MOLECULAR IMMUNOLOGY
·
2023
·
IF 3.6
Zhijun Zhao,Yongqing Tong,Yuting Kang,Zhuoran Qiu,Qiujie Li,Chao Xu,Geng Wu,Wei Jia,Pengtao Wang
Cigarette smoke is recognized as a major trigger for individuals with chronic obstructive pulmonary disease (COPD), leading to an amplified inflammatory response. The onset and progression of COPD are affected by multiple environmental and genetic risk factors, such as inflammatory mechanisms, oxidative stress, and an imbalance between proteinase and antiprotease. As a result, conventional drug therapies often have limited effectiveness. This study aimed to investigate the anti-inflammatory effect of sodium butyrate (SB) in COPD and explore its molecular mechanism, thereby deepening our understanding of the potential application of SB in the treatment of COPD. In our study, we observed an increase in the mRNA and protein expressions of inflammatory factors interleukin-1beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), Matrix metallopeptidase 9 (MMP9) and MMP12 in both NR8383 cell and rat models of COPD. However, these expressions were significantly reduced after SB treatment. Meanwhile, SB treatment effectively decreased the phosphorylation levels of nuclear transcription factor-kappa B (NF-κB) p65, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) and inhibited the nuclear translocation of these proteins in the COPD cells, leading to a reduction in the expression of various inflammatory cytokines. Additionally, SB also inhibited the expression level of the Nod-like receptor pyrin domain 3 (NLRP3) inflammasome, which consists of NLRP3, apoptosis-associated speck-like protein (ASC), and Caspase-1 in the cigeratte smoke extract (CSE)-stimulated cells. Our results showed that CSE down-regulated the mRNA levels of G-protein-coupled receptor 43 (GPR43) and GPR109A, while SB only up-regulated the expression of GPR43 and had no effect on GPR109A. Moreover, additional analysis demonstrated that the knockdown of GPR43 diminishes the anti-inflammatory effects of SB. It is evident that siRNA-mediated knockdown of GPR43 prevented the reduction in mRNA expression of IL-1β, IL-6, TNF-α, MMP9, and MMP12, as well as the expression of phosphorylated proteins NF-κB p65, JNK, and p38 MAPKs with SB treatment. These findings revealed a SB/GPR43 mediated pathway essential for attenuating pulmonary inflammatory responses in COPD, which may offer potential new treatments for COPD.
研究领域:
药理学
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肺科学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2020
·
IF 3.347
Qiongtao Song,Ying Zhao,Yanrong Yang,Xue Han,Junguo Duan
Iron overload toxicity has been implicated in retinal pigment epithelial cell injury in age-related macular degeneration. This study investigates the effects of astragaloside IV (AS-IV), a potential retinal protective agent, on the toxicity process of retinal iron overload in vivo and in vitro . AS-IV partially restored the retinal expression of rhodopsin and retinal pigment epithelium-specific 65 kDa protein, suppressed oxidative stress and inflammatory markers, and alleviated iron deposition and retinal pathological changes in vivo . Also, AS-IV inhibited the phosphorylation of p38 and ERK mitogen-activated protein kinases (MAPKs), as well as the nuclear translocation of nuclear factor-kappa B (NF-κB). Furthermore, AS-IV prevented cell death by decreasing the ratio of Bax/Bcl-2, caspase-3, and cleaved caspase-3 expression in vitro . Although there are no chelation effects between AS-IV and iron, AS-IV can reduce intracellular iron by regulating iron-handling proteins in ARPE-19 cells (Cav1.2, divalent metal transporter-1, transferrin receptor 1 , and heavy-chain ferritin). In conclusion, the results show that AS-IV has significant protective effects against retinal iron overload toxicity and suggest that iron regulation and the inhibition of MAPKs and NF-κB activation might be mechanisms underlying the effects of AS-IV.
研究领域:
眼科学
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药理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Mengyang Wang,Wei Liu,Zhuoqun Wang,Linxin Zhang,Jie Zhao,Yongwei Lai,Xiaoli Cui
Background Hypertension is an important risk factor for heart failure. Zhenwu Decoction (ZWD) is a classical Chinese medicinal recipe that has been extensively used to manage cardiovascular disorders throughout history. However, the fundamental processes involved in its effects were not clear. Objective In this study, we investigated the effects of ZWD on Ang II-induced cardiac remodeling and heart failure. Methods A hypertensive heart failure (HF) mice model was established via the micro-osmotic pump infusion of Ang II in C57BL/6 mice for 4 weeks. After two weeks of infusion, ZWD and valsartan were administered intragastrically for another two weeks to investigate their mechanisms of action.RNA sequencing of cardiac tissue was performed to investigate the mechanism of anti-heart failure action of ZWD, and potential binding proteins of Galloypaeoniflorin (GAL), an effective monomer component of ZWD, were verified by molecular docking, DARTS, CETSA and SPR. Results The results showed that ZWD conferred a protective effect against Ang II-induced cardiac dysfunction in mice by inhibiting cardiac hypertrophy and inflammation. RNA sequencing revealed that this cardioprotective effect was associated with the MAPKs/STAT2-NLRC5 signaling pathway. GAL alleviated the inflammatory response in mouse heart tissues and in vitro cultured cardiomyocytes by inhibiting the Ang II-stimulated MAPKs/STAT2-NLRC5 signaling pathway. The data suggest that deficiency of MAPKs or STAT2 in cardiomyocytes abolished the anti-inflammatory effects of GAL. Molecular docking, DARTS, CETSA and SPR techniques confirmed the binding of GAL and STAT2. Conclusion Our study suggests that ZWD protects the heart from damage caused by Ang II stimulation by targeting STAT2 through inhibiting the inflammatory response driven by the MAPK signaling pathway, indicating its promising application in the treatment of hypertensive heart failure.
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Ke Lin,Wu Luo,Na Yang,Lan Su,Hao Zhou,Xiang Hu,Yi Wang,Zia A. Khan,Weijian Huang,Gaojun Wu,Guang Liang
Background Kidney damage is a frequent event in the course of hypertension. Recent researches highlighted a critical role of non-hemodynamic activities of angiotensin II (Ang II) in hypertension-associated kidney fibrosis and inflammation. These activities are mediated through toll-like receptors (TLRs) but the mechanisms by which Ang II links TLRs to downstream inflammatory and fibrogenic responses is not fully known. In this study, we investigated the role of TLR adapter protein called myeloid differentiation primary-response protein-88 (MyD88) as the potential link. Methods C57BL/6 mice were administered Ang II by micro-osmotic pump infusion for 4 weeks to develop nephropathy. Mice were treated with small-molecule MyD88 inhibitor LM8. In vitro , MyD88 was blocked using siRNA or LM8 in Ang II-challenged renal tubular epithelial cells. Results We show that MyD88 is mainly located in tubular epithelial cells and Ang II increases the interaction between TLR4 and MyD88. This interaction activates MAPKs and nuclear factor-κB (NF-κB), leading to increased production of inflammatory and fibrogenic factors. Inhibition of MyD88 by siRNA or selective inhibitor LM8 supresses MyD88-TLR4 interaction, NF-κB activation, and elaboration of inflammatory cytokines and fibrosis-associated factors. These protective actions resulted in decreased renal pathological changes and preserved renal function in LM8-treated hypertensive mice, without affecting hypertension. Conclusion These results demonstrate that Ang II induces inflammation and fibrosis in renal tubular epithelial cells through MyD88 and present MyD88 as a potential point of intervention for hypertension-associated kidney disease.
研究领域:
药理学
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肾病学
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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
PHYTOMEDICINE
·
2022
·
IF 6.656
Mengyang Wang,Wu Luo,Tianxiang Yu,Shiqi Liang,Chunpeng Zou,Jinfeng Sun,Gao Li,Guang Liang
Background Heart failure is a common event in the course of hypertension. Recent studies have highlighted the key role of the non-hemodynamic activity of angiotensin II (Ang II) in hypertension-related cardiac inflammation and remodeling. A naturally occurring compound, diacerein , exhibits anti-inflammatory activities in various systems. Hypothesis/Purpose In this study, we have examined the potential effects of diacerein on Ang II-induced heart failure. Methods C57BL/6 mice were administered Ang II by micro-osmotic pump infusion for 4 weeks to develop hypertensive heart failure. Mice were treated with diacerein by gavage for final 2 weeks. RNA-sequencing analysis was performed to explore the potential mechanism of diacerein. Results We found that diacerein could inhibit inflammation, myocardial fibrosis , and hypertrophy to prevent heart dysfunction, without the alteration of blood pressure. To explore the potential mechanism of diacerein, RNA-sequencing analysis was performed, indicating that MAPKs/c-Myc pathway is involved in that cardioprotective effects of Diacerein. We further confirmed that diacerein inhibits Ang II-activated MAPKs/c-Myc pathway to reduce inflammatory response in mouse hearts and cultured cardiomyocytes . Deficiency of MAPKs or c-Myc in cardiomyocytes abolished the anti-inflammatory effects of diacerein. Conclusion Our results indicate that diacerein protects hearts in Ang II-induced mice through inhibiting MAPKs/c-Myc-mediated inflammatory responses, rendering diacerein a potential therapeutic candidate agent for hypertensive heart failure.
研究领域:
心脏病学
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药理学
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分子生物学
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炎症
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DOI
PubMed
高影响因子
PLANTA MEDICA
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2018
·Vol. 84
·期 11
·759-767
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IF 2.494
Zhen Zhang,Shuai Zhao,Xiaolei Li,Xiaoqi Zhuo,Wu Zhang,Qian Nie,Shuguang Wang,Lianqi Yan,Yu Sun
Wear debris-induced osteolysis is one of the major reasons for subsequent aseptic loosening after cementless hip arthroplasty. Increasing evidence suggests that receptor activator of nuclear factor kappa-B (NF-κB) ligand-mediated osteoclastogenesis and osteolysis are responsible for wear debris-induced aseptic loosening. In the present study, we explored the effect of amentoflavone (AMF) on inhibiting osteoclast generation and wear debris-induced osteolysis in vitro and in vivo. Twenty-four male C57BL/J6 mice were randomly divided into four groups: a sham group and groups with titanium wear debris treatment followed by intraperitoneal injection of various concentrations of AMF (0, 20, and 40 mg/kg/day). The micro computed tomography scanning and histological analysis were performed. Bone marrow-derived macrophages were cultured to investigate the effect of AMF on osteoclast generation and function. The results showed that AMF suppressed osteoclastogenesis, F-actin ring formation, and bone absorption without cytotoxicity. AMF prevented titanium wear debris-induced osteolysis in mice. AMF suppressed the relative proteins of NF-κB and mitogen-activated protein kinase (MAPKs) signaling pathways. Thus, the present study suggests that AMF derived from plants could inhibit osteoclastogenesis and titanium wear debris-induced osteolysis via suppressing NF-κB and MAPKs signaling pathways.
研究领域:
骨科
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药理学
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分子生物学
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DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2018
·
IF 3.185
Mu-Yang Li,Li Sun,Xiao-Tian Niu,Xiu-Mei Chen,Jia-Xin Tian,Yi-Di Kong,Gui-Qin Wang
The present study was conducted to evaluate the protective effects of astaxanthin against lipopolysaccharide (LPS)-induced inflammatory responses in Channa argus in vivo and ex vivo . Primary hepatocytes were exposed to different concentrations of LPS for 24 h to induce an inflammatory response, and the protective effects of astaxanthin against LPS-induced inflammation were studied ex vivo and in vivo. Hepatocytes exposed to LPS (5–20 μg mL −1 ) alone for 24 h resulted in a significant increase in lactate dehydrogenase release (LDH), Nitric oxide (NO) production and Malondialdehyde (MDA) content, 10 μg mL −1 LPS could induced inflammatory response in hepatocytes. Gene expression of TLR4 , NFkBp65, MAPKp38, TNF-α, IL-6 and IL-1β mRNA expression were also enhanced ex vivo (p < 0.05). In vivo test demonstrated that pretreatment with astaxanthin prevented the LPS-induced upregulation of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. Besides, astaxanthin blocked the expression of Toll-like receptor 4 (TLR4) and then suppressed the phosphorylation of nuclear transcription factor-kappa B (NF-κB) p65 and degradation inhibitor of NF-κBα (IκBα). Further study showed that astaxanthin could suppress the phosphorylation of p38, extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK) in mitogen-activated protein kinase (MAPK) signal pathway. In conclusion, our results suggest that astaxanthin played an anti-inflammatory role by regulating TLR4 and the NF-κB and MAPK signaling pathways in C. argus .
研究领域:
免疫学
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水生生物学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Xuefeng Wang,Baifei Hu,Haiming Hu,Shuhan Zhou,Mingzhu Yin,Xue Cheng,Zhigang Zhang,Hongtao Liu
Hepatitis B virus (HBV) infection is a serious global health problem that threatens the health of human. Tannic acid (TA), a natural polyphenol in foods, fruits, and plants, exhibits a variety of bioactive functions. In our research, we decide to explore the pharmacological mechanism of TA against HBV replication. Our results showed that TA effectively reduced the content of HBV DNA and viral antigens (HBsAg and HBeAg) in HepG2.2.15 cells. Meanwhile, TA significantly decreased the mRNA expression of HBV RNA, which include total HBV RNA, HBV pregenomic RNA, and HBV precore mRNA. Besides, TA evidently downregulated the activity of HBV promoters in HepG2.2.15 cells. Furthermore, we found that TA upregulated the expression of IL-8, TNF-α, IFN-α, and IFN-α-mediated antiviral effectors in HepG2.2.15 cells. On the contrary, TA downregulated the expression of IL-10 and hepatic nuclear factor 4 (HNF4α). In addition, TA activated the NF-κB and MAPK pathways that contributed to the inhibition of HBV replication. Finally, TA treatment led to the occurrence of autophagy, which accelerated the elimination of HBV components in HepG2.2.15 cells. Taken together, our results elucidated the suppressive effect of TA on HBV replication and provided inspiration for its clinical application in HBV treatment.
研究领域:
病毒学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2017
·
IF 3.671
Chanjuan Yue,Jin Chen,Ranran Hou,Weijun Tian,Kuanhui Liu,Deyun Wang,Yu Lu,Jiaguo Liu,Yi Wu,Yuanliang Hu
The antioxidant action and mechanism of selenizing schisandra chinensis polysaccharide (sSCP) were investigated in chicken embryo hepatocyte (CEH) taking schisandra chinensis polysaccharide (SCP) and N-acetyl-L-cysteine (NAC) as control. The CEH was cultured and treated with sSCP, then exposed to H 2 O 2 . The CEHs’ viability, apoptosis, ROS and antioxidase contents and the protein expression in MAPKs pathway and mitochondrion-dependence apoptotic signal pathway were assayed. The results showed that sSCP could significantly raise the cell viability and the activities of SOD, CAT and GSH-Px, decrease the cell apoptosis and the content of LDH, AST, ALT and MDA, down-regulate the protein expression of p-JNK 1 , p-ERK 1/2 , p-p38, Bax, Caspase 3 and cytochrome C, and up-regulate the protein expression of Bcl-2 in comparison with H 2 O 2 control group. The action of sSCP were stronger than those of SCP and NAC. These results indicated that selenylation modification could significantly enhance the antioxidant activity of SCP, sSCP could significantly protect hepatocyte from oxidative damage induced by H 2 O 2 , and its mechanism was by regulating the protein expression in MAPKs and mitochondrion-dependence apoptotic signaling pathways.
研究领域:
药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2019
·
IF 4.868
Qiang Chu,Xin Yu,Ruoyi Jia,Yaxuan Wang,Yiru Zhang,Shuang Zhang,Yangyang Liu,Yonglu Li,Wen Chen,Xiang Ye,Xiaodong Zheng
Apios americana Medikus was once widely accepted as staple food in India for a long time, and the tuber of which possesses high nutrients. During the past decades, most of the research has focused on the biological activity in the tubers of Apios americana Medikus whereas the leaves were ignored. In this study, the Apios americana Medikus leaf extract (ALE) was obtained and seven compounds were identified. LPS-induced RAW264.7 cells were used to study the anti-inflammation activity of ALE. As expected, ALE reduced the secretion of nitric oxide (NO) and inflammatory cytokines via inhibition of NF-κB and MAPK signaling together with activation of Nrf2-Keap1 and FOXO pathways, as well as alleviating the oxidative stress and mitochondrial dysfunction. In addition, ALE could activate HMGB1-Beclin1 and Sirt1-FoxO1 pathways and inhibit the Akt-mTOR signaling pathway to activate autophagy, protecting RAW264.7 cells from inflammation. In summary, our results suggested that ALE might help activate the anti-inflammation system, resulting in the prevention of LPS-induced damage in RAW264.7 cells.
研究领域:
药理学
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免疫学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Ruoyi Jia,Meng Chen,Yonglu Li,Xin Yu,Yaxuan Wang,Wen Chen,Xiang Ye,Yangyang Liu,Yong Jiang,Xiaodong Zheng
Tetrastigma hemsleyanum Diels et Gilg, a rare herbal plant native to China, possesses high medicinal value. More researches have focused on the flavones in the tubers of Tetrastigma hemsleyanum whereas polysaccharides attract few attentions. In this study, a purified polysaccharide (TTP-1) with the average molecular weights of 478.33 kDa was extracted from Tetrastigma hemsleyanum and conducted multiple analysis to identify its structural information. In vitro , TTP-1 could suppress the inflammation, cytotoxicity, genotoxicity, mitochondrial dysfunction and oxidative damage induced by LPS in RAW264.7 cells. Meanwhile, TTP-1 could attenuate inflammation via COX-2, iNOS, MAPKs pathways and ameliorate oxidative damage through Nrf2-Keap1, Sirt1-FoxO1 pathways in RAW264.7 cells. In vivo , the inflammation induced by LPS triggered the suppression of survival ratio and growing development, as well as the restrain of athletic ability in Caenorhabditis elegans . The treatment of TTP-1 reversed the situation induced by LPS. In a word, TTP-1 could ameliorate LPS-induced inflammation both in vitro and in vivo .
研究领域:
药理学
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免疫学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
·
2023
·
IF 5
Xiaoyi Shi,Meng Li,Qiming Huang,Liuming Xie,Zhibing Huang
Monacolin K (MK), a polyketo secondary metabolic compound of the mold genus Monascus, can promote the apoptosis of malignant cancer cells, possessing potential antitumor properties. However, its mechanism of action on gliomas remains unclear. Here, we explored and investigated the potential of the monacolin K’s antitumor effect on human glioma U251 cells and its possible molecular mechanism. Results showed that the application of 10 μM monacolin K inhibited the proliferation of U251 cells, with an inhibitory rate of up to 53.4%. Additionally, monacolin K induced the generation of reactive oxygen species and activated mitochondria-mediated pathways, including decreased MMP, activation of caspase3/caspase9, decreased Na+/K+-ATPase and Ca2+-ATPase activities, and disruption of the antioxidant system, resulting in the disruption of intracellular reduction–oxidation homeostasis. Monacolin K also activated MAPK and NF-κB pathways, upregulating P38 activity and downregulating JNK/ERK/P65/IκBα expression, ultimately leading to apoptosis of U251 cells. Importantly, monacolin K was not cytotoxic to normal human cells, hUC-MSCs. We concluded that monacolin K can induce apoptosis in U251 cells by triggering ROS-mediated oxidative damage and regulating MAPKs and NF-κB pathways.
研究领域:
肿瘤学
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细胞生物学
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药理学
✓ 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）