Chinese Medicine
·
2020
·Vol. 15
·期 1
·1-13
·
IF 2.96
Yang Yi-Yao,Wu Zhao-Yu,Zhang Hao,Yin Shi-Jun,Xia Fang-Bo,Zhang Qian,Wan Jian-Bo,Gao Jian-Li,Yang Feng-Qing
Background The dry root and rhizome of Salvia miltiorrhiza Bunge, or Danshen, is a well-known traditional Chinese medicine with anticoagulant activity. Taking into account that thrombin (THR) and factor Xa (FXa) play crucial roles in the coagulation cascade, it is reasonable and meaningful to screening THR and/or FXa inhibitors from Danshen. Methods Four extracts [butanol (BA), ethyl acetate (EA) and remained extract (RE) from 75% ethanol extract, and water extract (WE)] of Danshen were prepared, and their THR/FXa inhibitory activities were assessed in vitro. Then, the active EA extract was further separated by silica-gel column chromatography (SC), and its fractions (SC1–SC5) were analyzed by LC–MS. The principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA) were employed for predicting the specific marker compounds. The chemical structures of targeted compounds were identified by LC–MS/MS and their interactions with THR/FXa were analyzed by the molecular docking analysis. Results Danshen EA extract showed strong activity against THR and FXa, and its fractions (SC1–SC5) exhibited obvious difference in inhibitory activity against these two enzymes. Furthermore, four marker compounds with potential THR/FXa inhibitory activity were screened by PCA and OPLS-DA, and were identified as cryptotanshinone, tanshinone I, dihydrotanshinone I and tanshinone IIA. The molecular docking study showed that all these four tanshinones can interact with some key amino acid residues of the THR/FXa active cavities, such as HIS57 and SER195, which were considered to be promising candidates targeting THR and/or FXa with low binding energy (< − 7 kcal mol −1 ). Conclusions LC–MS combined with multivariate statistical analysis can effectively screen potential THR/FXa inhibitory components in Danshen.
研究领域:
中药学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2014
·Vol. 33
·期 2
·375-388
·
IF 3.55
Huang Run-Yue,Chu Yong-Liang,Jiang Ze-Bo,Chen Xiu-Ming,Zhang Xian,Zeng Xing
Background/Aims: The effects of glycyrrhizin treatment in lung cancer remain undetermined, despite extensive studies of the anti-tumor activities of glycyrrhizin. Methods: Lung adenocarcinoma A549 and NCI-H23 cell lines were used in this study. Cell growth was examined by MTS assays, while apoptosis and cell cycle were determined by flow cytometric analysis. Both real-time PCR and western blotting were used to examine the expression levels of thromboxane synthase (TxAS), and TxAS activity was measured using EIA detection of the biosynthesis of TxA2. TxAS was overexpressed in NCI-H23 cells by transfection with TxAS cDNA, while TxAS was inhibited by transfection with TxAS siRNA in A549 cells. For the mouse model of lung adenocarcinoma, the effects of glycyrrhizin on tumor growth were analyzed by western blot evaluation of TxAS, PTEN and survivin. TxAS activity was determined by EIA assay. Results: Glycyrrhizin suppressed cell growth in A549 cells, but not in NCI-H23 cells, by induction of apoptosis. TxAS was overexpressed in A549 cells, but the TxAS levels in NCI-H23 cells were minimal. Moreover, TxAS expression and activity were suppressed by glycyrrhizin. Glycyrrhizin had no additive effects with TxAS siRNA knockdown in suppressing A549 cell growth, whereas it completely suppressed cell growth of NCI-H23 cells transfected with TxAS cDNA. These results were further confirmed by the in vivo study. Conclusion: Our study suggests that the anti-tumor effect of glycyrrhizin in lung adenocarcinoma is, at least in part, TxAS-dependent. Therefore, glycyrrhizin is a promising anti-cancer agent for the treatment of lung adenocarcinoma
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2014
·
IF 6.451
Wenju Xu,Huayu Yi,Yali Yuan,Pei Jing,Yaqin Chai,Ruo Yuan,George S. Wilson
In this work, a sensitive electrochemical aptasensor for thrombin (TB) based on synergetic catalysis of enzyme and porous [email protected] core–shell nanostructure has been constructed. With the advantages of large surface area and outstanding catalytic performance, porous [email protected] core–shell nanostructures were firstly employed as the nanocarrier for the immobilization of electroactive toluidine blue (Tb), hemin/G-quadruplex formed by intercalating hemin into the TB aptamer (TBA) and glucose oxidase (GOx). As a certain amount of glucose was added into the detection cell, GOx rapidly catalyzed the oxidation of glucose, coupling with the local generation of H 2 O 2 in the presence of dissolved O 2 . Then, porous [email protected] nanoparticles and hemin/G-quadruplex as the peroxidase mimics efficiently catalyzed the reduction of H 2 O 2 , amplifying the electrochemical signal and improving the sensitivity. Finally, a detection limit of 0.037 pM for TB was achieved. The excellent performance of the aptasensor indicated its promising prospect as a valuable tool in simple and cost-effective TB detection in clinical application.
研究领域:
生物化学
·
医学检测
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2019
·
IF 4.916
Pengfei Yang,Xinyi Wang,Zhenggui Gu,Huihui Li,David D.Y. Chen,Xiaodi Yang
A 15-mer thrombin-binding aptamer (TBA) was discovered with specificity for thrombin. It forms a unique G-quadruplex (G4), which is postulated to be the molecular basis for its binding specificity. Many analytical methods make use of affinity binding between the thrombin and TBA as they form a very stable complex. We develop a strategy to stabilize TBA/G4's structure by introducing G4-interactive molecules, which may enhance its ability to recognize the target. Herein, a fast screening ESI-MS assay was employed to determine potential binding of natural products molecules with the TBA/G4 complex. The experimental results showed that four investigated natural alkaloids had apparent binding affinities. One of them, jatrorrhizine (L1), has been shown to bind strongly to the TBA/G4 mainly in 1:2 M ratio. Once the working conditions were established, the interaction of the jatrorrhizine with the TBA/G4 was explored using a combination of ESI-MS and spectroscopic techniques. Ligand-induced effects on TBA/G4 structure and its stability were examined by means of circular dichroism (CD). Jatrorrhizine inducing the G4 formation seems also to be the more effective in terms of thermal stabilization under the experimental conditions used. Both results of UV and fluorescence experiments undoubtedly showed a good binding affinity with the binding constant around 10 5 L mol −1 . The stacking interactions of jatrorrhizine with the G-tetrads in TBA/G4 were further confirmed by competition experiment. ESI-MS was carried out to determine the coexistence of 1:1 and 1:2 complexes in TBA/G4-L1 system, and showed a dynamical shift from 1:1 to 1:2 complex in minutes.
研究领域:
生物化学
·
分子生物学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2015
·
IF 5.636
Jing Li,Jingjing Wang,Xiang Guo,Qiong Zheng,Jing Peng,Hao Tang,Shouzhuo Yao
Carbon nanotubes (CNTs) labeled with aptamer and horseradish peroxidase (HRP) were used as a probe to amplify the impedimetric sensing of the aptamer–protein (with thrombin as the model) interaction. The HRP-biocatalyzed oxidation of 3,3-diaminobenzidine (DAB) in the presence of H2O2 and the postelectropolymerization of insoluble precipitates produced on the electrode supports were used as a signal amplification route for the sensing process. Thrombin was sensed by aptamer 1 immobilized on a glassy carbon electrode. The multiwalled CNT–aptamer 2–HRP probe was linked to the aptamer 1–thrombin complex through the thrombin–aptamer 2 interaction. The postelectropolymerization of biocatalyzed precipitates of DAB on the electrode greatly increased the electron-transfer resistance at the electrode–solution interface. Cyclic voltammetry and electrochemical impedance spectroscopy were employed to follow the stepwise fabrication of the aptasensor and impedimetric detection of thrombin. Thrombin concentration as low as 0.05 pM could be detected by this method. In addition, the proposed impedimetric aptasensor exhibits good sensitivity (5195 Ω decade–1), selectivity, and reproducibility. The aptasensor also has acceptable recovery for thrombin detection in complex protein sample.
研究领域:
生物化学
·
纳米技术
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Yufeng Dai,Jinxiang Chen,Jialong Fang,Shuxiao Liang,Hao Zhang,Haitao Li,Wei Chen
Thromboxane A 2 (TXA 2 ) is traditionally known for its role in inducing platelet aggregation, but our previous study has discovered its crucial involvement in hepatic glucolipid metabolism and adipose tissue inflammation. Ginkgolide B (GB), a naturally occurring terpene lactone, possesses various pharmacological functions through its antagonism of the platelet activating factor (PAF) receptor. However, the metabolic regulation mechanism link between the anti-obesity efficiency of GB and TXA 2 has remained elusive. Therefore, this research aimed to explore the potential of GB in protecting against obesity by inhibiting TXA 2 synthesis. The results showed that GB inhibited TXA 2 biosynthesis which shares a similar action with eicosapentaenoic acid (EPA) and aspirin. GB treatment ameliorated hyperglycemia by decreasing gluconeogenesis. Additionally, GB supplementation relieved hepatic lipid deposition and dyslipidemia. Furthermore, GB intervention promoted macrophage M2 polarization, thus mitigating adipose tissue inflammation. In summary, our study provided evidence that GB alleviated glucolipid metabolism disorders and adipose tissue inflammation through the inhibition of the TXA 2 pathway. These findings shed light on the mechanism underlying the anti-obesity efficacy of GB and lay foundations for the future use of GB as a functional dietary supplement to alleviate high-fat diet-induced obesity.
研究领域:
药理学
·
代谢
·
炎症
·
营养
✓ 已验证
产品关联
DOI
高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2017
·Vol. 41
·期 4
·1383-1392
·
IF 5.104
Deng Qing-Ping,Wang Mao-Jie,Zeng Xing,Chen George Gong,Huang Run-Yue
Background: Currently, there is a global attempt to identify potential anti-cancer agents with low toxicity. Previous studies have found that glycyrrhizin exerts anti-cancer action with low toxicity through suppressing thromboxane A2 (TxA2) in lung cancer cell lines. However, these effects have not yet been determined in animal models of lung cancer. Methods: Human lung adenocarcinoma xenografts were established in nude mice by the introduction of A549 cells with stable transfection of the TxA2 receptor (TPα). The animal model was confirmed by the hematoxylin and eosin (H&E) method. Tumor-bearing mice were then administered graded concentrations of glycyrrhizin, cisplatin or both. After the treatments, body weights of all animals were recorded, and immunohistochemistry staining of lung tissues and serum biochemistry detection of aspartate amino transferase (AST), alanine amino transferase (ALT), urea and creatinine were carried out. Results: Treatment with glycyrrhizin alone or the combination of cisplatin and glycyrrhizin profoundly reduced expression of thromboxane synthase (TxAS) as well as proliferating cell nuclear antigen (PCNA), recovered the body weight, and rescued damage of liver and kidney in tumor-bearing mice. Although it inhibited PCNA expression, cisplatin could not significantly suppress TxAS expression. Because of a positive feedback loop between TPα and TxAS, the effects of glycyrrhizin are possibly attributable to the suppression of the TxA2 pathway. Conclusions: This study provides in vivo evidence to support glycyrrhizin as a potential candidate for developing new regimens to overcome tumor progression and the resistance and toxicity of cisplatin
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2024
·
IF 5.6
Ruijie Xu,Zhijie Yao,Hao Zhang,Haitao Li,Wei Chen
Loss of susceptibility to anoikis signals is a crucial step in metastasis. Anoikis resistance therefore represents a promising adjuvant therapeutic target for cancer management. In this study, we have conducted a rationalized screening to search for novel leading anoikis sensitizer from daily foods. Among 19 tested dietary phytochemicals, the best results were obtained with apigenin, a natural component of celery. Phenotypically, apigenin sensitized breast cancer cells to anoikis, lowered the number of circulating tumor cells, and protected against breast cancer metastasis to lung in mice. Mechanistically, we demonstrated that the thromboxane A 2 (TXA 2 )-TXA 2 receptor (TP) axis has a critical role in acquired anoikis resistance by activating PI3K-Akt signaling pathway. Blockage of TXA 2 signaling up-regulated p53 as well as its target gene p21, caused a G1 phase arrest, and finally led to apoptosis in breast cancer cells. TXA 2 level was positively correlated with breast cancer cell anoikis rate, and apigenin significantly inhibited TXA 2 biosynthesis in vitro and in vivo. Collectively, we identified apigenin as a potent anoikis sensitizer with anti-metastatic properties in a mouse model of breast cancer, and these findings might provide a rationale for introducing apigenin supplementation to breast cancer patients.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Food Science and Human Wellness
·
2022
·
IF 8.022
Xiaofeng Zhang,Zhenhua Liang,Geoffrey Ivan Neil Waterhouse,Shengjun Jiang,Dongxiao Sun-Waterhouse,Jinmei Wang,Changyang Ma,Wenyi Kang
This is the first report on a polysaccharide (RCJ2-Ib) isolated from Rosa Chinensis Flos. RCJ2-Ib was obtained through the extraction with water, precipitation with ethanol, separation with DEAE-52 column and purification with DEAE-Sepharose Fast Flow column and Sephadex G100 column. GC, FT-IR and NMR analyses revealed that RCJ2-Ib (3.3 kDa) was a 1,4-linked polymannuronic acid containing substantial β - D -anomers units. The anticoagulant effect of RCJ2-Ib evaluated by using rabbit ear venous blood and an acute blood stasis rat model showed that RCJ2-Ib had obvious anticoagulant activity in regulating endogenous and exogenous coagulation pathways and reducing serum thromboxane B2 and endothelin-1. In addition, RCJ2-Ib could also increase the number of Lactobacillus and Escherichia coli . As a result, RCJ2-Ib has the potential to inhibit thrombosis and maintain the intestinal environment.
研究领域:
药理学
·
生物化学
·
医学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2019
·
IF 4.18
Ziru Zhang,Jianbo Ji,Dawei Zhang,Maoqiang Ma,Longru Sun
Background The root of Salvia miltiorrhiza f. alba (RSMA) (Lamiaceae) is used for the treatment of patients with thromboangiitis obliterans (TAO) in traditional Chinese medicine . Previously, a mixture of phenolic acids extracted from RSMA has shown significant protective effects on TAO rats. Purpose This study investigates the inhibitory effects of salvianolic acid B on TAO induced by sodium laurate injection in rats to explore the effective constituents of RSMA in TAO treatment. Methods TAO rats were developed using injected sodium laurate. After treatment with ligustrazine hydrochloride (15 mg/kg) and various doses of salvianolic acid B (10, 20, 40 mg/kg) by tail intravenous injection , levels of thromboxane B 2 (TXB 2 ), 6-keto-prostaglandin F 1α (6-keto-PGF 1α ) and endothelin-1 (ET-1) in plasma were determined using enzyme-linked immunosorbent assay. The right femoral arteries were studied by hematoxylin and eosin staining and immunohistochemical analysis to determine pathological changes and overexpression of tumor necrosis factor (TNF)–α and inducible nitric oxide synthase (iNOS) in the femoral artery walls of TAO rats. Results Salvianolic acid B significantly decreased the expressions of TXB 2 and ET-1 and increased the expression of 6-keto-PGF 1α in plasma, and significantly inhibited the overexpression of TNF-α and iNOS in the femoral artery walls of TAO rats at medium and high doses. Conclusion Salvianolic acid B has a protective effect on TAO rats. The mechanism may involve inhibition of thrombosis and TAO-associated inflammatory responses, which may explain the success of RSMA treatment of TAO in humans in traditional Chinese medical practice. Hence, it may be a potential drug for TAO treatment in conventional medicine.
研究领域:
药理学
·
免疫学
·
病理学
·
传统中药
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2018
·
IF 3.115
Yue Wei,Tingyun Ma,Hanxue Wang,Jianguo Xing,Yuwen Wang,Zhengyi Gu,Dandan Mu,Qiang Yin,Xuemei Cheng,Changhong Wang
Ethnopharmacological relevance Compound Muniziqi granule (CMG) is usually used as a traditional Uighur medicine to treat acne, chloasma , skin inflammation, primary dysmenorrhea (PDM), and menopausal syndrome . However, there are no sufficient data to support the clinic uses of CMG in PDM. Aim of the study This work aims to examine the effect of CMG as a treatment for PDM and reveal its possible therapeutic mechanism. Materials and methods In vivo and in vitro mouse PDM models were utilized in this study. The mouse uterine contraction was induced by oxytocin after progynova or estradiol benzoate pretreatment. CMG, alkaloid extracts from seeds of Peganum harmala (AEP), and 10% and 95% ethanol extracts from seeds of Nigella glandulifera (EEN10 and EEN95) were given to mice in three doses by gavage. The writhing times within 30 min after oxytocin treatment were recorded to evaluate the analgesic effect, and the glutathione peroxidase (GSH-Px), malondialdehyde (MDA), 6-keto-prostaglandin F 1α (6-k-PGF 1α ), prostaglandin F 2α (PGF 2α ), thromboxane B2 (TXB 2 ), and nitric oxide (NO) levels in uterine tissues and PGF 2α and MDA in serum were determined. The effects (contractile curve) of CMG, AEP, EEN10, and EEN95 on uterus contraction induced by oxytocin in isolated mouse uterus were recorded. Results In contrast to the control group, CMG, AEP, N10, and N95 could display analgesic activities dose dependently by reducing the writhing response of the PDM model mice. CMG, AEP, EEN10, and EEN95 could also remarkably decrease the level of PGF 2α , 6-k-PGF 1α , TXB 2 , NO and MDA in uterine tissues and PGF 2α and MDA in serum, whereas the activity of GSH-Px in uterine tissues was increased. Furthermore, CMG, AEP, EEN10, and EEN95 could significantly inhibit the frequency and amplitude of isolated uterus induced by oxytocin in a concentration-dependent manner. Conclusions CMG exhibited a significant protective effect on experimental PDM. The mechanisms are probably associated with abating lipid peroxidation and over-inflammatory reaction, and alleviating the contraction of isolated mouse uterus. The seeds of P. harmala and N. glandulifera in the CMG may play an important role in exerting protective effects on PDM. This study provides pre-clinic proof to the use of CMG in clinical practice of PDM.
研究领域:
药理学
·
传统医学
·
民族药理学
·
生殖健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2025
·Vol. 20
·期 1
·1-20
·
IF 2.8
Zhu Liang,Bi Yanchi,Liang Ting,Zhang Po,Xiao Xiao,Yu Tengbo
Background Osteoarthritis (OA) is considered an advancing chronic degenerative joint disease, leading to severe physical functional impairment of patients. Its development is closely related to increased inflammation and oxidative stress within the joint. Ginkgetin (GK), a natural non-toxic chemical, has proven anti-inflammatory, antioxidant, anti-tumor, and neuroprotective effects.Methods First, this study utilizes network pharmacology to explore the intrinsic connection between GK and OA. In vitro, SW1353 human cartilage cells were stimulated with Tert-butyl hydrogen peroxide (TBHP), and different GK concentrations were pre-treated to evaluate its protective effects. GK's anti-inflammatory and antioxidative effects were comprehensively assessed via MTT assay, western blot, cell immunofluorescence, ELISA, and transcriptome sequencing. Potential underlying mechanisms were also explored. In vivo, OA was induced in rats via anterior cruciate ligament transection (ACLT), and GK's impact on cartilage protection was further assessed via histological analysis and western blot.Results Network pharmacology has revealed that GK regulates OA via several key pathways, especially NF-κB, HIF-1, PI3K-AKT, and substances like reactive oxygen species. In vitro experiments showed GK effectively reverses oxidative stress damage from TBHP, inhibits inflammatory factor release, and protects Extracellular matrix (ECM) from degradation. These functions may be achieved via the NF-κB and MAPK signaling pathways. In vivo experiments showed GK significantly reduced proteoglycan loss from ACLT and inhibited matrix metalloproteinase 13 (MMP13) and ADAMTS5 (A disintegrin and metalloproteinase with thrombospondin motifs 5) production, effectively preventing cartilage degeneration in rats.Conclusion These findings suggest that GK has potential as a therapeutic agent for OA, offering new strategies and directions for OA treatment.
研究领域:
药理学
·
风湿病学
·
分子生物学
✓ 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）