Chemical Biology & Drug Design
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2016
·Vol. 88
·期 3
·329-340
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IF 2.802
Ke-Guang Cheng,Chun-Hua Su,Jia-Yan Huang,Jun Liu,Yuan-Ting Zheng,Zhen-Feng Chen
According to fused two bioactive moieties together by bonds covalently and available as a new single hybrid entity known as pharmacophore hybridization, a total of 10 targeted uridine–oleanolic acid hybrids were synthesized. Most of these hybrids showed excellent proliferation inhibition against tested Hep-G2, A549, BGC-823, MCF-7, and PC-3 tumor cell lines (IC 50 < 8 μ m ), even with some IC 50 values under 0.1 μ m . The detection of cytotoxicity selectivity revealed that hybrids 5 and 18 exhibited low cytotoxicity toward normal human liver cell HL-7702. Further studies revealed that selected hybrid 5 could induce apoptosis in Hep-G2 cells through the investigation of acridine orange/ethidium bromide, Hoechst 33258 fluorescence stainings, and annexin V/propidium iodide assay. It was also found that hybrid 5 could induce mitochondrial membrane potential disruption, arrest Hep-G2 cell line at G1 phase, and activate effector caspase-3/9 to trigger cell apoptosis.
研究领域:
药理学
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肿瘤学
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有机化学
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DOI
PubMed
高影响因子
MedChemComm
·
2016
·Vol. 7
·期 5
·972-981
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IF 2.319
Ke-Guang Cheng,Chun-Hua Su,Jia-Yan Huang,Heng-Shan Wang,Jun Liu,Yuan-Ting Zheng,Zhen-Feng Chen
A total of 16 targeted oleanolic acid–uracil/thymine hybrids were designed and synthesized as potential cytotoxic agents. Most IC50 values were under 10.0 μM, with some of them under 0.1 μM in vitro test against tested cells (Hep-G2, A549, BGC-823, MCF-7 and PC-3). These hybrids displayed much more potent inhibitory activities compared with oleanolic acid and commercial anticancer drug 5-fluorouracil (5-FU). The combination of fluorescence staining observation and flow cytometric analysis suggested that selected oleanolic acid–uracil hybrid 6a possessed clear cell apoptosis inducing effects. And the underlying mechanisms for the antitumor activity were associated with loss of the mitochondrial membrane potential, arrest of the Hep-G2 cell line at the G1 phase and activation of effector caspase-3/9 to trigger cell apoptosis.
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JOURNAL OF PHARMACY AND PHARMACOLOGY
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2026
·Vol. 78
·期 5
·
IF 3.7
Liu Chipu,Zhao Yue,Su Xiaoran,Sun Yajie,Jia Yugai
ObjectivesOleanolic acid (OA) is a natural anti-inflammatory triterpenoid. This study investigates its therapeutic potential against rheumatoid arthritis (RA), a chronic autoimmune condition characterized by inflammatory activity, and explores the novel mechanism of gut microbiota modulation in a rat model.MethodsThe anti-arthritic effect of OA was assessed in collagen-induced arthritis (CIA) in rats following oral or intravenous administration. Arthritis severity, joint pathology, and mesenteric Th17/Treg cell frequencies were evaluated. The role of gut microbiota was investigated using 16S rRNA sequencing and antibiotic ablation.Key findingsOral, but not intravenous, OA administration significantly alleviated arthritis and joint damage in CIA rats, indicating a gastrointestinal-dependent mechanism. Therapeutically, oral OA modulated gut microbiota by reducing Prevotella abundance and restored immune balance by decreasing Th17 and increasing Treg cell frequencies. This protective effect was abolished by co-treatment with antibiotics, confirming gut microbiota-dependency.ConclusionsTaken together, our findings show that the improvement in CIA after oral administration of OA is mainly due to changes in the structure and function of the gut microbiota. This study, therefore, suggests that OA is a promising therapeutic candidate for RA, based on its ability to restore the intestinal microenvironment.
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高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
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2026
·Vol. 78
·期 3
·
IF 3.7
Cheng Yawei,Li Gengliang,Li Yang,Ma Yugang,Xia Yujie,Zhang Chunye,Wang Xingchen
ObjectivesConventional pharmacotherapies afford only modest renoprotection in diabetic nephropathy (DN). Oleanolic acid (OA), a pentacyclic triterpenoid abundant in Traditional Chinese Medicine (TCM), mitigates DN, but its mechanism remains unclear. This study aimed to verify the hypothesis that OA protects podocytes by modulating autophagy, thereby exploring the potential therapeutic mechanism of OA in attenuating DN.MethodsHigh glucose-injured MPC5 podocytes were treated with OA to evaluate its impact on autophagy. Podocytes were further treated with graded concentrations of OA, rapamycin (an autophagy inducer), or 3-methyladenine (an autophagy inhibitor). Cell viability was quantified using the Cell Counting Kit-8 assay. Nuclear morphology was visualized by DAPI staining, autophagosomes were enumerated by transmission electron microscopy, and the expression of autophagy-related genes was determined by quantitative reverse transcription polymerase chain reaction. These complementary approaches were used to assess high-glucose-induced podocyte injury and the capacity of OA to enhance autophagy and attenuate cellular damage.Key findingsThe effective concentration window for OA was established at 5–10 μM. Within this concentration range, podocyte viability was significantly increased, accompanied by a higher autophagosome count and elevated expression of autophagosomal markers.ConclusionsOleanolic acid alleviates high glucose-induced podocyte injury by robustly activating autophagy, underscoring its potential as a sustainable therapeutic strategy for DN, along with other active compounds derived from TCM.
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Dan Zhang,Wei Tian,Li-Hang Chen,Tao Chen,Di Wu,Yinan Du,Jiangning Hu
Gastric ulcers (GC) are prevalent gastrointestinal disorders with complex etiologies, including Helicobacter pylori infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Curcumin (CUR), with its established anti-inflammatory and antioxidant properties, is limited in clinical application due to poor bioavailability. This study developed oleanolic acid-coated CUR nanoparticles (OC NPs) to enhance the efficacy of CUR in GC prevention. OC NPs were characterized by a spherical shape, demonstrating remarkable improvements in solubility and stability, maintaining structural integrity within biological systems and exhibiting excellent biocompatibility. In vitro studies showed OC NPs reduced inflammation and oxidative stress in GES-1 cells. In vivo , OC NPs effectively prevented ethanol-induced GC in mice by lowering inflammatory cytokines, while increasing antioxidant levels. Histological analysis confirmed enhanced gastric mucosal protection and reduced fibrosis and apoptosis. OC NPs demonstrated prolonged retention in the stomach, offering a targeted drug delivery system. These findings suggested OC NPs as a promising low-toxicity alternative for preventing GC.
研究领域:
药理学
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生物医学工程
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胃肠病学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2024
·
IF 6
Ming Cai,Yuan Zhang,Jie Zhen,Fan Yang,Xia Ou,Jihong Zhang,Fei Yu
Influenza A virus (IAV) leads to significant morbidity and mortality due to the seasonal epidemics and spread. We have demonstrated that oleanolic acid (OA) C28 glucose conjugates and OA trimers are capable of effectively blocking the recognition and interaction between the influenza virus and host cells. In this study, a series of OA-glucose trimers were designed and synthesized through the CuAAC reaction. All trimers underwent screening for anti-IAV activities in vitro. Among these, compounds 13a and 13b showed inhibitory activity against the influenza virus, with IC 50 values of 0.68 μM and 0.47 μM, respectively, demonstrating greater potency than oseltamivir (IC 50 = 1.36 μM). Results from the time-of-addition experiment and hemagglutination inhibition assay suggest that these OA-glucose trimers may disrupt the recognition between the HA protein of IAV and sialic acid receptors on host cells, thus blocking viral entry. Furthermore, it was found that compound 13b effectively inhibits IAV infection in BALB/c mice. This study has elucidated the structure-activity relationships of OA trimers against the influenza virus and highlighted the utility of multivalent OA conjugates for enhancing ligand-target interactions in anti-influenza virus drug design, laying a groundwork for future research into the antiviral applications of these natural products.
研究领域:
药理学
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病毒学
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有机合成化学
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PubMed
高影响因子
Chemistry Central Journal
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2016
·Vol. 10
·期 1
·1-11
·
IF 2.552
Mo Wei-bin,Su Chun-hua,Huang Jia-yan,Liu Jun,Chen Zhen-feng,Cheng Ke-guang
Background Oleanolic acid, which can be isolated from many foods and medicinal plants, has been reported to possess diverse biological activities. It has been found that the acylation of the hydroxyl groups of the A-ring in the triterpene skeleton of oleanolic acid could be favorable for biological activities. The pyrimidinyl group has been constructed in many new compounds in various anti-tumor studies.Results Five acyl oleanolic acid-uracil conjugates were synthesized. Most of the IC50 values of these conjugates were lower than 10.0 μM, and some of them were even under 0.1 μM. Cytotoxicity selectivity detection revealed that conjugate 4c exhibited low cytotoxicity towards the normal human liver cell line HL-7702. Further studies revealed that 4c clearly possessed apoptosis inducing effects, could arrest the Hep-G2 cell line in the G1 phase, induce late-stage apoptosis, and activate effector caspase-3/9 to trigger apoptosis.Conclusion sConjugates of five different acyl OA derivatives with uracil were synthesized and identified as possessing high selectivity toward tumor cell lines. These conjugates could induce apoptosis in Hep-G2 cells by triggering caspase-3/9 activity.Five acyl oleanolic aicd-uracil conjugates were synthesized. These conjugates exhibited selective cytotoxicity toward tumor cells achieved via inducing apoptosis by activation of caspase-3/9.
研究领域:
药理学
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肿瘤学
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药物化学
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DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
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2024
·
IF 2.3
Zhiping Che,Ruiguang Wang,Yuanhao Li,Wanying Yin,Huilu Sun,Shaobin Xu,Shaoyan Shuang,Yuee Tian,Xiaobo Huang,Genqiang Chen
Oleanolic acid is a pentacyclic triterpenoid extracted and isolated from the fruit of plants in the Ligustrum lucidum Ait. in the family Oleaceae. To discover biorational natural product-based pesticides, a series of oleanolic acid derivatives containing anhydride active skeletons were prepared by ingeniously introducing an active acyloxy group at its C-28 carboxyl position, and their structures were well characterized by 1H NMR, 13C NMR, HRMS, and m.p.. The stereochemical configuration of compound 8e was confirmed using single-crystal X-ray diffraction. Furthermore, bioactivities of these compounds as anti-oomycete and anti-fungal agents against two serious agricultural pests, Phytophthora capsici and Fusarium graminearum we assessed. Amongst evaluated compounds, 1) Compounds 8h and 8j displayed significant anti-oomycete against P. capsici, with EC50 values of 54.73 and 65.15 mg/L, respectively. 2) The target compounds have obvious selectivity, and their anti-oomycete activity is significantly better than their anti-fungal activity. 3) Interestingly, there are significant differences in the structure-activity relationship of different substituents or the same substituent at different positions anti-oomycete and anti-fungal against P. capsici and F. graminearum, respectively. The study provides an idea for further exploring the bioactivities of 28-acyloxyoleanolic acid derivatives, and develops the application of 28-acyloxyoleanolic acid derivatives containing anhydride in agriculture.
研究领域:
植物化学
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农药学
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农业科学
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PubMed
高影响因子
MOLECULAR CANCER THERAPEUTICS
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2019
·Vol. 18
·期 1
·62-74
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IF 4.856
Wang Hongzhi,Zhong Weilong,Zhao Jianmin,Zhang Heng,Zhang Qiang,Liang Yuan,Chen Shuang,Liu Huijuan,Zong Shumin,Tian Yixuan,Zhou Honggang,Sun Tao,Liu Yanrong,Yang Cheng
Oleanolic acid exhibits extensive pharmacologic activities and takes significant antitumor effects. Its pharmacologic mechanism, however, still remained to be further clarified. In this study, we demonstrated that oleanolic acid attenuated the migration and invasion abilities, resulting in the suppression of the epithelial–mesenchymal transition (EMT) process in liver cancer cells, and inhibited the tumor growth of the peritoneal lymphocytes–bearing mice. We further proved that inducible nitric oxide synthase (iNOS) may be the potential target of oleanolic acid. We confirmed that oleanolic acid could promote the dimerization of iNOS, activating it, and subsequently increasing the production of nitric oxide. Further experiments indicated that oleanolic acid promoted the nitration of specific proteins and consequently suppressed their EMT-related biological functions. Furthermore, it has been confirmed that oleanolic acid enhanced the antitumor effects of regorafenib in liver cancer treatment. These results deepened our understanding of the pharmacologic mechanism of the antitumor effect oleanolic acid, and the importance of nitric oxide synthetase as a therapeutic target for liver cancer treatment.
研究领域:
药理学
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肿瘤学
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分子生物学
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DOI
PubMed
高影响因子
MedChemComm
·
2019
·Vol. 10
·期 8
·1370-1378
·
IF 2.394
Chun-Mei Liu,Jia-Yan Huang,Li-Xin Sheng,Xiao-An Wen,Ke-Guang Cheng
Due to the obvious adverse effects of 5-fluorouracil that limit its clinical usefulness and considering the diverse biological activities of pentacyclic triterpenes, twelve pentacyclic triterpene-5-fluorouracil conjugates were synthesized and their antitumor activities were evaluated. The results indicated that all the single substitution targeted hybrids (7a–12a) possessed much better antiproliferative activities than the double substitution targeted hybrids (7b–12b). Hybrid 12a exhibited good antiproliferative activities against all the tested MDR cell lines. Furthermore, it was revealed that 12a could induce intracellular calcium influx, the generation of ROS, arrest the cell proliferation at the G1 phase, and activate the apoptotic signaling caspase-8, which eventually activates the apoptotic effector caspase-3 and causes the later nuclear apoptosis.
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高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2025
·
IF 4.7
Guangqi Guo,Zhen Zhang,Xiaoyang Xia,Zhixiong He,Nanjie Jiang,Xiang Liu,Xia Xiang,Yanan Xue
Berberine (BBR) and oleanolic acid (OA) are natural bioactive compounds with recognized anti-inflammatory properties. However, their therapeutic potential is often limited due to poor solubility and low bioavailability. Different from the traditional polymeric or lipidic-encapsulation strategies, this study successfully prepared carrier-free co-assembly BBR-OA nanoparticles (B-O NPs) using a solvent exchange method, which could achieve higher payload. Under optimal conditions, BBR and OA self-assembled to form uniform spherical nanoparticles, with an average particle size of approximately 130 nm. B-O NPs were negatively charged with a zeta potential of -42.43 mV and demonstrated improved water solubility and stability compared to the BBR and OA alone. The self-assemble mechanism of BBR and OA was further elucidated by molecular dynamics simulations and molecular docking analysis, highlighting the role of electrostatic and hydrogen bonding interactions. In vitro studies revealed that B-O NPs displayed obvious pH responsiveness and sustained BBR release capabilities in simulated gastric fluid (pH 2.0) and physiological buffer (pH 7.4) when compared to free BBR. Cellular experiments revealed that B-O NPs had enhanced cellular uptake and transmembrane transport ability. Moreover, in a lipopolysaccharide (LPS)-stimulated inflammatory model of RAW 264.7 macrophages, B-O NPs effectively reduced the intracellular reactive oxygen species (ROS) and downregulated the inflammatory mediators, including NO, TNF-α, IL-1β, and IL-6, showing significantly higher anti-inflammatory activity than free BBR, OA, or their physical mixture. These findings suggested that B-O NPs may provide a promising approach to improve the bioavailability and biological activity of small natural molecules.
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高影响因子
FOOD CHEMISTRY
·
2023
·
IF 8.8
Hanqing Wu,Linlu Zheng,Liangbin Lin,Hongyu Guo,Fafu Yang
Fluorescent sensors had been extensively applied on sensing various biomolecules effectively, but no fluorescent sensor for oleanolic acid was presented up to now. In this work, the first fluorescent sensor for oleanolic acid was designed and synthesized based on o-phenyl-bridged bis-tetraphenylimidazole ( PTPI ). PTPI was prepared by bridging two tetraphenylimidazole units and o-phenylenediamine via Schiff-base condensation in yield of 86%. PTPI showed high sensing selectivity for oleanolic acid among 26 biomolecules and ions. The blue fluorescence at 482 nm was enhanced by 4.5 times after sensing oleanolic acid in aqueous media. The fluorescence sensing ability of PTPI for oleanolic acid maintained stable in pH = 5–9. The detecting limitation was as low as 0.032 μM. The detecting mechanism was clarified as 1:1 binding stoichiometry by fluorescence Job’s plot, mass spectrometry, 1 H nuclear magnetic resonance and fourier transform infrared spectroscopy. The detecting ability of PTPI for oleanolic acid was successfully used for paper test and real samples of grapes and Kuding tea with recoveries in the range of 96.0%-106.0%, indicating the good application potential for on-site detecting oleanolic acid in real samples of fruits and food.
研究领域:
分析化学
·
生物化学
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DOI
PubMed
高影响因子
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