Pharmacognosy Magazine
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2024
·
IF 0.6
Zhao Chenghe,Wang Yao,Jing Shu,Lin Huijiao,Li He,Chen Jianguang,Xia Wei
Background: Drug-induced liver injury (DILI) is extremely common in clinical practice and needs to be focused. Anwulignan is a unique lignan monomer of Schisandrae Sphenantherae Fructus and is used as the main active ingredient of Wuzhi tablet, which is used for liver protection in clinical practice. In this study, an acute liver injury mouse model induced by acetaminophen and paracetamol (APAP) was used to observe its effects.Materials and Methods: An acute liver injury mouse model was established by intraperitoneally injecting APAP. Mice were divided into blank control (CON) group, APAP model (MOD) group, Anwulignan CON group, and Anwulignan MOD group. Anwulignan (6 mg/kg) or sodium carboxymethylcellulose (10 mL/kg) was intragastrically given to mice once a day, successively for 14 days. On day 14, 250 mg/kg APAP solution (10 mL/kg) or saline was injected intraperitoneally, and 12 h later, the mice were killed. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum of mice were tested. The liver index of mice was calculated, and the pathology of liver injury was evaluated by HE staining in mice. The activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) as well as the content of malondialdehyde (MDA) in the liver tissue were tested. The levels of kelch-like ECH-associated protein 1 (Keap-1), nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), BCL2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), caspase-3 and tumor suppressor protein (P53) mRNAs in the liver tissues of mice were detected by reverse transcription-PCR (RT-PCR), and the expression levels of Keap-1, Nrf2, HO-1, Bax, Bcl-2, caspase-3 and P53 proteins in the liver tissue of mice were detected by Western blot.Results: Anwulignan can alleviate the acute liver injury of mice. The down-regulation of the cyclophosphamide (CYP2E1) expression in the liver tissue of mice to reduce the hepatotoxicity of APAP, and the regulation of Nrf2-ARE signaling pathway-related gene expressions to play an antioxidant role and apoptosis-related gene expressions to inhibit the liver cell apoptosis may be involved in the mechanism through which Anwulignan can exert its effect.Conclusion: Anwulignan can alleviate the liver injury induced by APAP in mice, and this study may provide evidence for researching and developing some drugs and nutraceuticals used for preventing and treating liver injury.
研究领域:
药理学
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肝脏病学
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分子生物学
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DOI
高影响因子
REDOX REPORT
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2021
·
IF 4.412
Nabila Jahan,Apu Chowdhury,Ting Li,Ke Xu,Fen Wei,Sicen Wang
Background Progression of Benign Prostate hyperplasia (BPH) is vulnerable to oxidative stress (OS) and prostatic enlargement among the aging males through apoptosis deregulation. Our present study aimed to investigate the effect of neferine (NF) in the regulation of oxidative stress and apoptosis in human BPH-1 cells.Methods BPH epithelial cell line BPH-1 was treated with NF for 24 and 48 h. To measure oxidative stress (OS) we investigated MDA, SOD, and GST expression along with Nrf2 and its downstream gene and protein expression. Cell proliferation and apoptosis regulation was assayed with respective methods.Results Investigation revealed NF remarkably activate Nrf2 and its downstream proteins HO-1 and NQO1 at 48 h more substantially. Nrf2/Keap1 relative gene and protein expression indicated that NF might trigger Nrf2 upregulation by decreasing Keap1 expression. Both NF concentrations (3 µM and 9 µM) were able to deplete ROS and lipid peroxidation, concurrently, up-regulated SOD and GST. NF reduced cell proliferation significantly along with the regulation of apoptotic proteins Bax, Bcl2, Cyt-C, Caspase 9, and Caspase 3 at the same time (48 h).Conclusion This study is the first to manifest that NF may potentially regulate BPH by counterbalancing between OS and apoptosis through the activation of Nrf2-ARE pathway.
研究领域:
药理学
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泌尿学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
CHEMOSPHERE
·
2020
·
IF 5.778
Yilong Zou,Yongming Wu,Qiyu Wang,Jinbao Wan,Mi Deng,Wenqing Tu
Sodium p -perfluorous nonenoxybenzene sulfonate (OBS), a novel alternative to perfluorooctanesulfonate (PFOS), is widely used in industry as a surfactant, firefighting foam and photographic material. The occurrence of OBS in the aquatic environment has been recently reported, but little information is available on its accumulation and toxic effects in aquatic organisms. In this study, zebrafish larvae (3 d post-fertilization) were subjected to OBS (10, 100 μg/L) and PFOS (10 μg/L) for a period of 48 h, followed by a 24 h of depuration period. The bioconcentration and depuration kinetics, oxidative stress and possible molecular mechanisms of OBS and PFOS were investigated in zebrafish larvae. Our results showed that the uptake and depuration of both OBS and PFOS fitted well with a first-order kinetic model. The uptake rate constant of OBS was similar to that of PFOS, but the depuration rate constant was much higher than PFOS with a half-life of 69.7–85 h for OBS and 222.2 h for PFOS. The calculated BCFs of OBS and PFOS were 238.0–242.5 and 644.2, respectively. In our acute toxicity assay, the enhanced expression of Nrf2 protein accompanied by the upregulation of CAT and SOD protein expressions indicated OBS and PFOS induced oxidative stress in zebrafish larvae, and the Nrf2-ARE signaling pathway was involved in this process. Collectively, OBS has a lower bioconcentration potential than PFOS, but its toxic effect on oxidative stress was comparable to PFOS in zebrafish larvae.
研究领域:
环境科学
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毒理学
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水生生物学
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产品关联
DOI
PubMed
高影响因子
Computational and Mathematical Methods in Medicine
·
2022
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IF 2.809
Yanyan Hu,Wei Yang
Objective. To evaluate the potential therapeutic effect of paeoniflorin on acute lung injury induced by severe acute pancreatitis (SAP) and to initially explore the possible protective mechanisms of paeoniflorin. Method. The SAP lung injury rat model was established by retrograde injection of 5% sodium taurocholate to the cholangiopancreatic duct. H&E staining was used to detect pathological changes in rat lung tissue. W/D ratio method, serum amylase (AMY), and lipase activity were used to assess the degree of lung injury in rats. Oxidation indicators such as LDH, MDA, and SOD in lung tissue were measured. Levels of inflammatory factors TNF-α, IL-6, and IL-10 were measured in bronchoalveolar lavage fluid (BALF). At the same time, Western blot was used to detect the expression of related proteins in the Nrf2/ARE signaling pathway. Results. In SAP rats, paeoniflorin treatment could significantly alleviate lung injury conditions such as pulmonary edema and inflammatory cell infiltration in lung tissue and reduce serum amylase and lipase activities. Paeoniflorin can reduce the content of LDH and MDA in lung tissue and increase the content of SOD. In addition, ELISA results showed that paeoniflorin could inhibit the levels of TNF-α and IL-6 in BALF and upregulate the levels of IL-10. Paeoniflorin could upregulate the expression of Nrf2/ARE signaling pathway proteins Cyt-Nrf2, HO-1, and NQO1 in lung tissue of SAP rats. Conclusion. Paeoniflorin may improve acute lung injury in rats with severe pancreatitis by inhibiting inflammation and oxidative stress response. These effects may be related to activating the Nrf2/ARE signaling pathway.
研究领域:
药理学
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病理生理学
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分子生物学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2019
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IF 3.775
Maiquan Li,Weisu Huang,Fan Jie,Mengmeng Wang,Yongheng Zhong,Qi Chen,Baiyi Lu
Various phytochemicals have been reported to protect against oxidative stress. However, the mechanism underlying has not been systematically evaluated, which limited their application in disease treatment. Nuclear factor erythroid 2−related factor 2 (Nrf2), a central transcription factor in oxidative stress response related to numerous diseases, is activated after dissociating from the cytoskeleton−anchored Kelch−like ECH−associated protein 1 (Keap1). The Keap1–Nrf2 protein–protein interaction has become an important drug target. This study was designed to clarify whether antioxidantive phytochemicals inhibit the Keap1–Nrf2 protein–protein interaction and activate the Nrf2-ARE signaling pathway efficiently. Molecular docking and 3D−QSAR were applied to evaluate the interaction effects between 178 antioxidant phytochemicals and the Nrf2 binding site in Keap1. The Nrf2 activation effect was tested on a H 2 O 2 −induced oxidative−injured cell model. Results showed that the 178 phytochemicals could be divided into high−, medium−, and low−total−score groups depending on their binding affinity with Keap1, and the high−total−score group consisted of 24 compounds with abundant oxygen or glycosides. Meanwhile, these compounds could bind with key amino acids in the structure of the Keap1−Nrf2 interface. Compounds from high−total−score group show effective activation effects on Nrf2. In conclusion, phytochemicals showed high binding affinity with Keap1 are promising new Nrf2 activators.
研究领域:
药理学
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Emerging Contaminants
·
2026
·Vol. 12
·期 4
·100770
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IF 8.2
Si Dong,Yunyun Du,Yongliang Zheng,Ting Ding,Zhonghao Xiao,Suwei He,Shanshan Zhu,Yulian Li,Wenfeng He,Xiaoping Wang,Lingci Zeng,Fasheng Liu,Junquan Zeng
Hematotoxicity and immunotoxicity are common adverse effects observed in fish exposed to environmental pollutants; however, the molecular mechanisms underlying these toxicities remain poorly understood. To investigate these mechanisms, zebrafish were exposed to dicofol (DCF) under environmentally relevant conditions. DCF exposure led to increased reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT), and reduced nitric oxide (NO) content. Further analysis revealed a significant increase in TUNEL-positive cells in hematopoietic regions, accompanied by elevated expression of Bax/Bcl-2 , caspase-3 , and p53 . Antibody staining and Western blot (WB) analysis demonstrated that DCF impaired the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant system. Astaxanthin (AST) treatment alleviated DCF-induced damage to hematopoietic stem cells. These results show that DCF disrupts antioxidant homeostasis, aggravates oxidative stress, and ultimately triggers apoptosis in hematopoietic stem cells, offering new insights into strategies to prevent and control pollutant-induced toxicity.
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DOI
高影响因子
Stem Cells International
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2015
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IF 2.813
Meihui Chen,Yu Hou,Dingkun Lin
Polydatin, a glucoside of resveratrol, has been reported to possess potent antioxidative effects. In the present study, we aimed to investigate the effects of polydatin in bone marrow-derived mesenchymal stem cells (BMSCs) death caused by hydrogen peroxide (H2O2), imitating the microenvironment surrounding transplanted cells in the injured spinal cord in vitro. In our study, MTT results showed that polydatin effectively prevented the decrease of cell viability caused by H2O2. Hochest 33258, Annexin V-PI, and Western blot assay showed H2O2-induced apoptosis in BMSCs, which was attenuated by polydatin. Further studies indicated that polydatin significantly protects BMSCs against apoptosis due to its antioxidative effects and the regulation of Nrf 2/ARE pathway. Taken together, our results indicate that polydatin could be used in combination with BMSCs for the treatment of spinal cord injury by improving the cell survival and oxidative stress microenvironments.
研究领域:
药理学
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干细胞生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2018
·Vol. 19
·期 4
·1135
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IF 3.687
Maiquan Li,Tao Xu,Fei Zhou,Mengmeng Wang,Huaxin Song,Xing Xiao,Baiyi Lu
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor against oxidative stress and neurodegenerative disorders. Phenylethanoid glycosides (PhGs; salidroside, acteoside, isoacteoside, and echinacoside) exhibit antioxidant and neuroprotective bioactivities. This study was performed to investigate the neuroprotective effect and molecular mechanism of PhGs. PhGs pretreatment significantly suppressed H2O2-induced cytotoxicity in PC12 cells by triggering the nuclear translocation of Nrf2 and reversing the downregulated protein expression of heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), glutamate cysteine ligase-catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM). Nrf2 siRNA or HO-1 inhibitor zinc protoporphyrin (ZnPP) reduced the neuroprotective effect. PhGs showed potential interaction with the Nrf2 binding site in Kelch-like ECH-association protein 1 (Keap1). This result may support the hypothesis that PhGs are activators of Nrf2. We demonstrated the potential binding between PhGs and the Keap1-activated Nrf2/ARE pathway, and that PhGs with more glycosides had enhanced effects.Keywords:Keap1;Nrf2;Neuroprotective;PC12 cells;PhGs
研究领域:
神经科学
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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
BIOMEDICINE & PHARMACOTHERAPY
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2020
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IF 4.545
Zhishen Xie,Jianping Zhao,Hui Wang,Yali Jiang,Qiaoling Yang,Yu Fu,Huahui Zeng,Christian Hölscher,Jiangyan Xu,Zhenqiang Zhang
This study aims to investigate whether magnolol (MG), a natural neolignane compound, can prevent AD induced by beta-amyloid (Aβ) and the possible mechanisms involved. MG dose-dependently reduces Aβ deposition, toxicity and memory impairment caused by Aβ in transgenic C. elegans . More importantly, these effects are reversed by GW9662, a selective peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist. MG is more effective in enhancing PPAR-γ luciferase levels than honokiol (HK). Meanwhile, MG has the potential to bind with the ligand binding domain of PPAR-γ (PPAR-γ-LBD). As expected, MG inhibited the luciferase activity of NF-κB and its target genes of inflammatory cytokines, and this effect was blocked by GW9662. The luciferase activity of Nrf2-ARE expression can be activated by MG and decreased Aβ-induced reactive oxygen species (ROS). The target gene LXR of PPAR-γ is activated by MG, which upregulates ApoE and promotes microglia phagocytosis and the degradation of Aβ, and these effects were also reversed by GW9662. In summary, MG can attenuate Aβ-induced AD and the underlying mechanism is the reduction of inflammation and promotion of phagocytosis and degradation of Aβ, which is dependent on PPAR-γ.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2018
·Vol. 43
·期 12
·2435-2445
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IF 2.772
Zhang Man,Huang Li-Li,Teng Chen-Huai,Wu Fang-Fang,Ge Li-yun,Shi Yu-Juan,He Zheng-Le,Liu Lei,Jiang Cheng-Jie,Hou Ruo-Nan,Xiao Jian,Zhang Hong-Yu,Chen Da-Qing
Traumatic brain injury (TBI) is a serious public health and medical problem worldwide. Oxidative stress plays a vital role in the pathogenesis of TBI. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important factor in the cellular defense against oxidative stress, is activated following TBI. In this study, the protective effects of Isoliquiritigenin (ILG), a promising antioxidant stress drug, was evaluated as a protective agent against TBI. In a mouse model of controlled cortical impact Injury, we found that the ILG administration reduced the Garcia neuroscore, injury histopathology, brain water content, cerebral vascular permeability, the expression of cleaved caspase3, aquaporin-4, glial fibrillary acidic protein and the increased the expression of neurofilament light chain protein, indicating the protective effects against TBI in vivo. ILG treatment after TBI also restored the oxidative stress and promoted the Nrf2 protein transfer from the cytoplasm to the nucleus. We then used Nrf2−/− mice to test the protective effect of Nrf2 during ILG treatment of TBI. Our findings indicated that Nrf2−/− mice had greater brain injury and oxidative stress than wild-type (WT) mice and ILG was less effective at inhibiting oxidative stress and repairing the brain injury than in the WT mice. In vitro studies in SY5Y cells under oxygen glucose deprivation/re-oxygenation stimulation yielded results that were consistent with those obtained in vivo showing that ILG promotes Nrf2 protein transfer from the cytoplasm to the nucleus. Taken together, our findings demonstrate that Nrf2 is an important protective factor against TBI-induced injuries, which indicates that the protective effects of ILG are mediated by inhibiting oxidative stress after TBI via a mechanism that involves the promotion of Nrf2 protein transfer from the cytoplasm to the nucleus.
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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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
TOXICOLOGY
·
2016
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IF 3.817
Xu Wang,Yijie Bai,Guyue Cheng,Awais Ihsan,Feng Zhu,Yulian Wang,Yanfei Tao,Dongmei Chen,Menghong Dai,Zhengli Liu,Zonghui Yuan
Quinoxaline 1,4-dioxides (QdNOs) are widely used as a kind of antibacterial growth promoter in animal husbandry. The adrenal cortex was found to be one of the main toxic targets of QdNOs, accompanied by a decreased aldosterone level. However, the way in which QdNOs decrease production of the hormone aldosterone is far from clear. To illustrate the mechanism by which QdNOs damage the adrenal cortex and decrease aldosterone hormone levels, the QdNOs were screened to choose the drug with most toxic effects on aldosterone production, and then to reveal the mechanism between the gene and protein profiles in human adrenocortical cells (NCI-H295R cells). The results found that quinocetone (QCT) showed the highest adrenal toxic effect among QdNOs. After exposing H295R cells to 10 and 20 μM QCT for 24 h, compared with blank cells, the gene and protein expression profiles obtained were analyzed by microarray and MALDI TOF/TOF mass spectrometry, respectively. The results of microarray analysis suggested that ABCG1 and SREBF1, which were involved in the cholesterol biosynthetic and metabolic processes, and CYP17A1, NR4A2 and G6PD, which were related to aldosterone biosynthesis, were important molecular targets. It has been speculated that PKC and ERK pathways might be involved in the reduction of aldosterone production caused by QCT, through enhanced mRNA expression of CYP17A1. Additionally, JNK and p38MAPK signal transduction pathways might participate in apoptosis induced by QCT. Twenty-nine and 32 protein spots were successfully identified when cells were treated with 10 and 20 μM QCT, respectively. These identified proteins mainly included material synthesis and energy metabolism-related proteins, transcription/translation processing-related proteins, signal transduction proteins, cytoskeletal proteins, molecular chaperones, proteins related to response to stress, and transport proteins. Further investigations suggested that oxidative stress caused by QCT was exacerbated through disruption of the Keap1/Nrf2/ARE anti-oxidative stress pathway. Taken together, the data demonstrated for the first time that the Keap1/Nrf2/ARE pathway plays a crucial role in adrenal toxicity, and that CYP17A1 was the key switch to reduce the aldosterone production induced by QCT. Furthermore, large numbers of genes and proteins and entry points for research in the inhibition of aldosterone synthesis induced by QCT were offered, which will provide new insight into the adrenal toxicity of QdNOs and help to provide a theoretical foundation for the formulation of safety controls for products obtained from animals and to design new QdNOs with less harmful effects.
研究领域:
毒理学
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药理学
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内分泌学
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分子生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2023
·
IF 18.9
Zhiguo Lu,Ruichen Zhao,Yi Li,Jianze Wang,Jing Guo,Chaobo Bai,Jing Chen,Jun Yang,Yiwan Geng,Tianlu Zhang,Yanyue Wu,Xiyue Jiao,Yining Wang,Junliang Yuan,Xin Zhang
Reactive oxygen species (ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders. The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system. However, ROS under redox homeostasis regulates a wide range of life activities. Therefore, smart scavenging of excess ROS under pathological conditions is essential to treat chronic diseases safely. This study reports a smart antioxidant function enhancement (SAFE) strategy. On-demand release of nucleic acid drugs in a pathological ROS environment smartly activates the endogenous antioxidant system, thereby smartly alleviating oxidative stress in an exogenous antioxidant-independent manner. Through structural modulation and ligand modification, we develop SAFE nanoparticles based on nanohybrid complexes (SAFE-complex) adapted to brain delivery of nucleic acid drugs. SAFE-complex with homogeneous monodisperse structure efficiently treat ROS-related neurodegenerative diseases while protecting the major organ from oxidative stress damage. Moreover, SAFE-complex can stabilize storage in the form of freeze-dried powder. These data indicate that SAFE nanoparticles hold promise for treating ROS-related chronic diseases and comorbidities through rational transformation.
研究领域:
药理学
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纳米技术
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神经科学
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分子生物学
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治疗学
✓ 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）