ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2023
·
IF 3.9
Yinzhong Chen,Wei Guo,Weizhao Lu,Xiucheng Guo,Weilu Gao,Zongsheng Yin
Osteoarthritis (OA), the most common joint disease, is characterized by inflammation and cartilage degradation. Previous studies illustrated that Smad nuclear-interacting protein 1 (SNIP1) is an inhibitor of the TGF-β signal transduction pathway and SNIP1 has been reported as an anti-inflammatory factor. This study aimed to explore the role of SNIP1 in OA progression. In this study, the SNIP1 expression was evaluated in OA human and OA mice tissue and interleukin-1 beta (IL-1β)-induced chondrocytes . The Safranin-O (SO) staining and osteoarthritis research society international (OARSI) scoring system was used to evaluate cartilage injury. The gain- and loss-of-function studies for SNIP1 were performed in chondrocytes. The SNIP1 overexpression adenovirus was injected into mice by intra-articular injection. The SNIP1 expression was decreased in OA patients, OA mice, and IL-1β-stimulated chondrocytes. The cartilage injury of medial meniscus-induced OA (DMM-OA) mice at 8 weeks showed more severe than that at 4 weeks. The expression of SNIP1 was lower at 8 weeks than that at 4 weeks. In IL-1β-stimulated chondrocytes, SNIP1 overexpression reduced the expression of TNF-α and IL-6, alleviated ECM degradation, reduced the phosphorylation levels of p65 and IκBα , and decreased the p65 level in nuclear. Moreover, overexpression of SNIP1 alleviated cartilage injury in DMM-OA mice. In brief, our study suggested that SNIP1 alleviated OA and repressed inflammation by inhibiting the activation of NF-κB. This study might provide a new insight into OA treatment.
研究领域:
风湿病学
·
分子生物学
·
炎症
·
软骨生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
·
IF 4.932
Xiaohe Li,Qing Liang,Shaoyan Gao,Qiuyan Jiang,Fangxia Zhang,Ruiqin Zhang,Hao Ruan,Shuangling Li,Jiaoyan Luan,Ruxia Deng,Honggang Zhou,Hui Huang,Cheng Yang
Idiopathic pulmonary fibrosis (IPF) is a pathological consequence of interstitial pulmonary diseases, and is characterized by the persistence of fibroblasts and excessive deposition of extracellular matrix (ECM). The etiology of IPF is multifactorial. Although the role of inflammation in fibrogenesis is controversial, it is still recognized as an important component and epiphenomenon of IPF. Stimulus increase production of pro-inflammatory cytokines and activation of NF-κB, which will further promote inflammation response and myofibroblast transition. Lenalidomide is an immunomodulatory drug. Previous studies have revealed its anti-tumor effects through regulating immune response. Here we investigate the effect of lenalidomide on post-inflammation fibrosis. In vitro study revealed that lenalidomide inhibited NF-κB signaling in LPS-induced macrophage, and further attenuated macrophage-induced myofibroblast activation. Meanwhile, lenalidomide could inhibit TGF-β1-induced myofibroblast activation through suppressing TGF-β1 downstream MAPK signaling. In vivo study showed that lenalidomide inhibited pro-inflammatory cytokines TNF-α and IL-6 while enhanced anti-fibrotic cytokines IFN-γ and IL-10 in bleomycin-induced inflammation model, and attenuated pulmonary fibrosis and collagen deposition in the following fibrosis stage. In conclusion, our results demonstrate that lenalidomide possesses potential anti-fibrotic effects through suppressing NF-κB signaling.
研究领域:
药理学
·
肺科学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
·
2025
·
IF 2.5
Peiying Shi,Shuo Han,Yang Sun,Mengmeng Li,Xueling Xu
Pathological cardiac hypertrophy (CH) often progresses towards heart failure, which presents a serious threat to global public health security. Fortunately, peptides from animal venoms have emerged as potential drugs for the therapeutic care of cardiovascular diseases. This paper aims to investigate the therapeutic potentials and mechanism of bee venom (BV) using isoproterenol (ISO)-induced CH models in vivo and in vitro . Melittin was identified as the dominant component in air-dried BV using UPLC-Q/TOF-MS, and subsequently it confirmed that BV prevented electrocardiogram and echocardiography abnormalities, and attenuated morphological and histopathological alterations of hypertrophic hearts in mice. Mechanistically, through network pharmacology exploration, angiotensin-converting enzyme (ACE) and renin (REN) were predicted as the key targets of melittin against CH. This was further confirmed by the in vitro experimental results that BV significantly downregulated the protein or mRNA expression levels of CH markers (β-MHC, ANP, BNP), ACE, and IL-1β in ISO-induced hypertrophic cardiomyocytes. Furthermore, it was ascertained that BV inhibited JAK2/NF-κB signaling cascade via decreasing the protein expression ratio of p-JAK2/JAK2 and the protein expression level of NF-κB. This study showed that BV alleviated ISO-induced CH in vivo and in vitro via JAK2/NF-κB signaling cascade, providing a basis for treating CH with BV or melittin.
研究领域:
药理学
·
心血管医学
·
分子生物学
·
毒理学
·
生物医学研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2018
·Vol. 9
·期 7
·1-16
·
IF 5.638
Wang Zhe,Zhao Simeng,Song Lihua,Pu Yuzhi,Wang Qiang,Zeng Guangzhi,Liu Xing,Bai Ming,Li Shao,Gao Fabao,Chen Lijuan,Wang Chen,Tan Ninghua
Rubiaceae-type cyclopeptides (RAs) are a type of plant cyclopeptides from the Rubia that have garnered significant attention owing to their unique bicyclic structures and amazing antitumour activities. Our recent work has shown that RAs suppress inflammation and angiogenesis and induce apoptosis. However, the underlying mechanism and targets remained unknown. Nuclear factor κB (NF-κB) signaling pathway plays a critical role in these biological processes, prompting us to investigate whether and how RAs affect this pathway. By screening compound libraries using NF-κB-dependent luciferase reporter, we observed that RA-V is the best NF-κB inhibitor. Further experiments demonstrated that RA-V interrupted the TAK1–TAB2 interaction and targeted TAK1 in this pathway. Moreover, RA-V prevented endotoxin shock and inhibited NF-κB activation and tumor growth in vivo. These findings clarify the mechanism of RA-V on NF-κB pathway and might account for the majority of known bioactivities of RA-V, which will help RA-V develop as new antiinflammatory and antitumour therapies.
研究领域:
药理学
·
免疫学
·
癌症研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2016
·
IF 5.091
Shan Liu,Lingxin Zhu,Jie Zhang,Jingjing Yu,Xue Cheng,Bin Peng
Previous studies, including those from our laboratory, have demonstrated that the natural flavonoid isoliquiritigenin (ISL) is a promising agent for bone destructive diseases. However, the mechanisms underlying its anti-osteoclastogenic effects are still far from clear. Here, we evaluated the potential alterations of autophagy and nuclear factor-κB (NF-κB) during anti-osteoclastogenic effects by ISL in vitro and in vivo . We observed that ISL inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and suppressed autophagic microtubule-associated protein light chain 3 (LC3)-II and Beclin 1 accumulation. ISL treatment resulted in the interruption of several specific features for autophagy in osteoclast precursors, including acidic vesicular organelle formation, LC3-II accumulation, and appearance of autophagic vacuoles. The RANKL-stimulated expression levels of autophagy-related genes and proteins also diminished in ISL-treated osteoclast precursors. The reactivation of autophagy by rapamycin almost reversed the ISL-elicited anti-osteoclastogenic effects. Interestingly, ISL inhibited the RANKL-stimulated NF-κB expression and nuclear translocation, whereas the NF-κB inhibitor Bay 11-7082 markedly suppressed the RANKL-induced autophagic activation. Consistent with the in vitro results, the administration of ISL could attenuate osteoclastogenic cathepsin K , autophagic LC3, and NF-κB expression to protect against inflammatory calvarial bone erosion in vivo . Our findings highlight the inhibition of NF-κB-dependent autophagy as an important mechanism of ISL-mediated anti-osteoclastogenic activity.
研究领域:
药理学
·
免疫学
·
骨骼生物学
✓ 已验证
DOI
PubMed
高影响因子
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
·
2025
·Vol. 136
·期 6
·e70045
·
IF 3.3
Dong Yan,Yuanwei Fu,Jie Mei,Junhong Wang,Ayijiang Jiamaliding,Ying Liu,Zanmei Zhao,Qingbian Ma
Phosgene, used in large‐scale industrial production, is highly toxic and irritant. Accidental exposure can lead to varying degrees of injuries, with severe cases potentially resulting in acute lung injury or acute respiratory distress syndrome, resulting in a mortality rate of 40%–50%. The indirect damages of phosgene (inflammation and oxidative stress) are considered important factors in phosgene‐induced acute lung injury (P‐ALI). The expression of Liver X Receptor α (LXRα) significantly reduces during periods of inflammation. LXRs were initially discovered to be highly expressed in the liver, whereas LXRs are expressed in immune cells and vascular endothelial cells, playing a significant role in anti‐inflammatory and antioxidant responses. LXRα may have pulmonary protection in P‐ALI. However, evidence to verify this association is still lacking. In this study, rats were divided into six groups to explore the potential role of LXRα in P‐ALI. This study found that GW3965 effectively activated LXRα, upregulated its expression and downregulated the levels of proinflammatory cytokines, inhibited malondialdehyde activity while enhancing superoxide dismutase activity, suppressed apoptosis and ameliorated the pathological processes of P‐ALI, ultimately exerting pulmonary protection in P‐ALI. Further validation revealed that the pulmonary protective effect of LXRα may be associated with the PI3K/Akt and NF‐kB signalling pathways.
研究领域:
药理学
·
呼吸病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Chai Yuhui,Cai Yawen,Fu Yu,Wang Yingdi,Zhang Yiming,Zhang Xue,Zhu Lingpeng,Miao Mingxing,Yan Tianhua
Depression is a common and serious mental disorder. Data on its pathogenesis remain unclear and the options of drug treatments are limited. Here, we explored the role of pyroptosis, a novel pro-inflammatory programmed cell death process, in depression as well as the anti-depression effects and mechanisms of salidroside (Sal), a bioactive extract from Rhodiola rosea L. We established a corticosterone (CORT)-induced or lipopolysaccharide (LPS)-induced mice in vivo, and CORT, or nigericin (NLRP3 agonist)-induced PC12 cells in vitro. Our findings demonstrated that Sal profoundly mediated CORT or LPS-induced depressive behavior and improved synaptic plasticity by upregulating the expression of brain-derived neurotrophic factor (BDNF) gene. The data showed upregulation of proteins associated with NLRP3-mediated pyroptosis, including NLRP3, cleaved Caspase-1, IL-1β, IL-18, and cleaved GSDMD. The molecular docking simulation predicted that Sal would interact with P2X7 of the P2X7/NF-κB/NLRP3 signaling pathway. In addition, our findings showed that the NLRP3-mediated pyroptosis was regulated by P2X7/NF-κB/NLRP3 signaling pathway. Interestingly, Sal was shown to ameliorate depression via suppression of the P2X7/NF-κB/NLRP3 mediated pyroptosis, and rescued nigericin-induced pyroptosis in the PC12 cells. Besides, knock down of the NLRP3 gene by siRNA markedly increased the inhibitory effects of Sal on pyroptosis and proinflammatory responses. Taken together, our findings demonstrated that pyroptosis plays a crucial role in depression, and Sal ameliorates depression by suppressing the P2X7/NF-κB/NLRP3-mediated pyroptosis. Thus, our study provides new insights into the potential treatment options for depression.
研究领域:
神经科学
·
药理学
·
分子生物学
·
免疫学
·
精神病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Heart Journal
·
2022
·Vol. 63
·期 3
·578-590
·
IF 1.823
Haibo Du,Lianqin Ding,Tian Zeng,Di Li,Li Liu
Myocardial ischemia-reperfusion (I/R) injury is a serious complication of acute myocardial infarction. Long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) can regulate I/R-induced cardiomyocyte apoptosis. Here, we investigated the mechanism of SNHG15 activity in I/R-induced cardiomyocyte injury.SNHG15, microRNA (miR)-335-3p, and toll-like receptor 4 (TLR4) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell viability, proliferation, and apoptosis were gauged by Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2´-deoxyuridine (EDU) assay, and flow cytometry, respectively. The direct relationship between miR-335-3p and SNHG15 or TLR4 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays.SNHG15 was overexpressed in the infarcted area tissues of I/R mice and I/R-stimulated AC16 cells. SNHG15 knockdown alleviated I/R injury in AC16 cells. Mechanistically, SNHG15 directly targeted miR-335-3p, and miR-335-3p was a functional mediator of SNHG15. MiR-335-3p inhibited TLR4 expression by targeting TLR4, and miR-335-3p-mediated inhibition of TLR4 alleviated I/R-induced injury in AC16 cells. Moreover, SNHG15 regulated the TLR4/nuclear factor-κB (NF-κB) signaling pathway through miR-335-3p.Our findings identify a novel mechanism, the miR-335-3p/TLR4/NF-κB pathway, for the regulation of SNHG15 in myocardial I/R injury.
研究领域:
分子生物学
·
心脏病学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Biochemistry and Cell Biology
·
2022
·Vol. 101
·期 1
·
IF 3.73
Guihua Song,Suping Yu,Yan Zhang,Mengmeng Sun,Bingxue Zhang,Minghao Peng
Asthma is characterized by airway inflammation and remodeling. 2-Undecanone (methyl nonyl ketone), a volatile organic compound originating from Houttuynia cordata, has the potential to ameliorate inflammatory diseases. This study aimed to explore potential benefits of 2-undecanone in asthma. 2-Undecanone (100, 200, or 400 mg/kg) was administered intragastrically to ovalbumin (OVA)-challenged BALB/c mice. Lung tissues were collected to observe histopathological changes, and bronchoalveolar lavage fluid (BALF) was collected for the detection of inflammatory cells and cytokine production. The results showed that 2-undecanone ameliorated OVA-induced pathologic changes of lungs, including reducing inflammatory cell infiltration, goblet cell hyperplasia, and airway smooth muscle thickness. The number of inflammatory cells and the levels of IL-4, IL-5, IL-13, and IgE in BALF were decreased by 2-undecanone in asthmatic mice. Furthermore, abnormal activation of NF-κB pathway in lung tissues of asthmatic mice was impeded by 2-undecanone. In vitro, 2-undecanone (12.5, 25, or 50 µM) suppressed platelet-derived growth factor-BB-induced proliferation and migration of primary airway smooth muscle cells (ASMCs), and inhibited the switching of ASMCs from contractile phenotype to synthetic phenotype. Consistently, 2-undecanone blocked NF-κB activation in ASMCs. Collectively, 2-undecanone relieves asthma through alleviating airway inflammation and remodeling, and this beneficial effect is achieved by inhibiting NF-κB pathway.
研究领域:
免疫学
·
药理学
·
呼吸医学
✓ 已验证
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2021
·
IF 5.037
Mengyuan Fang,Wencui Wan,Qiuming Li,Weiwei Wan,Yang Long,Hongzhuo Liu,Xin Yang
Aim This study aimed to evaluate the effects of Asiatic acid (AA), a naturally occurring compound of pentacyclic triterpenoid, on the pathological processes of diabetic retinopathy (DR). Methods SD rats were induced to develop early DR by intraperitoneal injection of STZ (60 mg/kg). Four weeks after injection, the diabetic rats were orally administrated with 37.5 mg/kg or 75 mg/kg AA every day for four weeks. The integrity of blood-retinal barrier (BRB) was measured by Evans blue staining. The polarization of microglia was determined by real-time PCR, western blot, and ELISA assays. The inner BRB (iBRB) or outer BRB (oBRB) breakdown was induced in human retinal endothelial cells or APRE19 cells through co-culture with high glucose and LPS-stimulated microglia BV2 cells. The damage to the iBRB and oBRB was measured using transendothelial/transepithelial electrical resistance (TEER/TER) and FITC-conjugated dextran cell permeability assays. Key findings Results demonstrated that AA alleviated BRB breakdown, as evidenced by decreased protein expression of occludin, claudin-5, and ZO-1. Furthermore, AA treatment suppressed inflammation and M1 polarization, while it increased M2 polarization in the retina of DR rats. In vitro , the iBRB or oBRB breakdown was alleviated by AA. LPS-induced M1-polarization of BV2 cells under high glucose condition was also repressed through AA administration. Finally, we demonstrated that AA weakened the TLR4/MyD88/NF-κB p65 signaling pathway both in vivo and in vitro . Significance AA ameliorated early DR by regulating microglia polarization via the TLR4/MyD88/NF-κB p65 pathway. These data indicate that AA is a potential candidate for DR treatment.
研究领域:
药理学
·
眼科学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE
·
2019
·
IF 3.244
Lanqiu Zhang,Jinlu Zhang,Xiaolin Jiang,Lei Yang,Qi Zhang,Botao Wang,Lihua Cui,Ximo Wang
Neuroinflammation has been implicated in the mechanism underlying the progression of neurodegeneration and infectious neuropathology. Growing evidence suggest that hydroxytyrosol (3,4-dihydroxyphenil-ethanol, HT), one of the main polyphenols presented in extra virgin olive oil (EVOO), has shown potential anti-inflammatory and neuroprotective effects. However, the potential anti-neuroinflammation activity and underlying mechanism of HT remain poorly understood. The present study aimed to investigate the effects of HT on lipopolysaccharide (LPS)-induced inflammation in both in vitro and in vivo models and the associated molecular mechanism. Our results revealed that HT significantly reduced the production of pro-inflammatory mediators in BV2 microglia and primary microglia cells. Phenotypic analysis showed that HT significantly reduced M1 marker CD86 expression and increased M2 marker CD206 expression. In addition, HT significantly decreased the levels of phospho-NF-κB p65 and phospho-extracellular signal-regulated kinase (ERK) in a dose-dependent manner. Moreover, HT suppressed the LPS-induced Toll like receptor 4 (TLR4) in BV2 microglia. In vivo administration of HT following LPS injection significantly reduced some proinflammatory mediator levels and microglia/astrocyte activation in the brain. Together, these results suggest that HT suppressed the LPS-induced neuroinflammatory responses via modulation of microglia M1/M2 polarization and downregulation of TLR-4 mediated NF-κB activation and ERK signaling pathway.
研究领域:
神经科学
·
药理学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2023
·Vol. 9
·期 11
·e21871
·
IF 4
Tianhang Chen,Haixia Du,Huifen Zhou,Yu He,Jiehong Yang,Chang Li,Chenxing Wei,Daojun Yu,Haitong Wan
Yinhuapinggan granule (YHPG) is a traditional Chinese medicine prescription with rich clinical experience for the treatment of colds and coughs. The aim of this study is to investigate the protective effect of YHPG on multidrug-resistant (MDR) Acinetobacter baumannii ( A. baumannii ) infection in vivo and its potential anti-inflammatory mechanism. BALB/c mice were intranasally inoculated with MDR A. baumannii strain to establish the pneumonia infection model, and received intraperitoneally cyclophosphamide to form immunosuppression before attack. YHPG (6, 12 and 18 g/kg) was administered by gavage once a day for 3 consecutive days after infection. The protective effect of YHPG was evaluated by lung index, spleen index, thymus index, pathological changes of lung tissue and inflammatory factors (IL-1β, IL-6 and TNF-α) in serum. The expression of key targets of NF-κB/NLRP3 signaling pathway in vivo was analyzed by immunohistochemistry, immunofluorescence, reverse transcription quantitative PCR (RT-qPCR) and Western blot. The results showed that YHPG improved the lung index and its inhibition rate, immune organ indexes and lung pathological changes in infected mice, and significantly reduced IL-1β, IL-6 and TNF-α levels in serum. In addition, YHPG significantly down-regulated the mRNA and protein expression of NF-κB p65, NLRP3, ASC, Caspase-1, TNF-α, IL-6 and IL-1β in mice lung tissue. The results of the current study demonstrated that YHPG has significant protective effects on mice infected with MDR A.baumannii , which may be related to the regulation of inflammatory factors and NF-κB/NLRP3 signaling pathway, indicating that YHPG has a wide range of clinical application value and provides a theoretical basis for its treatment of MDR A.baumannii infection.
研究领域:
中药学
·
免疫学
·
感染性疾病研究
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）