JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
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2019
·Vol. 39
·期 9
·554-563
·
IF 1.774
Yan Yan,Pengchong Wang,Ying Sun,Yalin Dong,Jianfeng Xing
Previously, we reported that 3, 4-oxo-isopropylidene-shikimic acid (ISA) has therapeutic potential in experimental colitis in rats. This study aimed to elucidate the potential mechanisms of ISA on the inflammatory response in rats with 2, 4, 6-trinitrobenzenesulfonic acid-induced colitis. After the induction of colitis, rats were orally administered ISA for 12 days. Then, the expression levels of inflammatory cytokines, cell adhesion molecules, and matrix metalloproteinase (MMP) in the blood and colon tissues, and the protein level of nuclear factor kappa B (NF-κB) p65 in cytoplasm and nucleus of colon tissues were evaluated. As a result, an enhanced inflammatory response was observed in rats with experimental colitis. However, the treatment with ISA significantly ameliorated the inflammatory response, which was manifested as a significant decrease in the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, IL-8, TNF-α mRNA, P-selectin, E-selectin, intercellular cell adhesion molecule-1, MMP9 and MMP9 mRNA in rat blood and colon tissues, respectively, and a significant decrease in the levels of IFN-γ/IL-4, and the NF-κBp65 activity coefficient. Therefore, the therapeutic effect of ISA on experimental colitis may be related to its inhibitory effect on the expression of cytokines, adhesion molecules, and MMP9, which may be involved in the inhibition of the activation and nuclear translocation of NF-κBp65.
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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产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2025
·
IF 2.6
Shengjie Wang,Wei Liu,Chao Yang,Changwei Li,Xianlong Zhang
Implant-associated infections (IAI) present a significant clinical challenge. Effective prevention of and recovery from IAI is complex, involving antibacterial treatment and the promotion of bone integration. However, the current artificial implants used in clinics often lack effective antibacterial properties and have limited functionality. In this study, Lipopeptide 01 (LP01), a lipopeptide derived from the skin commensal Staphylococcus epidermidis is successfully immobilized, onto the porous surface of sulfonated Poly (ether-ether-ketone) (SPEEK) to create a novel artificial implant, LP01-PS. Both in vivo and in vitro experiments demonstrates that LP01-PS displays favorable material properties, biocompatibility, outstanding antibacterial characteristics, and the ability to promote bone formation. Mechanistically, LP01-PS enhances antibacterial activities by triggering TLR2/P65 signaling, upregulating the expression of LL37 and β-defensins in macrophages. Furthermore, it can boost the osteogenic differentiation capability of bone marrow mesenchymal stem cells (BMSCs) through the β-catenin signaling pathway, thereby facilitating bone formation. The discovery of LP01-PS with dual antibacterial and osteogenic effects, coupled with insights into its mode of action, suggests that LP01-PS can serve as a promising implant material to enhance the success rates of total joint replacement surgeries, mitigate the risks of infection and prosthetic loosening, and foster the repair and regeneration of bone tissue.
研究领域:
生物医学工程
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材料科学
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免疫学
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再生医学
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骨科
✓ 已验证
产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Xiaoliang Dong,Lu Qu,Bingxin Wang,Xiaowei Sha,Bo Wu,Yudong Sun,Xiaohua Pan,Juan Xiong,Jia Sun,Li-Long Pan
ABSTRACT Background Cardiovascular disease is one of the main causes of global mortality, and there is an urgent need for effective treatment strategies. Gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) promotes the development of cardiovascular diseases, and shizukaol C, a natural sesquiterpene isolated from Chloranthus multistachys with various biological activities, might exhibit beneficial role in preventing TMAO-induced vascular inflammation. Purpose The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of shizukaol C on TMAO-induced vascular inflammation. Methods The effect and underlying mechanism of shizukaol C on TMAO-induced adhesion molecules expression, bone marrow-derived macrophages (BMDM) adhesion to VSMC were evaluated by western blot, cell adhesion assay, co-immunoprecipitation, immunofluorescence assay, and quantitative Real-Time PCR, respectively. To verify the role of shizukaol C in vivo , TMAO-induced vascular inflammation model were established using guidewire-induced injury on mice carotid artery. Changes in the intima area and the expression of GSTpi, VCAM-1, CD68 were examined using haematoxylin-eosin staining, and immunofluorescence assay. Results Our data demonstrated that shizukaol C significantly suppressed TMAO-induced adhesion molecule expression and the bone marrow-derived macrophages (BMDM) adhesion in vascular smooth muscle cells (VSMC). Mechanically, shizukaol C inhibited TMAO-induced c-Jun N-terminal kinase (JNK)-nuclear factor-kappa B (NF-κB)/p65 activation, and the JNK inhibition was dependent on the shizukaol C-mediated glutathione-S-transferase pi (GSTpi) expression. By further molecular docking and protein-binding analysis, we demonstrated that shizukaol C directly binds to Keap1 to induce Nrf2 nuclear translocation and upregulated GSTpi expression. Consistently, our in vivo experiment showed that shizukaol C elevated the expression level of GSTpi in carotid arteries and alleviates TMAO-induced vascular inflammation. Conclusion : Shizukaol C exerts anti-inflammatory effects in TMAO-treated VSMC by targeting Keap1 and activating Nrf2-GSTpi signaling and resultantly inhibits the downstream JNK-NF-κB p65 activation and VSMC adhesion, and alleviates TMAO-induced vascular inflammation in vivo , suggesting that shizukaol C may be a potential drug for treating TMAO-induced vascular diseases.
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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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Yumei Sun,Jihong Wang,Peiyao Hu,Yi Tang,Yanwen Wang,Jianzhou Ye,Xuesong Yang,Junlin Yin
Tripterygium hypoglaucum (Lévl.) Hutch rhizome (THH) is mainly used in the clinical setting for the treatment of autoimmune diseases such as rheumatoid arthritis. In total, four active compounds were isolated from THH methanol extract （THH-MeOH）and identified. The HPLC results showed that the proportions of the active ingredients in THH-MeOH (i.e., celastrol, triptolide, and 3- O -acetyloleanolic acid) were 0.79 ‰, 0.46 ‰, and 0.76 ‰, respectively. THH-MeOH attenuated the M5-induced hyperproliferation of HaCaT cells, decreased the mRNA expression levels of inflammatory cytokines, and inhibited the phosphorylation of I κ B α , NF- κ B p65, MAPK, and STAT3/JAK2. Furthermore, THH-MeOH significantly reduced PASI scores in mice; reduced the level of Ki67 expression in skin tissues; decreased the expression of inflammatory cytokines in the skin lesions and serum; and ameliorated the IMQ-induced imbalance in the ROR γ t / Foxp3 ratio. The extract can attenuate psoriasis-like lesions by inhibiting cellular hyperproliferation, ameliorating inflammatory reactions, and modulating immune responses. Our work provides a theoretical basis to support the use of THH for treating psoriasis.
研究领域:
药理学
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免疫学
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皮肤科
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Shuang Luo,Jinrong He,Shaowei Huang,Xiaojing Wang,Yulin Su,Yanyang Li,Yanping Chen,Guanghua Yang,Bin Huang,Shaoju Guo,Lian Zhou,Xia Luo
Background Emodin is an active ingredient of traditional Chinese medicine Rheum palmatum L. and Polygonum cuspidatum , which possesses anti-inflammatory and intestinal mucosal protection effects. Our previous study found that emodin significantly alleviated ulcerative colitis induced by sodium dextran sulfate (DSS). In this study, we found the underlying mechanism of emodin on ulcerative colitis (UC). Purpose We aimed to further explore the mechanism of emodin in the treatment of ulcerative colitis from the perspective of metabolism and intestinal flora . Methods Ulcerative colitis was induced by 3% sodium dextran sulfate (DSS) on mice, and the mice were respectively treated with mesalazine , rosiglitazone , emodin, and emodin combined with GW9662 (PPARγ inhibitor) simultaneously. Weight changes , the disease activity index (DAI), colonic length, and pathologic changes in colon were used to evaluate the efficacy of emodin. LC-MS/MS was performed for metabolomics analysis of colon. In addition, intestinal flora was assessed using 16S rDNA sequencing. A vector-based short hairpin RNA (shRNA) method was used to silence PPARγ gene expression in Caco-2 cells. Results Emodin binds to the active site of PPARγ protein and forms hydrogen bond interaction with ARG288 and CYS285 amino acids. Furthermore, Emodin significantly promotes the protein expression of PPARγ, while inhibiting iNOS and NF-kB p65 in UC mice, however, this effect is hardly shown when it is combined with GW9662 (the inhibitor of PPARγ). Meanwhile, emodin suppresses the expression of iNOS in Caco-2 cells induced with IFNγ and IL-22, but has no effect on its expression in shPPARγ-Caco-2 cells. In addition, through activating PPARγ signal pathway , emodin is capable of regulating colonic metabolism including oxidative phosphorylation and citrulline metabolism and effecting luminal availability of oxygen and nitrate. This promotes the recovery of anoxic environment of colon epithelial cells, which strains the growth and expansion of Enterobacteriaceae . Conclusion The mechanism of Emodin in the treatment of ulcerative colitis relies on its regulation of PPARγ signal pathway, which could modulate colonic metabolism and restore intestinal homeostasis .
研究领域:
药理学
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胃肠病学
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分子生物学
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免疫学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Yang Chang,Yafei Xia,Xiaojun Liu,Putian Yu,Furong Fan,Yangyang Shi,Shixin Yan,Shu Yan
Background Cholestasis is a commonly occurring disorder induced by impaired bile flow, for which there is no effective treatment so far. Qingre Lidan decoction (QRLD) is a clinically used herbal compound for the long-term treatment of bile circulation disorders arising from inflammation and obstruction in the gallbladder and bile ducts. The objective of this study was to investigate the protective effect of QRLD on cholestatic liver injury and its possible mechanism. Methods α-Naphthyl isothiocyanate (ANIT) was used to induce cholestatic liver injury in rats. Liver histopathology and serum biochemical markers were used to assess QRLD's protective impact. The possible biomarkers and mechanism of the therapeutic benefits of QRLD were investigated using a UHPLC-based Q-Exactive Orbitrap MS / MS untargeted serum metabolomics technique together with 16 S rRNA microbiota profiling. Afterwards, using RT-qPCR as well as Western Blot techniques, the expression of pertinent indicators was determined. Results The intervention effect of QRLD was stronger at medium and high dosages than at low doses, and it dramatically decreased the levels of serum biochemical markers in cholestatic rats reflecting alterations in liver function and relieving ANIT-induced abnormalities in the liver's histopathology. Serum metabolomics showed that QRLD could affect the metabolic profile of cholestatic rats, mainly related to glycerophospholipid metabolism, taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, and histidine metabolic pathway. Additionally, analysis of 16 S rRNA gene sequencing indicated that QRLD could moderate ANIT-induced microbiota disorders, particularly Romboutsia, Bifidobacterium, Fusicatenibacter, Prevotella_9, Prevotellaceae_NK3B31_group and Prevotella_1. Other experimental results showed that QRLD significantly upregulated the mRNA and protein expression of PPARα, CYP7A1 and NTCP in the liver, inhibited the expression of p-IκBα, p-p65 and TNFα while increasing the anti-inflammatory factor IL-10, and downregulated the expression of MDA (a peroxidation product) and D -lactic acid (an intestinal barrier indicator) while increasing the expression of SOD and GSH. Conclusions QRLD can effectively regulate endogenous metabolites and microbiota disorders in cholestatic rats that are correlated with the attenuation of inflammation and oxidative stress.
研究领域:
药理学
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肝病学
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代谢组学
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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
Materials Today Bio
·
2024
·
IF 8.7
Tong Sha,Ze Wang,Jinwei Li,Yahong Wu,Jinbiao Qiang,Zhenming Yang,Yue Hu,Kaijuan Zheng,Shuyu Zhang,Haizhu Sun,Andrew K. Whittaker,Bai Yang,Hongchen Sun,Quan Lin,Ce Shi
Inflammatory osteolysis poses a significant worldwide threat to public health. However, current monotherapies, which target either the prevention of the inflammatory response or the attenuation of osteoclast (OC) formation, have limited efficacy due to the complexity of the bone immune system being overlooked. Herein, by means of modifying salmon calcitonin (sCT), a multifunctional nano-system (AuNDs-sCT) was designed to synergistically inhibit OC differentiation and reverse the inflammatory microenvironment against inflammatory osteolysis. On the one hand, AuNDs-sCT effectively restrained OC differentiation by binding to the calcitonin receptors on the surface of OC precursors, resulting in the down-regulation of OC-specific genes and proteins. The targeted capacity of AuNDs-sCT provided a more durable and precise therapeutic effect. On the other hand, AuNDs-sCT exhibited antioxidant and anti-inflammatory effects, which regulated the polarization “switch” from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype in macrophages by the inhibition of NF-κB p65 phosphorylation, thereby effectively reversed the local inflammatory microenvironment. Additionally, AuNDs-sCT served as a promising fluorescent probe, enabling real-time visualization of the therapeutic process. This capability is expected to optimize drug administration and evaluate therapeutic effects. In summary, by inhibiting OC differentiation and reprogramming macrophages, AuNDs-sCT successfully realized drug repurposing and achieved the “one arrow two eagles” therapeutic strategy, which offers a synergistic and effective treatment option for the clinical management of inflammatory osteolysis.
研究领域:
纳米技术
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免疫学
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骨科
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2023
·
IF 5.6
Ritian Jin,Jude Juventus Aweya,Rong Lin,Wuyin Weng,Jiaqi Shang,Dangfeng Wang,Yiling Fan,Shen Yang
VLATSGPG (VLA) was a DPP-IV inhibitory peptide isolated from salmon ( Salmo Salar ) skin. Here, we demonstrated that VLA inhibited the activation of PERK through the AKT signaling pathway. Furthermore, we investigated the effect of VLA on free fatty acid (FFA)-induced lipid accumulation disorder and inflammation in HepG2 cells, elucidating the potential regulatory mechanism in this nonalcoholic fatty liver disease cell model. VLA reduced the mRNA expression of adipogenic factors FAS, ACC, and SCD-1 through the PERK/eIF2α pathway and the level of apolipoprotein B-100 secretion. These may contribute to the reducing FFA-induced lipid accumulation in cells and reducing intracellular lipid levels. In addition, VLA increased IκBα mRNA expression via the PERK/IκBα pathway, inhibited the NF-κB p65 activation, and thus inhibited cell inflammation.
研究领域:
分子生物学
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细胞生物学
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药理学
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Wenbo Ge,Zhun Li,Yajun Yang,Xiwang Liu,Zhaohan Zhu,Lixia Bai,Zhe Qin,Xiao Xu,Jianyong Li,Shihong Li
Pathogenic Escherichia coli ( E. coli ) can cause intestinal diseases in humans and livestock, damage the intestinal barrier, increase systemic inflammation, and seriously threaten human health and the development of animal husbandry. In this study, we designed and synthesized a novel conjugate florfenicol sulfathiazole (FST) based on drug combination principles, and investigated its antibacterial activity in vitro and its protective effect on inflammatory response and intestinal barrier function in E. coli O78-infected mice in vivo . The results showed that FST had superior antibacterial properties and minimal cytotoxicity compared with its prodrugs as florfenicol and sulfathiazole. FST protected mice from lethal E. coli infection, reduced clinical signs of inflammation, reduced weight loss, alleviated intestinal structural damage. FST decreased the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, and increased the expression of claudin-1, Occludin, and ZO-1 in the jejunum, improved the intestinal barrier function, and promoted the absorption of nutrients. FST also inhibited the expression of TLR4, MyD88, p-p65, and p-p38 in the jejunum. The study may lay the foundation for the development of FST as new drugs for intestinal inflammation and injury in enteric pathogen infection.
研究领域:
药理学
·
微生物学
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免疫学
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兽医学
✓ 已验证
DOI
PubMed
高影响因子
INFLAMMATION
·
2024
·
IF 4.5
Liu Yadong,Zhang Guiqi,Wu Jiani,Meng Yi,Hu Jianyu,Fu Hao,Yang Dongfang
Intervertebral disc degeneration (IDD) diseases are common and frequent diseases in orthopedics. The caspase recruitment domain (CARD) and membrane-associated guanylate kinase-like protein 3 (CARMA3) is crucial in the activation of the NF-κB pathway. However, the biological function of CARMA3 in IDD remains unknown. Here, CARMA3 expression was elevated in nucleus pulposus (NP) tissues of IDD rats and nutrient deprivation (ND)-induced NP cells. The main pathological manifestations observed in IDD rats were shrinkage of the NP, reduction of NP cells, fibrosis of NP tissues, and massive reduction of proteoglycans. These changes were accompanied by a decrease in the expression of collagen II and aggrecan, an increase in the expression of the extracellular matrix (ECM) catabolic proteases MMP-3, MMP-13, and metalloprotease with ADAMTS-5, and an increase in the activity of the pro-apoptotic protease caspase-3. The expression of p-IκBα Ser32/36 and p-p65 Ser536 was also upregulated. However, these effects were reversed with the knockdown of CARMA3. Mechanistically, CARMA3 bound to BCL10 and MALT1 to form a signalosome. Knockdown of CARMA3 reduced the CARMA3-BCL10-MALT1 signalosome-mediated NF-κB activation. CARMA3 activated the NF-κB signaling pathway in a manner that bound to BCL10 and MALT1 to form a signalosome, which affects NP cell damage and is involved in the development of IDD. This supports CARMA3-BCL10-MALT1-NF-κB as a promising targeting axis for the treatment of IDD.
研究领域:
骨科
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分子生物学
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细胞生物学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
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2024
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IF 5.3
Dong Xie,Guangfu Lv,Yuchen Wang,Wenjing Zhang,Nian Li,Yao Duan,Qing Huang,Ge Chen,Zifeng Pi,Hao Yue
Tenghuang Jiangu Wan (THJGW) is a commonly utilized treatment for osteoarthritis (OA), yet its pharmacodynamic material basis and molecular mechanism remain inadequately understood. This study systematically characterized the in vitro and in vivo chemical components of THJGW using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The pharmacodynamic material basis of THJGW in the treatment of OA was explored through a target network pharmacology approach and molecular docking technology. Cellular experiments were subsequently employed to validate the molecular mechanisms. Consequently, a total of 134 components from THJGW were identified in vitro , comprising 45 flavonoids, 10 iridoid glycosides, 39 phenylethanoid glycosides, 9 phenylpropanoids, 11 organic acids, 4 phenolics, and 16 other compounds. Additionally, 38 prototype absorbed components in serum were characterized for the purpose of network construction. 11 key components and 10 core targets (VEGFA, STAT3, RELA/NF-κB p65, PIK3R1, PIK3CA, MMP9, MMP1, IL-6, HDAC1, and FGF2) were determined by the target network pharmacology. Through Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it was found that these intersection targets are associated with various signaling pathways such as pathways in cancer, lipid and atherosclerosis, and prostate cancer. Notably, the lipid and atherosclerosis pathway was closely linked to OA. The molecular docking results demonstrated strong binding affinities of the three core targets: IL-6, STAT3, and RELA/NF-κB p65. These results suggest that these targets may play a significant role for THJGW in treating OA. In vitro experiments showed that THJGW had notable protective effects on LPS-induced RAW264.7 macrophages by reducing levels of TNF-α and IL-6, and inhibiting phosphorylation expression of STAT3 and NF-κB p65 proteins related to the lipid and atherosclerosis pathway. This study provides insight into the pharmacodynamic material basis and mechanism of action for THJGW in the treatment of OA, which provide scientific evidence for the scientific application and improvement of quality standards for THJGW.
研究领域:
药理学
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生物化学
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分子生物学
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中医药
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产品关联
DOI
高影响因子
JOURNAL OF DRUG TARGETING
·
2023
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IF 4.5
Linlin Zhang,Lei Cheng,Zhemeng Chen,Yi Fang,Changjiang Li,Min Chen,Peijie He,Haitao Wu,Jianzhang Wu,Jian Chen
Hypopharyngeal carcinoma is notorious for its poor prognosis among all head and neck cancers, posing a persistent challenge in clinical settings. The continuous hyperactivation of the NFκB signalling pathway has been noted in various cancer types, including hypopharyngeal carcinoma. In our quest to develop a novel drug that targets hypopharyngeal cancer via the NFκB pathway, we employed curcumin, a well-known lead compound, and performed chemical modifications to create a mono-carbonyl analogue called L42H17. This compound exhibited exceptional stability and displayed an enhanced binding affinity to myeloid differentiation protein 2 (MD2). Consistent with expectations, L42H17 demonstrated the ability to inhibit TNF-α-induced phosphorylation of inhibitor of κB (IκB) kinase (IKK), prevent IκB degradation, and subsequently impede NFκB-p65 nuclear translocation in hypopharyngeal cancer cells. Additionally, L42H17 exhibited a remarkable capacity to induce cell cycle arrest at the G2-M phase by inactivating the cdc2-cyclin B1 complex. Moreover, it facilitated cell apoptosis by reducing Bcl-2 levels and augmenting the expression of cle-PARP and cle-caspase3. Importantly, we observed a significant enhancement in the anti-cancer efficacy of L42H17 in a patient-derived tumour xenograft (PDTX) model of hypopharyngeal carcinoma. In conclusion, our findings strongly suggest that L42H17 holds promise as a potential candidate drug for the treatment of hypopharyngeal carcinoma in the future.
研究领域:
肿瘤学
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药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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