JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Ping Chen,Cheng Lin,Qi Jin,Baibai Ye,Xinxu Liu,Keke Wang,Han Zhang,Jiahui Liu,Runan Zhang,Hao Huang,Chenning Zhang,Linfu Li
Ethnopharmacological relevance In TCM opinion, most of pneumonia is related to "lung heat". Sophora davidii (Franch.) Skeels flower was first documented in "Guizhou Herbal Medicine", and was recorded as having functions of clearing heat, detoxifying, and cooling blood. It can be used to treat lung heat cough. Aim of the study To investigate main mechanisms of Sophora davidii flower extract (SDFE) in Treating LPS-induced acute Pneumonia. Materials and methods Acute pneumonia models on BEAS-2B cells and rats were established using LPS. The rat model was used to verified the protective effects of SDFE through HE staining, lung tissue W/D ratio assay, white blood cell count analysis, and ammonia-induced coughing test. Network pharmacology was applied to predict the active compounds, core targets and main pathways of SDFE in treating acute pneumonia. Western Blot and ELISA kits were employed to validate representative proteins in selected pathway in vivo and in vitro . Results HE staining, lung tissue W/D ratio assay, white blood cell count analysis, and ammonia-induced coughing test showed SDFE could improve pathological features (leukocyte infiltration, pulmonary edema, lung injury and cough). Network pharmacology indicated MAPK/NF-κB pathway was the most relevant pathway. SDFE could significantly inhibit the expression of Fos and Jun, and the phosphorylation levels of p38, ERK, JNK, NF-κB and IκB. It also down-regulated the expression of pro-inflammatory factors (TNF-α, IL-6 and IL-1β). Conclusions SDFE can exert protective effects against acute pneumonia through the MAPK/NF-κB signaling pathway.
研究领域:
药理学
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免疫学
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中医药
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2021
·
IF 4.711
Huan Lan,Lu-Ying Zhang,Wen He,Wan-Ying Li,Zhen Zeng,Bo Qian,Chengqiang Wang,Jia-Le Song
The integrity and permeability of the intestinal epithelial barrier are important indicators of intestinal health. Impaired intestinal epithelial barrier function and increased intestinal permeability are closely linked to the onset and progression of various intestinal diseases. Sinapic acid (SA) is a phenolic acid that has anti-inflammatory, antihyperglycemic, and antioxidant activities; meanwhile, it is also effective in the protection of inflammatory bowel disease (IBD), but the specific mechanisms remain unclear. Here, we evaluated the anti-inflammatory of SA and investigated its potential therapeutic activity in LPS-induced intestinal epithelial barrier and tight junction (TJ) protein dysfunction. SA improved cell viability; attenuated epithelial permeability; restored the protein and mRNA expression of claudin-1, ZO-1, and occludin; and reversed the redistribution of the ZO-1 and claudin-1 proteins in LPS-treated Caco-2 cells. Moreover, SA reduced the inflammatory response by downregulating the activation of the TLR4/NF-κB pathway and attenuated LPS-induced intestinal barrier dysfunction by decreasing the activation of the MLCK/MLC pathway. This study demonstrated that SA has strong anti-inflammatory activity and can alleviate the occurrence of high intercellular permeability in Caco-2 cells exposed to LPS.
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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胃肠病学
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产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2023
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IF 3.6
Chen Min,Huang Shanjiao,Weng Shuoyun,Weng Junting,Guo Rongjie,Shi Bingbing,Liu Danjuan
Septic cardiomyopathy (SCM) is manifested by impairment of cardiac contractile function with myocardial mitochondrial dysregulation. Natural product, songorine (SGR), a diterpenoid alkaloid derived from the lateral root of Aconitum carmichaeli , has been reported for the treatment of heart failure. Here, the protective role of SGR in heart injury of SCM was investigated and its underlying action of mechanism was explored. Firstly, the mouse and cardiomyocytes (H9C2 cell) SCM model induced by LPS were established to evaluate the therapeutic effect of SGR. The in vivo results exhibited that SGR rescued the survival rate of SCM mice, restored the loss of ejection fraction (EF) and fractional shortening (FS), and reduced left ventricular systolic diameter and left ventricular diastole diameter (LVIDs, LVIDd) by echocardiography. SGR improved the mitochondrial biosynthesis and myocardial fiber structure and arranged them neatly by transmission electron microscope (TEM). Further, SGR inhibited inflammatory targets myeloperoxidase (MPO) and tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and plasminogen activator inhibitor-1 (PAI-1). And SGR activated the mitochondrial biosynthesis–related peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α), β-catenin, and matrix metallopeptidase 2 (MMP2) proteins. Meanwhile, the in vitro results showed that SGR promoted the increased the myocardial H9C2 cell viability, and mitochondrial biosynthesis and structure. SGR also blocked the inflammatory factors and reversed PGC-1α, β-catenin, and MMP2 in vitro, while SGR alleviated the myocardial cell apoptosis via flow cytometry. The findings indicate that SGR mitigates sepsis-caused myocardial damage by Wnt/β-catenin signaling pathway–mediated mitochondrial biosynthesis. SGR may be a promising candidate for treatment of SCM. Graphical Abstract
研究领域:
药理学
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心脏病学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2023
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IF 14.5
Huiwen Liu,Honglan Wang,Qiyu Li,Yiwei Wang,Ying He,Xuejing Li,Chunyan Sun,Onder Ergonul,Füsun Can,Zhiqing Pang,Bo Zhang,Yu Hu
Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro , the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo , the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.
研究领域:
药理学
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心血管疾病
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炎症
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纳米技术
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治疗学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2023
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IF 5.6
Jiangwei Ni,Ge Li,Ningfeng Dai,Zijiao Quan,Haibin Tong,Yu Liu
Objectives Acute lung injury (ALI) poses a serious threat to human health globally, particularly with the Coronavirus 2019 (COVID-19) pandemic. Excessive recruitment and infiltration of neutrophils is the major etiopathogenesis of ALI. Esculin, also known as 6,7-dihydroxycoumarin, is a remarkable compound derived from traditional Chinese medicine Cortex fraxini . Accumulated evidence indicates that esculin has potent anti-inflammatory effects, but its pharmaceutical effect against ALI and potential mechanisms are still unclear. Methods This study evaluated the protective effect of esculin against ALI by histopathological observation and biochemical analysis of lung tissues and bronchoalveolar lavage fluid (BALF) in lipopolysaccharide (LPS)-challenged ALI mice in vivo . The effects of esculin on N-formyl-met-leu-phe (fMLP)-induced neutrophil migration and chemotaxis were quantitatively assessed using a Transwell assay and an automated cell imaging system equipped with a Zigmond chamber, respectively. The drug affinity responsive target stability (DARTS) assay, in vitro protein binding assay and molecular docking were performed to identify the potential therapeutic target of esculin and the potential binding sites and pattern. Results Esculin significantly attenuated LPS-induced lung pathological injury, reduced the levels of pro-inflammatory cytokines in both BALF and lung, and suppressed the activation of NF-κB signaling. Esculin also significantly reduced the number of total cells and neutrophils as well as myeloperoxidase (MPO) activity in the BALF. Esculin impaired neutrophil migration and chemotaxis as evidenced by the reduced migration distance and velocity. Furthermore, esculin remarkably inhibited Vav1 phosphorylation, suppressed Rac1 activation and the PAK1/LIMK1/cofilin signaling axis. Mechanistically, esculin could interact with β 2 integrin and then diminish its ligand affinity with intercellular adhesion molecule-1 (ICAM-1). Conclusions Esculin inhibits β 2 integrin-dependent neutrophil migration and chemotaxis, blocks the cytoskeletal remodeling process required for neutrophil recruitment, thereby contributing to its protective effect against ALI. This study demonstrates the new therapeutic potential of esculin as a novel lead compound.
研究领域:
药理学
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免疫学
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病理生理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2024
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IF 3.3
Xu Han,Xiaqing Wu,Fanglin Liu,Huan Chen,Hongwei Hou
Inflammation is the physiological response of the immune system to injury or infection, typically manifested by local tissue congestion, swelling, heat, and pain. Prolonged or excessive inflammation can lead to tissue damage and the development of many diseases. The anti-inflammatory effects of natural ingredients have been extensively researched and confirmed. This study investigated the effects of Chlorogenic acid (CGA) isomers —— 3-Caffeolyquninic acid (3-CQA), 4-Caffeolyquninic acid (4-CQA), and 5-Caffeolyquninic acid (5-CQA) —— on the inflammatory response and oxidative stress reaction induced by LPS in RAW264.7 cells. Overall, 3-CQA exhibited the most significant reduction in levels of TNF-α, IL-6, NO, and ROS. 4-CQA showed superior inhibition of TNF-α compared to 5-CQA (p < 0.05), while no significant difference in other parameters. We further used DARTS and CETSA to demonstrate that CGA isomers have stable affinity with AKR1B1. As a positive control, the AKR1B1 antagonist epalrestat exhibited similar effects to the CGA isomers. 3-CQA having the smallest half-inhibitory concentration (IC50) for AKR1B1, while 4-CQA and 5-CQA have similar values. AutoDock simulations of the docking conformations revealed minimal differences in the average binding energies of the CGA isomers. The main differences were that VAL47 formed a hydrogen bond with 3-CQA, whereas GLN49 formed hydrogen bonds with 4-CQA and 5-CQA. Additionally, the number of hydrophobic bonds involving PHE122 and LEU300 varies. Our conclusion is that differences in non-covalent interactions result in the varying inhibitory abilities of CGA isomers on AKR1B1, which further affect the anti-inflammatory and antioxidant effects of CGA isomers.
研究领域:
药理学
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免疫学
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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
Journal of Functional Foods
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2018
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IF 3.47
Cuicui Duan,Yujuan Zhao,Cheng Huang,Zijian Zhao,Lei Gao,Chunhua Niu,Chao Wang,Xiaoxiao Liu,Chuan Zhang,Shengyu Li
Acute liver failure (ALF) is a life-threatening clinical condition resulting from massive apoptosis of hepatocytes. This study aims to examine the protective effects of Lactobacillus plantarum C88 on LPS/D-GalN-induced ALF and elucidate its underlying molecular mechanisms in mice. The results showed that L. plantarum C88 pretreatment significantly reduced the levels of plasma ALT and AST in mice with LPS/D-GalN–induced liver injury. L. plantarum C88 pretreatment decreased the secretion of inflammatory cytokines. In addition, L. plantarum C88 remarkably increased the expression levels and nuclear translocations of Nrf2 mRNA in liver tissues, but inhibited NF-κB nuclear translocations and P65, P38 phosphorylation levels. Moreover, L. plantarum C88 enhanced the intestinal mucosal barrier by upregulating the expressions of tight junction proteins as well as HIF-1α. These results suggest that L. plantarum C88 protects against ALF associated with Nrf2 and the MAPK/NF-κB signaling pathways.
研究领域:
药理学
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免疫学
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分子生物学
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胃肠病学
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产品关联
DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2023
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IF 5.8
Yinfeng Lyu,Meishu Tan,Meng Xue,Wenjing Hou,Chengyi Yang,Anshan Shan,Wensheng Xiang,Baojing Cheng
Antimicrobial peptides , as an integral part of the innate immune system, kill bacteria through a special mechanism of action, making them less susceptible to drug resistance. However, Lipopolysaccharide (LPS) as the permeation barrier on the bacterial membrane, inhibits the antibacterial activity of antimicrobial peptides and triggers the inflammatory response. GWKRKRFG is an LPS binding sequence with a β-boomerang motif that can be linked to antimicrobial peptides to enhance their LPS affinity and reduce the possibility of LPS-induced inflammatory responses. In this study, a series of hybrid peptides were designed by conjugating the reported LPS binding sequence to the C-/N-terminal sequences of the natural porcine antimicrobial peptide PMAP-23 to increase the LPS affinity of peptides. Among all the designed hybrid peptides, 4R-PP-G8 showed the best antibacterial activity, nonhemolytic activity, and excellent cell selectivity. The presence of LPS not only induced the secondary structure transformation of 4R-PP-G8 from a random structure to an α-helical structure but also reduced the antibacterial activity of 4R-PP-G8 in a dose-dependent manner, indicating the excellent binding ability of 4R-PP-G8 to LPS. The LPS/LTA binding assay further verified the interaction between the peptide and LPS. The membrane permeability test verified that 4R-PP-G8 possessed a strong capability to penetrate the bacterial membrane after interacting with LPS. More direct membrane disruption was observed under FE-SEM and TEM. In conclusion, we provided a simple and efficient method to improve the LPS binding ability of antimicrobial peptides and enhance their antimicrobial activity, resulting in the peptide 4R-PP-G8 with clinical application potential.
研究领域:
微生物学
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免疫学
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药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nanoscale Research Letters
·
2021
·Vol. 16
·期 1
·1-16
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IF 4.703
Zhou Lin,Huang Zhi,Yang Shanyi,Wei Jiarui,Xu Yan,Hu Lin,Guo Xinrong,Yuan Limin,Yuan Zexuan,Yang Xiaoping,Tao Xiaojun,Zhang Qiufang
Hydrophilic polyethylene glycol monomethyl ether (mPEG) was grafted onto Icariin (ICA) by succinic anhydride to form a polyethylene glycol-Icariin (mPEG-ICA) polymer. The structure of the polymer was characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). mPEG-ICA nanoparticles loaded with ICA were prepared by physical embedding of ICA by dialysis. The particle size was determined to be (220 ± 13.7) nm, and the ζ potential was (2.30 ± 1.33) mV by dynamic light scattering (DLS). Under a transmission electron microscope (TEM), the nanoparticles were spherical, and the morphology was regular. In the medium with pH 7.4, the drug release rate of mPEG-ICA nanoparticles reached (52.80 ± 1.70)% within 72 h. At pH 6.8, the cumulative drug release of nanoparticles reached (75.66 ± 0.17)% within 48 h. Treatment of the nanoparticles with LPS-treated H9c2 cells maintained cell viability, reduced LDH release and exerted antiapoptotic effects. Moreover, ICA-loaded mPEG-ICA nanoparticles significantly decreased the mRNA expression of the myocardial inflammatory cytokines TNF-α, IL-1β and IL-6M. In conclusion, ICA-loaded mPEG-ICA nanoparticles protected against LPS-induced H9c2 cell injury.
研究领域:
药学
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纳米技术
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细胞生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
·
2025
·Vol. 56
·期 2
·1-11
·
IF 2.2
Zhang Xiuping,Wang Shimin,Liang Lixia,Hu Fen,Zhang Xueluo,Cui Xiangrong,Zhang Zhiping,Wu Xueqing
Recurrent spontaneous abortion (RSA) brings tremendous difficulties to clinical treatment and prognosis. Pre-B-cell leukemia homeobox 1 (PBX1), as a functional transcription factor, involves in the regulation of cell apoptosis and proliferation. However, the underlying mechanism of PBX1 in RSA treatment has not been explored. We established a lipopolysaccharide (LPS)-induced abortion model and detected PBX1 expression with real-time PCR, western blot and immunohistochemistry. The PBX1-overexpressed adenovirus (AV-oePBX1) was infected into trophoblast cells treated with LPS to define the function of PBX1 on cell apoptosis, inflammation and NF-κB pathway. A luciferase reporter assay was conducted to validate the transcription regulation of PBX1 on transmembrane and ubiquitin like domain containing 1 (TMUB1). Compared to women with normal abortion, PBX1 was downregulated in the placental villous tissues of RSA patients. The placental tissues of LPS-treated mice also manifested notably reduction of PBX1 at mRNA and protein levels. PBX1 overexpression alleviated inflammation and apoptosis of trophoblast cells. Substantially, PBX1 was negatively correlated with TMUB1, which was highly expressed in RSA patients and LPS-treated mice. Moreover, PBX1 bound to TMUB1 promoter and inhibited its transcription. Interestingly, exogenous TMUB1 abolished the effects of PBX1 on apoptosis, inflammation, and NF-κB signal pathway. In total, PBX1 attenuated cell apoptosis and inflammation, and suppressed NF‐κB signal pathway induced by LPS through downregulating TMUB1 transcription. Therefore, PBX1 may be developed as a novel target for clinical treatment of RSA.
研究领域:
妇产科学
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分子生物学
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转化医学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2021
·
IF 4.432
Guanghui Xu,Huiqi Wan,Litao Yi,Wei Chen,Youhua Luo,Yiqi Huang,Xiaojuan Liu
Accumulating evidence showed that berberine possessed the anti-inflammatory action in various diseases caused by inflammation. However, it was still unclear whether both inhalation and injection with berberine produced pulmonary protective role in acute respiratory distress syndrome (ARDS). This study was aimed to evaluate the effects of both administration routes including inhalation and injection with berberine in ARDS induced by lipopolysaccharide (LPS) inhalation. Histopathological examination and weight of lung were evaluated. Phosphorylation of NF-κB, JAK2 and STAT3 were measured to assess the activity of inflammation related signaling pathways. Proinflammatory cytokines including interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the bronchoalveolar lavage fluid (BALF) and serum were also detected. The results showed that LPS caused the lung injury, while both administration routes with berberine attenuated the injury and improved the pulmonary morphology. In addition, the primary TLR4/NF-κB and secondary JAK2/STAT3 signaling pathways which were activated by LPS in lung were totally inhibited by berberine administration. Moreover, proinflammatory cytokines in both BALF and serum were decreased by berberine. Considering that molecular docking simulation indicated that berberine could bind with TLR4, the present suggested that the inhibition of the inflammation related TLR4/NF-κB and JAK2/STAT3 signaling pathways might be involved in the pulmonary protective effect of berberine in LPS-induced ARDS.
研究领域:
药理学
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呼吸医学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2023
·
IF 3.1
Chan-juan Chai,Yao Sun,Rui-fang Chi,Hui-yu Yang,Bin Yang,Bao Li
Cardiac remodeling (CR), characterized by cardiac hypertrophy and fibrosis, leads to the development and progression of heart failure (HF). Nowadays, emerging evidence implicated that inflammation plays a vital role in the pathogenesis of CR and HF. Astragaloside IV (AS-IV), an effective component of Astragalus membranaceus , exerts cardio-protective and anti-inflammatory effects, but the underlying mechanism remains not fully elucidated. This present study aimed to investigate the effects of AS-IV on cardiac hypertrophy and fibrosis in cultured H9C2 cells stimulated with LPS, as well as explore its underlying mechanisms. As a result, we found AS-IV could reduce the cell surface size, ameliorate cardiac hypertrophy and fibrosis in LPS-induced H9C2 cells. To specify which molecules or signaling pathways play key roles in the process, RNA-seq analysis was performed. After analyzing the transcriptome data, CCL2 has captured our attention, of which expression was sharply increased in model group and reversed by AS-IV treatment. The results also indicated that AS-IV could ameliorate the inflammatory response by down-regulating NF-κB signaling pathway. Additionally, a classical inhibitor of CCL2 (bindarit) were used to further explore whether the anti-inflammatory effect of AS-IV was dependent on this chemokine . Our results indicated that AS-IV could exert a potent inhibitory effect on CCL2 expression and down-regulated NF-κB signaling pathway in a CCL2-dependent manner. These findings provided a scientific basis for promoting the treatment of HF with AS-IV.
研究领域:
心脏病学
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药理学
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炎症
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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）