CURRENT MOLECULAR MEDICINE
·
2023
·
IF 2.5
Wang Qi,Zhang Aihua
Background: Oxidative stress is a key mechanism underlying arsenicinduced
liver injury, the Kelch-like epichlorohydrin-related protein 1 (Keap1)/nuclear
factor E2 related factor 2 (Nrf2) pathway is the main regulatory pathway involved in
antioxidant protein and phase II detoxification enzyme expression. The aim of the present
study was to investigate the role and mechanism of baicalein in the alleviation of
arsenic-induced oxidative stress in normal human liver cells.
Methods: Normal human liver cells (MIHA cells) were treated with NaAsO2 (0, 5, 10,
20 μM) to observe the effect of different doses of NaAsO2 on MIHA cells. In addition,
the cells were treated with DMSO (0.1%), NaAsO2 (20 μM), or a combination of NaAsO2
(20 μM) and Baicalein (25, 50 or 100 μM) for 24 h to observe the antagonistic effect
of Baicalein on NaAsO2. Cell viability was determined using a Cell Counting Kit-8
(CCK-8 kit). The intervention doses of baicalein in subsequent experiments were determined
to be 25, 50 and 100μM. The intracellular content of reactive oxygen species
(ROS) was assessed using a 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA)
probe kit. The malonaldehyde (MDA), Cu-Zn superoxide dismutase (Cu-Zn SOD) and
glutathione peroxidase (GSH-Px) activities were determined by a test kit. The expression
levels of key genes and proteins were determined by real-time fluorescence
quantitative polymerase chain reaction (qPCR) and Western blotting.
Results: Baicalein upregulated the protein expression levels of phosphorylated Nrf2
(p-Nrf2) and nuclear Nrf2, inhibited the downregulation of Nrf2 target genes induced by
arsenic, and decreased the production of ROS and MDA. These results demonstrate
that baicalein promotes Nrf2 nuclear translocation by upregulating p-Nrf2 and inhibiting
the downregulation of Nrf2 target genes in arsenic-treated MIHA cells, thereby enhancing
the antioxidant capacity of cells and reducing oxidative stress.
Conclusion: Baicalein alleviated arsenic-induced oxidative stress through activation
of the Keap1/Nrf2 signalling pathway in normal human liver cells.
研究领域:
毒理学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Zaheer Abbas,Jing Zhang,Yucui Tong,Baseer Ahmad,Junyong Wang,Haosen Zhang,Zhenzhen Li,Xubiao Wei,Rijun Zhang,Dayong Si
The objective of this study was to isolate and characterize antioxidant peptides from mulberry leaves fermented with Bacillus subtilis H4 and Bacillus amyloliquefaciens LFB112. The results indicated that fraction F4 (<1 kDa) exhibited superior DPPH activity compared to the F1 (>10 kDa), F2 (3–10 kDa), and F3 (1–3 kDa) fractions, and cytoprotective effect against lipopolysaccharides (LPS)-induced oxidative stress in RAW264.7 cells. Three novel peptides, FRFDP, RFGG, and GPPLAFGGGP, were identified in the F4 fraction of the mulberry leaf ferment, and docking results showed that these peptides could form stable carbon (covalent) and hydrogen bonds to the active sites of Keap1, thus regulating the Keap1-Nrf2 pathway by blocking the Nrf2 binding sites on Keap1. These peptides significantly upregulated the mRNA expression of Nrf2 , HO-1 , and NQO1 , providing indirect evidence of their potential to enhance cellular antioxidant defense via the possible activation of Keap1-Nrf2 pathway. Furthermore, these peptides showed good DPPH and ABTS scavenging activities, indicating their potential as antioxidant peptides. This study offers valuable insights into the integration of these novel peptides in developing mulberry leaf ferment as a functional food and their potential use as a feed additive.
研究领域:
食品科学
·
生物化学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
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
·
神经科学
·
生物信息学
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2023
·Vol. 46
·期 11
·1527-1534
·
IF 2
Bowen Li,Wentao Yu,Lan Yang
Osmundacetone (DHBAc) is an antioxidant compound that has been shown to have neuroprotective and immunomodulatory activities. However, few studies have estimated its effect on cerebral ischemia–reperfusion (I/R) injury. In this study, we investigated the protective effect of DHBAc on the brain tissue of rats with cerebral I/R injury. Rats were respectively given nimodipine (NI), low dose (L-DHBAc) and high dose (H-DHBAc) Osmundacetone, and they were killed under anesthesia after 24 h of reperfusion. And neurological impairment scores, cerebral infarct size and cerebral pathological changes were respectively detected, and mRNA expression of recombinant kelch like ECH associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression levels of caspase 3, cleaved caspase 3, heme oxygenase-1 (HO-1) and quinone oxidoreductase1 (NQO1) in ischemic brain tissue were measured. Compared with the I/R group, neurological impairment scores of the DHBAc groups were significantly decreased, and their infarct sizes were significantly smaller. DHBAc could improve the pathological status of brain tissue with cerebral I/R injury, including reducing number of inflammatory cells and area of vacuoles and restoring number of normal neurons. Expression levels of Keap1 mRNA and proteins of cleaved caspase3 were significantly decreased in the DHBAc groups than those of the I/R group, while expression levels of Nrf2 mRNA, HO-1 and NQO1 proteins were remarkably increased. The effect of H-DHBAc was similar to those of NI. These results suggest that DHBAc could mitigate damage to brain tissue in rats with cerebral I/R injury.
研究领域:
神经科学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Chengji Dong,Gaoxiang Yu,Xianhui Ma,Zhuliu Chen,Ningning Yang,Xuankuai Chen,Yingying Lai,Jiayi Zhao,Yanlan Gu,Kailiang Zhou,Weiyang Gao,Jian Ding,Xuwei Zhu
Background How to improve flap necrosis in distal flaps is still a popular topic in clinical flap research. Zingerone (ZIN), as a plant extract, has therapeutic effects on many diseases. The purpose of our study was to explore whether ZIN can promote the survival of ischaemic skin flaps and its specific mechanism. Methods An ischemic flap model was established in the dorsal region of mice. The changes of angiogenesis, oxidative stress, apoptosis and Keap1-Nrf2 related proteins in the skin flap were detected by immunofluorescence, western blot and qPCR. Overexpression of Keap1 by adeno-associated virus (AAV) was used to study the specific pathway and mechanism. Results The results showed that ZIN can induce angiogenesis and reduce oxidative stress and apoptosis to promote flap survival. Increased expression of Keap1 reversed the therapeutic effect of ZIN. Conclusion ZIN activates Nrf2 by inhibiting Keap1 activation, thus promoting angiogenesis and inhibiting oxidative stress and apoptosis.
研究领域:
外科手术
·
药理学
·
分子生物学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 13
·7395
·
IF 6.208
Xiaoqin Ding,Yan Chen,Lina Zhou,Ruoyun Wu,Tunyu Jian,Han Lyu,Yan Liu,Jian Chen
Bisdemethoxycurcumin (BDMC), a principal and active component of edible turmeric, was previously found to have beneficial effects on metabolic diseases. Chronic kidney disease (CKD) may benefit from its potential therapeutic use. Using a high-fat diet (HFD)-fed mouse model, we examined the effects of BDMC on renal injury and tried to determine how its associated mechanism works. A number of metabolic disorders are significantly improved by BDMC, including obesity, hyperglycemia, hyperinsulinemia, hyperlipidemia and inflammation. Further research on renal histopathology and function showed that BDMC could repair renal pathological changes and enhance renal function. Moreover, decreased serum malondialdehyde (MDA), elevated superoxide dismutase (SOD) activity, and the inhibition of renal reactive oxygen species (ROS) overproduction revealed the alleviation of oxidative stress after BDMC administration. In addition, renal Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) pathway was activated in BDMC-treated mice. In conclusion, these findings demonstrated BDMC as a potential therapy for HFD-induced CKD via the activation of the Keap1/Nrf2 pathway.Keywords:bisdemethoxycurcumin;chronic kidney disease;high-fat diet;Keap1/Nrf2 pathway;oxidative stress
研究领域:
药理学
·
肾病学
·
营养学
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产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2024
·
IF 3.5
Xianyao Tao,Xiaoyun Pan,Gang Zhao,Mingyu Xue,Yongjun Rui
In clinical flap practice, there are a lot of studies being done on how to promote the survival of distal random flap necrosis in the hypoxic and ischemic state. As a traditional Chinese medicine, dihydromyricetin (DHM) is crucial in preventing oxidative stress and apoptosis in a number of disorders. In this work, we examined the impact of DHM on the ability to survive of ischemia flaps and looked into its fundamental mechanism. Our results showed that DHM significantly increased the ischemic flaps' survival area, encouraged angiogenesis and blood flow, reduced oxidative stress and apoptosis, and stimulated KEAP1-Nrf2 (Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor) signaling pathways. Adeno-associated virus (AAV) upregulation of KEAP1 expression also negated the favorable effects of DHM on flap survival. By activating KEAP1-Nrf2 signaling pathways, DHM therapy promotes angiogenesis while reducing oxidative stress and apoptosis.
研究领域:
药理学
·
外科手术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Huan-Huan Xiao,Xue-Ying Li,Ying-Ying Chen,Jin-Xiang Zhou,Ting Zhang,Qiang-Ming Li,Li-Hua Pan,Jian-Ping Luo,Xue-Qiang Zha
The aim of this study was to identify novel antioxidant peptides from quinoa ( Chenopodium quinoa wild.) protein hydrolysates, which were prepared using enzyme combination methods. Eleven novel antioxidant peptides were screened through in silico evaluation, and their structure-activity relationships were further investigated. Molecular docking studies indicated that GPGGGGKGEMF (GF-11) exhibited a higher binding affinity and interaction capacity. GF-11 significantly reduced reactive oxygen species (ROS) levels to 43.20 and malondialdehyde (MDA) levels to 1.92 nmol/mg protein in oxidatively damaged RAW264.7 cells, while also significantly enhancing SOD, GSH-Px, and CAT activities to 25.33, 133.99, and 43.20 U/mg protein, respectively. Furthermore, GF-11 competed with Nrf2 for the binding site on Keap1, promoting the expression of Nrf2, HO-1, and NQO1 proteins, which ultimately activated the Keap1-Nrf2 pathway and mitigated oxidative damage. These findings provide a scientific basis for the application of quinoa antioxidant peptides in the development of functional foods.
研究领域:
食品科学
·
分子生物学
·
营养学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Bo Xu,Tiantian He,Hong Yang,Wenjie Dai,Ling Liu,Xiaoqian Ma,Jiaxue Ma,Guoqin Yang,Rui Si,Xing Du,Xufeng Fu,Xiuying Pei
Di-(2-ethylhexyl) phthalate (DEHP) is widely used in various plastics but has been demonstrated to cause female reproductive toxicity. However, the exact mechanism underlying the ovarian damage induced by DEHP remains unclear. In this study, DEHP was administered orally to 5-week-old female mice for 30 days at doses of 0, 250, 500, and 1000 mg/kg/day. The findings demonstrated that DEHP exposure disrupted ovarian function and follicular development as well as induced oxidative stress and autophagy in ovarian granulosa cells (GCs). Further, 200 µM mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP in vivo , induced autophagy in both human ovarian granulosa cells line (KGN) and mouse primary GCs within 24 h in vitro . However, it did not affect the p62-dependent autophagy flux. Furthermore, MEHP-induced autophagy was inhibited by the autophagy inhibitor 3-MA and exacerbated by the autophagy activator rapamycin, indicating that MEHP induces excessive autophagy in GCs. Subsequently, we found that MEHP-induced autophagic cell death was primarily attributed to oxidative damage from elevated intracellular ROS levels. Meanwhile, MEHP exposure induced nuclear translocation of erythroid-derived factor 2-related factor (Nrf2), a key regulator of antioxidant activity resulting in activating antioxidant effects. Interestingly, we also found that MEHP-induced increase in p62 competitively binds Keap1, thereby facilitating nuclear translocation of Nrf2 and establishing a positive feedback loop in antioxidant regulation. Therefore, this study demonstrated that inhibition of Nrf2 could aggravate oxidative damage and enhance excessive autophagy caused by MEHP, while activation of Nrf2 could reverse the trend. These findings have also been reinforced in studies of cultured ovaries in vitro . Our study suggests that the p62-Keap1-Nrf2 pathway may serve as a potential protective mechanism against DEHP-induced oxidative stress and excessive autophagy in mouse GCs.
研究领域:
生殖毒理学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER RESEARCH
·
2025
·
IF 16.6
Zhou Hai-Meng,Liu Yi,Shi Feng,Qiu Hao-Wen,Li Le,Shu Qi-Peng,Liu Yu-Ying,Wang Bai-Qi,Gao Meng,Du Run-Lei,Ke Shao-Bo,Zhang Xiao-Dong
Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, plays a crucial role in colorectal cancer (CRC) progression and therapeutic response. The NRF2 pathway is one of the critical axes in ferroptosis regulation, which governs oxidative stress resistance and iron homeostasis through its downstream targets, including HMOX1, SLC7A11, and others. However, HMOX1 and SLC7A11 exhibit contrasting roles in ferroptosis, with HMOX1 promoting ferroptosis via iron accumulation and lipid peroxidation, while SLC7A11 inhibits ferroptosis by enhancing antioxidant defenses. Here, we identified CLK2 as a key regulator of the delicate balance of the opposing effects of HMOX1 and SLC7A11. CLK2 stabilized KEAP1 to suppress NRF2 activity, resulting in the downregulation of HMOX1 and SLC7A11. Simultaneously, CLK2 downregulated p53, thereby relieving p53-mediated repression of SLC7A11. The dual regulation by CLK2 disrupted the balance between HMOX1 and SLC7A11, leading to excessive activation of HMOX1 in the absence of CLK2, ultimately sensitizing CRC cells to ferroptosis. Additionally, CLK2 promoted CRC proliferation and tumorigenesis in patient-derived organoids, cell lines, and mouse models. Furthermore, combining the ferroptosis inducer Erastin with Oxaliplatin significantly enhanced anti-tumor efficacy in CLK2-deficient xenograft models. Together, this study establishes CLK2 as a critical inhibitor of ferroptosis via the KEAP1/NRF2/HMOX1 and p53/SLC7A11 axes, supporting its potential as a therapeutic target for CRC.
研究领域:
癌症生物学
·
分子生物学
·
细胞死亡
·
信号转导
·
肿瘤学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Chi Feng,Xichuang Cheng,Mula Na,Fenglun Zhang,Jiufang Duan,Li Ji,Jianxin Jiang
Galactomannan comes from a wide range of plant resources and has some biological activities, but its bioavailability is limited due to its large molecular weight and complex structure. In this study, three degradation methods (H 2 O 2 , ultrasound, and β-mannanase) combined with ethanol fractional precipitation (25 %, 50 %, and 75 %) were used to degrade and separate Gleditsia sinensis galactomannans (GSG), and the physicochemical properties and biological activities of GSG after degradation were analyzed. Comprehensive comparison indicates that H 2 O 2 exhibits had a better degradation effect. After 4 h of degradation using 4 % H 2 O 2 , the yield of GSG precipitated with 50 % ethanol was 37.06 % (the yield of undigested GSG is 1.80 %). Simultaneously, the molecular weight (reduced from 225.25 to 36.87 kDa) and viscosity were significantly reduced under this condition, while the solubility was increased. In addition, the low-molecular-weight GSG (LGSG) obtained by 4 % H 2 O 2 /50 % ethanol showed the strongest free radical scavenging activity in vitro . Furthermore, the results of in vivo antioxidant assays showed that LGSG inhibited Aflatoxin B1-induced developmental toxicity by regulating gene expression in the Keap1 / Nrf2 pathway. LGSG also promoted Nrf2 -mediated expression of the lipid metabolism genes ppar-α and cpt1 , while suppressing expression of the fatty acid synthesis genes fas and scd-1 . Therefore, the liver recovered from lipid peroxidation induced nonalcoholic fatty liver disease (NAFLD). The present study introduces a method for green and efficient preparation of LGSG, indicates its potential as a nutritional product.
研究领域:
食品科学
·
生物化学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2025
·
IF 3.5
Yue Che,Xiaozhu Wang,Qian Li,Xiyi Peng,Zhen Liu,Wenhui Xu,Mei Jing,Ting Wang,Jian Gao,Weiling Wang
A B S T R A C T Exposure to 4-vinylcyclohexene diepoxide (VCD) has been associated to reproductive toxicity, However, the dynamic ovarian function alterations over time in rats and the underlying mechanisms remain unclear. This study investigated the effects of VCD on ovarian function in female Sprague-Dawley (SD) rats on the 25, 60 and 135 days after VCD injection and discovered related mechanisms. Our results showed that VCD had little ovotoxicity on the 25 th day, as no significant changes were observed except for the reduction of preantral follicles. However, on the 60 th day and 135 th day, rats exhibited irregular estrous cycles, abnormal serum sex hormone levels, ovarian morphological damage, decreased primordial and preantral follicles, and increased atretic follicles. We further found that on the 60 th and 135 th day, VCD might exert ovotoxicity by decreasing antioxidant enzyme levels, inhibiting of the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) and PTEN-induced putative kinase 1 (PINK1)/E3 ubiquitin ligase (Parkin) signaling pathway. Interestingly, on the 25 th day, KEAP1/NRF2 and PINK1/Parking signaling pathway were activated. This study provided a wider application in using laboratory rodents as a model of ovarian failure and highlighted that VCD-induced ovotoxicity was linked to the regulation of the KEAP1/NRF2 and PINK1/Parkin signaling pathways.
研究领域:
生殖毒理学
·
分子生物学
✓ 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）