INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2018
·Vol. 19
·期 4
·1135
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IF 3.687
Maiquan Li,Tao Xu,Fei Zhou,Mengmeng Wang,Huaxin Song,Xing Xiao,Baiyi Lu
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor against oxidative stress and neurodegenerative disorders. Phenylethanoid glycosides (PhGs; salidroside, acteoside, isoacteoside, and echinacoside) exhibit antioxidant and neuroprotective bioactivities. This study was performed to investigate the neuroprotective effect and molecular mechanism of PhGs. PhGs pretreatment significantly suppressed H2O2-induced cytotoxicity in PC12 cells by triggering the nuclear translocation of Nrf2 and reversing the downregulated protein expression of heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), glutamate cysteine ligase-catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM). Nrf2 siRNA or HO-1 inhibitor zinc protoporphyrin (ZnPP) reduced the neuroprotective effect. PhGs showed potential interaction with the Nrf2 binding site in Kelch-like ECH-association protein 1 (Keap1). This result may support the hypothesis that PhGs are activators of Nrf2. We demonstrated the potential binding between PhGs and the Keap1-activated Nrf2/ARE pathway, and that PhGs with more glycosides had enhanced effects.Keywords:Keap1;Nrf2;Neuroprotective;PC12 cells;PhGs
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Bioengineered
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2020
·
IF 2.205
Aimin Liu,Buxin Zhang,Wei Zhao,Yuanhui Tu,Qingxing Wang,Jing Li
Psoriasis is a chronic inflammatory skin disease that affects approximately 2% of worldwide population, and causing long-term troubles to the patients. Therefore, it is urgent to develop safe and effective therapeutic drugs. Catalpol is a natural iridoid glucoside, that has several remarkable pharmacological effects, however, whether catalpol can alleviated psoriasis has not been explored. The goal of the present work is to study the role of catalpol in psoriasis in vivo and in vitro. Imiquimod-induced psoriasis-like mice were applied with different concentrations of catalpol for 8 consecutive days. The severity degree of psoriasis was estimated and the skin pathological changes were detected by H&E staining. Also, TNF-α-stimulated keratinocytes were treated with different concentrations of catalpol, then the oxidative stress and inflammation factors, as well as the expression of SIRT1 and activation of NF-kB and MAPK pathways were measured. The results showed that catalpol reduced the erythema, scaling, ear thickness, and changed pathological phenotypes in the lesioned skin region in mice. Treatment with catalpol significantly suppressed the oxidative stress and inflammatory reactions in vivo and in vitro, as reflected by the decreased secretion or expression of oxidative stress indicators and proinflammatory factors. Furthermore, the SIRT1 was up-regulated and the NF-κB and MAPKs signaling pathways were suppressed by the treatment of catalpol in vivo and in vitro. In summary, our data suggested that catalpol may have a therapeutic property of psoriasis by ameliorating oxidative stress and inflammation partly through SIRT1 mediated suppression of NF-κB and MAPKs pathways.Abbreviation: CAT: catalase; ELISA: enzyme-linked immunosorbent assay; GSH: glutathione; HRP: horseradish peroxidase; IMQ: imiquimod; JNK: c-Jun NH 2-terminal kinases; MAPKs: mitogen-activated protein kinases; MDA: malondialdehyde; NC: negative control group; NF-kB: nuclear factor kappa B; PASI: psoriasis area and severity index; PVDF: polyvinylidene difluoride membranes; qRT-PCR: quantitative real time polymerase chain reaction; ROS: reactive oxygen species; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel; SIRT1: silent information regulator 1; SOD: Cu/Zn superoxide dismutase
研究领域:
药理学
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皮肤科
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Min Chen,Xiaodong Wang,Bo Hu,Jian Zhou,Xin Wang,Wei Wei,Hua Zhou
Echinacoside is a natural ingredient with various pharmacological activities . In this study, we investigated the protective effects of echinacoside on cardiomyocytes (rat H9c2 cells) in an anoxia/reperfusion (A/R) model. Further, the regulatory function of sodium-calcium exchanger protein 3 (SLC8A3/NCX3) as well as the protein kinase B (AKT) signaling were studied. The present results indicated that echinacoside protected against A/R-induced apoptosis in a dose manner, which was characterized by a decrease in the apoptosis and caspase 3 protein levels in H9c2 cells. Further, Ca 2+ uptake were dose-dependently reduced in H9c2 cells by echinacoside under A/R conditions. Whereas, relative mRNA expression of SLC8A3 and protein levels of SLC8A3 and p-AKT showed opposite tendency. On the one hand, the A/R-induced abnormalities in H9c2 cells were remarkably ameliorated by activated p-AKT and over-expression of SLC8A3 but aggravated by inhibited p-AKT, and the aggravated effection were ameliorated by echinacoside. Moreover, protein levels of SLC8A3 were positively regulated by p-AKT signaling. On the other hand, apoptosis and Ca 2+ uptake as well as protein levels of caspase 3 were significantly increased by SLC8A3 silencing in H9c2 cells under normoxic conditions, and this symptom was remarkably reversed by echinacoside or Nimodipine (an antagonis of Ca 2+ ) treatment . Collectively, echinacoside has showed a cardioprotective effect against A/R treatment in a dose dependent manner in vitro, and this cardioprotective effect was potentially achieved via up-regulating p-AKT and SLC8A3.
研究领域:
药理学
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心脏病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING RESEARCH & DESIGN
·
2022
·
IF 4.119
Chunying Li,Fang Nie,Changyin Feng,Mengfei Tian,Meiting Yu,Chunjian Zhao,Yujie Fu
A creative dual-template molecularly imprinted polymer (Fe 3 O 4 @MCM-41-MIPs) with good magnetic properties and specific recognition of echinacoside and acteoside was prepared by surface imprinting. Echinacoside and acteoside served as dual templates, 4-vinylpyridine (4-VP) was used as a functional monomer , the cross-linker was ethylene glycol dimethacrylate (EGDMA), and the selected initiator was azobisisobutyronitrile (AIBN). The prepared Fe 3 O 4 @MCM-41-MIPs were applied to the selective separation and enrichment of echinacoside and acteoside from Cistanche deserticola Y. C. Ma ( C. deserticola ). The resulting Fe 3 O 4 @MCM-41-MIPs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), laser particle size scanning and vibration sample magnetometry (VSM). The results of the isotherm adsorption experiment showed that the maximum adsorption capacities of Fe 3 O 4 @MCM-41-MIPs for echinacoside and acteoside were 6.02 and 1.63 mg·g -1 , respectively, at 298 K. The pseudo-second-order reaction mechanism showed that the equilibrium adsorption capacities of Fe 3 O 4 @MCM-41-MIPs for echinacoside and acteoside were 4.81 and 0.93 mg·g -1 , respectively. The characterization of Fe 3 O 4 @MCM-41-MIPs showed that the imprinted layer with dual-template molecules was wrapped on the outside of the carrier, and the obtained Fe 3 O 4 @MCM-41-MIPs showed good saturation magnetization , desirable capacity for echinacoside and acteoside adsorption, and satisfactory reuse (echinacoside and acteoside maintained relative adsorption rates of 97.5% and 95.8% after five cycles). After separation, the purities of echinacoside and acteoside were 33.50% and 27.00%, respectively. In addition, in the selective adsorption experiment, the synthesized Fe 3 O 4 @MCM-41-MIPs showed better selectivity for echinacoside and acteoside than their structural analogs. Therefore, this method proved to be sustainable, rapid and highly efficient for the separation and enrichment of echinacoside and acteoside.
研究领域:
中药化学
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分离科学
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产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Jiao Wei,Zongmei Zheng,Xinxin Hou,Fengjing Jia,Yuan Yuan,Fuwen Yuan,Feng He,Liang Hu,Ling Zhao
Ethnopharmacological relevance Echinacoside (ECH) is the dominant phenylethanoid glycoside-structured compound identified from our developed herbal formula Huangci granule, which has been previously reported to inhibit the invasion and metastasis of CRC and prolong patients’ disease-free survival duration. Though ECH has inhibitory activity against aggressive colorectal cancer (CRC) cells, its anti-metastasis effect in vivo and the action mechanism is undetermined. Given that ECH has an extremely low bioavailability and gut microbiota drives the CRC progression, we hypothesized that ECH could inhibit metastatic CRC by targeting the gut microbiome . Aim of the study The purpose of this study was to investigate the impact of ECH on colorectal cancer liver metastasis in vivo and its potential mechanisms. Materials and methods An intrasplenic injection-induced liver metastatic model was established to examine the efficiency of ECH on tumor metastasis in vivo . Fecal microbiota from the model group and the ECH group were separately transplanted into pseudo-sterile CRLM mice in order to verify the role of gut flora in the ECH anti-metastatic effect. The 16S rRNA gene sequence was applied to analyze the structure and composition of the gut microbiota after ECH intervention, and the effect of ECH on short-chain fatty acid (SCFAs)-producing bacteria growth was proven by anaerobic culturing in vitro . GC-MS was applied to quantitatively analyze the serum SCFAs levels in mice. RNA-seq was performed to detect the gene changes involving tumor-promoting signaling pathway. Results ECH inhibited CRC metastasis in a dose-dependent manner in the metastatic colorectal cancer (mCRC) mouse model. Manipulation of gut bacteria in the mCRC mouse model further proved that SCFA-generating gut bacteria played an indispensable role in mediating the antimetastatic action of ECH. Under an anaerobic condition, ECH benefited SCFA-producing microbiota without affecting the total bacterial load, presenting a dose-dependent promotion on the growth of a butyrate producer, Faecalibacterium prausnitzii ( F.p ). Furthermore, ECH-reshaped or F.p -colonized microbiota with a high butyrate-producing capability inhibited liver metastasis by suppressing PI3K/AKT signaling and reversing the epithelial-mesenchymal transition (EMT) process, whereas this anti-metastatic ability was abrogated by the butyrate synthase inhibitor heptanoyl-CoA. Conclusion This study demonstrated that ECH exhibits oral anti-metastatic efficacy by facilitating butyrate-producing gut bacteria, which downregulates PI3K/AKT signaling and EMT. It hints at a novel role for ECH in CRC therapy.
研究领域:
药理学
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肿瘤学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Jingjing Lin,Lu Deng,Ailin Qi,Hong Jiang,Di Xu,Yuehui Zheng,Zixuan Zhang,Xiaoman Guo,Beilei Hu,Peijun Li
Hypoxic-ischemic encephalopathy (HIE) is a brain damage caused by perinatal hypoxia and blood flow reduction. Severe HIE leads to death. Available treatments remain limited. Oxidative stress and nerve damage are major factors in brain injury caused by HIE. Catalpol, an iridoid glucoside found in the root of Rehmannia glutinosa, has antioxidant and neuroprotective effects. This study examined the neuroprotective effects of catalpol using a neonatal rat HIE model and found that catalpol might protect the brain through inhibiting neuronal ferroptosis and ameliorating oxidative stress. Behavior tests suggested that catalpol treatment improved functions of motor, learning, and memory abilities after hypoxic-ischemic injury. Catalpol treatment inhibited changes to several ferroptosis-related proteins, including p-PI3K, p-AKT, NRF2, GPX4, SLC7A11, SLC3A2, GCLC, and GSS in HIE neonatal rats. Catalpol also prevented changes to several ferroptosis-related proteins in PC12 cells after oxygen-glucose deprivation. The ferroptosis inducer erastin reversed the protective effects of catalpol both in vitro and in vivo . We concluded that catalpol protects against hypoxic-ischemic brain damage (HIBD) by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis.
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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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Shuai Dong,Xingyuan Bai,Bin Chen,Minzhe Fan,Qi Liu,Yubo Zhao,Linsen Li*,Dan Zhu
Background: Panzerina lanata (Lanata) is generally used to treat pustule infection in Inner Mongolia folk medicine and is called “the holy medicine for pustule.” However, the pharmacological mechanism of Lanata in treating pustule infection is still unclear.Aims: This study aimed to investigate the therapeutic effects of Lanata on skin infection and explore the underlying mechanisms.Methods: A skin wound methicillin-resistant Staphylococcus aureus (MRSA) infection mouse model was established to evaluate the healing effect of Lanata on infected wounds. In vitro assays were also conducted to determine the antibacterial activity of Lanata. Flow cytometry and immunohistochemistry were used to dynamically detect the number of neutrophils in the bone marrow, peripheral blood, and MRSA-infected wound. Protein expression in the infected wound skin was detected by a protein chip. Using an air pouch MRSA infection mouse model, the number of neutrophils, reactive oxygen species (ROS) level in neutrophils, and neutrophil extracellular trap (NET) formation were dynamically detected by flow cytometry and immunofluorescence. RNA-seq, RT-qPCR, flow cytometry, ELISA, and CXC chemokine receptor 2 (CXCR2) and P-selectin glycoprotein ligand-1 (PSGL-1) inhibitors were used to explore the mechanism of Lanata in regulating neutrophils.Results: In vitro assays showed that Lanata had no direct antibacterial activity. In skin wound MRSA-infected mouse, Lanata promoted the rapid migration of neutrophils from the bone marrow via peripheral blood to the wound site to eradicate MRSA in the acute stage of infection and accelerate wound healing. Skin protein chip analysis showed that Lanata upregulated CXCR2 and PSGL-1 protein levels in skin wounds. Furthermore, analysis using the air pouch MRSA infection mouse model found that Lanata not only promoted the rapid migration of neutrophils from peripheral blood to the air pouch but also enhanced the activation of neutrophils, including the increase of ROS and the release of NETs, and upregulated the expression of CXCR2, PSGL-1, and myeloperoxidase (MPO) in neutrophils. Inhibition of CXCR2 and MPO significantly attenuated the effect of Lanata on promoting migration and activation of neutrophils.Conclusion: Panzerina lanata resists MRSA infection by promoting migration and activation of neutrophils to rapidly eradicate MRSA.
研究领域:
药理学
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免疫学
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微生物学
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传染病学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
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2022
·
IF 4.145
Yanling Zhang,Zhiyun Du,Dan Li,Zhuo Wan,Tianyi Zheng,Xuehui Zhang,Yingjie Yu,Xiaoping Yang,Qing Cai
Due to the inflammatory responses associated with defect occurrence and materials implantation, immunoregulation has emerged as a promising strategy to enhance bone regeneration . It has been widely reported that a material could facilitate osteogenesis if it can guide macrophages to anti-inflammatory M2 phenotype, vice versa, a substrate will influence macrophage phenotype if it is osteoinductive. However, few studies have looked into the intercellular crosstalking directly. Herein, the compound catalpol was selected for its multiple functions to study the interactions between bone marrow mesenchymal stromal cells (BMSCs) and macrophages. This iridoid glucoside exhibits excellent anti-inflammatory and osteoinductive activities. The effects of catalpol on mediating M1/M2 polarization of macrophages, inhibiting osteoclast differentiation , promoting osteogenesis and angiogenesis were systematically investigated to correlate the biological responses of BMSCs and macrophages. To extend its in vivo application, the catalpol was then loaded onto an electrospun polylactide/gelatin composite fibrous mesh and subcutaneously implanted to evaluate the local inflammation and ectopic osteogenesis. The results revealed that the functions of catalpol displayed in modulating cellular behaviors are via cell paracrine to strengthen intercellular crosstalking, hence demonstrating that catalpol itself could serve as a promising bioactive stimulator for bone tissue engineering.
研究领域:
组织工程
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生物材料
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免疫学
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细胞生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
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IF 4.36
Xuanhao Chen,Xiaoyan Wang,Lin Ma,Shiming Fang,Jin Li,Evans Owusu Boadi,Jun He,Xiu-mei Gao,Yu Wang,Yan-xu Chang
Ethnopharmacological relevance Viticis fructus ( VF ) has been widely used in alleviating the swelling and pain, owning to its pharmacologically active components including agnuside, 10- O -vanilloylaucubin, luteolin and casticin. Aim of the study The pharmacokinetic profiles of the absorbed components from aqueous and ethanolic extracts of VF in rat plasma were performed, and explored the molecular mechanisms of absorbed components via network pharmacology . Materials and methods Ultra-performance liquid chromatography-tandem mass spectroscopy (UHPLC-MS/MS) was employed to identify the absorbed components from rat plasma. Liquid-liquid extraction with ethyl acetate was used to purify the plasma samples. Plasma pharmacokinetics parameters of the components absorbed were analyzed after oral administration of both extracts. Network pharmacology was used to predict the biological functions and potential signaling pathways of VF . The anti-cancer effects of VF extract and absorbed components have been confirmed by in vitro experiments. Results The method was very sensitive with lower limit of quantification (LLOQ) of 1.0, 2.5, 0.2 and 0.5 ng/mL for agnuside, 10- O -vanilloylaucubin, luteolin and casticin, respectively. With the exception of 10- O- vanilloylaucubin which was not detected in the ethanolic extract of VF , all other components were detected in both extracts in plasma. The pharmacokinetic parameters of the four components from rat plasma were significantly different between the two extracts. According to the results of network pharmacology, the absorption components of VF are enriched in 32 key pathways, and 15 pathways are related to cancer. Ultimately, the anti-cancer effects, as well as the signaling pathways of VF ethanolic extract and absorbed components were verified by in vitro experiments. Conclusion The optimized, sensitive and validated UHPLC-MS/MS method was successfully applied for the plasma pharmacokinetics comparison analysis of the two VF extracts. The combination of network pharmacology and pharmacokinetics provides a useful method to elucidate the biological effects and molecular mechanism of the absorbed components of VF .
研究领域:
药理学
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药代动力学
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网络药理学
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中药
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
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2024
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IF 5.6
Xiang Li,Xiao Xu,Ying Dong,Shusheng Fan,Xueyang Ren,Yuan Zheng,Jiamu Ma,Feng Zhang,Qingyue Deng,Xianxian Li,Yingyu He,Mengyu Sun,Wei Liu,Mengxia Li,Qing Xia,Yan Zhang,Gaimei She
Fufang E ’ jiao Jiang (FEJ) as a healthy food consisting of medicine food homology materials approved by China’s Ministry of Health has been extensively applied to replenish qi and nourish blood, and it has a positive impact on women’s health. To find out the material basis and mechanism of FEJ, a systematic “compound-effect-target” analysis including chemical composition resolution, zebrafish, network pharmacology, molecular docking, transcriptome, and bibliometric analysis was adopted. 124 chemical components including ginsenosides, and phenylethanoid glycosides in FEJ were discovered, and effects of FEJ on promoting the generation of immune cells, erythropoiesis and angiogenesis in zebrafish were exhibited. Based on network pharmacology, molecular docking and in vivo activity assay, 6 compounds including jionoside A1, isoacteoside, echinacoside, acteoside, lobetyolin, and rehmannioside D were identified as active components of FEJ. Transcriptome data showed that several pathways such as complement and coagulation cascades, ECM-receptor interaction, and PI3K-Akt signaling pathway were associated with proangiogenic effect of FEJ. 19 common targets were obtained through combined analysis of network pharmacology and transcriptomics, and 5 targets of them were verified by PCR. The bibliometric analysis of these common targets revealed that FEJ was related to energy metabolism, pathway in cancer, etc., which was consistent with the results of network pharmacology and transcriptome. The studies suggested that FEJ could replenish qi and nourish blood through multi-compound and multi-targets.
研究领域:
药理学
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免疫学
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血液学
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血管生成
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转录组学
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网络分析
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分子生物学
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产品关联
DOI
高影响因子
Food & Function
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2022
·Vol. 14
·期 1
·171-180
·
IF 6.317
Xinlin Chen,Ying Wu,Yucheng Gu,Jianguang Luo,Lingyi Kong
A great deal of attention has been paid to the seeds of Paeoniae lactiflora pall., an underutilized food resource, since its extract exhibits excellent α-glucosidase (GAA) inhibitory activity. In the present study, to gain further insight into this plant and find out potent GAA inhibitors, we established a novel ligand fishing strategy by introducing a competitive inhibitor as an indicator. After the successful establishment of this approach was verified by a series of methods, including kinetic assay, fluorescence determination, and HPLC, the newly developed ligand fishing method was applied to acquire potent GAA inhibitors from P. lactiflora seeds. Nine bioactive compounds were captured, and seven of them were identified as suffruticosol A, suffruticosol B, resveratrol, vitisin E, luteolin, trans-δ-viniferin, and ampelopsin E. The data of their GAA inhibitory activity demonstrated that these constituents were vigorously active against GAA with IC50 values of 1.67–30.47 μM, while such value of 1-DNJ was 228.77 μM. Among them, vitisin E and ampelopsin E were reported to show such inhibitory activity for the first time. Collectively, our findings provide valuable clues for the further utilization of P. lactiflora seeds as a functional food, and offer a new avenue for acquiring potent inhibitors from natural resources.
研究领域:
药理学
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天然产物化学
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生物化学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Reproductive Biology
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2022
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IF 2.089
Juan Zhao,Yong Tan,Zhe Feng,Yahong Zhou,Feihong Wang,Ge Zhou,Jing Yan,Xiaowei Nie
Oxidative stress plays a central role in polycystic ovary syndrome (PCOS). Catalpol (CAT) is the active ingredient of Rehmannia glutinosa Libosch which has therapeutic effect on PCOS. However, little is known about the mechanism of CAT in PCOS. PCOS rats were induced by subcutaneous injection of dehydroepiandrosteronec for four weeks and then were treated with CAT (50 mg/kg) or carboxyl methyl cellulose (the solvent of CAT) or normal saline for another 4 weeks. Histopathological observation of ovarian tissues, the levels of testosterone, estradiol and progesterone in rat plasma samples, the oxidative stress related-indexes and the expressions of NF-κB pathway-related proteins were determined. KGN cell (human ovarian granulosa cell line) was used as PCOS cell model and was transfected with siSIRT1 in the presence of CAT. The viability, proliferation and apoptosis of cells and the levels of SIRT1 and NF-κB pathway-related proteins were measured. CAT lessened the anthropometric indices and improved ovarian damage in PCOS model rats, and reduced the levels of testosterone, estradiol, progesterone and MDA , increased GSH content, and elevated the activities of catalase, GSH-Px and SOD in ovarian tissues of PCOS model rats. CAT up-regulated SIRT1 level and inhibited the activation of NF-κB signaling pathway in PCOS rat model and KGN cells. Silencing SIRT1 increased the viability and proliferation, whilst decreased the apoptosis of CAT-treated KGN cells. Silencing SIRT1 counteracted the effect of CAT on the level of oxidative stress-related factors and NF-κB signaling pathway in KGN cells. CAT attenuated PCOS by regulating SIRT1 mediated NF-κB signaling pathway.
研究领域:
药理学
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内分泌学
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细胞生物学
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分子生物学
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生殖医学
✓ 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）