JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Zhongying Wang,Rui Xue,Mengying Lv,Yunyun Qi,Wei Yu,Zhiyong Xie,Wen Chen,Xinjun Wang,Xing Tian,Bo Han
Ethnopharmacological relevance Galla chinensis , a traditional Chinese herbal medicine, was widely used to treat ulcerative colitis (UC) in folk prescriptions, however, its active ingredients and mechanism of action in the treatment of UC remain unclear. Aim of the study The aim of our study was to discover the lead compounds and anti-inflammatory active ingredients of Galla chinensis and clarify their molecular mechanism for UC treatment. Materials and methods The ingredients of Galla chinensis were prepared by column and mass spectrometry guided preparative chromatography. Besides, the relationship among the ingredients of Galla chinensis and targets was predicted by systems pharmacology. Additionally, Lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as in vitro model. The cell viability, the level of the pro-inflammatory factors, the generation of reactive oxygen species (ROS), and trans epithelial electric resistance (TEER) values were detected to screen out the active ingredients of Galla chinensis . Moreover, 4% dextran sodium sulfate (DSS)-induced ulcerative colitis mice were used as the UC animal model. The disease activity index (DAI), pathological degree of colon tissue, activities of antioxidant-related enzymes and expression level of pro-inflammatory cytokines were performed to assess the anti-UC effects of the active ingredients. Meanwhile, the mRNA expression level of inflammatory factors and antioxidant related genes were analyzed by real-time quantitative polymerase chain reaction (Q-PCR). And the expression of nuclear factor erythroid-2 related factor 2 (Nrf2) pathway related proteins, intestinal mucosal proteins and nuclear factor kappa-B (NF-κB) pathway related proteins in colon tissues were analyzed by Western Blotting . Results Herein, a stepwise tracking strategy was adopted to screen out the anti-inflammatory active ingredients of Galla Chinensis based on "preparative chromatography pharmacology combined with mass spectrometry guidance and system". 11 categories of ingredients of Galla chinensis were prepared and ethyl gallate (EG) was screened out the lead compound and anti-inflammatory active ingredient of Galla Chinensis through in silico , in vitro and in vivo studies. In addition, EG had a significant therapeutic effect on ameliorating DSS-induced UC mice and protected intestinal mucosal integrity through Nrf2 and NF-κB signaling pathway. Conclusion Ethyl gallate was the lead compound and anti-inflammatory active ingredient in Galla chinensis . And it was discovered for the first time that EG could treat mice with ulcerative colitis. This research not only found the lead compound of Galla Chinensis for UC treatment and determined the possible mechanism, but also provided valuable references for finding lead compounds from natural products by systems pharmacology coupled with equivalent components group technology.
研究领域:
药理学
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药物化学
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炎症性肠病
·
中药
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系统生物学
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产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2022
·
IF 3.204
Chao Wang,Quan-Hao Wei,Zhen-Qiang Xin,Lin-Lin Tian,Jun-Sheng Zhang,Hua Zhang
Chemical fractionation of the EtOH extract of the roots of a traditional Chinese herb, Morinda officinalis , afforded an array of methyl 2-naphthoate derivatives ( 1 – 9 ) including four pairs of enantiomers ( 1 – 4 ), two pimarane diterpenes and two ursane triterpenoids . Among them, eight compounds ( 1a / 1b - 3a / 3b , 11 and 13 ) were reported in the current work for the first time. The structures of the new compounds, including their absolute configurations, were defined by spectroscopic analyses in combination with quantum chemical electronic circular dichroism (ECD) and gauge-independent atomic orbital (GIAO) NMR calculations. All the isolates were evaluated for their inhibitory effect on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, and the enantiomers 1a and 3b exhibited moderate activity with IC 50 values of 41.9 and 26.2 μM. Meanwhile, compound 3b also dose-dependently inhibited the secretion of two pro-inflammatory cytokines TNF-α and IL-6 in the same cell model.
研究领域:
药理学
·
天然产物化学
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药物化学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Liwei Xue,Xiaosheng Jin,Tingting Ji,Rongzhou Li,Xiaoju Zhuge,Fang Xu,Zijiao Quan,Haibin Tong,Weilai Yu
Objectives Luteolin, known for its multifaceted therapeutic properties against inflammatory diseases, holds potential for addressing the unmet need for effective treatments in ulcerative colitis (UC), a prevalent subtype of inflammatory bowel disease (IBD). This study aimed to comprehensively assess luteolin's therapeutic efficacy in a dextran sulfate sodium (DSS)-induced colitis mouse model, shedding light on its anti-UC mechanisms. Methods Our investigation encompassed in vivo assessments of luteolin's therapeutic potential against DSS-induced colitis through rigorous histopathological examination and biochemical analyses. Furthermore, we scrutinized luteolin's anti-inflammatory prowess in vitro using lipopolysaccharide (LPS)-stimulated RAW264.7 cells and primary peritoneal macrophages. Additionally, we quantitatively evaluated the impact of luteolin on C–C motif chemokine ligand 2 (CCL2)-induced macrophage migration employing Transwell and Zigmond chambers. Furthermore, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assay, and molecular docking were employed to identify potential therapeutic targets of luteolin and investigate their binding sites and interaction patterns. Results Luteolin demonstrated therapeutic potential against DSS-induced colitis by ameliorating colitis symptoms, restoring intestinal barrier integrity, and inhibiting proinflammatory cytokine production in the colonic tissues. Moreover, luteolin demonstrated robust anti-inflammatory activity in vitro , in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and primary peritoneal macrophages. Notably, luteolin suppressed the phosphorylation of IKKα/β, IκBα, and p65, along with preventing IκBα degradation in LPS-treated RAW264.7 cells and peritoneal macrophages. Furthermore, luteolin impaired the migratory behavior of RAW264.7 cells and peritoneal macrophages, as evidenced by reduced migration distance and velocity of luteolin-treated macrophages. Mechanistically, luteolin was found to antagonize IKKα/β, subsequently inhibiting IKKα/β phosphorylation and the activation of NF-κB signaling. Conclusion Luteolin emerges as a promising lead compound for the clinical therapy of colitis by virtue of its ability to ameliorate DSS-induced colitis, antagonize IKKα/β, suppress NF-κB signaling, and impede macrophage activation and migration.
研究领域:
药理学
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免疫学
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胃肠病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Pengyue Li,Yongshuai Jing,Xiaoyue Qiu,Huina Xiao,Yuguang Zheng,Lanfang Wu
The purified polysaccharides fraction, DOP-2, was prepared from Dioscorea opposita Thunb ( D. opposita ). This study combined in vitro and in vivo experiments to comprehensively investigate the index changes in RAW264.7 cells and immunocompromised mice under DOP-2 intervention, aiming to elucidate the potential mechanisms of immunomodulatory effects of DOP-2. DOP-2 (10 ∼ 500 μg/mL) significantly elevated the levels of NO, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) factors secreted by RAW264.7 cells, and restored the body weight of immunosuppressed mice and improve the degree of injury to the immune organ index, resulting in significant immunomodulatory effects. Notably, DOP-2 promoted the production of short-chain fatty acids (SCFAs) in immunosuppressed mice and modulated the composition of their gut microflora. These findings highlight the potential benefits of DOP-2 therapy in improving immune function and gut health, and will provide a theoretical basis for the application of D. opposita polysaccharides as an immunomodulatory adjuvant.
研究领域:
免疫学
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药理学
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微生物学
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产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2025
·
IF 4.2
Xin-Ke Shao,Lu Fan,Jie-Li Zhou,Kai Wang
The development of novel molecular probes for real-time monitoring of aminopeptidase N (APN) activity is crucial for understanding inflammatory bowel disease (IBD) progression. Here, we present a new probe, HDAPN, a near-infrared (NIR) activatable fluorescent probe based on a hemicyanine scaffold, designed for selective APN detection. Structural characterization confirmed the molecular integrity of the probe, while spectroscopic studies demonstrated its exceptional photostability and response. HDAPN exhibits a remarkable "turn-on" response (720 nm emission) upon APN-mediated cleavage, with outstanding sensitivity (LOD = 0.82 ng/mL) and linearity under physiological conditions. The probe showed minimal cross-reactivity with interferents (e.g., ROS, metal ions, and other enzymes) and successfully detected LPS-induced APN upregulation in RAW264.7 macrophages. In DSS-induced colitis models, HDAPN enabled non-invasive visualization of APN activity, with fluorescence intensity correlating with disease severity (2-fold increase in severe colitis). Comprehensive toxicity evaluations confirmed its biosafety in vitro and in vivo . These findings highlight the potential of HDAPN as a robust tool for studying APN-associated pathophysiology and therapeutic development.
研究领域:
生物化学
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分子成像
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炎症性肠病
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荧光探针
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酶学
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生物医学光学
✓ 已验证
DOI
高影响因子
ACS Sensors
·
2024
·
IF 8.2
Fangkun Yang,Ning Huangfu,Jiaxi Shen,Jiajun Ying,Hengyi Mao,Yongfang Yin,Pengpeng Su,Ruochi Zhao,Xiao Chen,Hailiang Zhu,Wenming He,Hanbin Cui,Kai Wang
Cardiovascular diseases (CVDs) are a major global health concern, highlighting the need for effective diagnostic tools. Zinc ions (Zn2+) play a role in CVDs, but their detection is challenging. This study presents a multifunctional optical sensor, HD-Zn, designed to detect Zn2+ in relation to CVDs. We developed a novel fluorescence probe, HD-Zn, by conjugating N,N-di(2-picolyl)ethylenediamine (DPEN) to HD via an amide bond, which results in fluorescence quenching due to photoinduced electron transfer (PeT). Adding Zn2+ significantly increased fluorescence intensity in the near-infrared region (NIR-I). The probe showed a linear response to varying Zn2+ concentrations, with a detection limit of 9.8 nM, appropriate for physiological conditions. Fluorescence imaging in RAW264.7 macrophages indicated lower intracellular Zn2+ levels in foam cells compared to healthy cells, linked to CVDsprogression. In vivo imaging in mouse models showed decreased fluorescence intensity in the aorta with disease progression. Our findings confirm that HD-Zn is a reliable tool for measuring Zn2+ levels in plaques and demonstrate its biosafety for detecting Zn2+ in serum and urine, offering potential for clinical applications in CVDs diagnosis and monitoring.
研究领域:
医学诊断
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光学传感
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心血管研究
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分子生物学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Zhenhao Li,Haitao Pan,Jihong Yang,Dongjie Chen,Yu Wang,Han Zhang,Yiyu Cheng
Background Xuanfei Baidu Formula (XBF) is an effective traditional Chinese medicine (TCM) remedy for treating coronavirus disease 2019 (COVID-19) in China. This herbal medicine has shown effects in reducing clinical symptoms and shortening the average length of hospital stay for COVID-19 patients. Previous studies have demonstrated that XBF alleviates acute lung injury (ALI) by regulating macrophage-mediated immune inflammation, but the mechanisms of action remain elusive. Purpose This study aimed to evaluate the lung-protective and anti-inflammatory effects of XBF and its underlying mechanisms. Methods Here, XBF's effects were investigated in an ALI mouse model induced by inhalation of atomized lipopolysaccharide (LPS). Besides, the LPS-induced inflammation model in RAW264.7 cells was used to clarify the underlying mechanisms of XBF against ALI. Results Our results showed that XBF treatment alleviated LPS-induced lung injury, as evidenced by reduced histopathological changes, pulmonary alveoli permeability, fibrosis, and apoptosis in the lung tissues. In addition, inflammation was alleviated as shown by decreased levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β in serum and bronchoalveolar lavage fluid (BALF), and reduced white blood cell (WBC) count in BALF. Furthermore, consistent with the in vivo assay, XBF inhibited LPS-induced inflammatory cytokines release and pro-inflammatory polarization in RAW264.7 cells. Mechanistically, XBF increased mitochondrial fusion by upregulating Mfn1 and attenuated NLRP3 inflammasome activation by repressing Casp11, respectively, to inhibit NF-κB and MAPK pathways, thus repressing pro-inflammatory macrophage polarization. Conclusion In this study, we demonstrate that XBF exerts anti-ALI and -inflammatory effects by recovering mitochondrial dynamics and reducing inflammasome activation, providing a biological illustration of the clinical efficacy of XBF in treating COVID-19 patients.
研究领域:
药理学
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免疫学
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细胞生物学
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中医
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DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2020
·Vol. 20
·期 9
·2000116
·
IF 3.416
Jingjing Ye,Xindan Zhang,Wenqi Xie,Min Gong,Meihong Liao,Qinghan Meng,Jiajia Xue,Rui Shi,Liqun Zhang
Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) for relieving inflammatory reactions can lead to severe side effects. It is of great importance to configure new dosing strategies for alleviating the side effects of NSAIDs. In this work, an enzyme-responsive anti-inflammatory prodrug capable of generating indomethacin upon the trigger of inflammation is developed. A monomer is first prepared after the esterification of carboxyl groups of indomethacin by hydroxyl groups of N -(2-hydroxyethyl) acrylamide. Then, a polymer prodrug, with indomethacin linked through ester bonds on the side chain, is synthesized by free radical polymerization of the monomer. The therapeutic drug component can be triggered to release from the prodrug under the stimulation of cholesterol esterase, mimicking the inflammation environment. On the contrary, there is only a small amount of drug released in the absence of the enzyme. Therefore, the drug can be triggered to release under the stimulation of an environment mimicking inflammation. Furthermore, the in vitro studies at the cellular level indicate that the enzyme-responsive prodrug can efficiently relieve inflammatory responses induced by lipopolysaccharide in RAW264.7 macrophage cells while indicating no cytotoxicity.
研究领域:
药理学
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药物递送系统
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炎症研究
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聚合物化学
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DOI
PubMed
高影响因子
EXPERIMENTAL PHYSIOLOGY
·
2021
·Vol. 106
·期 3
·653-662
·
IF 2.969
Xiujin Shi,Yi Zhang,Baidi Lin,Yang Zhou,Wei Suo,Juanjuan Wei,Lin Zhang,Jie Lin,Fucheng Xiao,Limin Zhao,Yang Lin
New Findings What is the central question of this study? Does danthron alleviate experimental atherosclerosis by inhibiting the formation of foam cells? What are the main findings and their importance? Danthron improved serum lipid profiles and significantly reduced the atherosclerotic plaque areas and lipid accumulation in the aortic root of ApoE −/− mice. Danthron inhibited foam cell formation in oxidized low-density lipoprotein-induced RAW264.7 macrophages. Furthermore, danthron exerted its function in atherosclerosis at least partly through activating the AMP-activated protein kinase–sirtuin 1 signalling pathway. These findings suggest that danthron has the potential to alleviate atherosclerosis. Danthron, an ingredient isolated from Rheum palmatum L., has been revealed to reduce lipid accumulation in vitro . This study aimed to discover the effects of danthron on the development of atherosclerosis and to delineate the underlying mechanisms. For in vivo studies, male ApoE −/− mice were fed a high-fat diet and orally treated with danthron (30 or 60 mg/kg/day) for 12 weeks. For in vitro studies, RAW264.7 cells were induced by oxidized low-density lipoprotein (ox-LDL, 50 μg/ml) for 48 h and subsequently administered danthron at appropriate concentrations for 24 h. AMP-activated protein kinase (AMPK) inhibitor compound C was added to ox-LDL-stimulated RAW264.7 cells 2 h before danthron administration to confirm the role of the AMPK signalling pathway in the regulation by danthron of foam cell formation. We found that danthron improved serum lipid profiles, and significantly reduced atherosclerotic plaque areas and lipid accumulation in the aortic root of atherosclerotic mice. Moreover, danthron upregulated the mRNA and protein expression of ATP-binding cassette transporter A1 (ABCA1), ABCG1 and liver X receptor α (LXRα), which play a crucial role in lipid metabolism, and activated the AMPK–sirtuin 1 (SIRT1) pathway. In an in vitro study, danthron inhibited foam cell formation in ox-LDL-induced RAW264.7 macrophages with an increase in the expression of ABCA1, ABCG1 and LXRα as well as activation of the AMPK–SIRT1 pathway. Furthermore, compound C abolished the effects of danthron on lipid accumulation and the protein expression of ABCA1/G1 and LXRα in vitro . Our results highlight that danthron possesses potential benefits in alleviating experimental atherosclerosis by targeting foam cell formation by activating the AMPK–SIRT1 signalling pathway.
研究领域:
心血管疾病
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Xuedi Zhang,Xue Zhao,Shanshan Tie,Haitao Wang,Mingqian Tan
Oil in water (O/W) nanocarriers were prepared for cellular enhanced astaxanthin delivery using a (3-carboxypropyl) triphenylphosphonium bromide (TPP)-modified casein by an ultrasonic self-emulsification method. The nanocarriers of casein emulsion loaded with astaxanthin and casein modified by TPP emulsion encapsulated with astaxanthin were 227 and 543 nm, respectively, with a spherical shape. The thermal stability and resistance to ultraviolet (UV) radiation ability of astaxanthin were significantly improved after encapsulation by the nanocarriers. The fluorescence colocalization imaging proved an accumulated effect of astaxanthin encapsulated in casein emulsion nanocarriers modified by TPP. Meanwhile, the astaxanthin loaded on TPP-modified nanocarriers could significantly protect the mitochondrial membrane potential from depolarization in the normal rat kidney (NRK) cells after oxidative damage. The cell viability assay demonstrated that the astaxanthin loaded on TPP-modified nanocarriers could enhance the growth of NRK and RAW264.7 cells as compared with astaxanthin encapsulated by casein emulsion without TPP modification.
研究领域:
纳米技术
·
药学
·
细胞生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2016
·
IF 2.551
Zhilin Qi,Shimei Qi,Liefeng Ling,Jun Lv,Zunyong Feng
Salidroside (SAL) is an active ingredient isolated from the Rhodiola rosea , has potent anti-inflammatory effect, but the mechanism is still elusive. The purpose of this study is to verify the effects of SAL on LPS-induced inflammatory response and investigate the possible underlying molecular mechanism. RAW264.7 cells were pre-incubated with SAL for 2 h, then stimulated with or without LPS for another 16 h. The levels of TNF-α, MCP-1, IL-6, and PGE2 were detected by ELISA , and the production of NO was determined by nitrite analysis. The expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected by Western blotting . In RAW264.7 cells and murine peritoneal macrophages, the activation of signal molecules was also measured by Western blot. The nuclear translocation of STAT3 was determined by Laser confocal and nucleocytoplasmic separation experiments. Our results showed that SAL attenuated the productions of TNF-α, IL-6, MCP-1, PGE2 and NO dose dependently. SAL also suppressed LPS-induced expressions of iNOS and COX-2 significantly. Further studies revealed that SAL down-regulated the phosphorylation of JAK2-STAT3 signaling pathway and reduced the nuclear translocation of STAT3 induced by LPS in RAW264.7 cells and primary peritoneal macrophages. In addition, consistent with the results in vitro, in the model of mice acute lung injury (ALI) induced by LPS, SAL reduced the infiltration of inflammatory cells and decreased the levels of serum TNF-α and IL-6 obviously. Taken together, these data indicated that SAL exerted anti-inflammatory action via down-regulating LPS-induced activation of JAK2-STAT3 pathway and suppressing STAT3 transfer into the nucleus at least in part.
研究领域:
药理学
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免疫学
·
细胞生物学
·
炎症
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 3
·1472-1481
·
IF 6.317
Jiaxuan Li,Yu Li,Xuedi Zhang,Song Miao,Mingqian Tan,Wentao Su
Fruit juice is one of the most popular drinks, which requires strict processing conditions to ensure its quality, especially to prevent enzymatic browning and turbidity loss. In this work, a new strategy for the preparation of composite nanofibers for juice clarification and anti-browning control was proposed. The strategy used microfluidic spinning to combine Fucoxanthin (Fx), hydroxypropyl-γ-cyclodextrin (HP-γ-CD) and polyvinyl pyrrolidone (PVP) to prepare Fx/HP-γ-CD-PVP (PCF) nanofibers, which not only reflected the excellent antioxidant properties of cyclodextrin-wrapped Fx, but also achieved a more optimized juice clarification agent dosage. Molecular docking technique was used to prove that the stable inclusion complex of Fx and HP-γ-CD could be formed by hydrogen bonding when the molar ratio of Fx to HP-γ-CD was 1 : 2, and the binding energy was as low as −10.23 kcal mol−1. SEM, XRD, FT-IR and TGA were used to characterize the structure of the composite nanofibers, which showed that the thermal stability and water solubility of the embedded Fx were improved. Further studies showed that the apple juice with PCF nanofibers containing inclusion complexes of Fx and HP-γ-CD at a molar ratio of 1 : 2 (PCF 1 : 2) could significantly improve the DPPH and ABTS radical scavenging activity, and could significantly protect the cell membrane integrity of RAW264.7 cells against H2O2 oxidative damage. Finally, the effects of PCF nanofibers on the quality of fresh juice were studied, including clarification experiment and sensory evaluation. The results showed that the dosage of PVP in PCF 1 : 2 was only about 4% of the conventional dosage, and the browning index of fresh juice was significantly reduced with the best clarification. The available data provided in this study would provide a promising safety strategy for the food processing of fresh juice and the extension of its storage life.
研究领域:
食品科学
·
纳米技术
·
生物技术
·
化学工程
✓ 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）