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
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
·
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
·
纳米技术
·
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
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
✓ 已验证
DOI
PubMed
高影响因子
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
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分子生物学
·
爬虫动物毒素研究
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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
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
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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
FOOD CHEMISTRY
·
2024
·
IF 8.5
Fukai Li,Enning Zhou,Min Wang,Fei Pan,Jian Zhou,Mengrui Yang,Tongtong Wang,Liang Li,Liming Wu,Qiangqiang Li
Reducing the allergenicity of edible insects is crucial for the comprehensive utilization of insect resources. Phospholipase A2 (PLA2) exists in various edible insects and mammalian tissues, which can cause serious allergic reactions. Herein, we constructed a magnetic nanocomposite with photo/chemical synergistic capability to mitigate the allergenicity of PLA2. The formation of prepared nanocomposite was systematically confirmed using various techniques. The nanocomposite exhibited uniform diameters, abundant functional groups, excellent magnetic capabilities. An effective photo/chemical method was established to reduce the allergenicity of PLA2 in vitro. The feasibility of the method was demonstrated through circular dichroism, fluorescence spectrum and IgE-binding analysis. The allergenicity and IgE-binding effect of PLA2 were significantly reduced due to conformational changes after nanomaterial treatment. These results demonstrate the sensitivity and effectiveness a strategy for reducing PLA2 allergenicity, providing a basis for development of nanomaterials to reduce the risk of novel food allergies in response to edible insect products.
研究领域:
纳米技术
·
过敏学
·
食品科学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Metabolism
·
2024
·
IF 27.7
Kan Huang,Zilun Li,Xi He,Jun Dai,Bingding Huang,Yongxia Shi,Dongxiao Fan,Zefeng Zhang,Yunchong Liu,Na Li,Zhongyu Zhang,Jiangyun Peng,Chenshu Liu,Renli Zeng,Zhipeng Cen,Tengyao Wang,Wenchao Yang,Meifeng Cen,Jingyu Li,Shuai Yuan,Lu Zhang,Dandan Hu,Shuxiang Huang,Pin Chen,Peilong Lai,Liyan Lin,Jielu Wen,Zhengde Zhao,Xiuyi Huang,Lining Yuan,Lifang Zhou,Haoliang Wu,Lihua Huang,Kai Feng,Jian Wang,Baolin Liao,Weiping Cai,Xilong Deng,Yueping Li,Jianping Li,Zhongwei Hu,Li Yang,Jiaojiao Li,Youguang Zhuo,Fuchun Zhang,Lin Lin,Yifeng Luo,Wei Zhang,Qianlin Ni,Xiqiang Hong,Guangqi Chang,Yang Zhang,Dongxian Guan,Weikang Cai,Yutong Lu,Fang Li,Li Yan,Meng Ren,Linghua Li,Sifan Chen
Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2β1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2β1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.
研究领域:
心血管研究
·
微生物组学研究
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血栓机制
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2024
·
IF 4.7
Qi Wu,Kexin Liu,Ruijuan Hou,Xingxing Wu,Xiaoyu Ruan,Mao Wang,Zhiting Sun,Lingchang Meng,Guoliang Dai,Changyin Li,Jing Wu,Genglin Mu
Purpose Inflammatory bowel disease (IBD) is a serious disease that affects the metabolism and inflammatory responses of human beings. From the perspective of traditional Chinese medicine, damp-heat syndrome is one of the main syndromes of IBD. Rhizoma Paridis, also known as the root of Paris polyphylla, a well-known herbal medicine used in China, is used to treat IBD with damp-heat syndrome (IBD-DH). However, uncertainty still exists regarding the underlying mechanisms and the impact of Rhizoma Paridis on IBD-DH.Methods The rats in the model (DAT) and medication administration (Rhizoma Paridis total saponins (RPTS) and Pennogenin (PN)) groups were given a high temperature and high humidity environment, high fat and high sugar diet combined with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish the model of experimental colitis of damp-heat type, and the normal control group (RNC) rats were given a normal diet at normal temperature and humidity. Damp-heat control group (DNC) was set with the same condition as DAT without TNBS. Hematoxylin-Eosin (HE) staining was used to observe the histopathological morphology of the rat colorectum. The expression of the metabolism-related genes (Phospholipase A2 (sPLA2, cPLA2), and phosphatidylethanolamine N-methyltransferase (PEMT)) was assessed by using real-time quantitative PCR analysis (RT–qPCR). And the levels of the metabolism-related proteins (sPLA2, cPLA2), S100A8/9, Arg-1, and cytokines were detected by enzyme-linked immunosorbent assay (ELISA) kit. To investigate lipids and amino acids which closely associated with the IBD and IBD-DH, lipid pseudotargeted metabolomics with UHPLC-TQ/MS analysis method, as well as targeted quantitative amino acid analysis were performed.Results Our data showed that RPTS (50 mg/kg) and PN (20 mg/kg) significantly ameliorated the severity of TNBS-induced colitis and downregulated the levels of circulating proinflammatory cytokines. Compared with RNC group, lipid pseudotargeted metabolomics demonstrated that glycerophospholipids, sphingolipids, carnitine, and glycerolipids were the four most perturbed lipid classes, and amino acids targeted metabolomics demonstrated that serine, N-acetylneuraminic acid, histidine, proline, taurine, and kynurenine changed significantly in DAT group . Correlation analyses showed tight associations between most of differential metabolites and proinflammatory cytokines. RPTS and PN both regulated glycerophospholipid metabolism and sphingolipid metabolism. However, both of them did not have a significant effect on amino acid modulation. RPTS and PN potentially regulated sPLA2, cPLA2, and PEMT.Conclusion These results showed that RPTS (50 mg/kg) and PN (20 mg/kg) effectively alleviated rats’ colitis of damp-heat type, affected cytokines, and altered lipid metabolism without significant modulation on amino acid metabolism.
研究领域:
中医
·
药理学
·
代谢组学
·
炎症
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
·
2015
·
IF 3.628
Y.N. Lin,R. Jia,Y.H. Liu,Y. Gao,L.L. Wang,J.P. Kou,B.Y. Yu
Ruscogenin, a natural steroidal sapogenin, presents in both food and medicinal plants. It has been found to exert significant anti-inflammatory activities. Considering that activation of neutrophil is a key feature of inflammatory diseases, this study was performed to investigate the inhibitory effect of ruscogenin and its underlying mechanisms responsible for neutrophil activation. Ruscogenin displayed potent antioxidative effects against Formyl-Met-Leu-Phe (FMLP)-induced extra- and intracellular superoxide generation in mouse bone marrow neutrophils, with IC 50 values of 1.07 ± 0.32 μM and 1.77 ± 0.46 μM, respectively. Phorbol myristate acetate (PMA)-elicited extra- and intracellular superoxide generation were also suppressed by ruscogenin, with IC 50 values of 1.56 ± 0.46 μM and 1.29 ± 0.49 μM, respectively. However, ruscogenin showed weak inhibition in NaF-induced response. Inhibition of superoxide generation was mediated neither by a superoxide-scavenging ability nor by a cytotoxic effect. Furthermore, ruscogenin inhibited the membrane translocation of p47phox and p67phox. It reduced FMLP-induced phosphorylation of cytosolic phospholipase A 2 (cPLA 2 ) and p21-activated kinase (PAK). The cellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) expression were increased by ruscogenin. Moreover, ruscogenin inhibited phosphorylation of protein kinase B (Akt), p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK). In addition, the inhibitory effects of ruscogenin on superoxide production and the phosphorylation of Akt, p38MAPK, and ERK1/2 were reversed by PKA inhibitor (H89), suggesting a PKA-dependent mechanism. In summary, our data suggest that ruscogenin inhibits activation of neutrophil through cPLA 2 , PAK, Akt, MAPKs, cAMP, and PKA signaling pathways. Increased PKA activity is associated with suppression of the phosphorylation of Akt, p38MAPK, and ERK1/2 pathways.
研究领域:
药理学
·
免疫学
·
细胞生物学
✓ 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）