IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2022
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IF 3.712
Haihua Zhang,Wuying Lang,Sufen Li,Chao Xu,Xiumin Wang,Yunyu Li,Zhiqiang Zhang,Tonglei Wu,Minshan Feng
Objective Corynoline is an active substance extracted from Corydalis bungeana Turcz and exerts a therapeutic effect in multiple diseases by alleviating inflammatory response. The present study sought to elucidate the role of corynoline in ulcerative colitis (UC).Methods The experimental colitis models were induced in BALB/c mice via receiving a drinking water supplemented with 3.5% (I) dextran sulfate sodium (DSS) ad libitum for 7 days.Results Corynoline administration inhibited body weight loss, colon shortening, disease activity index and colonic pathomorphological changes in DSS-treated mice. Besides, corynoline down-regulated the levels of pro-inflammatory interleukin (IL)-1β, IL-6 and tumor necrosis factor Alpha (TNF-α), as well as decreased myeloperoxidase (MPO) activity in the colon of DSS-treated mice. In addition, severe oxidative stress in the colonic tissues of DSS-treated was mitigated by corynoline treatment. However, these beneficial effects were reversed by a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor ML385 intervention. Further evidence confirmed that corynoline promoted Nrf2 nuclear migration and heme oxygenase-1 gene expression in the colonic tissues of UC mice. Besides, corynoline treatment restrained colonic nuclear factor-kappa B (NF-κB) activation as proved by the decrease in phosphorylation and nuclear translocation of NF-κB.Conclusions Corynoline ameliorates DSS-induced mouse colitis, which may provide a promising therapeutic strategy for UC treatment.
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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DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2023
·
IF 4.8
Wei-guang Yang,Ao Sun,Rong Zhu,Nan Liu,Wei-jie He,Lin-lin Liu
Background Artemisinin (ART) is a safe and effective antimalarial drug. In recent years, antimalarial drugs have demonstrated a good therapeutic efficacy in IgA nephropathy, suggesting that this may become a new treatment option.Purpose We aimed to evaluate the effect and mechanism of artemisinin in IgA nephropathy.Methods In this study, CMap database was used to predict the artemisinin therapeutic effect for IgA nephropathy. A network pharmacology approach was applied to explore the unknown mechanism of artemisinin in IgA nephropathy. We used molecular docking to predict the binding affinity of artemisinin with the targets. A mouse model of IgA nephropathy was established to investigate the therapeutic effect of artemisinin on IgA nephropathy. In vitro, the cell counting Kit-8 assay was used to evaluate the cytotoxicity of artemisinin. Flow cytometry and PCR assays were used to detect the effects of artemisinin on oxidative stress and fibrosis in lipopolysaccharide (LPS)-stimulated mesangial cells. Western blot and immunofluorescence were used to detect the expression of pathway proteins.Results CMap analysis showed artemisinin may reverse the expression levels of differentially expressed genes in IgA nephropathy. Eighty-seven potential targets of artemisinin in the treatment of IgA nephropathy were screened. Among them, 15 hub targets were identified. Enrichment analysis and GSEA analysis indicated that response to reactive oxygen species is the core biological process. AKT1 and EGFR had the highest docking affinity with artemisinin. In vivo, artemisinin could improve renal injury and fibrosis in mice. In vitro, artemisinin attenuated LPS-induced oxidative stress and fibrosis promoted AKT phosphorylation and Nrf2 nuclear translocation.Conclusion Artemisinin reduced the level of fibrosis and oxidative stress with IgA nephropathy through the AKT/Nrf2 pathway, which provided an alternative treatment for IgAN.
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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生物信息学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2025
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IF 3.5
Ziyang Huang,Ruijia Xu,Zhongjun Wan,Chao Liu,Jinquan Li,Jun He,Li Li
Cadmium (Cd) is a prevalent heavy metal pollutant known to cause lung damage. However, the mechanisms underlying Cd-induced lung injury and the associated therapeutic strategies remain unclear. By establishing Cd-induced lung damage models both in vivo and in vitro , we observed that Cd inhibited the Nrf2/HO-1 signaling pathway, disrupted the redox balance in lung tissue, accelerated endoplasmic reticulum (ER) stress, and promoted ferroptosis, ultimately leading to lung injury. Melatonin (Mel), a potent reactive oxygen species (ROS) inhibitor with high antioxidative efficacy, mitigated the increasing in ROS and the decreasing in superoxide dismutase levels induced by Cd, as well as the upregulation of PERK-eIF2α-ATF4 signaling associated with ER stress, through the activation of the Nrf2/HO-1 signaling pathway. Furthermore, Mel administration not only prevented Cd-induced iron overload but also reduced lipid peroxidation levels, thereby improving mitochondrial morphological alterations. Collectively, our results demonstrated that Mel treatment alleviated Cd-induced lung injury by inhibiting oxidative stress, which in turn ameliorated ER stress and ferroptosis through the activation of the Nrf2/HO-1 pathway.
研究领域:
毒理学
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分子生物学
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呼吸系统医学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
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IF 4.7
Xingfang Zhang,Liang Gao,Jianv Wang,Wei Zhang,Dong Xu,Yanhua Wang,Tianlong Liu,Kai Gao,Zhen Ren,Yi Ding
β-Bisabolene, a bioactive sesquiterpene extracted from myrrh—a substance utilized for ischemic stroke treatment—has known therapeutic potential. Nevertheless, the exact mechanisms underlying its beneficial effects on ischemic stroke, along with its potential targets, remain to be fully elucidated. This study aimed to investigate the therapeutic potential of β-Bisabolene in ameliorating ischemic stroke, identify its potential targets and interactions, and explore the underlying pathways involved. Bioinformatics analyses, including network pharmacology and analysis of GEO transcriptomic datasets, were performed to predict the potential targets and mechanisms of β-Bisabolene in ischemic stroke treatment. Preliminary computational validation was achieved through molecular similarity comparisons, molecular docking studies, and molecular dynamics simulations. In vitro experiments were then conducted to confirm the protective effects of β-Bisabolene on microglia injured by oxygen‒glucose deprivation and to validate the findings from the bioinformatics analyses. The results revealed that β-Bisabolene reduces the levels of the proinflammatory cytokines TNF-α, IL-1β and NO; decreases reactive oxygen species levels; and decreases the expression of COX-2, P38, ERK and Keap1. Moreover, it increases the expression of Arg-1, Nrf2, NQO1 and HO-1. These effects are associated with improved survival rates of oxygen–glucose deprivation–damaged microglia. In conclusion, β-Bisabolene may exert anti-inflammatory and antioxidant effects to ameliorate microglial injury induced by ischemic stroke by antagonizing COX-2 and mediating the MAPK signaling pathway and Keap1/Nrf2 pathway. This study provides valuable insights into the therapeutic potential of β-Bisabolene for the treatment of ischemic stroke.
研究领域:
药理学
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神经科学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
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2025
·Vol. 18
·期 4
·548
·
IF 4.8
Huiming Xue,Zhen Feng,Chang Jin,Yue Zhang,Yongxing Ai,Jing Wang,Meizhu Zheng,Dongfang Shi
Objectives: Ischemic stroke is a severe neurological disorder with high morbidity, mortality, and disability rates, posing a substantial burden on patients, families, and healthcare systems. Soy isoflavone (SI), a naturally occurring phytoestrogen, has demonstrated promising neuroprotective effects. This study aimed to evaluate the anti-stroke efficacy of SI and elucidate its underlying mechanisms through integrated phytochemical profiling, network pharmacology, and both in vitro and in vivo experimental validation.Methods: Active constituents of SI were extracted via reflux and identified using liquid chromatography–mass spectrometry (LC-MS). Network pharmacology was employed to predict therapeutic targets and signaling pathways. The neuroprotective effects of SI were first assessed in PC12 cells subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) injury in vitro. For in vivo evaluation, transient cerebral ischemia–reperfusion injury was induced using the bilateral common carotid artery occlusion (BCCAO) model in adult male ICR rats (27.3 ± 1.8 g; 6–8 weeks old), obtained from the Shanghai Experimental Animal Center, Chinese Academy of Sciences. Forty-eight rats were randomly assigned into four groups (n= 12): sham, model (BCCAO), SI-treated (100 mg/kg, oral gavage for 5 days), and edaravone (EDA)-treated (10 mg/kg, i.p., positive control). All procedures were approved by the Institutional Animal Care and Use Committee of Changchun Normal University (Approval No. 2024003, 13 March 2024) and conducted in accordance with the NIH guidelines and ARRIVE 2.0 reporting standards.Results: In vitro, SI significantly enhanced PC12 cell viability from 57.23 ± 2.88% to 80.76 ± 4.43% following OGD/R. It also reduced intracellular Ca2+by 58.42%, lactate dehydrogenase (LDH) release by 37.67%, caspase-3 activity by 55.05%, and reactive oxygen species (ROS) levels by 74.13% (p< 0.05). A flow cytometry analysis revealed that OGD/R increased the apoptosis rate from 5.34% (control) to 30.85% (model group), which was significantly attenuated by SI treatment, especially in the 560 µg/mL group (20.00%), followed by the 140 and 280 µg/mL groups. In vivo, SI improved neurological scores from 8.3 ± 1.09 to 6.8 ± 1.68, reduced cerebral infarction volume by 18.49%, and alleviated brain edema by 10.42% (p< 0.05). SI also decreased malondialdehyde (MDA) and LDH levels by 31.15% and 39.46%, respectively, while increasing the activity of antioxidant enzymes: superoxide dismutase (SOD) by 11.70%, catalase (CAT) by 26.09%, and glutathione peroxidase (GSH-px) by 27.55% (p< 0.01). Scratch assay results showed that SI restored the impaired migratory ability of the OGD/R-treated PC12 cells, further supporting its role in cellular repair. A Western blot analysis demonstrated the upregulation of nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) and the downregulation of Kelch-like, ECH-associated protein 1 (Keap1) in the cerebral ischemia–reperfusion model.Conclusions: These findings indicate that soy isoflavone confers significant neuroprotective effects against cerebral ischemia–reperfusion injury by enhancing endogenous antioxidant defense mechanisms, reducing oxidative stress, inhibiting apoptosis, and promoting cell migration. The protective effects are likely mediated through the activation of the Nrf2/Keap1 signaling pathway, supporting the therapeutic potential of SI in ischemic stroke treatment.
研究领域:
药理学
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2022
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IF 5.572
Xue-Yan Dai,Shi-Yong Zhu,Jian Chen,Mu-Zi Li,Yi Zhao,Milton Talukder,Jin-Long Li
Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant. It has been determined that DEHP is involved in multiple health disorders. Lycopene (Lyc) is a natural carotenoid pigment , with anti-inflammatory and antioxidant properties. However, it is not clear whether Lyc can protect the spleen from DEHP-induced oxidative damage. A total of 140 mice were randomly divided into seven groups (n = 20) and continuously gavaged with corn oil, distilled water, DEHP (500 or 1000 mg/kg BW/day) and/or Lyc (5 mg/kg BW/day) for 28 days. Histopathological and ultrastructural results showed a DEHP-induced inflammatory response and mitochondrial injuries. Moreover, DEHP exposure induced redox imbalance, which resulted in the up-regulation of ROS activity and MDA content, and the down-regulation of T-AOC, T-SOD and CAT in the DEHP groups. Simultaneously, our results also demonstrated that DEHP-induced kelch-like ECH-associated protein 1 (Keap1) expression was downregulated, and the expression levels of P62, nuclear factor erythroid 2-related factor (NRF2) and their downstream target genes were up-regulated. However, the supplementary Lyc reverted these changes to normal levels. Together, Lyc prevented DEHP-induced splenic injuries by regulating the P62-Keap1-NRF2 signaling pathway. Hence, the protective effects of Lyc might be a therapeutic strategy to ameliorate DEHP-induced splenic damage.
研究领域:
环境科学
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医学
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分子生物学
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DOI
PubMed
高影响因子
RUSSIAN CHEMICAL BULLETIN
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2025
·Vol. 74
·期 3
·807-817
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IF 0
Balakina A. A.,Amozova V. I.,Stupina T. S.,Mumyatova V. A.,Podgurskaya A. D.,Gadomsky S. Ya.
A new method for the synthesis of pyridoxine salts with dicarboxylic acids was proposed. The specific features of the synthesis include the preliminary generation of free pyridoxine from the hydrochloride form by treatment with a solution of triethylamine in chloroform and conduction of the reaction of pyridoxine with dicarboxylic acid in a specially selected solvent mixture. The combination of pyridoxine as a known antioxidant and fumarate as an activator of the transcription factor Nrf2 in one molecule gave rise to a unique structure, bis[3-hydroxy-4,5-bis(hydroxymethyl)-2-methylpyridinium] fumarate (DPNF). In vitro experiments showed the ability of this compound to bind superoxide, suppress lipid peroxidation processes, and behave as a mitochondrial cytoprotective agent and Nrf2 activator. The results of the study can be used to develop a new type of drugs based on activators of the transcription factor Nrf2 to protect cells and tissues from oxidative damage.
研究领域:
药物化学
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生物化学
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分子生物学
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DOI
Antioxidants
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2023
·Vol. 12
·期 9
·1685
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IF 7
Lingyu Xie,Yibin Xu,Xiaoqing Ding,Kaixuan Li,Shuang Liang,Danlei Li,Yongxia Wang,Aikun Fu,Weixiang Yu,Xiuan Zhan
Earlier studies have shown that selenomethionine (SM) supplements in broiler breeders had higher deposition in eggs, further reduced the mortality of chicken embryos, and exerted a stronger antioxidant ability in offspring than sodium selenite (SS). Since previous studies also confirmed that Se deposition in eggs was positively correlated with maternal supplementation, this study aimed to directly investigate the antioxidant activities and underlying mechanisms of SS and SM on the chicken hepatocellular carcinoma cell line (LMH). The cytotoxicity results showed that the safe concentration of SM was up to 1000 ng/mL, while SS was 100 ng/mL. In Se treatments, both SS and SM significantly elevated mRNA stability and the protein synthesis rate of glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), two Se-containing antioxidant enzymes. Furthermore, SM exerted protective effects in the H2O2-induced oxidant stress model by reducing free radicals (including ROS, MDA, and NO) and elevating the activities of antioxidative enzymes, which performed better than SS. Furthermore, the results showed that cotreatment with SM significantly induced apoptosis induced by H2O2on elevating the content of Bcl-2 and decreasing caspase-3. Moreover, investigations of the mechanism revealed that SM might exert antioxidant effects on H2O2-induced LMHs by activating the Nrf2 pathway and enhancing the activities of major antioxidant selenoenzymes downstream. These findings provide evidence for the effectiveness of SM on ameliorating H2O2-induced oxidative impairment and suggest SM has the potential to be used in the prevention or adjuvant treatment of oxidative-related impairment in poultry feeds.Keywords:selenomethionine;sodium selenite;antioxidants;glutathione peroxidase;Nrf2
研究领域:
动物科学
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生物化学
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细胞生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2019
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IF 4.527
Hongyan Yu,Jian Zhang,Qiang Ji,Kaiyuan Yu,Peiyan Wang,Miao Song,Zheng Cao,Xueyan Zhang,Yanfei Li
The present study aimed to investigate whether melatonin (MT) treatment can attenuate immunotoxicity induced by aluminum chloride (AlCl 3 ) in rat spleen. Forty-eight healthy male Wistar rats were randomly allocated and treated with AlCl 3 and/or MT. Rats were orally administered with AlCl 3 for 90 days, from 61st days, rats were injected intraperitoneally with MT for 30 days. Firstly, we found that MT relieved the AlCl 3 -induced immunosuppression by improving spleen structural damage, CD3 + and CD4 + T lymphocyte subsets, IL-2 and TNF-α mRNA expressions and decreasing CD8 + T lymphocyte subsets. Secondly, MT attenuated the AlCl 3 -induced oxidative stress in rat spleen by decreasing the levels of ROS and MDA , while increasing the activities of SOD and CAT. Thirdly, MT relieved the AlCl 3 -induced apoptosis in rat spleen by increasing the MMP and Bcl-2 mRNA and protein expressions, while decreasing apoptosis rates, activity of Caspase-3 and pro-apoptotic gene expression. Finally, MT increased Nrf2 nuclear translocation, and Nrf2 target genes (HO-1, NQO1, SOD1 and CAT) mRNA expressions in the spleen of AlCl 3 -exposed rat. These results suggest that MT may alleviate AlCl 3 -induced immunotoxicity by inhibiting oxidative stress and apoptosis associated with the activation of Nrf2 signaling pathway, which could lay the foundation for the treatment of AlCl 3 immunotoxicity.
研究领域:
药理学
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免疫学
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毒理学
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DOI
PubMed
高影响因子
NEUROTOXICITY RESEARCH
·
2022
·Vol. 40
·期 2
·596-604
·
IF 3.978
Wang Fei,Li Wu-lin,Shen Li-juan,Jiang Ting-ting,Xia Jian-jun,You Da-li,Hu Shan-you,Wang Li,Wu Xiao
Intracerebral hemorrhage (ICH) is the deadliest type of stroke. Oxidative stress was considered to play an important role in ICH-induced secondary injury. Crocin, the main compound isolated from Crocus sativus L., possesses a potential anti-oxidative function in many types of diseases including ICH. In the current study, the protective role of crocin in ICH-induced brain injury was investigated in the ICH model. The ICH-induced brain edema and neurological deficits were analyzed by brain edema measurement and neurological testing. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity and the content of malondialdehyde (MDA) were assessed by a total superoxide dismutase assay kit. The expressions of ferroptosis-related genes were verified by quantitative real-time PCR (qPCR) and western blotting. The ICH-induced brain edema and neurological deficits were significantly decreased after treatment with crocin. Moreover, the SOD and GSH-px activities were obviously increased in the ICH with crocin-treated group compared with the ICH group, while the content of MDA was markedly decreased after treatment with crocin. Crocin inhibited ferroptosis of neuron cells, as evidenced by increased Fe 2+ concentration and the expression of GPX4, FTH1, and SLC7A11. Mechanistically, crocin treatment increased the expression and nuclear translocation of Nrf2. Our data suggest that crocin alleviates intracerebral hemorrhage–induced neuronal ferroptosis by facilitating Nrf2 nuclear translocation.
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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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2024
·
IF 3.8
Yunfei Wei,Meiyu Jin,Hao Yu,Xiaoning Hou,Lilei Zhao,Lu Ding,Jiaqi Cheng,Jiazhang Qiu,Haihua Feng
Glycyrrhiza glabra L. is a common heritage herbal medicine rich in antioxidant compounds such as flavonoids and triterpenoids. Non-alcoholic fatty liver disease has been the global prevalent chronic liver disorder. To investigate the curative role and mechanism of the Glycyrrhiza glabra L. crude extract on NAFLD, in vitro , we used oleic acid, palmitic acid, ML-385 and 3-MA to stimulate HepG2 cells. In vivo , we used Tyloxapol to inject mice intraperitoneally to establish an acute model, and high-fat diet to feed wild-type, Nrf2 -/- and ATG5 flox/flox mice to establish a chronic model. We used high performance liquid chromatography to analyse the content of major bioactive components in the Glycyrrhiza glabra L. crude extract. Our study found the Glycyrrhiza glabra L. crude extract could effectively alleviate lipid accumulation in non-alcoholic fatty liver disease, activate Nrf2 and promote autophagy. However, this alleviating effect disappeared when the Nrf2 and autophagy were inhibited separately. Our study demonstrates that crude extraction of active ingredients from traditional herbal medicines may be a potentially inexpensive, rapid and safe approach to alleviate lipid accumulation in non-alcoholic fatty liver disease.
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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产品关联
DOI
高影响因子
NEUROCHEMICAL RESEARCH
·
2022
·Vol. 48
·期 2
·579-590
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IF 4.414
Shen Mengya,Zheng Yuantie,Li Ge,Chen Yinqi,Huang Lili,Wu Jianzhang,Hong Chenglv
Abstract Antioxidants represent a potential therapy for cerebral ischemia–reperfusion injury (CIRI). Compounds which exhibit both direct and indirect antioxidative activity may potentially exert improved effects. Hence, we aimed to assess whether the dual antioxidant DH-217, a derivative of DHAP clinically used to treat coronary heart disease, can reduce oxidative stress damage and elucidate the underlying mechanism. Hydrogen peroxide (H 2 O 2 )-induced and Middle Cerebral Artery Occlusion (MCAO)-induced damages were used to imitate oxidative stress. The antioxidation of DH-217 was determined by MTT, ROS, colony and DPPH assay. Besides, immunofluorescence, Real-Time PCR Analyses, western blotting and si-RNA/Plasmid-induced protein expression were used for mechanism validation. DPPH scavenging assay evidenced DH-217 was a well free radical scavenger. Cell survival assay also showed that DH-217 had a significant cytoprotection through direct and indirect clearance mechanisms. Further, it clearly inhibited oxidative stress-induced IkappaB kinase beta (IKKβ) phosphorylation and increased heme oxygenase-1 (HO-1) expression. Significantly, these antioxidant beneficial effects were reversed by HO-1 inhibitor, si-nuclear erythroid 2-related factor 2 (Nrf2) and IKKβ plasmid. Meanwhile, DH-217 had a good neuroprotective effect on CIRI rats. The dual antioxidant DH-217 has potential reference value for drug development of CIRI. Furthermore, inhibition of IKKβ phosphorylation and activation of Nrf2/HO-1 could be a promising antioxidant pathway. Graphical Abstract Dual antioxidant DH-217 not only has the ability of directly scavenging ROS, but also can clear it by targeting IKKβ/Nrf2/HO-1 signal axis. Inhibition of IKKβ phosphorylation and activation of Nrf2/HO-1 may be a promising antioxidant pathway for CIRI.
研究领域:
药理学
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神经科学
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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
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