CHEMICO-BIOLOGICAL INTERACTIONS
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2023
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IF 5.1
Yiqiu Liu,Musen Lin,Xingrui Mu,Lin Qin,Junyu Deng,Ye Liu,Xingqian Wu,Wenjie He,Huiwen Pang,Felicity Han,Chengxin Sun,Xuqiang Nie
S olanesol is a tetra sesquiterpene enol with various biological activities . Modern medical studies have confirmed that solanesol has the function of lipid antioxidation and scavenges free radicals. This study aimed to investigate the protective effect of solanesol against oxidative damage induced by high glucose on human normal hepatocytes (L-02 cells) and its possible mechanism. The results showed that solanesol could effectively improve the decrease of cell viability induced by high glucose, decrease the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in the extracellular medium, increased the enzyme activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), balanced the level of reactive oxygen species (ROS) in cells, inhibited lipid peroxidation of all kinds of biological membranes, and restored mitochondrial membrane potential (MMP). In addition, Solanesol also inhibited the expression of Keap1, promoted the nuclear translocation of Nrf2 by hydrogen bonding with Nrf2, and activated the expression of downstream antioxidant factors NQO1 and HO-1. Altogether, these findings suggest that solanesol may be a potential protectant against diabetic liver injury.
研究领域:
药理学
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细胞生物学
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分子生物学
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糖尿病研究
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DOI
PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 8
·1596
·
IF 3.06
Yi Ma,Yunhui Feng,Wanling Zeng,Huibo Luo
This study aimed to investigate the antioxidant activity and release behavior of anthocyanin (ANC) loaded within FA-g-MD wall (ANC-FA-g-MD microcapsule) in vitro. The microencapsulation of ANC was prepared by spray drying and displayed a biphasic release profile. The combination of ANC and FA-g-MD (0.0625–1 mg/mL) showed a higher antioxidant activity than that of both individuals. A possible intermolecular interaction between ANC and FA-g-MD was studied by UV-vis spectra. Intracellular reactive oxygen species (ROS), 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, and protein expression of quinone oxidoreductase 1(NQO1), glutathione reductase (GSR) and γ-glutamate cysteine ligase catalytic subunit (γ-GCLC) were measured through human colon cancer cells (HT-29). After a 24-hour incubation of the HT-29, the combinations (0–60 μg/mL) exhibited a high potential to diminish the ROS level. And the distinct upregulated expressions of GCLC and NQO1 of HT-29 were detected after treatment with combinations compared to those of single ones. These results suggested that the ANC-FA-g-MD microcapsules exerts enhanced antioxidant effect with capability of the modulation of GCLC and NQO1.Keywords:antioxidant;oxidative stress;anthocyanin;HT-29
研究领域:
食品科学
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药理学
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营养学
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细胞生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2019
·
IF 8.456
Qiufang Chen,Jun Zhou,Zhe Chen,Qing Luo,Jian Xu,Guanbin Song
Amplifying intracellular oxidative stress effectively destroys cancer cells. In addition, iron-mediated Fenton reaction converts endogenous H2O2 to produce hypertoxic hydroxyl radical (•OH), resulting in irreversible oxidative damage to combat tumor cells. This method is known as chemodynamic therapy (CDT). Overexpressed glutathione (GSH) in tumor cells efficiently scavenges •OH, significantly reducing the curative effects of CDT. To overcome this challenge and enhance intracellular oxidative stress, iron oxide nanocarriers loaded with β-lapachone (Lapa) drugs (Fe3O4-HSA@Lapa) were constructed and had both Fenton-like agents and GSH depletion properties to amplify intracellular oxidative stress. Release of Lapa selectively increases tumor site-specific generation of H2O2 via NAD(P)H: quinone oxidoreductase 1 (NQO1) catalysis. Subsequently, the iron ions released from the ionization of Fe3O4 in the acidic environment selectively convert H2O2 into highly toxic •OH by Fenton reaction, dramatically improving CDT with minimal systemic toxicity due to low NQO1 expression in normal tissues. Meanwhile, released Lapa consumes GSH in the tumor, amplifying oxidative stress and enhancing the efficacy of CDT. Designed Fe3O4-HSA@Lapa nanoparticles (NPs) exhibit perfect targeting capability, prolonged blood circulation, and increased tumor accumulation. Furthermore, Fe3O4-HSA@Lapa NPs effectively enhance the inhibition of tumor growth and reduce the side effects of anticancer drugs. This work establishes a remarkably enhanced tumor-selective CDT against NQO1-overexpressing tumors by significantly inducing intratumoral oxidative stress with minimal side effects.
研究领域:
癌症研究
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纳米医学
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诊疗学
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药学科学
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产品关联
DOI
PubMed
高影响因子
Cell Death Discovery
·
2023
·Vol. 9
·期 1
·1-15
·
IF 7
Lu Yang-yang,Zhu Chun-yang,Ding Yi-xin,Wang Bing,Zhao Shu-fen,Lv Jing,Chen Shu-ming,Wang Sha-sha,Wang Yan,Wang Rui,Qiu Wen-sheng,Qi Wei-wei
Cepharanthine (CEP), a bioactive compound derived from Stephania Cephalantha Hayata , is cytotoxic to various malignancies. However, the underlying mechanism of gastric cancer is unknown. CEP inhibited the cellular activity of gastric cancer AGS, HGC27 and MFC cell lines in this study. CEP-induced apoptosis reduced Bcl-2 expression and increased cleaved caspase 3, cleaved caspase 9, Bax, and Bad expression. CEP caused a G2 cell cycle arrest and reduced cyclin D1 and cyclin-dependent kinases 2 (CDK2) expression. Meanwhile, it increased oxidative stress, decreased mitochondrial membrane potential, and enhanced reactive oxygen species (ROS) accumulation in gastric cancer cell lines. Mechanistically, CEP inhibited Kelch-like ECH-associated protein (Keap1) expression while activating NF-E2 related factor 2 (Nrf2) nuclear translocations, increasing transcription of Nrf2 target genes quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutamate-cysteine ligase modifier subunit (GCLM). Furthermore, a combined analysis of targeted energy metabolism and RNA sequencing revealed that CEP could alter the levels of metabolic substances such as D (+) - Glucose, D-Fructose 6-phosphate, citric acid, succinic acid, and pyruvic acid, thereby altering energy metabolism in AGS cells. In addition, CEP significantly inhibited tumor growth in MFC BALB/c nude mice in vivo, consistent with the in vitro findings. Overall, CEP can induce oxidative stress by regulating Nrf2/Keap1 and alter energy metabolism, resulting in anti-gastric cancer effects. Our findings suggest a potential application of CEP in gastric cancer treatment.
研究领域:
肿瘤学
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药理学
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细胞生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2018
·Vol. 19
·期 4
·1135
·
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
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2026
·
IF 4.3
Ngwe Phar Ku,Zhu Jing,Ling Hao,Gao Mengmeng,Guo Chengxiang,Hu Yinan,Wang Jicang
Lead (Pb), a persistent and highly toxic environmental contaminant, induces severe multi-organ toxicity, with the liver as a primary target. Naringenin (Nar), a natural flavonoid with established antioxidant properties, shows potential in mitigating chemical-induced liver injury; however, its protective mechanism against Pb hepatotoxicity remains unclear. This study investigated the hepatoprotective effects and underlying mechanisms of Nar in Pb-exposed rats. Thirty-six five-week-old male Sprague-Dawley rats were randomly assigned to six groups ( n = 6): control, three Pb-treated groups (15, 30, and 60 mg/kg), co-treatment group (60 mg/kg Pb + 50 mg/kg Nar), and Nar-alone group (50 mg/kg). After 8 weeks, Pb exposure induced significant liver injury, evidenced by histopathological lesions (e.g., central venous congestion and inflammation), elevated serum levels of ALT, AST, and LDH, and oxidative stress (increased MDA; decreased CAT, T-SOD, and GSH). At the molecular level, Pb exposure suppressed the Nrf2/NQO1 pathway, upregulated Keap1, and impaired autophagic flux, as indicated by a decreased LC3-II/LC3-I ratio, accumulated p62, and a disrupted PINK1/Parkin pathway. Corroborating the impaired flux, transmission electron microscopy (TEM) revealed an accumulation of autophagic vacuoles, indicative of blocked autophagic degradation. Crucially, Nar co-treatment effectively mitigated these Pb-induced disturbances by activating the Nrf2/NQO1 pathway to counteract oxidative stress and restored autophagic flux, which was supported by the reversal of p62 accumulation and normalization of the LC3-II/LC3-I ratio. In conclusion, Nar protects against Pb-induced hepatotoxicity by concurrently alleviating oxidative stress and restoring autophagic function, supporting its potential as a therapeutic agent. Graphical
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
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2020
·
IF 6.306
Yao Pan,Ze-Yuan Deng,Xuan Chen,Bing Zhang,Yawei Fan,Hongyan Li
Phenolic acids (caffeic acid, p -coumaric acid,) and carotenes (β-carotene, lycopene) were mixed in different ratios to investigate antioxidant interactions on H 2 O 2 -induced H9c2 cells with ezetimibe (inhibitor of carotenes membrane transporters). Cellular uptake of carotenes, expression of membrane transporters, reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H dehydrogenase quinone1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) were analyzed. Results revealed that phenolic acids increased cellular uptake of carotenes and expression of their membrane transporters. Combination groups contained more phenolic acids showed synergistic effects. For example, β-carotene: caffeic acid = 1:2 significantly suppressed the intracellular ROS (+EZT, 66.34 ± 51.53%) and enhanced the accumulation of nucleus-Nrf2 (+EZT, 30.23 ± 5.30) compared to the groups contained more β-carotene (+EZT, ROS: 75.48 ± 2.55%, nucleus-Nrf2: 19.48 ± 4.22). This study provided an implication of functional foods formulation and demonstrated that antioxidant synergism may due to the up-regulation of carotenes membrane transporters by phenolic acids.
研究领域:
药理学
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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
·
2026
·
IF 6.1
Shaoying Gong,Jiachen Zheng,Lin Wang,Ruoyu Wu,Jianchun Han,Yongxin She
Decabromodiphenyl ether (BDE-209), a widely used polybrominated diphenyl ether, is a persistent environmental pollutant with intestinal toxicity. Arabinogalactan possesses antioxidant and anti-inflammatory properties, but its ability to counteract BDE-209-induced intestinal epithelial barrier (IEB) damage remains unclear. This study examined the protective effects of arabinogalactan on BDE-209-induced IEB damage and the underlying mechanisms. Arabinogalactan significantly restored barrier integrity, as evidenced by increased transepithelial electrical resistance and reduced FITC-dextran permeability. Mechanistically, it attenuated oxidative stress by regulating the levels of reactive oxygen species, glutathione, and malonaldehyde and the activity of superoxide dismutase and reducing the secretion of inflammatory cytokines (IL-1β, IL-6, and TNF-α). Arabinogalactan also preserved tight junction protein expression (claudin-1, zonula occludens [ZO]-1, occludin), lowered intracellular Ca²⁺, and activated the Nrf2/HO-1/NQO1 pathway. Taken together, these findings suggest that arabinogalactan inhibits oxidative stress and inflammation by regulating the Nrf2/NQO1/HO-1 signaling pathway to upregulate TJ expression, thereby alleviating BDE-209-induced IEB damage.
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DOI
PubMed
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
·
2022
·
IF 4.336
Hong-shuang Liu,Man-yu Zhou,Xi Zhang,Ya-lan Li,Jing-wei Kong,Xin Gao,Dong-yu Ge,Jia-jing Liu,Pei-guang Ma,Gui-ying Peng,Yan Liao
The hepatic protective role of Sagittaria sagittifolia polysaccharide (SSP) and its possible mechanism were discussed in mice and L02 hepatocytes injured by heavy metals mixture of Cd + Cr (VI) + Pb + Mn + Zn + Cu. After 30-day intervention, blood and liver samples were collected for the relevant assessments. Methyl thiazolyl tetrazolium (MTT) assay showed 24 h was the best protecting point and the SSP protection at 1 mg/mL was strongest in L02 hepatocytes. SSP can alleviated hepatic injury, as evidenced by significantly decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the malondialdehyde (MDA) content, also increased the superoxide dismutase (SOD) activity and glutathione (GSH), total sulphydryl (T-SH) contents. SSP effectively reduced pathological damage of mice and accumulation of heavy metals in liver, as well as decreased the level of reactive oxygen species (ROS) in L02 hepatocytes. After SSP treatment, the protein expressions or gene transcription of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD( P )H dehydrogenase, quinone 1 (NQO1) and heme oxygenase1 (HO-1) decreased in L02. The protein expression of Nrf2 and NQO1 were increased while HO-1 was decreased in liver. Besides, SSP can attenuates apoptosis through reducing the protein expression of Bcl-2-associated X protein (Bax) and caspase-3, and increasing B-cell lymphoma gene 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl). SSP protects against six-heavy-metal-induced hepatic injury in mice and L02 hepatocytes. Supported by Nrf2 gene silencing, the mechanisms may correlate with activating Nrf2 pathway to mitigate oxidative stress and apoptosis.
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Xiaodi Gong,Jing Wang,Linlin Yang,Lijuan Li,Xiaoyan Gao,Xiao Sun,Jingfeng Bai,Jichang Liu,Xin Pu,Yudong Wang
Chemodynamic therapy (CDT) relies on the tumor microenvironment (e.g., high H 2 O 2 level) responsive Fenton-like reactions to produce hydroxyl radicals (·OH) against tumors. However, endogenous H 2 O 2 is insufficient for effective chemodynamic responses. An NAD(P)H: quinone oxidoreductase 1 (NQO1) high catalase (CAT) low therapeutic window for the use of NQO1 bioactive drug β-lapachone (β-Lap) is first identified in endometrial cancer (EC). Accompanied by NADH depletion, NQO1 catalyzes β-Lap to produce excess H 2 O 2 and initiate oxidative stress, which selectively suppress NQO1 high EC cell proliferation, induce DNA double-strand breaks, and promote apoptosis. Moreover, shRNA-mediated NQO1 knockdown or dicoumarol rescues NQO1 high EC cells from β-Lap-induced cytotoxicity. Arginine-glycine-aspartic acid (RGD)-functionalized iron-based metal-organic frameworks (MOF(Fe)) further promote the conversion of the accumulated H 2 O 2 into highly oxidative ·OH, which in turn, exacerbates the oxidative damage to RGD-positive target cells. Furthermore, mitophagy inhibition by Mdivi-1 blocks a powerful antioxidant defense approach, ultimately ensuring the anti-tumor efficacy of stepwise-amplified reactive oxygen species signals. The tumor growth inhibition rate (TGI) is about 85.92%. However, the TGI of MOF(Fe)-based synergistic antitumor therapy decreases to only 50.46% in NQO1-deficient KLE tumors. Tumor-specific chemotherapy and CDT-triggered therapeutic modality present unprecedented therapeutic benefits in treating NQO1 high EC.
研究领域:
肿瘤学
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药学
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生物医学工程
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Yanzi Zhao,Yujing Niu,Xuefei Wang,Peng Wan,Zhanfei Ma,Jian Sun,Shoufang Jiang,Ling Xue,Nan Liu
Indium-tin oxide nanoparticles (Nano-ITO) are widely used in various applications as infrared shielding materials, which increase the risk of occupational exposure. According to reports, Nano-ITO can cause indium lung disease in occupational exposed workers, but the specific mechanism of Nano-ITO-induced pulmonary toxicity remains unclear. In this study, 50 8-week-old male Sprague-Dawley rats were divided into five groups (10 rats in each group) as follows: control group (physiological saline), 1.2 mg/kg Nano-ITO group, 6 mg/kg Nano-ITO group, N-Acetyl-L-Cysteine (NAC) control group (200 mg/kg), and NAC + Nano-ITO group (200 mg/kg NAC intraperitoneal injection, after 1.5 h, 6 mg/kg Nano-ITO intratracheal instillation), twice a week for 12 weeks. Pathological and ultrastructural changes in the rat lung tissue, immunofluorescence assays, immunohistochemistry, protein and mRNA levels of apoptosis- and autophagy-related genes were measured. The levels of ROS, MDA, H 2 O 2 , and LDH, and the activities of T-AOC and SOD, were determined using oxidative stress assay kits. The results showed that Nano-ITO caused strong pulmonary inflammation, pulmonary alveolar proteinosis, and pulmonary interstitial fibrosis. In addition, Nano-ITO-induced oxidative stress in rat lungs presented as increased levels of ROS and H 2 O 2 in the lungs, increased LDH and MDA levels, SOD and T-AOC activity in BALF, and activation of the Nrf2/NQO1/HO-1 signaling pathway. Intriguingly, Nano-ITO significantly increased the protein expression of microtubule-associated protein light chain 3 (LC3-II), the protein levels of autophagy-related genes 5 (ATG5), and Beclin-1 (BECN1), and reduced the protein levels of phosphatidylinositol 3-kinase (PI3K) in lung tissues. In addition, transmission electron microscopy (TEM) showed a significant increase in autophagic vesicles in the cytoplasm of lungs treated with Nano-ITO, indicating that Nano-ITO induces autophagy in rat lungs. Moreover, apoptosis also participates in Nano-ITO-induced pulmonary injury in a synchronous manner, as evidenced by the enhancement of TUNEL-positive signals and activation of the apoptosis pathway (Bax and Bcl-2 positive proportions). NAC supplementation restored most of the pathological structural features of rat lung tissue to their physiological range and effectively weakened apoptosis, as demonstrated by the notable reductions in TUNEL, Bax, and Bcl-2 protein expression levels in the lungs. Although autophagy was detected in the lungs of rats in the Nano-ITO and NAC + Nano-ITO groups, we discovered that NAC could rescue the expression of ATG5 and BECN1 induced by Nano-ITO, thus indicating that exposure to Nano-ITO promotes pulmonary apoptosis and autophagy by mediating oxidative stress. These results indicate that Nano-ITO can cause pulmonary injury by inducing oxidative stress, which activates apoptosis and autophagy, ultimately leading to alveolar proteinosis and interstitial fibrosis.
研究领域:
毒理学
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纳米技术
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呼吸医学
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分子生物学
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药理学
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病理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2014
·
IF 3.63
Demei Xu,Lihua Hu,Chuanyang Su,Xiaomin Xia,Pu Zhang,Juanli Fu,Wenchao Wang,Duo Xu,Hong Du,Qiuling Hu,Erqun Song,Yang Song
This study investigated the protective effects of curcumin on tetrachloro- p -benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS , COX-2, IL-1β, IL-6, TNF-α and NF-κB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling.
研究领域:
药理学
·
毒理学
·
肝病学
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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）