Journal of Functional Foods
·
2024
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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
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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
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
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外科手术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Frontiers
·
2025
·
IF 6.9
Xiaoli Qin,Yan Lu,Yawen Luo,Yafang Cui,Kai Zhao,Yang He,Muhammad Aziz ur Rahman,Shengnan Min,Wenfang Wang,Fuyu Yang,Binghai Cao,Huawei Su
Alfalfa is rich in flavonoid compounds, which are known for their antioxidative and anti-inflammatory properties, suggesting therapeutic potential for alfalfa flavonoids (AF) in inflammation-related diseases. This study investigated the effects of AF on Salmonella -induced colitis, a severe inflammatory bowel disorder characterized by oxidative damage and inflammatory response. In vitro, antioxidant assays revealed AF's concentration-dependent radical scavenging, significantly reducing electron paramagnetic resonance (EPR) signals for HO • and O 2 •− by 42% and 54%, respectively. In vivo, AF treatment significantly mitigated body weight (BW) loss by 6%, increased colon length by 11%, and reduced liver and spleen weights by 19% and 81%, respectively, compared to the colitis group. Mechanistically, AF suppressed inflammation by downregulating the Toll-like receptor 4 (TLR4)/IκB/nuclear factor-κB (NF-κB)/cyclooxygenase-2 (COX-2) pathway and inhibiting nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby lowering levels of pro-inflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], interleukin 1 beta [IL-1β]). Concurrently, AF enhanced antioxidant defense via the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels while increasing catalase (CAT) (69%), glutathione peroxidase (GPx) (83%), and superoxide dismutase (SOD) (21%) activities. Moreover, AF preserved epithelial and mucosal barriers by reducing apoptosis and upregulating tight junction proteins (Claudin1, ZO-1, E-cadherin) and goblet cell marker Ulex europaeus (Gorse) Agglutinin I (UEA-1). Microbiota analysis revealed that AF significantly enriched beneficial bacteria, including Akkermansia , Oscillibacter , and butyrate-producing taxa, thereby counteracting Salmonella -induced dysbiosis. Furthermore, AF restored the disrupted profile of short-chain fatty acids (SCFAs), strengthening the relationship between symbiotic microbiota and mucosal defense. Overall, AF exerted multifaced protection against Salmonella -induced colitis by alleviating oxidative stress, stabilizing intestinal homeostasis, and thus attenuating inflammation. These findings make AF a promising phytopharmaceutical for the prevention and treatment of inflammatory diseases.
研究领域:
药理学
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微生物学
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
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
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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
Frontiers in Pharmacology
·
2021
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IF 5.811
Gao Ping,Du Xiaoyi,Liu Lili,Xu Hua,Liu Maochang,Guan Xinlei,Zhang Chengliang
Tacrolimus-induced chronic nephrotoxicity (TIN) hinders its long-term use in patients. However, there are no drugs available in the clinic to relieve it at present. Astragaloside IV (AS-IV) is a saponin extract of the Astragalus which is widely used in the treatment of kidney disease. This study aimed to investigate the effect of AS-IV on TIN and its underlying mechanism. Herein, C57BL/6 mice were treated with tacrolimus and/or AS-IV for 4 weeks, and then the renal function, fibrosis, oxidative stress and p62-Keap1-Nrf2 pathway were evaluated to ascertain the contribution of AS-IV and p62-Keap1-Nrf2 pathway to TIN. Our results demonstrated that AS-IV significantly improved renal function and alleviated tubulointerstitial fibrosis compared with the model group. The expression of fibrosis-related proteins, including TGF-β1, Collagen I and α-SMA, were also decreased by AS-IV. Furthermore, AS-IV relieved the inhibition of tacrolimus on antioxidant enzymes. The data in HK-2 cells also proved that AS-IV reduced tacrolimus-induced cell death and oxidative stress. Mechanistically, AS-IV markedly promoted the nuclear translocation of Nrf2 and the renal protective effects of AS-IV were abolished by Nrf2 inhibitor. Further researches showed that phosphorylated p62 was significantly increased after AS-IV pretreatment. Moreover, AS-IV failed to increase nuclear translocation of Nrf2 and subsequent anti-oxidative stress in HK-2 cells transfected with p62 siRNA. Collectively, these findings indicate that AS-IV relieve TIN by enhancing p62 phosphorylation, thereby increasing Nrf2 nuclear translocation, and then alleviating ROS accumulation and renal fibrosis.
研究领域:
药理学
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肾病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
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IF 3.4
Shijie Fan,Ying Zhao,Qingqing Zhao,Diyun Xu,Xi Chen,Jibo Han,Ziming Fang,Guang Liang,Yunjie Zhao
Hypertension engenders numerous complications, including hypertensive renal disease (HRD). Recent studies have underscored the significance of redox homeostasis in hypertension-associated kidney disorders. Carnosol (Car) has been identified as a potent antioxidant in other diseases. Nevertheless, its role in HRD remains uncertain. This research evaluated the therapeutic impact of Car on HRD and explored its pharmacological mechanism. Car (40 mg/kg) effectively ameliorated kidney injury and oxidative stress (OS) induced by angiotensin II (Ang II) both in vitro and in vivo. Mechanistically, Car facilitates the phosphorylation of p62 through its interaction with mTOR, leading to the degradation of KEAP1, the release of NRF2, and the subsequent upregulation of antioxidant genes. Blocking mTORC1 eliminated Car-induced p62 activation and its antioxidant functions. In summary, our research has demonstrated that Car activates the p62-KEAP1-NRF2 pathway to alleviate the kidney injury and OS caused by Ang II. Consequently, Car may emerge as a promising candidate for the prevention and treatment of Ang II-induced kidney injury.
研究领域:
药理学
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分子生物学
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肾脏病学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER RESEARCH
·
2025
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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
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分子生物学
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细胞死亡
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信号转导
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肿瘤学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 13
·7395
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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
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肾病学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nutrients
·
2022
·Vol. 14
·期 15
·3102
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IF 6.706
Ning Li,Liuding Wen,Tiange Li,Huijie Yang,Mingwu Qiao,Tianlin Wang,Lianjun Song,Xianqing Huang,Mingming Li,Erkigul Bukyei,Fangyu Wang
Many researchers have found that Pb exposure can cause oxidative stress damage to the body’s tissue. Black soybean peptide (BSP) has a variety of physiological functions, especially in terms of oxidative stress. Nevertheless, the mitigation function of BSPs on Pb-induced oxidative stress damage in PC12 cells has not been clearly defined. In this study, cell viability was detected by CCK8. Oxidative stress indicators, such as ROS, GSH/GSSG, MDA, SOD, CAT, GPx, and GR, were tested with biochemical kit. Protein expression of Keap1, Nrf2, and TXNIP was measured by Western blot. Compared with the control group, Pb reduced the cell viability of PC12 cells. However, BSP treatment significantly increased the viability of PC12 cells induced by lead exposure (p< 0.05). Lead can enrich the contents of MDA and ROS, but decrease the amount of CAT, SOD, GR, GPx, and GSH/GSSG in PC12 cells, while BSP can alleviate it (p< 0.05). Lead can enhance the expression of Keap1 and TXNIP proteins, but reduce Nrf2 expression. In contrast, BSPs reversed this phenomenon (p< 0.05). BSPs can alleviate oxidative stress injury induced by lead in PC12 cells through the Keap1/Nrf2/TXNIP signaling pathway.Keywords:black soybean peptide;Pb;PC12 cells;Keap1/Nrf2/TXNIP;oxidative stress
研究领域:
毒理学
·
细胞生物学
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药理学
✓ 已验证
产品关联
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2021
·Vol. 10
·期 11
·2765
·
IF 4.35
Fanghua Guo,Rong Tsao,Chuyao Li,Xiaoya Wang,Hua Zhang,Li Jiang,Yong Sun,Hua Xiong
As a processing by-product, green pea hull (GPH) was found to be rich in phenolic components in our previous studies. In this study, UHPLC-LTQ-OrbiTrap-MS (Ultra performance liquid chromatography-linear ion trap orbitrap tandem mass spectrometry) technique was used to quantify polyphenols, and DSS (sodium dextran sulfate)-induced colitis mouse model was established to explore the effect of GPH extracts on colitis. The results showed that quercetin and its derivatives, kaempferol trihexanside and catechin and its derivatives were the main phenolic substances in the extract, reaching 2836.57, 1482.00 and 1339.91 µg quercetin/g GPH extract, respectively; GPH extracts can improved inflammatory status, repaired colonic function, regulated inflammatory factors, and restored oxidative balance in mice. Further, GPH extracts can activate Keap1-Nrf2-ARE signaling pathway, regulate downstream antioxidant protease and gut microbiota by increasing F/B value and promoting the growth ofLactobacillaceaeandLachnospiraceae, and improve the level of SCFAs (short-chain fatty acids) to relieve DSS-induced colitis in mice. Therefore, GPH may be a promising dietary resource for the treatment of ulcerative colitis.Keywords:polyphenols;colitis;UHPLC-LTQ-OrbiTrap-MS;GPH extracts;Keap1-Nrf2;gut microbiota
研究领域:
药理学
·
营养学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOFACTORS
·
2021
·Vol. 48
·期 1
·190-203
·
IF 6.113
Huijie Chen,Jianqing Chen,Xu Shi,Lu Li,Shiwen Xu
Bisphenol A (BPA) has caused serious pathologies in varying organs of humans and animals, especially reproductive organs. Naringenin (NRG) is a flavanone compound that has shown protective effects against several environmental chemicals through suppression of oxidative stress and activation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Herein, we described the discovery path of NRG inhibition on apoptosis in BPA exposed swine testis (ST) cells through targeting Kelch-like ech-associated protein (Keap1). We found that NRG could specifically bound to the active residues of DGR domain in Keap1, thereby activating Nrf2 signaling pathway, and then increasing the levels of SOD, GPx and CAT, and finally inhibiting oxidative stress and mitochondrial apoptosis induced by BPA in ST cells. Altogether, our results showed that NRG inhibits oxidative stress and mitochondrial apoptosis induced by BPA in ST cells by targeting Keap1/Nrf2 signaling pathway, indicating that NRG could serve as an antagonistic therapy against BPA.
研究领域:
毒理学
·
生殖生物学
·
药理学
✓ 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）