EUROPEAN JOURNAL OF PHARMACOLOGY
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2021
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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.
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CNS Neuroscience & Therapeutics
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2019
·Vol. 25
·期 5
·575-590
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IF 3.394
Xin Jin,Ming-Yan Liu,Dong-Fang Zhang,Xin Zhong,Ke Du,Ping Qian,Wei-Fan Yao,Hua Gao,Min-Jie Wei
Summary Aims Baicalin (BAI), a flavonoid compound isolated from the root of Scutellaria baicalensis Georgi, has been established to have potent anti-inflammation and neuroprotective properties; however, its effects during Alzheimer's disease (AD) treatment have not been well studied. This study aimed to investigate the effects of BAI pretreatment on cognitive impairment and neuronal protection against microglia-induced neuroinflammation and to explore the mechanisms underlying its anti-inflammation effects. Methods To determine whether BAI plays a positive role in ameliorating the memory and cognition deficits in APP (amyloid beta precursor protein)/PS1 (presenilin-1) mice, behavioral experiments were conducted. We assessed the effects of BAI on microglial activation, the production of proinflammatory cytokines, and neuroinflammation-mediated neuron apoptosis in vivo and in vitro using Western blot, RT-PCR, ELISA, immunohistochemistry, and immunofluorescence. Finally, to elucidate the anti-inflammation mechanisms underlying the effects of BAI, the protein expression of NLRP3 inflammasomes and the expression of proteins involved in the TLR4/NF-κB signaling pathway were measured using Western blot and immunofluorescence. Results The results indicated that BAI treatment attenuated spatial memory dysfunction in APP/PS1 mice, as assessed by the passive avoidance test and the Morris water maze test. Additionally, BAI administration effectively decreased the number of activated microglia and proinflammatory cytokines, as well as neuroinflammation-mediated neuron apoptosis, in APP/PS1 mice and LPS (lipopolysaccharides)/Aβ-stimulated BV2 microglial cells. Lastly, the molecular mechanistic study revealed that BAI inhibited microglia-induced neuroinflammation via suppression of the activation of NLRP3 inflammasomes and the TLR4/NF-κB signaling pathway. Conclusion Overall, the results of the present study indicated that BAI is a promising neuroprotective compound for use in the prevention and treatment of microglia-mediated neuroinflammation during AD progression.
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JOURNAL OF CELLULAR BIOCHEMISTRY
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2019
·Vol. 120
·期 10
·18509-18523
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IF 3.448
Yujie Yao,Xueyuan Hu,Xiujing Feng,Yuan Zhao,Manyu Song,Chaoran Wang,Honggang Fan
Dexmedetomidine (DEX) prevents kidney damage caused by sepsis, but the mechanism of this effect remains unclear. In this study, the protective molecular mechanism of DEX in lipopolysaccharide (LPS)-induced acute kidney injury was investigated and its potential pharmacological targets from the perspective of inhibiting oxidative stress damage and the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation. Intraperitoneal injection of DEX (30 μg/kg) significantly improved LPS (10 mg/kg) induced renal pathological damage and renal dysfunction. DEX also ameliorated oxidative stress damage by reducing the contents of reactive oxygen species, malondialdehyde and hydrogen peroxide, and increasing the level of glutathione, as well as the activity of superoxide dismutase and catalase. In addition, DEX prevented nuclear factor-kappa B (NF-κB) activation and I-kappa B (IκB) phosphorylation, as well as the expressions of NLRP3 inflammasome-associated protein and downstream IL-18 and IL-1β. The messengerRNA (mRNA) and protein expressions of toll-like receptor 4 (TLR4), NADPH oxidase-4 (NOX4), NF-κB, and NLRP3 were also significantly reduced by DEX. Their expressions were further evaluated by immunohistochemistry, yielding results were consistent with the results of mRNA and protein detection. Interestingly, the protective effects of DEX were reversed by atipamezole-an alpha 2 adrenal receptor (α 2 AR) inhibitor, whereas idazoxan-an imidazoline receptor (IR) inhibitor failed to reverse this change. In conclusion, DEX attenuated LPS-induced AKI by inhibiting oxidative stress damage and NLRP3 inflammasome activation via regulating the TLR4/NOX4/NF-κB pathway, mainly acting on the α 2 AR rather than IR.
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CHEMOSPHERE
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2018
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IF 4.427
Feibo Xu,Qiang Ji,Jian Zhang,Wanyue Huang,Zheng Cao,Yanfei Li
Aluminum (Al), a common environmental pollutant, has been reported to inhibit the immune functions of macrophage. However, the mechanisms involved remain unclear. In this study, murine peritoneal macrophages were exposed to 0, 0.27, 0.54, and 1.08 mg/mL of aluminium chloride (AlCl 3 ) for 24 h, and then treated with 1 μg/mL lipopolysaccharide (LPS) for another 6 h. No addition of both AlCl 3 and LPS serviced as control group. We observed that AlCl 3 has cytotoxicity in murine peritoneal macrophages, showing a decrease in cell viability and an increase in lactate dehydrogenase release. Besides, AlCl 3 exposure restrained the LPS-induced NLR pyrin domain containing 3 (NLRP3) inflammasome activation presented as NLRP3 expressions reduction, caspase-1 cleavage inhibition and interleukin 1 beta (IL-1β) maturation lessened. Meanwhile, AlCl 3 exposure decreased LPS-induced IKKβ activity, IκBα phosphorylation, the phosphorylation and mRNA expression of NF-κB p65, as well the genes expression and concentration in medium supernatant of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). The results suggested that AlCl 3 inhibited the activation of NF-κB signaling pathway induced by LPS, which maybe one of the upstream signals involved in the inhibition of NLRP3 inflammasome activation by AlCl 3 . This research can provide theoretical basis for understanding the immune toxicity of Al, and deepening the cognition of Al exposure hazards to immune response.
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MOLECULES
·
2018
·Vol. 23
·期 7
·1788
·
IF 3.098
Hong-Xin Cui,Ji-Hong Chen,Jing-Wan Li,Fang-Rong Cheng,Ke Yuan
Myrica rubra(MR) is rich in anthocyanins, and it has good anti-cancer, anti-aging, antioxidant, and antiviral effects. The proportion of disability and death caused by ischemic stroke gradually increased, becoming a major disease that is harmful to human health. However, research on effects of anthocyanin from MR on cerebral ischemia-reperfusion (I/R) injury is rare. In this study, we prepared eight purified anthocyanin extracts (PAEs) from different types of MR, and examined the amounts of total anthocyanin (TA) and cyanidin-3-O-glucoside (C-3-G). After one week of PAE treatment, the cerebral infarction volume, disease damage, and contents of nitric oxide and malondialdehyde were reduced, while the level of superoxide dismutase was increased in I/R mice. Altogether, our results show that Boqi1MR contained the most TA (22.07%) and C-3-G (21.28%), and that PAE isolated from Dongkui MR can protect the brain from I/R injury in mice, with the mechanism possibly related to the Toll-like receptor 4 (TLR4)/ nuclear factor-κB (NF-κB) and NOD-like receptor pyrin domain-containing 3 protein (NLRP3) pathways.Keywords:Myrica rubra;anthocyanins;cyanidin-3-O-glucoside;cerebral ischemia-reperfusion;TLR4/NF-κB;NLRP3
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2016
·
IF 2.73
Kegang Linghu,Dan Lin,Hong Yang,Yini Xu,Yanyan Zhang,Ling Tao,Yan Chen,Xiangchun Shen
1,8-Cineole (also known as eucalyptol) is a monoterpene that occurs naturally in many aromatic plants, 1,8-cineole has been reported to ameliorate dysfunction of endothelial cells. However, the mechanism of action of 1,8-cineole is incompletely understood. We investigated the protective effect of 1,8-cineole on lipopolysaccharide (LPS)-induced human umbilical vein endothelial cell (HUVEC) injury and the underlying mechanisms. HUVECs were preincubated with 1,8-cineole for 1.5 h, then exposed to LPS for 12 h. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase leakage assays showed 1,8-cineole reduced LPS-induced HUVEC injury significantly. Results from enzyme linked immunosorbent assays revealed that 1,8-cineole suppressed LPS-induced secretion of interleukin-6 and interleukin-8, and recovered nitric oxide to normal levels. 1,8-Cineole decreased phosphorylation of nuclear factor-kappa B (NF-κB) p65 and expression of inducible nitric oxide synthase , and simultaneously improved protein levels of endothelial nitric oxide synthase . Immunofluorescence confirmed 1,8-cineole moderates nuclear translocation of NF-κB. These results suggest that 1,8-cineole ameliorates HUVEC dysfunction significantly, and that this effect at least involves NF-κB suppression.
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NEUROTOXICITY RESEARCH
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2016
·Vol. 31
·期 2
·259-268
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IF 3.14
Zhang Yaqiong,Gao Lingyue,Cheng Zhihua,Cai Jiayi,Niu Yixuan,Meng Weihong,Zhao Qingchun
Impaired hippocampal neurogenesis and neuroinflammation are involved in the pathogenesis of radiation-induced brain injury. Kukoamine A (KuA) was demonstrated to have neuroprotective effects through inhibiting oxidative stress and apoptosis after whole-brain irradiation (WBI) in rats. The aim of this study was to investigate whether administration of KuA would prevent radiation-induced neuroinflammation and the detrimental effect on hippocampal neurogenesis. For this study, male Wistar rats received either sham irradiation or WBI (30 Gy single dose of X-rays) followed by the immediate injection of either KuA or vehicle intravenously. The dose of KuA was 5, 10, and 20 mg/kg, respectively. The levels of pro-inflammatory cytokines were assayed by ELISA kits. The newborn neurons were detected by 5-bromo-2-deoxyuridine (BrdU)/neuronal nuclei (NeuN) double immunofluorescence. Microglial activation was measured by Iba-1 immunofluorescence. The expression of Cox-2 and the activation of nuclear factor κB (NF-κB), activating protein 1(AP-1), and PPARδ were evaluated by western blot. WBI led to a significant increase in the level of TNF-α, IL-1β, and Cox-2, and it was alleviated by KuA administration. KuA attenuated microglial activation in rat hippocampus after WBI. Neurogenesis impairment induced by WBI was ameliorated by KuA. Additionally, KuA alleviated the increased translocation of NF-κB p65 subunit and phosphorylation of c-jun induced by WBI and elevated the expression of PPARδ. These data indicate that KuA could ameliorate the neuroinflammatory response and protect neurogenesis after WBI, partially through regulating the activation of NF-κB, AP-1, and PPARδ.
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PHYTOMEDICINE
·
2024
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IF 6.7
Canchao Jia,Minjuan Yang,Guanlin Xiao,Zhihao Zeng,Lingjie Li,Yangxue Li,Jieyi Jiang,Aili Xu,Jinyan Qiu,Ruiyin Tang,Dongmei Li,Dezheng Jia,Canhui Xie,Guangying Wu,Dake Cai,Xiaoli Bi
Backgrounds Idiopathic pulmonary fibrosis (IPF) is a persistent and advanced pulmonary ailment. The roles of innate immunity and adaptive immunity are pivotal in the evolution of IPF. An ill-adjusted interaction between epithelial cells and immune cells is responsible for initiating the epithelial–mesenchymal transition (EMT) process and sustaining chronic inflammation, thereby fostering fibrosis progression. The intricacy of IPF pathogenesis has hindered the availability of efficacious agents. Elephantopus scaber Linn. (ESL) is a canonical Chinese medicine with significant immunoregulatory effects, and its aqueous extract has been proven to attenuate IPF symptoms in bleomycin (BLM)-induced mice. However, the underlying mechanism through which ESL relieves IPF remains unclear. Aim To validate whether ESL reverses IPF by mediating the immune response and EMT. Methods : Ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and UPLC were used to identify the components and determine the concentrations of the specific compounds in the ESL. Network pharmacology and molecular docking were applied to predict the potential mechanism underlying the anti-IPF effect of ESL. BLM-induced IPF mice were used to validate the anti-IPF effect of ESL, and lung tissue was collected to test putative pathways involved in inflammation and EMT via immunohistochemistry (ICH), real-time quantitative polymerase chain reaction (RT–qPCR) and Western blotting. Results Sixty-one compounds were identified, and thirteen main ingredients were quantified in the ESL. In silico experiments predicted that the IPF-mediated reversal of adverse effects by ESL would be related to interruption of the Toll-like receptor 4 (TLR4)/nuclear factor-k-gene binding (NF- ĸ B) inflammatory pathway and the transforming growth factor-beta l (TGF-β1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O3 (FOXO3a) fibrosis pathway. In vivo experiments showed that ESL alleviates BLM-induced lung inflammation and fibrosis by reducing neutrophil aggregation and fibroblast foci, similar to the effects of the positive control drug pirfenidone (PFD). ESL markedly inhibited the transcription of TNF-α, IL-1 β, and IL-6, which are downstream genes of the NF-κB signaling pathway. Furthermore, the protein levels of TLR4 and p-NF- κ B were correspondingly inhibited in response to ESL treatment. Additionally, ESL reverses BLM-induced changes in the expression of EMT-related biological characteristic indicators (collagen I [COLIA1], E-cadherin, and alpha smooth muscle actin [ α -SMA]) at the messenger ribonucleic acid (mRNA) level and markedly inhibits the expression of EMT-related upstream proteins (TGF- β 1, p-PI3K, p-Akt, and p-FOXO3a). Conclusion Our research suggested that ESL attenuates BLM-induced IPF through mediating the EMT process via the TGF-β1/PI3K/Akt/FOXO3a signaling pathway and inhibiting inflammation through the TLR4/NF-κB signaling pathway, highlighting that ESL can serve as an immunoregulator for relieving the abnormal immune response and reversing the EMT in IPF.
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JOURNAL OF ENVIRONMENTAL MANAGEMENT
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2025
·
IF 8.4
Ke Li,Kun Wang,Tong Xu,Chencong Lyu,Xuejiao Yang,Hongjin Lin,Shiwen Xu
With the widespread application of the brominated flame retardant tetrabromobisphenol A (TBBPA), it poses a threat to human health, especially intestinal health. Quercetin (Que) is a flavonol compound with anti-inflammatory and antioxidant properties. However, whether Que can prevent TBBPA-induced intestinal toxicity remains unknown. Therefore, in this study, a TBBPA (75 μM) exposure model and a Que (0.1 μM) treatment model were established using mouse colon epithelial cells (MCEC). The p38 pathway, pyroptosis, and intestinal barrier function-related indicators were analyzed using an oxidative stress reagent kit, immunofluorescence staining, western blotting, and qRT-PCR. The results showed that TBBPA exposure dose-dependently reduced cell viability, impaired the antioxidant function of cells, promoted ROS accumulation, activated the p38 signalling pathway, induced pyroptosis, and decreased the expression levels of ZO-1, Occludin, and Claudin-1. Notably, Que treatment significantly restored the antioxidant enzyme activity in MCEC cells, reduced the ROS level, inhibited the p38 axis, alleviated MCEC cell pyroptosis, and recovered the intestinal barrier function. Further studies found that using LX-3 (a p38 activator) treatment disrupted the therapeutic effect of Que. In summary, Que can exert a protective effect by inhibiting the ROS-mediated p38 pathway, thereby alleviating the damage of TBBPA to MCEC cells.
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2024
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IF 3.3
Jun-qi Zhan,Jun-xin Wu,Jing-jing Fu,Gao-shang Li,Fang Wu,Yue-wen Chen
BACKGROUND Giant salamander protein peptide is a peptide with rich functional properties. Giant salamander protein peptide KGEYNK (KK-6) is a peptide with both antioxidant and anti-inflammatory properties. The antioxidant and anti-inflammatory mechanisms of KK-6 are still unclear. When we studied the functional mechanism of KK-6, we found that the antioxidant property of KK-6 has a synergistic and promoting effect on anti-inflammatory properties. RESULTS KK-6 enhances cellular resistance to LPS via the MAPK/NF-κB signaling pathway, leading to increased levels of inflammatory factors: interleukin-1β (764.81 ng mL −1 ), interleukin-6 (1.06 ng mL −1 ) and tumor necrosis factor-α (4440.45 ng mL −1 ). KK-6 demonstrates potent antioxidant properties by activating the Nrf2 signaling pathway, resulting in elevated levels of antioxidant enzymes (glutathione peroxidase: 0.03 μg mL −1 ; superoxide dismutase: 0.589 μg mL −1 ) and a reduction in the concentration of the oxidative product malondialdehyde (967.05 μg mL −1 ). CONCLUSION Our findings highlight the great potential of KK-6, a peptide extracted from giant salamander protein, as a remedy for intestinal inflammation. Through its dual role as an antioxidant and anti-inflammatory agent, KK-6 offers a promising avenue for alleviating inflammation-related damage and oxidative stress. This study lays the foundation for further exploration of giant salamander products and highlights their importance in health and novel food development. © 2024 Society of Chemical Industry.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Ziwei Gao,Jinyang Ren,Chang Ke,Deyu Yang,Kexing Wang,Qi Wang,Xinyan Chen,Cong Chang,Zhenpeng Qiu,Chao Cai,Zhongshi Zhou,Yan Meng
An inulin-type fructan (CPS0.2B) from an edible traditional Chinese medicine (TCM) named Codonopsis pilosula was found to exhibit immunological enhancement both in vitro and in vivo. However, the commercial inulin, which has an almost identical molecular weight and monosaccharide composition as CPS0.2B, exhibited almost no biological activity in vitro. We found that this difference was attributed to the smaller particle size of CPS0.2B, facilitating enhanced cellular uptake through endocytosis. Further investigation into the corresponding immune-enhancing effect using THP-1 macrophage cells indicated that CPS0.2B can effectively activate the MAPK and NF-κB signaling pathways by stimulating the p65 protein both inside and outside the cell membrane. Additionally, in vivo strudy further confirmed CPS0.2B had an immune-enhancing effect on CTX-induced immune suppression model in mice. This study confirmed the immune-enhancing activity and related mechanisms of the inulin-type fructan CPS0.2B and, more importantly, demonstrated the significant role of the advanced structure of the polysaccharides in immunomodulatory effects.
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JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Yan Zhou,Tian Wen,Shan Yang,Binru Meng,Jing Wei,Jing Zhang,Lun Wang,Xiaofei Shen
Ethnopharmacological relevance Cichorium intybus is a traditional medicinal herb for hepatitis treatment in China and Europe. Sesquiterpene lactones are the main active ingredients in C. intybus . However, their structure-activity relationship (SAR) and molecular mechanisms of anti-inflammatory and hepatoprotective effects require further elucidation. Aim of the study To identify new sesquiterpene lactones from C. intybus , and further evaluate their anti-inflammatory effects, SAR, and mechanisms of anti-inflammatory and hepatoprotective properties. Methods Identification of sesquiterpene lactones from C. intybus using chromatographic fractionation, NMR, and mass spectrometry. The repression of inflammation was evaluated in RAW264.7 macrophages incubated with LPS. Western blotting was employed to investigate the anti-inflammatory mechanisms. The hepatoprotective effect was measured in LPS/D-galactosamine (D-GalN)-induced acute hepatitis in mice. Results We identified 3 new sesquiterpene lactones and 15 known analogues from C. intybus . SAR analysis showed that the α-methylene-γ-lactone moiety was essential for their anti-inflammatory properties. Furthermore, 8-deoxylactucin was identified as the most potent anti-inflammatory component in LPS-induced RAW264.7 macrophages by reduction of nitric oxide production via inhibiting iNOS expression, and suppression of IL-1β, IL-6, and TNF-α expression. Mechanistically, 8-deoxylactucin not only blocked LPS-induced IKKα/β phosphorylation, IκBα phosphorylation and degradation, and NF-κB nuclear accumulation, but also enhanced NRF2 expression and nuclear translocation, HO-1 and NQO1 expression, and reduced ROS generation in vitro . In vivo , 8-deoxylactucin mitigated LPS/D-GalN-induced acute hepatitis, which manifested as reduction in inflammatory infiltration, live injury, serum levels of AST and ALT, and production of pro-inflammatory cytokines and 4-hydroxynonenal. Conclusion 8-Deoxylactucin, the sesquiterpene lactone isolated from C. intybus , exerted anti-inflammatory and hepatoprotective effects by blocking NF-κB activation and enhancing NRF2 activation.
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