INTERNATIONAL IMMUNOPHARMACOLOGY
·
2018
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IF 3.118
Zheng Li,Haihua Feng,Yue Wang,Bingyu Shen,Ye Tian,Lin Wu,Qiaoling Zhang,Meiyu Jin,Guowen Liu
Rosmarinic acid (RA) has antioxidation, anticancer, antibacterial, anti-inflammatory and various biological functions. In our study, we aim to evaluate effects of RA on acute liver injury caused by LPS and d -galactosamine ( d -GalN) and its underlying molecular mechanism in mice. Our findings showed that RA could protect C57BL/6 mice from LPS/ d -GalN-induced acute liver injury, which not only reflected on declining aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of the serum, but also restrained the phosphorylation of nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinase (ERK1/2) and p38 protein expression and the content of tissue myeloperoxidase (MPO) elevation. Moreover, RA could enhance the level of glutathione-dependent peroxidase (GSH-PX). Furthermore, RA promoted that nuclear factor erythroid-2-related factor 2 (Nrf2) transported into nucleus, and then up-regulated heme oxygenase 1 (HO-1), glutamate-cysteine ligase catalytic (GCLC), glutamate cysteine ligase modifier (GCLM) and quinone oxidoreductase (NQO1). These results indicated that RA could protect the mice from acute liver injury induced by LPS/ d -GalN.
研究领域:
药理学
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肝病学
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免疫学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
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IF 5.279
Jinwen Yuan,Siyan Che,Li Zhang,Zheng Ruan
Luteolin, a dietary flavonoid, has gained increasing interest as an intestinal protectant. This study aimed to evaluate the reparative effect of luteolin against ethanol-induced intestinal barrier damage in a Caco-2 cell monolayer model and the potential mechanisms. Luteolin attenuated ethanol-induced intestinal barrier injury, by increasing transepithelial monolayer resistance (TEER, 27.75 ± 14.75% of the ethanol group, p < 0.01), reducing Lucifer yellow flux (13.21 ± 1.23% of ethanol group, p < 0.01), and upregulating the expression of tight junction (TJ) proteins zonulin occludin-1 (ZO-1), occludin, and claudin-1 (37.963 ± 8.62%, 17.69 ± 7.35%, and 29.40 ± 8.08% of the ethanol group, respectively, p < 0.01). Further mechanistic studies showed that luteolin suppressed myosin light chain 2 (MLC) phosphorylation, myosin light chain kinase (MLCK) activation, nuclear factor kappa-B (NF-κB) nuclear translocation, and mitogen-activated-protein-kinase (MAPK) phosphorylation. Moreover, luteolin also acted as antioxidants indirectly by upregulating antioxidant-responsive-element (ARE) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation to relieve ethanol-induced oxidative damage and TJ dysfunction. The results of the study indicate that luteolin may play an effective role in relieving intestinal barrier damage, and this effect is at least partially due to its indirect antioxidant capacity.
研究领域:
药理学
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细胞生物学
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胃肠病学
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分子生物学
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DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2025
·Vol. 31
·期 2
·e70238
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IF 5
Shihao Chen,Linqian Zhao,Xing Jin,Qichang Liu,Yuqing Xiao,Huiqin Xu
The AST activates the Nrf2/GPX4 signaling pathway to regulate glutathione metabolism and inhibit ferroptosis to preventing epileptic seizures.
研究领域:
神经科学
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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
Food & Nutrition Research
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2022
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IF 3.221
Yue-hong Lu,Yue Hong,Tian-yang Zhang,You-xia Chen,Zhao-jun Wei,Chun-yan Gao
Background Rosmarinic acid (RA) has biological and pharmaceutical properties and shows hepatoprotective potential. However, the hepatoprotective mechanism of RA needs to be further elucidated in vivo and in vitro. Objective This study was aimed to evaluate the protective effect of RA on carbon tetrachloride (CCl 4 )-induced liver injury and elucidate the hepatoprotective mechanism of RA in vivo and in vitro. Design In vivo, the mice were orally administrated with RA (10, 20, and 40 mg/kg bw) daily for 28 consecutive days, and 1% CCl 4 (5 mL/kg bw, dissolved in peanut oil) was used to induce liver injury. In vitro, the big rat liver (BRL) hepatocytes were pretreated with RA (0.2, 0.4, and 0.8 mg/mL) for 3 h, and then the hepatocytes were treated with CC1 4 (final concentration, 14 mM) for 3 h to induce cell injury. The related indexes, including hepatic function, oxidative stress, protein expression of nuclear-factor erythroid 2-related factor 2 (Nrf2) pathway, inflammation, histopathological change, hepatocyte apoptosis, and mitochondrial membrane potential, were evaluated. Results Oral administration of RA to mice considerably decreased the CCl 4 -induced elevation of serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), triacylglycerols (TG), total cholesterol (TC), total bilirubin (TBIL), hepatic reactive oxygen species (ROS), malondialdehyde (MDA), nitric oxide (NO), 8-hydroxydeoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). RA also increased the levels of hepatic glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) and the protein expressions of Nrf2, quinine oxidoreductase (NQO1), and heme oxygenease-1 (HO-1). Histopathological examinations indicated that RA (20 and 40 mg/kg bw) alleviated the liver tissue injury induced by CCl 4 . Moreover, RA inhibited the hepatocyte apoptosis caused by CCl 4 based on TUNEL assay. In vitro, RA pretreatment remarkably recovered the cell viability and reduced the CCl 4 -induced elevation of AST, ALT, lactate dehydrogenase (LDH), ROS, and 8-OHdG. Immunohistochemistry staining demonstrated that pretreatment with RA markedly inhibited the expression of IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and Caspase-3 in CCl 4 -treated hepatocytes. Additionally, RA pretreatment significantly decreased the elevation of mitochondrial membrane potential in CCl 4 -treated hepatocytes. Conclusions RA exerted a protective effect against CCl 4 -induced liver injury in mice through activating Nrf2 signaling pathway, reducing antioxidant damage, suppressing inflammatory response, and inhibiting hepatocyte apoptosis. RA could attenuate BRL hepatocyte ROS production, DNA oxidative damage, inflammatory response, and apoptosis induced by CCl 4 exposure.
研究领域:
药理学
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肝病学
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分子生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Mengmeng Zhang,Jingbo Liu,Yiding Yu,Wenshuo Ren,Rui Yuan,Xuanting Liu,Xiaomin Shang,Zhiyang Du,Meng-Lei Xu,Ting Zhang
Genistein (GEN) is the most abundant aglycone in soy isoflavones and is a key factor distinguishing soybeans from other food sources. It holds significant nutritional value and exhibits notable biological activity. However, the low water solubility of genistein limits its widespread application. To improve its water solubility, this study prepared γ-cyclodextrin (γ-CD)/GEN inclusion complexes and investigated their mechanism of action in alleviating hydrogen peroxide-induced oxidative stress damage in PC12 cells. The results showed that γ-CD/GEN could be uniformly and stably dispersed in the system. Cell experiments indicated that γ-CD/GEN significantly increased cell survival after treatment with organic hydrogen peroxide, and promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the expression of glutathione peroxidase 4 (GPx4). It also improved mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels, thereby alleviating cell damage caused by oxidative stress. Further Nrf2 knockdown experiments revealed that γ-CD/GEN failed to provide protection, and no protective effect was observed under RSL3 intervention. In conclusion, γ-CD/GEN exerts antioxidant effects by activating the Nrf2/GPx4 pathway, thereby reducing oxidative stress damage induced by organic hydrogen peroxide, providing a theoretical basis for the development of novel antioxidants.
研究领域:
药理学
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分子生物学
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神经科学
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产品关联
DOI
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2023
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IF 4.7
Guanglu Wang,Jiajia Guo,Yeyun Ma,Yue Xin,Xiaomeng Ji,Ying Sun,Jian Zhang,Jingquan Dong
The increasing concern over environmental pollution caused by the pesticide avermectin used in aquaculture has attracted significant attention. The use of avermectin, a neurotoxic pesticide, in aquatic environments leads to toxic effects on non-target organisms, particularly causing harm to fish. The phenolic compound ferulic acid possesses excellent anti-inflammatory and antioxidant capabilities. This study was conducted by establishing a chronic exposure experiment to avermectin, proposes the use of ferulic acid as a dietary additive to protect the carp brain from damage caused by exposure to avermectin. Furthermore, it investigates the anti-inflammatory and antioxidant effects of ferulic acid in the carp brain under chronic exposure to avermectin. The experimental results demonstrate that ferulic acid can alleviate brain tissue inflammation and oxidative stress by modulating the Nrf2/Keap1 and NF-κB signaling pathways . It protects the carp brain from chronic avermectin-induced damage, preserves the integrity of the carp blood-brain barrier, enhances the levels of feeding factors, and thereby alleviates carp growth inhibition. These findings provide new therapeutic strategies and a theoretical foundation for the sustainable development of carp aquaculture.
研究领域:
水产养殖
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毒理学
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药理学
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神经科学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
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2024
·
IF 5.2
Kai Yang,Xiaoxiao Yu,Zihao Guo,Zhihao Fang,Hongyu Zhang,Wanyangchuan Zhang,Changxu Liu,Yanchao Ji,Zhichao Dong,Qiang Gu,Jiahao Yao,Chang Liu
Aims Non-alcoholic fatty liver disease (NAFLD) has risen as a significant global public health issue, for which vertical sleeve gastrectomy (VSG) has become an effective treatment method. The study sought to elucidate the processes through which PIM1 mitigates the advancement of NAFLD. The Pro-viral integration site for Moloney murine leukemia virus 1 (PIM1) functions as a serine/threonine kinase. Bioinformatics analysis revealed that reduced PIM1 expression in NAFLD. Methods To further prove the role of PIM1 in NAFLD, an in-depth in vivo experiment was performed, in which male C57BL/6 mice were randomly grouped to receive a normal or high-fat diet for 19 weeks. They were operated or delivered the loaded adeno-associated virus which the PIM1 was overexpressed (AAV-PIM1). In an in vitro experiment, AML12 cells were treated with palmitic acid to induce hepatic steatosis. Key findings The results revealed that the VSG surgery and virus delivery of mice alleviated oxidative stress, and apoptosis in vivo. For AML12 cells, the levels of oxidative stress, apoptosis, and lipid metabolism were reduced via PIM1 upregulation. Moreover, ML385 treatment resulted in the downregulation of the NRF2/HO-1/NQO1 signaling cascade, indicating that PIM1 mitigates NAFLD by targeting this pathway. Significance PIM1 alleviated mice liver oxidative stress and NAFLD induced by High-fat diet by regulating the NRF2/HO-1/NQO1 signaling Pathway.
研究领域:
肝病学
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分子生物学
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病理学
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药理学
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产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2020
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IF 3.375
Xiugui Wei,Hongyuan Wang,Xuemei Sun,Xiukun Huang,Wanpeng Xu,Yingqin Liang,Lin Liu,Siyan Mo,Xing Lin,Jun Lin
The purpose of this study is to evaluate the protective effect of 4-hydroxy-2(3H)-benzoxazolone from Acanthus ilicifolius (HBAI) on acute liver injury induced by acetaminophen in mice and its mechanism. Mice were continuously treated with HBAI (200, 100, 50 mg/kg) once a day for 10 days. After that, the mice were fasted for 8 hours, followed by intraperitoneal injection of acetaminophen (300 mg/kg). The results showed that HBAI pretreatment significantly reduced acetaminophen-induced liver tissue congestion, hepatocyte apoptosis and necrosis, and inflammatory cell infiltration. HBAI could effectively reduce the levels of serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, reactive oxygen species and malondialdehyde. Interestingly, the activities of liver catalase, superoxide dismutase, glutathione and glutathione reductase were enhanced by HBAI pretreatment. Moreover, HBAI pretreatment alleviated acetaminophen-induced hepatocyte apoptosis by regulating the expression of Bcl-2 family proteins and the mitochondrial function. Further study showed that HBAI pretreatment effectively promoted the expression of Nrf2 and its signal downstream HO-1, NQO1, GCLC, GCLM, and MGST-1, suggesting the activation of the Nrf2/HO-1 signaling pathway. Meanwhile, HBAI attenuated the phosphorylation of NF-κBp65, IKKα/β, and IκBα, as well as the expression of NF-κBp50, which indicated that HBAI blocked the signal transduction of NF-κB pathway. In conclusion, HBAI protects against acetaminophen-induced acute liver injury by inhibiting the NF-κB and activating Nrf2/HO-1 signaling pathways.
研究领域:
药理学
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毒理学
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肝病学
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产品关联
DOI
PubMed
高影响因子
RENAL FAILURE
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2023
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IF 3
Chenlei Lv,Tianyang Cheng,Bingbing Zhang,Ke Sun,Keda Lu
Objectives: Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus. This study investigated the mechanism of triptolide (TP) in podocyte injury in DN.Methods: DN mouse models were established by feeding with a high-fat diet and injecting with streptozocin and MPC5 podocyte injury models were induced by high-glucose (HG), followed by TP treatment. Fasting blood glucose and renal function indicators, such as 24 h urine albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and kidney/body weight ratio of mice were examined. H&E and TUNEL staining were performed for evaluating pathological changes and apoptosis in renal tissue. The podocyte markers, reactive oxygen species (ROS), oxidative stress (OS), serum inflammatory cytokines, nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway-related proteins, and pyroptosis were detected by Western blotting and corresponding kits. MPC5 cell viability and pyroptosis were evaluated by MTT and Hoechst 33342/PI double-fluorescence staining. Nrf2 inhibitor ML385 was used to verify the regulation of TP on Nrf2.Results: TP improved renal function and histopathological injury of DN mice, alleviated podocytes injury, reduced OS and ROS by activating the Nrf2/heme oxygenase-1 (HO-1) pathway, and weakened pyroptosis by inhibiting the nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome pathway. In vitro experiments further verified the inhibition of TP on OS and pyroptosis by mediating the Nrf2/HO-1 and NLRP3 inflammasome pathways. Inhibition of Nrf2 reversed the protective effect of TP on MPC5 cells.Conclusions: Overall, TP alleviated podocyte injury in DN by inhibiting OS and pyroptosis via Nrf2/ROS/NLRP3 axis.
研究领域:
药理学
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肾病学
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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
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Liangliang Kong,Yan Liu,Jingwei Li,Yanyan Wang,Pengmin Ji,Qifeng Shi,Min Han,Hanyang Xu,Weiping Li,Weizu Li
Ethnopharmacological relevance Ginseng is a valuable herb in traditional Chinese medicine. Modern research has shown that it has various benefits, including tonifying vital energy, nourishing and strengthening the body, calming the mind, improving cognitive function, regulating fluids, and returning blood pressure, etc. Rg1 is a primary active component of ginseng. It protects hippocampal neurons, improves synaptic plasticity, enhances cognitive function, and boosts immunity. Furthermore, it exhibits anti-aging and anti-fatigue properties and holds great potential for preventing and managing neurodegenerative diseases (NDDs). Aim of the study The objective of this study was to examine the role of Rg1 in treating chronic inflammatory NDDs and its molecular mechanisms. Materials and methods In vivo , we investigated the protective effects of Rg1 against chronic neuroinflammation and cognitive deficits in mice induced by 200 μg/kg lipopolysaccharide (LPS) for 21 days using behavioral tests, pathological sections, Western blot, qPCR and immunostaining. In vitro experiments involved the stimulation of HT22 cells with 10 μg/ml of LPS, verification of the therapeutic effect of Rg1, and elucidation of its potential mechanism of action using H2DCFDA staining, BODIPY™ 581/591 C11, JC-1 staining, Western blot, and immunostaining. Results Firstly, it was found that Rg1 significantly improved chronic LPS-induced behavioral and cognitive dysfunction in mice. Further studies showed that Rg1 significantly attenuated LPS-induced neuronal damage by reducing levels of IL-6, IL-1β and ROS, and inhibiting AIM2 inflammasome. Furthermore, chronic LPS exposure induced the onset of neuronal ferroptosis by increasing the lipid peroxidation product MDA and regulating the ferroptosis-associated proteins Gpx4, xCT, FSP1, DMT1 and TfR, which were reversed by Rg1 treatment. Additionally, Rg1 was found to activate Nrf2 and its downstream antioxidant enzymes, such as HO1 and NQO1, both in vivo and in vitro . In vitro studies also showed that the Nrf2 inhibitor ML385 could inhibit the anti-inflammatory, antioxidant, and anti-ferroptosis effects of Rg1. Conclusions This study demonstrated that Rg1 administration ameliorated chronic LPS-induced cognitive deficits and neuronal ferroptosis in mice by inhibiting neuroinflammation and oxidative stress. The underlying mechanisms may be related to the inhibition of AIM2 inflammasome and activation of Nrf2 signaling. These findings provide valuable insights into the treatment of chronic neuroinflammation and associated NDDs.
研究领域:
神经药理学
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药理学
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神经科学
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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
EXPERIMENTAL ANIMALS
·
2019
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IF 1.208
Sheng Li,Hongwei Yang,Xiaolong Chen
Sulforaphane (SFN) is abundant in cruciferous plants, providing significant protection against many chronic diseases. With the aim of clarifying the efficacy of sulforaphane in diabetic retinopathy (DR), a series of systematic studies were carried out in the present study. Male Sprague Dawley rats were intraperitoneally injected with streptozotocin (STZ, 65 mg/kg), and those with confirmed diabetes mellitus were given different doses of SFN (0.5 and 1 mg/kg/d) for 12 weeks. In vitro, Müller cells exposed to 25 mM glucose were treated with 2.5 µM SFN. The results indicated that SFN significantly reduced the generation of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and enhanced the activity of antioxidant enzymes (GSH, SOD, and CAT) in the retina of STZ rats. Further, SFN enhanced the nuclear accumulation of Nrf2 and increased the expression of HO-1 and NQO1, two major antioxidants downstream to Nrf2, in the injured retina. In addition, retinal expression levels of NLRP3, cleaved caspase-1 p20, IL-1β p17, and ASC were dramatically increased in STZ-induced DR, and this was abolished by SFN intervention. In vitro, high glucose-induced inflammation and oxidative stress damage in Müller cells were attenuated by SFN. SFN also exerted antioxidant effects, activated the Nrf2 pathway, and inhibited the NLRP3 inflammasome in Müller cells. In conclusion, our work demonstrates that SFN attenuates retinal inflammation and oxidative stress induced by high glucose and activates the antioxidative Nrf2 pathway and inhibits the formation of the NLRP3 inflammasome in vivo and in vitro.
研究领域:
药理学
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糖尿病学
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眼科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
·
2024
·Vol. 59
·期 9
·6231-6242
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IF 2.6
Mengmeng Zhang,Tianchui Wang,Sixian Ou,Yucong Zou,Xuan Xin
Summary Betaine is a natural antioxidant lacking the ability to scavenge free radicals. Although it has been shown to exert antioxidant function by enhancing the expression of antioxidant enzymes, its mechanism has not yet been elucidated. This study explored the role and mechanism of the transcription factor NF-E2-associated factor 2 (Nrf2)-Kelch-like epichlorohydrin-associated Protein 1 (Keap1) antioxidant reaction element (ARE) pathway in betaine-mediated enhancement of antioxidant enzyme expression. Results derived from real-time quantitative PCR, Western blot, quantitative methylation-specific PCR, and inhibitors assay experiments showed that betaine activated the Nrf2-Keap1-ARE pathway, leading to an increase in the mRNA level of superoxide dismutase, glutathione peroxidase, and heme oxygenase-1. The mechanism may involve betaine's promotion of DNA methyltransferase expression, resulting in increased methylation of Keap1 DNA promoter, which ultimately reduces the level of Keap1 mRNA. Therefore, betaine can directly activate the Nrf2-Keap1-ARE pathway by increasing the methylation level of Keap1 DNA promoter, thereby improving the expression of antioxidant enzymes. This study will contribute to unveiling a new antioxidant mechanism for betaine.
研究领域:
分子生物学
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药理学
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生物化学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）