JOURNAL OF MOLECULAR RECOGNITION
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2018
·Vol. 31
·期 7
·e2705
·
IF 1.868
Hua-xin Zhang,Dan Zhou,Qing-hua Xia
In this work, the interaction of an anti-HIV drug lamivudine and human serum albumin (HSA) was studied by multispectroscopic and molecular modeling methods. The fluorescence emission spectra showed that the fluorescence of HSA was quenched by lamivudine through static mechanism with HSA-lamivudine complex produced at ground state. According to the binding equilibriums observed at 4 different temperatures, the number of binding site, binding constant, enthalpy change, entropy change, and Gibbs free energy change of the interaction were calculated. The results indicated that there was only 1 main binding site under present concentration condition, and then, the location of this binding site was ascertained by molecular probe experiments using warfarin and ibuprofen as site markers. The interaction was a spontaneous and exothermic process. Hydrogen bonds and van der Waals force were the major power that fixed lamivudine on Sudlow's site I in subdomain IIA of HSA molecule. The distance between donor and acceptor was determined by Förster's nonradiative fluorescence resonance energy transfer theory. Circular dichroism spectra exhibited the alteration of HSA's secondary structures. Molecular modeling investigation revealed the structure of HSA-lamivudine complex, including the conformation of lamivudine in binding site, the amino residues close to lamivudine, and the interaction forces between receptor and ligand. The study may be beneficial to therapists in understanding the distribution of lamivudine in vivo and explaining its drug-resistant mechanism in clinical diagnosis.
研究领域:
药理学
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分子生物学
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生物物理化学
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药物代谢
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结构生物学
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DOI
高影响因子
JOURNAL DE MYCOLOGIE MEDICALE
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2018
·
IF 1.606
K. Xu,J.L. Wang,M.P. Chu,C. Jia
Objective The aim of this study was to investigate the antibiofilm activity of coumarin against Candida albicans . Methods The efficacy of coumarin against biofilm formation and the mature biofilm of C. albicans was quantified by crystal violet (CV) staining and the 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) reduction assay. The effect of coumarin on C. albicans adhesion was assessed on polystyrene plates and by using the cell surface hydrophobicity (CSH) assay. The morphological transition of C. albicans was conducted in two types of hyphae-inducing media at 37 °C. The expression of hypha/biofilm-related genes was evaluated using qRT-PCR analysis. A rescue experiment involving addition of exogenous cyclic adenosine monophosphate (cAMP) was performed to investigate the involvement of cAMP in the yeast-to-hyphae transition. A C. albicans -infected Caenorhabditis elegans model was used to test the anti-virulence efficacy of coumarin. Results Treatment with coumarin strongly affected the capacity of C. albicans to form biofilm and significantly impaired the preformed mature biofilm. The addition of coumarin notably inhibited C. albicans adhesion, CSH, and filamentation . The expression of some adhesion- and hypha-related genes, including HWP1 , HYR1 , ECE1 , and ALS3 , was remarkably down-regulated upon exposure to coumarin. Supplementation with cAMP partly rescued the coumarin-induced defects in hyphal development. Finally, coumarin prolonged survival in C. albicans -infected nematodes. Conclusion Coumarin inhibited C. albicans biofilm, which was associated with attenuated adhesion and hyphal growth.
研究领域:
微生物学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
·
2019
·
IF 4.027
Yu-Heng Hu,Jie Yang,Yun Zhang,Ke-Chun Liu,Teng Liu,Jie Sun,Xiao-Jing Wang
The work is focused on the design of drugs that prevent and treat Alzheimer’s disease (AD) and its complications. A series of 3–(4-aminophenyl)-coumarin derivatives designed, synthesised, fully characterised and evaluated in vitro/vivo. The biological assay experiments showed that some compounds displayed a clearly selective inhibition for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among all compounds, compound 4m exhibited the highest AChE inhibition with an IC50 value of 0.091 ± 0.011 µM and compound 4k exhibited the highest BuChE inhibition with an IC50 value of 0.559 ± 0.017 µM. A zebrafish behaviour analyser (Zebrobox) was used to determine the behavioural effects of the active compound on the movement distance of the aluminium chloride-induced zebrafish. Compound 4m offered a potential drug design concept for the development of therapeutic or preventive agents for AD and its complications.
研究领域:
药理学
·
神经科学
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药物设计
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DOI
PubMed
高影响因子
ANTI-CANCER DRUGS
·
2019
·Vol. 30
·期 1
·46-55
·
IF 1.801
Lin Fuxing,Yang Jie,Muhammad Umair,Sun Jing,Huang Zhenghua,Li Wei,Lv Fengxia,Lu Zhaoxin
Bacillomycin D can inhibit the growth of Aspergillus ochraceus in food samples. In addition, it can induce apoptosis in and inhibit the proliferation of cancer cells, although the details of this mechanism are unknown. In this study, we separated bacillomycin D-C14, D-C15, D-C16
monomers from the Bacillus subtilis strain fmbJ. The bacillomycin D monomers containing longer fatty acid chains better induced apoptosis in Bgc-823, Sgc-7901, and Hgc-27 gastric cancer cells. The Bgc-823 cell line was the most sensitive. Acridine orange-ethidium bromide staining indicated
that bacillomycin D-C16-induced Bgc-823 cell death by triggering apoptosis, characterized by membrane blebbing, cellular shrinkage, and DNA fragmentation. Flow cytometric analysis showed a bacillomycin D-C16 dose-dependent trigger of Bgc-823 apoptosis. Bacillomycin D-C16-induced the mitochondrial
pathway, as indicated by a reduced Bcl-2/Bax expression ratio, enhanced cytochrome C release, and higher levels of cleaved caspase-3. Furthermore, bacillomycin D-C16 effectively repressed phosphorylation of the serine–threonine protein kinase Akt at Ser-473 and increased the levels of
the FoxO3a protein. The combination of the PI3K/Akt-inhibitor BEZ235 with bacillomycin D-C16 enhanced the apoptosis of Bgc-823 cells. Together, these findings indicated that bacillomycin D-C16 induces apoptosis through the PI3K/Akt and FoxO3a signaling pathways.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
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药理学
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DOI
PubMed
高影响因子
INTEGRATIVE CANCER THERAPIES
·
2019
·
IF 2.634
Decai Tang,Shuo Zhang,Xiaoxia Shi,Jiafei Wu,Gang Yin,Xiying Tan,Fuyan Liu,Xingdong Wu,Xiangyu Du
Normalizing the disordered tumor vasculature, rather than blocking it, is a novel method for anticancer therapy. Astragali polysaccharide (APS) and curcumin were reported to be active against carcinomas. However, the effect and mechanism of the combination of APS and curcumin on vascular normalization in hepatocellular carcinoma (HCC) was not clear. In the present study, effects of combined APS and curcumin on tumor vascular normalization were evaluated in HepG2 tumor-bearing mice. Photoacoustic tomography (PAT) was performed to observe the morphological structure of tumor vessels in vivo. The microstructure of the tumor vessels was also analyzed through scanning electron microscopy. Additionally, the expression of CD31 and NG2 was analyzed by immunohistochemical staining. Tumor vessels of HepG2 tumor-bearing mice treated with the combination were sparse with uniform growth, morphology rules, and complete vascular walls, which had fewer branches and sprouts. ECs of tumor vessels were arranged regularly and were tightly connected, tending toward normalization. The expression of CD31 was reduced while NG2 was increased significantly by the combination of APS and curcumin. The results indicated that APS and curcumin in combination showed a better effect on inhibiting tumor growth in an orthotopic nude-mouse model of HCC. More important, the combination induced normalization of tumor vascular better than APS or curcumin administration alone, improving the morphological structure of tumor vessels and promoting maturation of tumor vessels. The results of the present study provided a reasonable possibility for combination therapy of APS and curcumin in the treatment of HCC via tumor vascular normalization.
研究领域:
肿瘤学
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药理学
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分子生物学
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成像技术
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产品关联
DOI
PubMed
高影响因子
Journal of Cancer
·
2019
·
IF 3.182
Mingtong Ye,Nengzhi Pang,Ting Wan,Yuanling Huang,Tianyi Wei,Xuye Jiang,Yujia Zhou,Yufeng Huang,Hainan Yang,Zhenfeng Zhang,Lili Yang
Switching aerobic respiration to anaerobic glycolysis of cancer cells plays an important role in development and progression of acquired resistance. Since vitamin C enabled the inhibition of glycolysis of cancer cells, and erlotinib-resistant sub-line of HCC827 (ER6 cells) switched its metabolic features to higher glycolysis for survival, we hypothesize that vitamin C is able to inhibit glycolysis of ER6 cells. In this study, we found that both reduced vitamin C and oxidized vitamin C (DHA) could selectively suppress the viability of ER6 cells. DHA was efficient in inhibiting glycolysis and leading to energy crisis, which could be one mechanism for overcoming drug resistance to erlotinib of ER6 cells. Our data suggest that applying DHA could be a novel treatment strategy for NSCLC with acquired resistance to targeted therapy.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Biological Sciences
·
2019
·
IF 4.067
Haotian Li,Xinran Zhang,Xi Qi,Xu Zhu,Liming Cheng
Endoplasmic reticulum (ER) stress-induced neuronal apoptosis is a crucial pathological process of spinal cord injury (SCI). In our previous study, icariin (ICA) showed neuroprotective effects in SCI. However, the relationships between ER stress and ICA in SCI are unclear yet. Therefore, whether ICA could ameliorate SCI via attenuating ER stress was investigated in vitro and in vivo . Adult mice were established SCI model and received vehicle solution or ICA by gavage once per day in vivo . The primary cultured cells were treated with or without thapsigargin (TG), ICA or LY294002 to induce ER stress in vitro . Motor dysfunction, neuronal apoptosis, tissue damage and inhibition of PI3K/AKT pathway were induced by ER stress after SCI. But ICA administration significantly enhanced motor recovery and protected spinal cord tissues against infraction and hemorrhage, etc. post injury. Meanwhile, the expression of ER stress markers ATF6, IRE1α, GRP78, XBP1 and eIF2α was decreased, while the level of p-AKT/AKT was increased by ICA. Furthermore, ICA significantly inhibited the expression of ER stress apoptotic proteins caspase-12, CHOP, Bax/Bcl-2, caspase-9 and caspase-3. Moreover, immunofluorescence double staining indicated that ICA reduced GRP78, CHOP and TUNEL positive neurons following SCI. However, this beneficial effect of ICA was abolished by PI3K/AKT inhibitor LY294002 in vitro . Finally, ICA preserved the ultra-structure of ER by transmission electron microscope histologically. This study suggested that the neuroprotective effect of ICA on motor recovery and neuronal survival was related to attenuating ER stress via PI3K/AKT signaling pathway after SCI.
研究领域:
神经科学
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药理学
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分子生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy
·
2019
·Vol. 29
·期 1
·46-53
·
IF 1.754
Peng Wei,Han Ping,Yu Luyao,Chen Ying,Ye Bingzhu,Qin Luping,Xin Hailiang,Han Ting
The fruits of Xanthium strumarium L., Asteraceae, have been used for various diseases in Chinese folk medicine, including allergic rhinitis, tympanitis, arthritis, ozena etc. The current study was aimed to investigate the therapeutic effects of caffeoylquinic acids from fruits of X. strumarium on allergic rhinitis in animals. The toxicity test indicated that the caffeoylquinic acids have no obvious toxicity. By using HPLC assays combined with reference standards, ten caffeoylquinic acids were identified as the predominant constituents. Anti-allergic activities of the caffeoylquinic acids were evaluated using passive cutaneous anaphylaxis test and Schultz-Dale test; dimethylbenzene induced ear edema test was performed to evaluate its anti-inflammatory effect. Then, the allergic rhinitis model in rats was established to evaluate the therapeutic effects of the caffeoylquinic acids against allergic rhinitis with the following indexes: allergic rhinitis symptom scores, serum levels of pro-inflammatory cytokines, histopathological examination, and histamine release. Our study revealed that the caffeoylquinic acids showed obvious anti-allergic and anti-inflammatory properties, and its treatments were beneficial for ameliorating the nasal symptoms, decreasing pro-inflammatory cytokines, and inhibiting the releases of histamine. Collectively, the caffeoylquinic acids might be utilized as effective and safe disease therapeutic agents for allergic rhinitis.
研究领域:
药理学
·
免疫学
·
过敏
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植物化学
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产品关联
DOI
高影响因子
CHEMISTRY & BIODIVERSITY
·
2019
·Vol. 16
·期 3
·e1800581
·
IF 1.449
Jia Sun,Jin-Hai Yu,Jun-Sheng Zhang,Xiu-Qing Song,Jie Bao,Hua Zhang
Fourteen chromane derivatives of seven pairs of enantiomers ( 1 – 14 ) have been obtained from the ethanolic extract of the flower buds of Tussilago farfara L. Their structures with absolute configurations have been elucidated by detailed spectroscopic analyses, chemical methods, and particularly comparison of experimental ECD spectra with theoretically computed ones. Biological evaluations revealed that they did not show cytoprotective, antimicrobial, and α - glucosidase inhibitory activities. Graphical
研究领域:
植物化学
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药理学
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药物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
·
2019
·Vol. 294
·期 8
·2628-5268
·
IF 4.106
Ailin Yang,Haitao Fan,Yanan Zhao,Xiaonan Chen,Zhixiang Zhu,Xiaojun Zha,Yunfang Zhao,Xingyun Chai,Jun Li,Pengfei Tu,Zhongdong Hu
Trametes robiniophila Murr. (Huaier) is a mushroom with a long history of use as a medicinal ingredient in China and exhibits good clinical efficacy in cancer management. However, the antitumor components of Huaier and the underlying molecular mechanisms remain poorly understood. Here, we isolated a proteoglycan with a molecular mass of ∼5.59 × 104 Da from Huaier aqueous extract. We named this proteoglycan TPG-1, and using FTIR and additional biochemical analyses, we determined that its total carbohydrate and protein compositions are 43.9 and 41.2%, respectively. Using biochemical assays and immunoblotting, we found that exposing murine RAW264.7 macrophages to TPG-1 promotes the production of nitric oxide (NO), tumor necrosis factor α (TNFα), and interleukin-6 (IL-6) through Toll-like receptor 4 (TLR4)-dependent activation of NF-κB and mitogen-activated protein kinase (MAPK) signaling. Of note, the TPG-1 treatment significantly inhibited the tumorigenesis of human hepatoma HepG2 cells likely at least in part by increasing serum levels of TNFα and promoting leukocyte infiltration into tumors in nude mice. TPG-1 also exhibited good antitumor activity in hepatoma H22-bearing mice and had no obvious adverse effects in these mice. We conclude that TPG-1 exerts antitumor activity partially through an immune-potentiating effect due to activation of the TLR4–NF-κB/MAPK signaling cassette. Therefore, TPG-1 may be a promising candidate drug for cancer immunotherapy. This study has identified the TPG-1 proteoglycan as an antitumor agent and provided insights into TPG-1’s molecular mechanism, suggesting a potential utility for applying this agent in cancer therapy.
研究领域:
免疫学
·
肿瘤学
·
药理学
·
真菌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY AND PHYSICS OF LIPIDS
·
2019
·
IF 2.536
Yuan Gao,Shimin Wu,Renhuai Cong,Junyong Xiao,Fangli Ma
Schisandra chinensis is a medicinal and edible plant that contains various bioactive compounds. Among these, lignans are the major functional compounds. Nevertheless, detailed information about lignans in Schisandra chinensis oil remains scarce. A powerful UPLC-Q/TOF-MS method was established for the rapid identification of the lignan constituents of Schisandra chinensis oils. The results showed that 21 lignans have been unambiguously identified, and four lignans have been tentatively identified in the Schisandra chinensis oils. In addition, semi-quantitative analysis indicated that the total lignan content in the Schisandra chinensis oils was distributed from 67.73 ± 0.06 to 87.61 ± 1.83 mg/g. Schisandrin and schisandrin B were the most abundant lignans in the Schisandra chinensis oils, their content ranging from 15.85 ± 0.09 to 20.57 ± 0.38 mg/g. Additionally, this study provided a systematic characterization of lignans in Schisandra chinensis oil and indicated that the oil might be used as lignan-related functional foods.
研究领域:
植物化学
·
分析化学
·
药理学
✓ 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）