MOLECULES
·
2015
·Vol. 20
·期 4
·6273-6283
·
IF 2.416
Yun-Feng Zheng,Juan-Hua Wei,Shi-Qi Fang,Yu-Ping Tang,Hai-Bo Cheng,Tian-Lin Wang,Cun-Yu Li,Guo-Ping Peng
Two novel oleanane-type triterpene saponins, licorice-saponin P2 (1) and licorice-saponin Q2 (3), together with nine known compounds2,4–11, have been isolated from the water extract of the roots ofGlycyrrhiza inflata. The structures of these compounds were elucidated on the basis of spectroscopic analysis, including 2D-NMR experiments (1H–1H COSY, HSQC, HMBC and ROESY). Inin vitroassays, compounds2–4,6and11showed significant hepatoprotective activities by lowering the ALT and AST levels in primary rat hepatocytes injured by D-galactosamine (D-GalN). In addition, compounds2–4,6,7and11were found to inhibit the activity of PLA2with IC50values of 6.9 μM, 3.6 μM, 16.9 μM, 27.1 μM, 32.2 μM and 9.3 μM, respectively, which might be involved in the regulation of the hepatoprotective activities observed.Keywords:Glycyrrhiza inflate;genusGlycyrrhiza;triterpene saponin;hepatoprotective;phospholipase A2
研究领域:
药用植物化学
·
肝脏保护研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2019
·Vol. 40
·期 10
·1334-1342
·
IF 4.01
Lu Bin,Chen Xiao-bing,Hong Yu-cai,Zhu Hong,He Qiao-jun,Yang Bo,Ying Mei-dan,Cao Ji
Ferroptosis is a newly characterized iron-dependent form of nonapoptotic regulated cell death triggered by lipid reactive oxygen species (LOOH). The dysregulation of ferroptosis is highly related to cancer, and the induction of ferroptosis is also proposed as a potential strategy for cancer therapy. Although several key regulators have been identified that are involved in ferroptosis, the molecular mechanism underlying this process remains largely unknown. Here, we report that Peroxiredoxin-6 (PRDX6) is a bona fide negative regulator of ferroptotic cell death. The knockdown of intracellular PRDX6 significantly enhances LOOH and ferroptotic cell death triggered by ferroptosis inducers (Erastin and RSL-3), which is correlated with the transcriptional activation of heme oxygenase-1. Moreover, overexpression of heme oxygenase-1 enhances both Erastin- and RSL-3-triggered LOOH, suggesting that heme oxygenase-1 mediates PRDX6 silencing-enhanced ferroptosis. More importantly, the application of a specific PRDX6 phospholipase A2 (iPLA2) inhibitor, MJ-33, synergistically enhances the ferroptosis induced by Erastin, suggesting that PRDX6 removes LOOH through its iPLA2 activity. Thus, our findings reveal an essential role of PRDX6 in protecting cells against ferroptosis and provide a potential target to improve the antitumor activity of ferroptosis-based chemotherapy.
研究领域:
癌症生物学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY AND PHYSICS OF LIPIDS
·
2019
·
IF 2.536
Dandan Li,Xueqin An,Yao Mu
A novel liposomal hydrogel with enzyme triggered release of drug as drug carrier was presented for usage of infected wound. The liposomal hydrogel was prepared by an acombined method of thin-film evaporation and supercritical carbon dioxide technique (TE-scCO 2 ) with freeze-drying. In the liposomal hydrogel, curcumin as a model drug was embedded in the bilayer of the liposomes, and the liposomes were encapsulated in the gelatin-chitosan hydrogel. Phospholipase A 2 (PLA 2 ) riched in wound exudate was served tactfully as a trigger to hydrolyze lecithin in liposome and destroy the liposomes to release drug. Hydrolysis of phospholipids in liposomes was monitored by fluorescence assay of the released curcumin, and relationship between the hydrolysis of lecithin and the release of drug was discussed. The microstructure changes of the liposome after treated by PLA 2 were probed by using florescence probeembedded in the liposomes for the first time. Besides, relationship between the microstructure of liposome and hydrolysis of liposome was revealed. This liposomal hydrogel can not only inhibit the degradation of drug in conveying process and enhance the efficiency of drug release to the infected skin, but also the release of drugs can be on demand by PLA 2 biological activity changed with wound exudate in infected tissue.
研究领域:
药剂学
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生物材料学
✓ 已验证
DOI
高影响因子
RSC Advances
·
2025
·Vol. 15
·期 20
·15490-15496
·
IF 4.6
Hong Ding,Yao Nie,Zhen Chen,Wanchao Zuo,Juan Cao,Zihan Ling,Yanmin Ju,Ming Chen
Lateral flow immunoassay (LFIA) based on gold nanoparticles (AuNPs) has emerged as a rapid and cost-effective tool for point-of-care diagnostics, yet it remains limited by its low sensitivity in colorimetric detection. Herein, we report a black palladium nanoparticle (PdNP)-based LFIA system for the detection of lipoprotein-associated phospholipase A2 (Lp-PLA2), a key biomarker of cardiovascular diseases. The intrinsic black color of PdNPs provided higher visual discriminability at low concentrations compared with AuNPs. Moreover, PdNP probes synthesized through chemical covalent conjugation with antibodies had the advantages of enhancing the target recognition ability. The PdNP-based LFIA achieved a 12-fold lower visual detection limit and a 100-fold wider linear range compared with AuNP-based LFIA. Moreover, clinical validation detection results using 57 serum samples were in strong accordance with the clinical methods. This work not only establishes PdNP-based LFIA to address the long-standing sensitivity limitations of colorimetric LFIA, but also offers a robust diagnostic tool for early cardiovascular disease diagnosis in resource-limited settings.
研究领域:
医学诊断
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纳米技术
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF LIPOSOME RESEARCH
·
2025
·
IF 4.3
Zhicheng Su,Yanjiao Liu
This study aimed to design a novel liposome containing GA modified phosphatidylcholine lipid (GA-PC Lip) and determine its susceptibility to tumor over-expressed secretory phospholipase A2 (sPLA2) and its anti-cancer effect compared to conventional liposomes (Convention Lip). The liposomes were characterized for size, drug loading, encapsulation efficiency, and stability. A 6-CF release assay was conducted to assess the sensitivity of the liposomes to the tumor-overexpressed secretory phospholipase A2 (sPLA2). In vitro experiment, the sPLA2 levels in the Colo205 cell culture medium were detected by the Elisa kit and the anti-cancer effect of the oxaliplatin (L-OHP) loaded GA-PA Lip was analyzed by the CCK-8 assay. Results showed that both of L-OHP loaded formulations (GA-PC Lip and Convention Lip) had similar particle sizes of ∼100 nm and close entrapment efficiency values of 4.5–4.8%. The results of CF release assay indicated that the labeled GA-PC Lip had released more quickly than CF labeled Convention Lip in the presence of Bv sPLA2 and GA-PC Lip had a release of about 95% 6-CF at 2 h, whereas Convention Lip only released about 13% 6-CF. In addition, the average concentrations of sPLA2 in the cell-conditioned medium (CCM) of Colo205 cancer cells increased with incubation time and L-OHP loaded GA-PC Lip had much greater anti-proliferative activity than Convention Lip against Colo205 cells. These findings suggest that GA-PC Lip is an ideal complex for sPLA2-triggered release and has potential applications in enzyme-triggered smart anti-cancer drug release system to increase the anti-cancer effect.
研究领域:
药理学
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肿瘤学
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药物递送系统
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2021
·Vol. 26
·期 8
·2255
·
IF 4.412
Nan Wei,Jun Zhao,Guimei Wu,Wenjuan Cao,Pei Luo,Zhifeng Zhang,Gang Chen,Lu Wen
As a consequence of recent progression in biomedicine and nanotechnology, nanoparticle-based systems have evolved as a new method with extensive applications in responsive therapy, multimodal imaging, drug delivery and natural product separation. Meanwhile, the magnetic nanoparticulate system has aroused great interest for separation and purification because of its excellent magnetic properties. Phospholipase A2(PLA2) is a highly expressed regulator to promote the growth of various cancers and is an ideal target to treat cancers. In this study, a novel strategy based on ligand–receptor interactions to discover novel PLA2inhibitors was established, in which PLA2-functionalized Fe3O4@PLGA-PEG-NH2magnetic nanoparticles were used as a supporting material combined with high-performance liquid chromatography–mass spectrometry, aiming to accelerate the discovery of novel PLA2inhibitors from natural sources such as mangrove endophytic fungi. Under the optimized ligand fishing conditions, six target compounds were ultimately fished and identified to be cyclic peptides (1–3) and sterols (4–6), which compounds1,2and4–6have well-documented cytotoxicities. Compound3exerted better inhibitory effect on A549 cells by experiment. In conclusion, PLA2-functionalized Fe3O4@PLGA-PEG-NH2magnetic nanoparticles-based ligand fishing provided a feasible, selective and effective platform for the efficient screening and identification of antitumor components from natural products.Keywords:magnetic nanoparticles;ligand fishing;phospholipase A2;endophytic fungus
研究领域:
生物医学工程
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纳米技术
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药理学
·
真菌学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Yanping Wu,Gen-You Liao,Hua-Jing Ke,Pi Liu
Objective We aimed to investigate the effects of snake-derived phospholipase A2 inhibitor (PLA2) from Sinonatrix percarinata and Bungarus multicinctus on acute pancreatitis in vivo and in vitro and assess the mechanisms.Methods The levels of platelet-activating factor (PAF) and tumor necrosis factor (TNF)-α were detected by ELISA, and the characteristics of autophagy were detected by transmission electron microscopy and Western blotting (LC3, p62, and ATG5).Results In vitro experiments showed that PLA2 treatment caused obvious formation of autophagic bodies. By contrast, Sinonatrix and Bungarus peptides reduced the number of autophagic bodies. The concentrations of PAF and TNF-α, and the expressions of p62, autophagy-related 5 (ATG5), and microtubule-associated protein 1A/1B-light chain 3 (LC3)II/LC3I in the PLA2-treated group were significantly higher than in the control group (P<0.05). The concentrations of PAF and TNF-α, and the expressions of p62, ATG5, and LC3II/LC3I in the Sinonatrix or Bungarus peptide treatment groups were significantly lower than in the PLA2-treated cells (P<0.05). In the pancreatic tissue, autophagic bodies were observed in the model group; autophagic bodies were remarkably reduced in Sinonatrix or Bungarus peptide-treated groups compared with the model group. In vivo experiments also showed that the levels of PAF and TNF-α, and the expressions of p62, ATG5, and LC3II/LC3I were significantly higher in the model group than in the control group (P<0.05). The levels of PAF and TNF-α in the model group, and the expressions of p62, ATG5, and LC3II/LC3I in Sinonatrix or Bungarus peptide-treated groups were significantly lower than in the model group (P<0.05).Conclusion Sinonatrix or Bungarus peptide could ameliorate the features of acute pancreatitis, likely through regulating autophagy.
研究领域:
药理学
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炎症研究
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分子生物学
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DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2020
·
IF 0
Qin Wang,Liming He,Donghao Fan,Wenlang Liang,Xiaochen Wang,Jiyu Fang
Environment-responsive drug delivery is a promising approach for tailoring the drug release in drug therapy. In this study, we develop lipid tubules by the self-assembly of 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC). These lipid tubules are capable of encapsulating hydrophobic dexamethasone (Dex) and hydrophilic dexamethasone sodium phosphate (DSP) simultaneously. In vitro studies show that the lipid tubules can be internalized by cells with no significant toxicity. We find that phospholipase (PLA2) is able to slowly digest the lipid tubules and trigger the sustained release of Dex and DSP. After being subcutaneously administrated to the inflammatory sites of arthritic rats, we show that a single dose of drug-loaded lipid tubules can remarkably inhibit the degree of joint swelling at the inflammatory sites and suppress the content of proinflammatory cytokines in inflamed tissues for a long time by this sustained release of both Dex and DSP triggered by the highly expressed PLA2 at the inflamed sites. Our results highlight the potential of using PLA2-responsive lipid tubules as on-demand carriers for treating inflammatory diseases.
研究领域:
药理学
·
药物递送系统
·
炎症性疾病
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
Toxins
·
2024
·Vol. 16
·期 11
·494
·
IF 3.9
Chenying Yang,Li Ding,Qiyi He,Xiya Chen,Haiting Zhu,Feng Chen,Wanzhou Yang,Yuexin Pan,Zhiyuan Tai,Wenhao Zhang,Zeyuan Yu,Zening Chen,Xiaodong Yu
Kraits are venomous snakes of the genusBungarusfrom the familyElapidae. Their venom typically demonstrates neurotoxicity; however, the toxicity is significantly influenced by the snake’s species and geographical origin. Among theBungarusspecies,Bungarus suzhenaeandB. bungaroideshave been poorly studied, with little to no information available regarding their venom composition. In this study, a proteomic approach was employed using LC-MS/MS to identify proteins from trypsin-digested peptides. The analysis revealed 102 venom-related proteins from 18 distinct functional protein families in the venom ofB. suzhenae, with the primary components being three-finger toxins (3-FTx, 25.84%), phospholipase A2(PLA2, 40.29%), L-amino acid oxidase (LAAO, 10.33%), Kunitz-type serine protease inhibitors (KUN, 9.48%), and snake venom metalloproteinases (SVMPs, 6.13%). In the venom ofB. bungaroides, 99 proteins from 17 families were identified, with primary components being 3-FTx (33.87%), PLA2(37.91%), LAAO (4.21%), and KUN (16.60%). Enzymatic activity assays confirmed the presence of key venom enzymes. Additionally, the LD50 values forB. suzhenaeandB. bungaroideswere 0.0133 μg/g and 0.752 μg/g, respectively, providing a reference for toxicity studies of these two species. This research elucidates the proteomic differences in the venoms of these two species, offering a foundation for developing antivenoms and clinical treatments for envenomation.
研究领域:
毒理学
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蛋白质组学
·
分子生物学
·
爬虫动物毒素研究
·
抗蛇毒血清开发
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临床毒理学
·
酶学
✓ 已验证
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yun Wang,Jiawei Wu,Jiaying Zhu,Chujie Ding,Wanfeng Xu,Haiping Hao,Jun Zhang,Guangji Wang,Lijuan Cao
Ethnopharmacological relevance The traditional Chinese medicine (TCM) preparation, Shengmai Yin (SMY), is widely applied in cardiovascular disease treatments. However, the pharmacological mechanism of its therapeutic effects has not been fully clarified. Aim of this study This study aimed to clearly define the efficacy and underlying mechanism of SMY and its active components in protecting against atherosclerosis. Materials and methods The pharmacological effects of SMY and its components were evaluated upon a mouse hypercholesteremia model induced by a high cholesterol diet (HCD) for 12 weeks and Apoe −/− mice, a mouse atherosclerosis model. Pathological indicators including serum cholesterol levels, cytokines and histological changes in aortic root plaques were assessed. Untargeted metabolomic, untargeted lipidomic and targeted lipidomic changing profiles were investigated to clarify pharmacological mechanisms. Results SMY and red ginseng crude extracts (GE) significantly decreased the serum cholesterol levels in hypercholesteremia mice and reduced the aortic root plaque areas and exerted antiatherogenic efficacy in Apoe −/− mice. Moreover, total red ginseng saponin extracts (TGS) showed the most apparent improvement on maintaining lipid homeostasis, representing the effects of red ginseng in SMY on atherosclerosis treatment. Mechanically, TGS inhibited serum secreted phospholipase A 2 (sPLA 2 ) activity and lowered the serum levels of lysophosphatidylcholine (lysoPC), which is a risk factor for atherosclerosis. Conclusions Our findings revealed that ginsenosides from SMY exerted therapeutic effects on atherosclerosis by maintaining lipid homeostasis including cholesterol and lysoPCs.
研究领域:
药理学
·
心血管疾病
·
传统中药
·
代谢组学
·
脂质组学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2018
·Vol. 410
·期 29
·7645-7653
·
IF 3.307
Zhang Dong-Ping,Wang Ling-E,Liu Xiao-Ying,Luo Zhi-Hua,Zheng Lei,He Yun,Zhang Bo
A facile and feasible photoelectrochemical (PEC) immunoassay based on plasmon-enhanced energy transfer between gold nanoparticles (AuNPs) and CdS quantum dots (QDs)/g-C 3 N 4 nanosheets was developed for the ultrasensitive detection of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ). To construct such a sensing platform, the immunosensor was prepared by immobilizing Lp-PLA 2 on a CdS QDs/g-C 3 N 4 -modified electrode. A competitive-type immunoreaction was utilized for Lp-PLA 2 detection, with AuNP-labeled anti-Lp-PLA 2 antibody used as the competitor. Introducing AuNPs with the specific antibody for the antigen target Lp-PLA 2 led to heavy quenching of the photocurrent of CdS QDs/g-C 3 N 4 due to the plasmon-enhanced energy transfer between AuNPs and CdS QDs. The quenching efficiency decreased with increasing target Lp-PLA 2 concentration. Under optimal conditions, the PEC immunosensor presented a good photocurrent response to the target Lp-PLA 2 in the dynamic linear range of 0.01–300 ng mL −1 , with a low detection limit of 5.3 pg mL −1 . Other biomarkers and natural enzymes did not interfere with response of this system. The reproducibility and accuracy of this method for the analysis of human serum specimens were evaluated, and the results given by the method developed here were found to closely correspond to the results obtained with commercial Lp-PLA 2 ELISA kits. Importantly, this protocol offers promise for the development of exciton–plasmon interaction-based PEC detection systems.
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研究领域:
分析化学
·
生物化学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Jing-Mei Lu,Xiang Xu,Fumie Aosai,Ming-Yue Zhang,Lu-Lu Zhou,Lian-Xun Piao
Toxoplasma gondii ( T. gondii )-derived heat shock protein 70 ( T.g. HSP70) is a toxic protein that downregulates host defense responses against T. gondii infection. T.g. HSP70 was proven to induce fatal anaphylaxis in T. gondii infected mice through cytosolic phospholipase A 2 (cPLA 2 ) activated-platelet-activating factor (PAF) production via Toll-like receptor 4 (TLR4)-mediated signaling. In this study, we investigated the effect of arctiin (ARC; a major lignan compound of Fructus arctii ) on allergic liver injury using T.g. HSP70-stimulated murine liver cell line (NCTC 1469) and a mouse model of T. gondii infection. Localized surface plasmon resonance, ELISA, western blotting, co-immunoprecipitation, and immunofluorescence were used to investigate the underlying mechanisms of action of ARC on T. gondii -induced allergic acute liver injury. The results showed that ARC suppressed the T.g. HSP70-induced allergic liver injury in a dose-dependent manner. ARC could directly bind to T.g. HSP70 or TLR4, interfering with the interaction between these two factors, and inhibiting activation of the TLR4/mitogen-activated protein kinase/nuclear factor-kappa B signaling, thereby inhibiting the overproduction of cPLA 2 , PAF, and interferon-γ. This result suggested that ARC ameliorates T.g. HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of inflammatory mediators, providing a theoretical basis for ARC therapy to improve T.g. HSP70-induced allergic liver injury.
研究领域:
免疫学
·
药理学
·
寄生虫学
·
肝病学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）