查找使用阿拉丁产品的科研文献

Liposomal co-delivered oleanolic acid attenuates doxorubicin-induced multi-organ toxicity in hepatocellular carcinoma

Muhammad Sarfraz,Attia Afzal,Shahid Masood Raza,Sajid Bashir,Asadullah Madni,Muhammad Waseem Khan,Xiang Ma,Guangya Xiang

Doxorubicin in combination with other cytotoxic drugs has clinical advantages. However, doxorubicin-induced cardiotoxicity negatively impacts clinical utility and outcomes. Cardiotoxicity can result from increased oxidative stress or from a local cytochrome P450 mediated increase in 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE). Oleanolic acid (OA) is a natural pentacyclic triterpenoid with free radical scavenging, cardioprotective, and P450-mediated cyclooxygenase-upregulating properties. We investigated co-delivery of liposomal OA and doxorubicin in a HepG2 model of hepatocellular carcinoma (HCC). OA attenuated the cardiotoxicity induced by doxorubicin without compromising its anticancer activity. Apoptosis assays revealed that co-delivery of DOX and OA produced a synergistic anticancer effect. However, the drugs had antagonistic effects on cardiomyocytes. Female BALB/c nude mice treated with OA- and DOX-loaded liposomes (ODLs) exhibited reduced tumor growth, stable body weight, and stable organ indices. Reduced 20-HETE production suggested ODLs had limited cardiotoxicity. No changes in biochemical or histopathological markers were observed in mice treated with ODLs. Tailored co-delivery of OA and DOX may thus be an effective therapeutic strategy for treating HCC.

Optimized formulation of multivesicular liposomes loaded with oleanolic acid enhanced anticancer effect in vitro

Yunlong Wang,Yuling Luo,Chunhong Li,Xiaoqin Zhang,Chao Pi,Lu Yu,Shurong Wang,Zhirong Zhong

Formulation and HPLC-UV−Based Quantification of Nanoliposomes Co-Encapsulating Genistein and Oleanolic Acid

Amna Naz,Muhammad Farooq,Muhammad Sarfraz,Ahsanullah Unar,Rouheena Shakir,Hafiz Arfat Idrees,Nadia Anwar

Oleanolic acid (OL) and genistein (GN) are bioactive compounds known for their anti-inflammatory, antioxidant, antiviral, cardioprotective, and anticancer properties. Their synergistic therapeutic potential motivated the development of a hybrid nanoformulation, comprising GN nanoparticles incorporated into an OL-loaded liposomal system named GOL. The formulation was extensively characterized for particle size, polydispersity index, zeta potential, entrapment efficiency, and pharmacokinetic behavior, demonstrating its suitability for co-delivery of both drugs. To accurately quantify OL and GN in the GOL system, a robust HPLC-UV method was developed and validated. Simultaneous determination was challenging due to distinct chemical and spectral properties; OL showed λmax at 210–215 nm, while GN had λmax at 215, 270, and 336 nm. Optimization using a Box–Behnken design yielded a method using a C18 column with a methanol–acetonitrile–water–tetrahydrofuran (60:20:8:12, v/v) mobile phase and detection at 230 nm. Retention times were 4.8 and 9.9 min for OL and GN. Plasma samples were processed via simple protein precipitation. The method met ICH validation criteria for sensitivity, selectivity, accuracy, precision, robustness, and stability. Finally, the developed method was successfully applied to analyze both drugs from the GOL nanoformulation in both biological fluids and polymeric matrices, enabling a reliable assessment of drug content and stability.

Construction and Self-Assembly of Oleanolic Acid–Short Peptide Hydrogels Based on Supramolecular Interaction

Shunmei He,Jun Zheng,Fujing Huang,Ying Zhou,Wei Li,Yajie Jiang,Hao Chen,Lei Fu,Xianweng Song

Oleanolic acid (OA), a natural product with diverse biological activities, faces clinical limitations due to its poor bioavailability caused by hydrophobic pentacyclic structure. To address this issue, we designed a novel class of oleanolic acid–short peptide derivatives (OA-GFFK) by conjugating OA with a water-soluble short peptide (glycine-phenylalanine-phenylalanine-lysine, GFFK). Molecular dynamics simulation (MD) and density functional theory (DFT) predicted its gelation properties, and OA-GFFK was successfully transformed into supramolecular hydrogels via a simple three-step process (dissolution-ultrasonication-resting). Structural characterization revealed that gelation is driven by π–π stacking and hydrogen bonding, leading to a nanofiber network. And the hydrogels exhibited excellent self-healing, shear response, biocompatibility, and antibacterial activity. This study details a research process for the design and simple preparation of oleanolic acid-short peptide derivative hydrogels, providing design insights and a theoretical basis for developing OA derivatives.

Oleanolic acid inhibits cholesterol synthesis by suppressing the expression and enzymatic activity of HMGCR

Fang Luo,WenLuer Meng,Ruo-Shi Hao,Xiangxuan Yang,Jinbo Yang,Ye-Wei Huang,Jun Sheng,Xuanjun Wang

This study investigated the impact of Oleanolic Acid (OA) on cholesterol metabolism and. MTT assays demonstrated that OA had no cytotoxic effects on HepG2 cells at concentrations below 20 μM. Subsequent experiments focused on 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), a key enzyme in cholesterol biosynthesis. OA significantly reduced HMGCR protein expression without affecting other enzymes. Further investigations revealed that OA reduced the protein and mRNA expression of HMGCR and its upstream regulator Sterol regulatory element binding protein-2 (SREBP-2) in HepG2 cells. OA activated Adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK), enhancing HMGCR phosphorylation and inhibiting its activity. Molecular docking experiments suggested that OA could suppress HMGCR enzymatic activity through hydrophobic interactions, reducing catalytic efficiency. Overall, OA downregulated HMGCR expression and activity, leading to decreased cholesterol synthesis. These findings highlight OA’s regulatory role in cholesterol metabolism and its potential for improving atherosclerosis (AS), supporting its application in functional food development.

A Self-assembled Nanoparticle Platform Based on Amphiphilic Oleanolic Acid Polyprodrug for Cancer Therapy

Wang Ying-Sa,Li Gui-Liang,Zhu Shang-Bin,Jing Fan-Chen,Liu Run-Dong,Li Sai-Sai,He Jing,Lei Jian-Du

Oleanolic acid (OA) is a pentacyclic triterpenoid compound with extensive biological effects, such as anti-inflammatory and anticancer activities. However, the application of OA in chemotherapy is hampered by its poor solubility and severe adverse effects. To solve the problems, we developed a self-assembled nanoparticle platform based on amphiphilic oleanolic acid polyprodrug, poly[oligo(ethylene glycol) methyl ether methacrylate]- b -poly[oleanolic acid methacrylate] (POEGMA- b -POAMA), encapsulating 10-hydroxycamptothecin (HCPT) to achieve efficient cancer therapy. The polyprodrug was prepared via reversible addition-fragmentation chain transfer polymerization (RAFT), and could self-assemble to prepare POEGMA- b -POAMA/HCPT nanoparticles (NPs). The obtained nanoparticles exhibited appropriate particle size, excellent drug stability, good drug loading capacity, and high drug loading efficiency. In vitro drug release indicated that the drug release was prolonged to 132 h. The POEGMA- b -POAMA/HCPT NPs enhanced cell cytotoxicity in 4T1 cells and MCF-7 cells and could be efficiently uptaken by 4T1 cells. Furthermore, in vivo antitumor efficiency showed that the POEGMA -b -POAMA/HCPT NPs had great antitumor efficiency with considerably low adverse effects in the treatment of the 4T1 mouse breast tumor xenograft tumor. Therefore, POEGMA -b -POAMA/HCPT NPs provide great potential as a platform for drug delivery applications.

Inhibitory mechanism of two allosteric inhibitors, oleanolic acid and ursolic acid on α-glucosidase

Huafang Ding,Xing Hu,Ximing Xu,Guowen Zhang,Deming Gong

Glycemic control which can be efficaciously regulated by inhibiting α-glucosidase activity is an effective therapy for diabetes mellitus. This work is to investigate the kinetics and inhibition mechanism of oleanolic acid and ursolic acid on α-glucosidase. Oleanolic acid and ursolic acid exhibited potent inhibitory activities with IC 50 values of (6.35   ±   0.02)   ×   10 −6 and (1.69   ±   0.03)   ×   10 −5   mol   L −1 respectively in a reversible and non-competitive manner. Both of them binding to α-glucosidase induced the conformational change and intrinsic fluorescence quenching of α-glucosidase. The binding constants of oleanolic acid and ursolic acid with α-glucosidase at 298   K were (2.04   ±   0.02)   ×   10 3 and (1.87   ±   0.02)   ×   10 3   L   mol −1 , respectively. Docking results showed that oleanolic acid and ursolic acid bound in different allosteric sites of cavity 2 and cavity 4 on α-glucosidase, respectively, which triggered allosteric regulation to perturb conformational dynamics of α-glucosidase, eventually leading to a decrease of catalytic activity of the enzyme. The substrate was not catalyzed by α-glucosidase to generate further products due to formation of a nonreactive ternary complex of oleanolic acid– or ursolic acid–α-glucosidase–substrate. The combination of oleanolic acid and ursolic acid displayed a significant synergistic inhibition on α-glucosidase.

Synthesis and biological evaluation of novel oleanolic acid analogues as potential α-glucosidase inhibitors

Ying-Ying Zhong,Hui-Sheng Chen,Pan-Pan Wu,Bing-Jie Zhang,Yang Yang,Qiu-Yan Zhu,Chun-Guo Zhang,Su-Qing Zhao

Considerable interest has been attracted in oleanolic acid and its analogues because of their hypoglycemic activity. In this study, a series of novel oleanolic acid analogues against α-glucosidase were synthesized and their biological activities were evaluated in vitro and in vivo. In vitro α-glucosidase inhibition activity results indicated that most of the designed analogues exhibited prominent inhibition activities, especially compounds 10 , 15 , 16 and 26 which with the IC 50 values of 0.33 ± 0.01, 0.98 ± 0.06, 0.69 ± 0.01 and 0.72 ± 0.21 μM, respectively. Enzyme kinetic studies on the most potent compounds reveled that derivatives 10 , 15 , 16 and 26 were noncompetitive inhibitors. Moreover, the docking studies were carried out to prove that the four compounds could interact with the hydrophobic region of the active pocket and form hydrogen bonds to enhance the binding affinity of them with the α-glucosidase. Cytotoxicity evaluation assay demonstrated a high level of safety profile of the active compounds ( 10 , 15 , 16 and 26 ) against normal 3T3 cell line. Furthermore, the in vivo actual pharmacological potential studies on derivatives 10 , 15 , 16 and 26 showed that the hypoglycemic effects of them were comparable to that of positive control, acarbose .

Oleanolic acid cubic liquid crystal nanoparticle-based thermosensitive gel attenuates knee osteoarthritis symptoms in rats

Zhiqi Shi,Fan Jia,Xiaoyu Tang,Qing Li

Background Knee osteoarthritis (KOA) is a prevalent degenerative joint disease with limited effective treatment options. Oleanolic acid (OA) possesses promising anti-inflammatory and cartilage-protective properties, but its clinical application is hindered by poor solubility and rapid metabolism. Purpose This study aimed to develop an oleanolic acid-loaded liquid crystalline nanogel (OANG) for intra-articular delivery and to systematically evaluate its therapeutic effects and potential mechanisms in a rat KOA model. Methods OA-loaded nanoparticles were prepared and incorporated into a thermosensitive Poloxamer gel base to form OANG. A papain-induced KOA rat model was established. Rats were administered OANG (high/low dose) intra-articularly, with celecoxib as a positive control. Evaluations included behavioral tests, micro-computed tomography, histological analyses (hematoxylin and eosin, transmission electron microscopy, immunohistochemistry), enzyme-linked immunosorbent assay of synovial fluid, serum, and hippocampus, Western blot (WB), network pharmacology, and molecular docking. Results OANG exhibited sustained-release properties and improved joint lubrication. Treatment with OANG significantly alleviated KOA-induced pain and depression-like behaviors, reduced cartilage degradation and subchondral bone sclerosis, and downregulated levels of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6) and cartilage degradation markers (C-terminal cross-linked telopeptide of type II collagen, cartilage oligomeric matrix protein) in synovial fluid. It also enhanced antioxidant capacity (increased superoxide dismutase, glutathione peroxidase; decreased malondialdehyde) and modulated the expression of key cartilage proteins (increased Collagen II; decreased matrix metalloproteinase 13; regulated glycogen synthase kinase-3β/SRY-box transcription factor 9, β-catenin, and Yes-associated protein). Furthermore, OANG ameliorated hippocampal oxidative stress and inflammation (decreased Cleaved caspase-3, Malondialdehyde; increased IL-10). Network pharmacology and docking suggested the involvement of peroxisome proliferator-activated receptor gamma, mitogen-activated protein kinase 3, prostaglandin-endoperoxide synthase 2, and pathways such as estrogen signaling and cyclic adenosine monophosphate signaling.

Preparation of a molecularly imprinted Poly(OA[AMI] supramolecular hydrogel) for selectively enriching oleanolic acid

Jie-Ping Fan,Ping Gan,Feng-Hui Tao,Hui-Ping Chen,Hai-Long Peng,Yu-De Liu,Chun-Fang Xie

Oleanolic acid possesses a wide variety of pharmacological activities and spreads in various plants, but always co-exist with its isomers ursolic acid. Separating oleanolic acid with high efficacy from ursolic acid contaminated plant extracts is quite important. This study prepared a molecularly imprinted poly(OA[AMI] supramolecular hydrogel) (MIPSHG@OA) for selectively enriching oleanolic acid, by using the 1-allyl-3-methylimidazolium oleanolic salt (OA[AMI]) as hydrogelator, template, functional monomer and basement. The preparation conditions were optimized as 12.5 mg OA[AMI], 40 mg MBA, 4 ml solvent, 10 mg APS, and 30 μl TEMED. The characterization by FT-IR spectra, TG analysis, SEM image and equilibrium swelling ratio showed a sheet and porous structure and a large equilibrium swelling ratio of the obtained MIPSHG@OA. The adsorption performance showed the obtained MIPSHG@OA was homogeneous on the surface and uniform on the adsorption sites, the adsorption of oleanolic acid on the polymers was chemisorption and monolayer, the adsorbed oleanolic acid molecules did not interact with each other, the MIPSHG@OA had high competitive recognition performance and imprinting efficiency on oleanolic acid, and had good recyclability. In the solid phase extraction application, the results demonstrated that the synthesized MIPSHG@OA could selectively enrich oleanolic acid.

Oleanolic acid attenuates obesity through modulating the lipid metabolism in high-fat diet-fed mice

Guangjie Zhang,Huiying Zhang,Ruiyi Dong,Hongmei Zhao,Junfeng Li,Weiming Yue,Zheng Ma

As a natural pentacyclic triterpenoid, oleanolic acid has hepatoprotective, anti-inflammatory, and antioxidant activities. This work performed the in vitro experiments and animal assay to explore whether oleanolic acid alleviates lipid accumulation induced by high-fat diet by mediating PPARγ. Oil red O staining showed that oleanolic acid can reduce lipid accumulation in HepG2 cells, which were treated with oleic acid and palmitic acid. Immunofluorescence, western blot analysis, and RT-qPCR showed that oleanolic acid could promote nuclear translocation of PPARγ and reduce the expression level of PPARγ, C/EBP-β, and SREBP-1c. The results of in vivo experiments indicated that dietary intervention with oleanolic acid can effectively improve the fat accumulation in liver tissue and attenuate the level of IL-6 and TNF-α in serum caused by high-fat diet. Meanwhile, oleanolic acid did not cause lesions in vital organs at the experimental concentrations. In addition, the computer simulation indicated that oleanolic acid could directly bind to PPARγ with a reasonable and stable docking conformation. The above research results can provide new evidence for oleanolic acid to prevent nonalcoholic fatty liver disease.

Oleanolic acid alleviating ischemia-reperfusion injury in rat severe steatotic liver via KEAP1/NRF2/ARE

Yilin Pi,Huaiwen Zuo,Yuxin Wang,Weiping Zheng,Huiyuan Zhou,Lamei Deng,Hongli Song

Severe steatosis in donor livers is contraindicated for transplantation due to the high risk of ischemia–reperfusion injury (IRI). Although Ho-1 gene-modified bone marrow mesenchymal stem cells (HO-1/BMMSCs) can mitigate IRI, the role of gut microbiota and metabolites in this protection remains unclear. This study aimed to explore how gut microbiota and metabolites contribute to HO-1/BMMSCs-mediated protection against IRI in severe steatotic livers. Using rat models and cellular models (IAR20 and THLE-2 cells) of steatotic liver IRI, this study revealed that ischemia–reperfusion led to significant liver and intestinal damage, heightened immune responses, impaired liver function, and altered gut microbiota and metabolite profiles in rats with severe steatosis, which were partially reversed by HO-1/BMMSCs transplantation. Integrated microbiome and metabolome analyses identified gut microbial metabolite oleanolic acid as a potential protective agent against IRI. Experimental validation showed that oleanolic acid administration alone alleviated IRI and inhibited ferroptosis in both rat and cellular models. Network pharmacology and molecular docking implicated KEAP1/NRF2 pathway as a potential target of oleanolic acid. Indeed, OA experimentally upregulated NRF2 activity, which underlies its inhibition of ferroptosis and protection against IRI. The gut microbial metabolite OA protects against IRI in severe steatotic liver by promoting NRF2 expression and activity, thereby inhibiting ferroptosis.