydrogels (LMWSHs) induced by heating are rarely reported. In this work, a simple salt of oleanolic acid (OA) and choline ([choline][OA]) was used as the natural product hydrogelator (NPHG) to form LMWSHs. Unlike common sol–gel transitions, the OA-based LMWSH displayed a unique property with which the system could undergo a phase transition from the sol state to the gel state upon heating. Moreover, the phase separation was observed in sol and gel states when the temperature was elevated with nonreversible transparent–turbid transitions. LMWSHs showed good stability and injectability and the potential to be a drug delivery vehicle for sustained release of drugs. In this regard, this work provided a facile approach to designing an OA-based NPHG for preparing heat-induced LMWSHs.
研究领域:
药学
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材料科学
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天然产物化学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
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2023
·Vol. 28
·期 3
·1414
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IF 4.6
Liyao Tang,Yan Zhang,Jinrun Xu,Qingfan Yang,Fukuan Du,Xu Wu,Mingxing Li,Jing Shen,Shuai Deng,Yueshui Zhao,Zhangang Xiao,Yu Chen
Efficient and mild synthetic routes for bioactive natural product derivatives are of current interest for drug discovery. Herein, on the basis of the pharmacophore hybrid strategy, we report a two-step protocol to obtain a series of structurally novel oleanolic acid (OA)-dithiocarbamate conjugates in mild conditions with high yields. Moreover, biological evaluations indicated that representative compound3eexhibited the most potent and broad-spectrum antiproliferative effects against Panc1, A549, Hep3B, Huh-7, HT-29, and Hela cells with low cytotoxicity on normal cells. In terms of the IC50values, these OA-dithiocarbamate conjugates were up to 30-fold more potent than the natural product OA. These compounds may be promising hit compounds for the development of novel anti-cancer drugs.Keywords:structural modification;oleanolic acid;natural product derivative;dithiocarbamate;hybrid strategy;antitumor activity
研究领域:
药理学
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肿瘤学
·
有机化学
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Kan He,Xia Meng,Jinxing Su,Shangquan Jiang,Min Chu,Bei Huang
The therapeutic mechanism of oleanolic acid (OA) in breast cancer has been widely reported, but little has been known about the combined effects of transcriptome and gut microbiome. In this study, the phenotypic effect of oleanolic acid on mice was tested at the end of the administration cycle, and RNA sequencing on murine tumor tissue and 16S-rRNA sequencing on intestinal contents were conducted to analyze gene expression profiles and microbial diversity between the control group and OA treated group using 4T1-induced mice breast cancer model. As a result, it has been confirmed that oleanolic acid would play a significant inhibitory effect on the development of breast tumors in mice. Based on the integrative analysis of the transcriptomic and metagenomic data, it was found that the abundance of Lactobacillus in the intestinal flora of mice significantly increased in the OA group. Moreover, the up-regulation of Il10 had a significant effect on inhibiting the tumor progression, which played a role through cytokine-cytokine receptor interaction pathway.
研究领域:
肿瘤学
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微生物组学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
·
IF 5.4
Chen Liu,Wanchun Du,Liang Zhang,Jiacheng Wang
Curcumin (Cur) is a natural polyphenol that is one of the most valuable natural products. However, its use as a functional food is limited by low water solubility, chemical instability and poor bioavailability. In this study, a supramolecular co-assembly strategy was used to construct an oleanolic acid-curcumin (OLA-Cur) co-assembly composite nano-slow-release treatment system. As a co-assembled compound, OLA is a widely present pentacyclic triterpenoid compound with multiple biological activities in the plant kingdom, which is expected to jointly alleviate the damaging effects of papain-induced mouse osteoarthritis model. The OLA-Cur NPs shows the solid core-shell structure, which can effectively improve the water solubility of Cur and OLA, and has good stability and sustained release characteristics. The analysis results show that the two compounds are mainly assembled through hydrogen bonding interactions, hydrophobic interactions, and π - π stacking interactions. The OLA-Cur NPs can inhibit the release of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β induced by LPS in RAW264.7 mouse macrophages, promote the secretion of anti-inflammatory cytokine IL-10, and improve the oxidative stress index of hydrogen peroxide induced human rheumatoid arthritis synovial fibroblasts. In addition, it has a certain improvement effect on cartilage and subchondral bone damage in mouse osteoarthritis models. These findings suggest that constructing co-assembled composite nanoparticles based on pure natural compounds may break through the limitations of a variety of important nutritional ingredients in functional foods.
研究领域:
药理学
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纳米技术
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生物医学工程
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风湿病学
✓ 已验证
DOI
PubMed
高影响因子
TETRAHEDRON
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2017
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IF 2.651
Zhenyu Tian,Kun Meng,Yanhong Shi,Naixia Zhang,Xuehui Liu,Hongwei Jin,Yongmin Zhang,Lihe Zhang,Demin Zhou,Sulong Xiao
A newly synthesized hexavalent oleanolic acid/per- O -methylated α -cyclodextrin conjugate shows significant differences in NMR spectra with previously synthesized analogs. Characterization of the product by 1 H NMR, 13 C NMR, COSY, HSQC , HMBC , TOCSY , NOE, and ROESY experiments were performed. Detailed investigations revealed that the compound has two conformations in solution and the ratio of them was 1:1. Further variable-temperature NMR study revealed that the two conformations were stable at temperature range of 273–323 K in CDCl 3 solution.
研究领域:
有机化学
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药物化学
✓ 已验证
DOI
高影响因子
Analytical Methods
·
2013
·Vol. 5
·期 19
·5227-5233
·
IF 1.855
Sha Peng,Jing Cheng,Miao Zhang,Mi Chen,Hongbin Zhou,Min Cheng
A very simple and effective method for the extraction and determination of oleanolic acid (OA) and ursolic acid (UA) in Radix Actinidiae chinensis was developed using ultrasound-assisted dispersive liquid–liquid microextraction (UA-DLLME) and high performance liquid chromatography–mass spectrometry (HPLC–MS). Ethanol was used as the solvent to extract OA and UA from Radix Actinidiae chinensis, assisted by ultrasonic waves. When the extraction process was finished, the two target analytes in the extraction solvent were rapidly transferred from the ethanol extract to another extraction solvent (chloroform) with the help of a dispersive solvent (tetrahydrofuran) by using DLLME. A series of extraction parameters were investigated and optimized. Under the most favorable conditions, the limits of detection (LOD, S/N = 3) and enrichment factors were 2.0 ng g−1, 89.4 and 6.0 ng g−1, 84.5 for OA and UA, respectively. The recoveries of the spiked sample solutions at three different concentration levels of 200, 500 and 1000 ng g−1 ranged between 88.2 and 96.6%. The proposed method was the first successfully applied for the extraction and determination of OA and UA in Radix Actinidiae chinensis.
研究领域:
药学
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分析化学
✓ 已验证
产品关联
DOI
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
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2020
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IF 4.006
Huafang Ding,Mengting Ni,Guowen Zhang,Yijing Liao,Xing Hu,Ying Zhang,Deming Gong
Non-enzymatic glycation can produce advanced glycation end products (AGEs), inducing a series of diabetic complications. In this study, oleanolic acid (OA) was found to inhibit the formation of fructosamine and α-dicarbonyl compounds, while AGEs was almost suppressed by OA at the concentration of 500 μg/mL. Moreover, OA exhibited strong anti-fibrillation and antioxidant abilities. It decreased the production of dityrosine, N′- formylkynurenine and kynurenine with strong ·OH and O 2 · − scavenging capacities. The binding of OA with lysine and arginine of bovine serum albumin (BSA) prevented BSA from the attack of sugars. The C−12 in the C ring of OA was predicted to trap methylglyoxal (MGO), forming the OA−MGO adduct. The antioxidant and MGO trapping abilities together with the secondary structure protection may be the main mechanism of anti-glycation ability of OA. These findings suggest that foods rich in OA are promising sources of anti-glycation agents. The study also provides a theoretical basis for the further functional research of OA in the prevention and treatment of diabetic complications.
研究领域:
药理学
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生物化学
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糖尿病研究
✓ 已验证
DOI
高影响因子
Nanomedicine
·
2025
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IF 3.9
Dan Zhang,Beiwei Zhu,Yu Xu,Fengxian Luo,Tao Chen,Lihang Chen,Xinchuang Wang,Di Wu,Jiangning Hu
Aim This study aims to develop and assess the therapeutic potential of oleanolic acid nanoparticles (OA NPs) in treating ulcerative colitis (UC).Materials & methods OA NPs were synthesized using an emulsion solvent evaporation method, forming spherical nanoparticles with an average diameter of 138.1 nm. The nanoparticles were designed to target the colon through the enhanced permeability and retention (EPR) effect. Network pharmacology and molecular docking identified key inflammatory pathways, and in vitro (RAW264.7 cells) and in vivo (DSS-induced UC mouse model) experiments evaluated their anti-inflammatory effects and therapeutic efficacy.Results OA NPs successfully targeted the colon and demonstrated improved bioavailability. In vitro experiments showed that OA NPs reduced oxidative stress and inflammation by downregulating pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and promoting macrophage polarization from M1 to M2. In the DSS-induced UC mouse model, oral administration of OA NPs significantly alleviated colitis symptoms, improved colon length, reduced inflammation, and mitigated tissue damageConclusion OA NPs mitigate UC pathology through targeted delivery, enhanced stability, and modulation of inflammatory pathways, providing a promising approach for UC treatment. Further studies are needed to evaluate their long-term safety and clinical applicability.
研究领域:
药理学
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生物医学工程
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消化病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Food Measurement and Characterization
·
2021
·Vol. 15
·期 4
·3408-3418
·
IF 2.431
Xie Zhike,He Ming,Zhai Yuhan,Xin Feifei,Yu Shuyan,Yu Shaoxuan,Xiao Haifang,Song Yuanda
Abstract Inhibition of α-glucosidase is considered as an effective approach to treat type 2 diabetes. Therefore, it is of great significance to study the inhibition of this enzyme. In the present study, the inhibitory activity of oleanolic acid (OA) on α-glucosidase and their interaction mechanism were investigated. The inhibition kinetic analysis showed that OA reversibly inhibited α-glucosidase activity in a mixed-type manner with an IC 50 value of 3.04 ± 0.05 µM, and the inhibition followed a multi-phase kinetic process with a first-order reaction. The change of enthalpy and entropy indicated that the binding of OA to glucosidase was mainly driven by hydrophobic interaction and hydrogen bonding, and the binding distance was estimated at 3.51 nm. Synchronous fluorescence, circular dichroism (CD) and Fourier transform infrared spectra (FT-IR) showed that the binding of OA to α-glucosidase induced rearrangement and conformational changes of the enzymes. The molecular docking illustrated that OA entered the active center of α-glucosidase and interacted with the amino acid residues Asp-352 and ultimately inhibiting the enzyme activity. Graphic Abstract
研究领域:
药理学
·
生物化学
·
糖尿病研究
✓ 已验证
产品关联
DOI
高影响因子
STEROIDS
·
2019
·
IF 2.136
Shu-Qi Dong,Shuang-Shuang Wang,Ji-Xiao Zhu,Rong-Hao Mu,Cheng-Fu Li,Di Geng,Qing Liu,Li-Tao Yi
Our previous study has demonstrated that oleanolic acid produced an antidepressant-like effect in mice exposed to chronic stress. Considering that serine/threonine-protein kinase 1 (SGK1) is involved in stress response, the present study aimed to evaluate the involvement of SGK1 in the antidepressant-like effects of oleanolic acid in depression-like mice induced by long term corticosterone (CORT) injection. Behaviors, SGK1, brain-derived neurotrophic factor (BDNF) and its downstream targets were assessed after administration with oleanolic for three weeks. The results indicated that oleanolic acid increased the sucrose preference and decreased the immobility time. In addition, oleanolic acid decreased SGK1 and activated BDNF-AKT/mTOR signaling in the hippocampus of CORT-induced animals. However, we found that GSK650394, an inhibitor of SGK1 did not exert any effects on the behaviors, GR levels and BDNF signaling. The number of spines in hippocampal neurons was not changed by GSK650394 as well. Taken together, this study demonstrated that oleanolic acid produced the antidepressant-like effects, which might be related to the down-regulation of SGK1. However, inhibition of SGK1 directly lacks the effects in the treatment of depression.
研究领域:
药理学
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神经科学
·
精神病学
✓ 已验证
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2025
·Vol. 13
·期 8
·
IF 3.8
Tian Chen,Shaolan Liu,Fei Yang,Zhangxuan He,Menghua Tang,Lu Ge,Hongyi Zhang,Sijie Liu,Xiaolei Zhu,Mengqi Peng,Heng Zhang,Wenxu Cheng,Yi Sun
Invasive fungal infections and emerging antifungal resistance mediated by pathogenic fungi, notably Candida spp., Aspergillus spp., Cryptococcus neoformans, and Exophiala dermatitidis, pose a critical challenge to global public health systems. This study evaluated the synergistic antifungal activity of oleanolic acid (OA) combined with five azole agents (itraconazole [ITR], voriconazole [VOR], posaconazole [POS], isavuconazole [ISA], and fluconazole) against Candida spp., Aspergillus spp., E. dermatitidis, and C. neoformans. Using CLSI-compliant broth microdilution assays (M27-A3/M38-A2), we determined the minimum inhibitory concentrations (MICs) of oleanolic acid against four fungal pathogens and evaluated in vitro synergistic interactions with five azoles to assess their therapeutic potential. OA exhibited no intrinsic fungicidal activity when administered alone. However, synergistic inhibition was observed in specific azole combinations across tested pathogens: Candida spp. (n = 18) demonstrated 33% (6/18) and 56% (10/18) synergy rates with ITR and POS, respectively. Aspergillus spp. (n = 30) showed enhanced synergism at 80% (24/30) for ITR and 97% (29/30) for POS. All OA-azole combinations were synergistic against C. neoformans (n = 8), with rates of 75% (6/8) for ITR, 75% (6/8) for VOR, 87.5% (7/8) for ISA, and 100% (8/8) for POS. In contrast, E. dermatitidis (n = 21) responded only to OA/POS (52%, 11/21). Overall synergistic frequencies were POS (75%, 58/77) > ITR (47%, 36/77) > ISA (9%, 7/77) > VOR (8%, 6/77). The OA-azole combinations demonstrated significant reductions in azole MIC values and exhibited synergistic antifungal activity, particularly against Aspergillus spp. and C. neoformans. While the mechanistic basis of OA’s chemosensitization remains uncharacterized, its multi-target pharmacological profile underscores potential utility in combating antifungal resistance.
研究领域:
医学真菌学
·
药理学
·
微生物学
·
抗菌素耐药性
·
药物协同
✓ 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）