BIOMATERIALS
·
2020
·
IF 10.317
Guangzhen Yang,Mengni Fan,Jingwu Zhu,Chen Ling,Lihuang Wu,Xin Zhang,Ming Zhang,Jiayi Li,Qingqiang Yao,Zhongwei Gu,Xiaojun Cai
Specifically inhibiting the proliferation of activated macrophages and clearing the high levels of reactive oxygen species (ROS) secreted by macrophages is crucial for osteoarthritis (OA) treatment. Moreover, if the clearance of these high levels of ROS can be simultaneously used to induce oxidation-responsive release of anti-inflammatory drugs, the therapeutic effect of OA may be further improved. Here, a multifunctional anti-inflammatory drug (CPHs) based on a peptide dendrimer nanogel was constructed by physically encapsulating CORM-401 and wrapping its surface with folic acid (FA)-modified hyaluronic acid (HA). CPHs is capable of efficiently entering activated macrophages via FA- and HA-mediated specific targeting effects and then rapidly release large amounts of CO by massive consumption of H 2 O 2 . The generated CO effectively suppresses the secretion of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α by inhibiting cell proliferation ; inducing the activation of heme oxygenase (HO-1), and downregulating the expression of p38 MAPK , NF-kB (p50/p65) and TLR-2. In vivo experiments further confirmed that CPHs can massively deplete ROS in OA joints and effectively suppress the degradation of articular cartilage and their extracellular matrix. More importantly, CPHs is non-toxic to normal macrophages, and the high levels of CO generated in the joints do not result in notable changes in the HbCO levels in blood. Together, these results show that CPHs is an effective and safe anti-inflammatory drug and has essential application prospects in OA treatment.
研究领域:
药理学
·
炎症
·
纳米技术
·
骨科
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2022
·Vol. 27
·期 5
·160
·
IF 3.115
Yuzhu Cao,Keqin Lu,Yawen Xia,Yufei Wang,Aiyun Wang,Yang Zhao
Background: The interactions between platelets and tumor cells are well-known to play important roles in the progression of malignant tumors. Danshensu, a main water-soluble component of Salvia miltiorrhiza, can resist platelet aggregation and exert significant anti-tumor effects on various types of tumors. However, whether Danshensu could inhibit the progression of malignant tumors by suppressing the activities of platelets had not been reported. Methods: The effects of Danshensu on the platelet activity and epithelial-mesenchymal transformation (EMT)-like invasive phenotype of SW620 colon cancer cells were assessed by stimulating with the supernatants from co-cultured platelets and SW620 cells with direct contact (SCP). The expression and secretion of proteins were determined by western blot and enzyme-linked immunosorbent assay (ELISA), respectively. Hematoxylin and eosin (H&E) staining was performed to analyzed the histopathology of tumor tissues and immunohistochemical staining was conducted to examine the protein expression in tumors. Results: Co-incubation of SW620 cells with platelets directly or SCP both generated long spindle-shaped invasive phenotype. Pretreatment of platelets with Danshensu (25 μM) inhibited the morphological changes of SW620 cells induced by SCP, which was associated with the inhibitory effects of Danshensu on platelet secretion. Danshensu diminished the secretion of a list of biological factors in SCP, including interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β and vascular endothelial growth factor (VEGF) that are all involved in tumor cell EMT and chemoresistance. Moreover, Danshensu up-regulated the expression of E-cadherin but down-regulated the levels of N-cadherin and Vimentin, resulting in the repression of SW620 cell migration. It was also shown that Danshensu enhanced the sensitivity of SW620 cells to oxaliplatin by suppressing the expression of MDR1. Furthermore, Danshensu could not only reduced the growth of subcutaneous tumors and liver metastasis that induced by SCP, but also down-regulated the expression of MDR1 in vivo. Mechanistic studies revealed that Danshensu suppressed the activation of the TGF-β/Smad signaling pathway. Conclusions: Danshensu attenuated EMT-like characteristics and chemoresistance by inhibiting secretion capability of platelets and activation of the TGF-β/Smad signaling pathway, suggesting that it may be optimized to be a therapeutic agent for fighting against colon cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2023
·Vol. 71
·期 4
·269-276
·
IF 1.7
Xiaoran Ning,Yanhui Ni,Jingjing Cao,Huaxing Zhang
Rheumatoid arthritis (RA) is a common autoimmune disease with increased cardiovascular disease risk. Liquiritigenin (LG) is a triterpene with anti-inflammatory properties. Our study aimed to explore the effect of LG on RA and the cardiac complication. Collagen-induced arthritis (CIA) mice with LG treatment exhibited obvious alleviation in histopathological changes, accompanied by the decreased expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-17A in synovium and serum. LG attenuated cartilage destruction by reducing matrix metalloproteinase (MMP)-3 and MMP-13 expression in the synovium of CIA mice. The echocardiography results proved the alleviation of cardiac dysfunction in CIA mice. The electrocardiogram, biochemical, and histochemical analysis proved the cardioprotection effect of LG against RA. The decreased expression of inflammatory factors (TNF-α, IL-1β, and IL-6) and fibrotic markers (fibronectin, Collagen I, and Collagen III) in cardiac tissues of CIA mice further corroborated the attenuation of myocardial inflammation and fibrosis by LG. Mechanistic studies showed that LG could inhibit transforming growth factor β-1 (TGF-β1) and phos-Smad2/3 expression in cardiac tissues of CIA mice. Our study suggested that LG could relieve RA and its cardiac complication probably by inhibiting the TGF-β1/Smad2/3 pathway. All these suggested that LG might be a potential candidate for RA and its cardiac complication therapy.
研究领域:
免疫学
·
风湿病学
·
心脏病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2020
·
IF 4.679
Yonghua Cui,Yi Che,Hongxin Wang
A large number of studies showed that aluminum (Al) has potential neurotoxicity to human and animal bodies. Al-treated animals showed anxiety-like behavior, oxidative stress , neuroinflammation and γ-aminobutyric acid (GABA) changes. Bergamot essential oil (BEO) is a kind of well-known plant extract from the fresh fruit of bergamot. Previous studies suggested that BEO improved mood and relieved symptoms of stress-induced anxiety. This study was designed to study the effects of BEO on anxiety-like behavior, oxidative stress, neuroinflammation and GABA system in aluminum trichloride (AlCl 3 ) treated rats. Results showed that AlCl 3 exposure induced anxiety-like behavior in the elevated plus maze and the open field test. Moreover, AlCl 3 exposure decreased the level of GABA and the activity of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in the hippocampus (HP) and the frontal cortex (FC). In addition, AlCl 3 exposure increased the levels of malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) and the levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the HP and the FC. To the contrary, co-administration of BEO and AlCl 3 improved the anxiety-like behavior, GABA system, oxidative stress and neuroinflammation. These results indicated that BEO can alleviate the anxiety-like behavior of AlCl 3 -exposed rats through the combined action of antioxidant, anti-inflammatory and GABA regulation.
研究领域:
神经毒理学
·
药理学
·
行为神经科学
✓ 已验证
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2025
·
IF 2.5
Tingli Qu,Shasha Suo,Liqiu Yan,Liwei Wang,Taigang Liang
Astragaloside IV (ATS) is an active component of Astragalus membranaceus, which has immune regulation and anti-inflammatory effects. However, owing to its large molecular weight and poor solubility in water, the therapeutic effects of ATS are limited. We aimed to prepare astragaloside IV-chitosan (ATS-CS) nanoparticles and determine their anti-inflammatory effect and mechanism of action on RAW264.7 cells using metabolomics. The size of the ATS-CS nanoparticles was 200.3 nm with a zeta potential of 30.5 mV, and the encapsulation rate and drug loading were 69% and 13%, respectively. ATS-CS nanoparticles not only significantly decreased the increase of NO, IL-6 and TNF-α levels induced by LPS, but also exerted an anti-inflammatory effect by acting on arginine and proline, glutathione, sphingolipid, glycerophospholipid, and glycine, serine, and threonine metabolism. Our findings confirmed that ATS-CS nanoparticles have good anti-inflammatory activity and showed that the activity of high molecular weight can be increased by producing nanoparticles. Our study paves the way for exploring the mechanism of nanoparticles through metabolomics.
研究领域:
药理学
·
纳米技术
·
免疫学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Guofeng Wu,Fenbo Ma,Yizhebang Xue,Ying Peng,Liqiu Hu,Xiaowo Kang,Qili Sun,Dong Fang Ouyang,Bin Tang,Lijun Lin
A chondroitin sulfate zinc (CSZn) complex was prepared by an ion-exchange method. The purified product was characterized by energy-dispersive X-ray spectroscopy, high-performance chromatography, elemental analysis , Fourier transform infrared spectroscopy , inductively coupled mass spectrometry , and nuclear magnetic resonance spectroscopy . The CSZn demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus and satisfied MTT cell viability (NIH3T3 fibroblasts) at ≤50 μg/mL. RT-PCR demonstrated significant promotion by CSZn of fibroblast growth factor beta (β-FGF), collagen III (COLIIIα1), vascular endothelial growth factor (VEGF) and reduction of cytokines IL-6, IL-1β & TNF-alpha. An in vivo rat full-thickness wound healing model demonstrated significant wound healing of CSZn relative to controls of saline treatment, zinc chloride treatment and chondroitin treatment. CSZn has demonstrated promising antibacterial and wound healing properties making it deserving of consideration for more advanced wound healing applications.
研究领域:
药学
·
伤口愈合
·
生物材料
·
生物医学工程
·
微生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Guoqin Zhang,Jianhua Sun,Meiqi Liu,Zhixiang Tian,Zicheng Ma,Bingyu Hao,Jintang Ning,Xiaoliang Ren,Meng Wang,Ping Wang,Jiunian Li,Hailin Li,Jian Ni,Yi Liu
Polygoni multiflori radix (PM) is a well-known tonic herb. It has been reported that PM could cause idiosyncratic inflammatory liver injury in some individuals. In this study, we investigated the mechanism of PM-induced idiosyncratic inflammatory liver injury in zebrafish and rat models based on pharmacodynamics and pharmacokinetics. The zebrafish were administered with polygoni multiflori radix extract (PME), emodin (EMO), and 2,3,5,4′-tetrahydroxystilbene-2-Ο-β- D -glucoside (TSG) after lipopolysaccharide (LPS) treatment, to establish an idiosyncratic inflammation model. In zebrafish with idiosyncratic inflammation, PME, EMO, and TSG decreased liver area and brightness and increased the number of immune cells around the colliculi. PME+LPS produced hepatocyte damage, aggravated mitochondrial and endoplasmic reticulum damage, and increased AST and ALT activity. RT-PCR showed that PME and EMO up-regulated the expression of IL-6, IL-1β, and INF-γ, and PME down-regulated expression of FXR and SHP. In rats with idiosyncratic inflammation, AST and ALT activities increased significantly, and liver tissues showed pathological damage. An efficient and sensitive LC-MS/MS method was established for the pharmacokinetic study of EMO and TSG in rats with idiosyncratic inflammation. The AUC 0−t was higher for EMO and TSG in the model group compared with the normal group. The MRT 0−t was significantly prolonged in EMO, while CL z/F was significantly reduced. The present results suggested that the absorption of potentially toxic components of PM increased and metabolism slowed down under inflammatory stress, and PM induced idiosyncratic liver injury via the FXR-SHP axis.
研究领域:
药理学
·
毒理学
·
肝病学
·
药代动力学
·
斑马鱼模型
·
大鼠模型
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Environmental Science-Nano
·
2023
·Vol. 10
·期 12
·3389-3400
·
IF 7.3
Shuoli Ma,Wen-Xiong Wang
Marine hydrosphere is in grave danger if extreme weather conditions, such as high temperatures and heat waves, become the norm. The functional characteristics of nano Zn oxides (nZnO) might provide a “booster substance” that helps marine species to endure environmental stress. In the present study, physiological indicators and simulated severe environments were used to evaluate the antioxidative ability of nZnO in marine rabbitfish Siganus fuscescens, with an aim to help them resist extreme environmental stress. Rabbitfish were exposed to different diets with ZnSO4 and nZnO at the optimum requirement level (Zn content of 62.5 μg g−1), and then challenged with a low dissolved oxygen concentration and higher temperature. We demonstrated that dietary nZnO promoted the anti-oxidation defense system of the rabbitfish by improving the activities of the antioxidant enzymes, i.e., catalase (CAT), superoxide dismutase (SOD), and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio without tissue damage. Compound stressors reduced the median survival duration of the rabbitfish from 4.25 h to 2.5 h (dietary exposure) and 9 h to 5.75 h (dietary nZnO exposure) compared to single environmental stress. nZnO downregulated the HIF gene expression and increased the prolyl hydroxylase (PHD) activity in the liver of the rabbitfish. After 10 h of extreme environmental exposure, the gene expression results indicated that nZnO inhibited the NF-κB/IL-1β/IL-6 pathway and TNF-α/Bcl-2/Bax/caspase 9 pathway and activated the akt/mTOR/elovl5 and elovl8 pathway of the rabbitfish to maintain the resilience of the fish under the extreme environment. These results strongly suggested that nZnO may improve the anti-oxidation ability of fish to resist extreme environments.
研究领域:
海洋生物学
·
环境科学
·
水产养殖
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2018
·
IF 2.559
Fan Zhang,Chenhong Zhang
Intracerebral hemorrhage (ICH) is reported as a common and often fatal type of stroke accompanied with high morbidity and mortality, and it frequently results in long-lasting neurological dysfunctions. However, the pathogenesis that contributes to ICH has not been fully understood. Rnf112, also known as Znf179, is a member of the RING finger protein family. The expression of Rnf112 is abundant in the brain and is modulated during brain progression and development. The study aimed to explore the role of Rnf112 in brain injury after ICH, as well as the underlying molecular mechanisms. The results indicated that ICH led to a significant decrease in Rnf112, which was confirmed in oxyhemoglobin (oxyHb)-incubated astrocytes and microglial cells. Moreover, the Rnf112 knockout (Rnf112 −/− ) mice and wild type (WT) mice induced by ICH were further employed. Compared to the WT/ICH group, Rnf112 −/− mice exhibited accelerated brain injury, as evidenced by the increased brain water contents and neurological deficit scores (NDS). In comparison to WT/ICH group, a remarkable up-regulation in the release of pro-inflammatory cytokines, including tumor necrotic factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, was observed in perihematoma tissues of Rnf112 −/− mice on day 3 post-ICH. The process was along with promoted glial fibrillary acidic protein (GFAP) and Iba1 expression and reduced NeuN levels. Furthermore, ICH-induced increases in toll-like receptor (TLR)-4 and myeloid differentiation primary response protein (MyD88) expression were exacerbated by the loss of Rnf112. The phosphorylated expression of IKKα, inhibitor of NF-κB (IκBα) and nuclear factor-kappa B (NF-κB) induced by ICH in perihematoma tissues of mice was markedly enhanced in Rnf112 −/− mice. Rnf112 repression-induced inflammatory response was verified in lipopolysaccharide (LPS)-incubated glial cells . In contrast, over-expressing Rnf112 markedly attenuated ICH-induced brain injury by restraining inflammation via inactivating TLR-4/NF-κB pathway. In summary, our findings suggested that Rnf112 expression was highly involved in the progression of ICH, and targeting Rnf112 signaling might be a promising therapeutic strategy against ICH development.
研究领域:
神经科学
·
分子生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2019
·
IF 3.448
Pan Chen,Hongliang Yao,Weiwei Su,Yudong He,Keling Cheng,Yonggang Wang,Wei Peng,Peibo Li
Aims Sleep deficiency has been reported to be associated with some oral health problems. Oral ulcers are very common lesions of the oral mucosa, which severely impact patients' quality of life. However, the association between sleep deficiency and the oral ulcer remains unknown. The present study aims to explore the effects of sleep deficiency on oral ulcers. Main methods Rats were divided into normal control group (n = 30) and oral ulcer group (OU group, n = 50). Model rats with phenol-induced oral ulcers were deprived of sleep for 72 h by using the modified multiple platform technique. Key findings Sleep deprivation worsened oral ulcers and delayed healing process in rats. In addition, sleep deprivation increased the γ-aminobutyric acid (GABA, P < 0.01) and 5-hydroxytryptamine (5-HT, P < 0.05) levels in serum and brain, the corticotrophin (ACTH, P < 0.05), corticosterone (CORT, P < 0.01), immunoglobulin (Ig)M ( P < 0.01), tumor necrosis factor-alpha (TNF-α) ( P < 0.01), interleukin (IL)-1β ( P < 0.01), IL-6 ( P < 0.01), IL-8 ( P < 0.01), monocyte chemoattractant protein-1 (MCP-1) ( P < 0.01), and 8-hydroxy-deoxyguanosine (8-OHdG, P < 0.01) levels in serum. Sleep deprivation also up-regulated malonaldehyde (MDA) ( P < 0.05), TNF-α ( P < 0.05), and IL-1β ( P < 0.01) levels in oral mucosa tissue and delayed superoxide dismutase (SOD, P < 0.05) activity recovery. Significance These data suggest that sleep deprivation impaired the oral ulcer healing in rat oral mucosa, and the mechanisms of this effect are probably related to neuro-immuno-endocrine system and oxidative stress.
研究领域:
神经科学
·
免疫学
·
内分泌学
·
口腔健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Yule Wang,Huimin Wu,Zhu Han,Hongda Sheng,Yuhan Wu,Yingchao Wang,Xinran Guo,Yan Zhu,Xuecai Li,Yi Wang
Background As a leading cause of death and disability, alternative therapies for stroke are still limited by its complicated pathophysiological manifestations. Guhong injection (GHI), consisting of safflower aqueous extract and aceglutamide, has been widely applied for the clinical treatment of cerebrovascular diseases , especially ischemic stroke and post-stroke recovery, in China. Recently, a series of studies have reported the positive effect of GHI against cerebral ischemia/reperfusion injury via targeting various molecular mechanisms. However, questions remain on whether treatment with GHI contributes to better functional recovery after stroke and if so, the potential mechanisms and active substances. Purpose The aim of this work was to explore the potential therapeutic possibilities of GHI for the neurological and behavioral recovery after stroke and to investigate the underlying molecular mechanisms as well as active substances. Methods The neural and motor deficits as well as cortical lesions after GHI treatment were investigated in a mouse model of transient ischemic stroke. Based on the substance identification of GHI, network pharmacology combined with an experimental verification method was used to systematically decipher the biological processes and signaling pathways closely related to GHI intervention in response to post-stroke functional outcomes. Subsequently, ingenuity pathway analysis (IPA) analysis was performed to determine the anti-stroke active substances targeting to the hub targets involved in the significant molecular pathways regulated by GHI treatment. Results Therapeutically, administration of GHI observably ameliorated the post-stroke recovery of neural and locomotor function as well as reduced infarct volume and histopathological damage to the cerebral cortex in subacute stroke mice. According to 26 identified or tentatively characterized substances in GHI, the compound-target-pathway network was built. Bioinformatics analysis suggested that inflammatory and apoptotic pathways were tightly associated with the anti-stroke effect of GHI. Based on protein-protein interaction network analysis, the hub targets (such as NF-κB p65, TNF-α, IL-6, IL-1β, Bax, Bcl-2, and Caspase-3) involved in inflammation and apoptosis were selected. On the one hand, immunofluorescence and ELISA results showed that GHI (10 ml/kg) treatment obviously reduced NF-κB p65 nuclear translocation as well as decreased the abnormally elevated concentrations of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) in damaged cortex tissues. On the other hand, GHI (10 ml/kg) treatment significantly downregulated the number of TUNEL-positive apoptotic cells in ischemic cortex and effectively restored the abnormal expression of Bax, Bcl-2, and Caspase-3. Based on the results of IPA, hydroxysafflor yellow A, baicalin , scutellarin , gallic acid , syringin , chlorogenic acid , kaempferol , kaempferol-3-O-β-rutinoside, and rutin acted synergistically on core targets, which could be considered as the active substances of GHI. Conclusion Overall, the current findings showed that the beneficial action of GHI on improving post-stroke functional recovery of subacute stroke mice partly via the modulation of cortical inflammation and apoptosis. These findings not only provide a reliable reference for the clinical application of GHI, but also shed light on a promising alternative therapeutic strategy for ischemic stroke patients .
研究领域:
神经病学
·
药理学
·
分子生物学
·
中风研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Fanghua Guo,Rong Tsao,Chuyao Li,Xiaoya Wang,Hua Zhang,Li Jiang,Yong Sun,Hua Xiong
Green pea hulls are a byproduct of the processing of green pea and are rich in phenolic substances. In the present study, in vitro digestion, human colonic adenocarcinoma cell line (Caco-2) monolayer, and the Caco-2/macrophage cell lines of the murine origin (Raw264.7) coculture model were established to investigate the release of polyphenols, absorption, and transport of digestive products and their effects on inflammation and intestinal barrier. During the digestive process, polyphenols were constantly released from the pea hulls, reaching the maximum amount in the small intestine (total phenolic content (TPC): 5.41 ± 0.04 mg gallic acid (GAE)/g dry weight (DW)), and the digestive products (800 μg/mL) could reduce the secretion of NO (50.9%), IL-6 (50.6%), and TNF-α (24.6%) and inhibit the mRNA expression of cyclooxygenase-2 (COX-2) (37.2%) and inducible nitric oxide synthase (iNOS) (91.1%) compared with the lipopolysaccharide (LPS) group. A total of 12 phenolic components were quantified by ultraperformance liquid chromatography-linear ion trap orbitrap tandem mass spectrometry (UHPLC-LTQ-OrbiTrap-MS) technology. Kaempferol trihexoside in digestive products could be absorbed and transported (1.25 ± 0.13 ng quercetin/mL). The digestive products could promote the expression of claudin-1 (210.8%), occludin (64.9%), and zonulin occludin-1 (ZO-1) (52.0%) compared with the LPS group and exert anti-inflammatory effects after being absorbed. The results indicated that pea hull polyphenols could be continuously released and absorbed to play a positive role in protecting the intestinal barrier and anti-inflammatory activity.
研究领域:
食品科学
·
营养学
·
药理学
·
细胞生物学
·
炎症研究
✓ 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）