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Keap1-Nrf2
Journal of Cosmetic Dermatology · 2024 · IF 2.3

Dendrobium officinale flowers' topical extracts improve skin oxidative stress and aging

Xing-Li-Shang He,Ning Wang,Xi Teng,Nan-Nan Wang,Zhi-Yi Xie,Ying-Jie Dong,Min-Qiu Lin,Ze-Hua Zhang,Mei Rong,Yi-Gong Chen,Bo Li,Gui-Yuan Lv,Su-Hong Chen

Background Dendrobium officinale flowers (DOF) have the effects of antiaging and nourishing yin, but it lacks pharmacological research on skin aging. Objective Confirming the role of DOF in delaying skin aging based on the “in vitro animal–human” model. Methods In this experiment, three kinds of free radical scavenging experiments in vitro, D-galactose-induced aging mouse model, and human antiaging efficacy test were used to test whether DOF can improve skin aging through anti-oxidation. Results In vitro experiment shows that DOF has certain scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical, hydroxyl free radical, and superoxide free radical, and its IC 50 is 0.2090 μg/mL, 15.020, and 1.217 mg/mL respectively. DOF can enhance the activities of T-AOC, SOD, CAT, and GSH Px in the serum of aging mice, increase the content of GSH, and reduce the content of MDA when administered with DOF of 1.0, 2.0, and 4.0 g/kg for 6 weeks. In addition, it can enhance the activity of SOD in the skin of aging mice, increase the content of Hyp, and decrease the content of MDA, activated Keap1/Nrf2 pathway in the skin of aging mice. Applying DOF with a concentration of 0.2 g/mL on the face for 8 weeks can significantly improve the skin water score and elasticity value, reduce facial wrinkles, pores, acne, and UV spots, and improve the facial brown spots and roughness. Conclusion DOF can significantly improve skin aging caused by oxidative stress, and its mechanism may be related to scavenging free radicals in the body and improving skin quality.

CAS / MDL: 69-72-7
研究领域: 药理学 · 化妆品科学 · 衰老研究 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Untargeted serum and liver metabolomics analyses reveal the gastroprotective effect of polysaccharide from Evodiae fructus on ethanol-induced gastric ulcer in mice

Jiang-Hong Luo,Wan-Shuang Zou,Jing Li,Wei Liu,Jing Huang,Hu-Wei Wu,Jian-Lin Shen,Fei Li,Jia-Shuang-Wei Yuan,An-Kang Tao,Liang Gong,Jun Zhang,Xiao-Yin Wang

This study aimed at investigating the gastroprotective effect of Evodiae fructus polysaccharide (EFP) against ethanol-induced gastric ulcer in mice. Biochemical indexes along with untargeted serum and liver metabolomics were determined. Results showed that pre-treatment of EFP alleviated ethanol-induced gastric ulcer in mice. EFP lessened oxidative stress and inflammation levels of stomachs, showing as increments of SOD and GSH-Px activities, GSH content and IL-10 level, and reductions of MDA and IL-6 levels. Meanwhile, EFP activated the Keap1/Nrf2/HO-1 signaling pathway through increasing Nrf2 and HO-1 protein expressions, and decreasing Keap1 protein expression. Serum and liver metabolomics analyses indicated that 10 metabolic potential biomarkers were identified among normal control, ulcer control and 200 mg/kg·bw of EFP groups, which were related to 5 enriched metabolic pathways including vitamin B6 metabolism, nicotinate and nicotinamide metabolism, pentose phosphate pathway, bile secretion and ascorbate and aldarate metabolism. Further pearson's correlation analysis indicated that there were some positive and negative correlations between the biomarkers and the biochemical indexes. It could be concluded that the gastroprotection of EFP might be related to anti-oxidative stress, anti-inflammation, activation of Keap1/Nrf2/HO-1 signaling pathway and alteration of metabolic pathways. This study supports the potential application of EFP in preventing ethanol-induced gastric ulcer.

CAS / MDL: 73590-58-6
研究领域: 药理学 · 胃肠病学 · 代谢组学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD RESEARCH INTERNATIONAL · 2025 · IF 8

Integrative discovery of novel antioxidant peptides from bovine hide via peptidomics-guided molecular simulation, quantum chemistry, and experimental validation

Xuanying Xin,Sungkwon Park,Wen Zhang,Jia Yu,Sun Jin Hur,Xiangzi Li,Seong-Ho Choi

Conventional identification methods for antioxidant peptides from bovine hide collagen suffer from poor specificity and high costs. This study employed an integrated approach combining peptidomics, molecular simulation, and quantum chemical calculations to identify ten highly active antioxidant peptides from 6006 candidates. Molecular docking revealed that the peptides bound strongly to the Keap1 protein (binding energies: −7.19 to −12.26 kcal/mol) Quantum chemical calculations demonstrated superior electron-donating capacity, while Fukui function analysis identified key active sites. Cellular assays showed all ten synthetic peptides (1 mg/mL) significantly reduced H₂O₂-induced ROS levels in RAW264.7 cells, enhanced SOD/GSH-Px activities, inhibited MDA accumulation, and upregulated the expression of genes in the Nrf2 signaling pathway, which was further confirmed by Western Blot analysis of key proteins in the Keap1-Nrf2 axis. Computational parameters strongly correlated with cellular antioxidant efficacy, with SGPOGPOGP showing optimal protective effects. This tripartite validation strategy provides an innovative paradigm for efficient discovery of bovine hide-derived antioxidant peptides.

CAS / MDL: 144-48-9
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food Bioscience · 2024 · IF 4.8

Ingredients in Rhus chinensis Mill. fruits oil relieve fatigue by reducing oxidative damage and regulating energy metabolism and gut microbiota

Meimei Shan,Xingrui Xu,Chuanqi Chu,He Wang,Chengting Zhang,Shengbao Cai

Fatigue is an intricate physiological phenomenon, causing serious secondary concerns and bioregulation disorders. The objective of this research was to look into the anti-fatigue effect and potential mechanisms of natural ingredients in methanol extract of edible oil from Rhus chinensis Mill. fruits (PMRO). Results showed that a total of 18 fatty acids and 9 anacardic acids were identified by GC-MS and UHPLC-ESI-HCES/MS in PMRO. PMRO significantly increased the weight-bearing swimming time. Further investigations showed that PMRO significantly improved physiological indexes related to fatigue and regulated the oxidative stress (Keap1/Nrf2) and energy metabolism (AMPK/PGC-1α)-related proteins expression to exert anti-fatigue effects. The 16S rRNA sequence analysis indicated that a potential role of PMRO in modulating the abundance of gut bacteria and influencing the short-chain fatty acids content, thereby exerting an anti-fatigue effect. Therefore, the natural ingredients in PMRO may hold promise as a dietary supplement capable of delaying body fatigue.

研究领域: 营养学 · 药理学 · 微生物学 · 生物化学
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Bioactive Materials · 2024 · IF 18

A two-pronged approach to inhibit ferroptosis of MSCs caused by the iron overload in postmenopausal osteoporosis and promote osseointegration of titanium implant

Yulu Yang,Xianhui Zhang,Yao Yang,Pengfei Gao,Wuzhe Fan,Tao Zheng,Weihu Yang,Yu Tang,Kaiyong Cai

Postmenopausal osteoporosis (PMOP) is a prevalent condition among elderly women. After menopause, women exhibit decreased iron excretion, which is prone to osteoporosis. To design a specific titanium implant for PMOP, we first analyze miRNAs and DNA characteristics of postmenopausal patients with and without osteoporosis. The results indicate that iron overload disrupts iron homeostasis in the pathogenesis of PMOP. Further experiments confirm that iron overload can cause lipid peroxidation and ferroptosis of MSCs, thus breaking bone homeostasis. Based on the findings above, we have designed a novel Ti implant coated with nanospheres of caffeic acid (CA) and deferoxamine (DFO). CA can bind on the Ti surface through the two adjacent phenolic hydroxyls and polymerize into polycaffeic acid (PCA) dimer, as well as the PCA nanospheres with the repetitive 1,4-benzodioxan units. DFO was grafted with PCA through borate ester bonds. The experimental results showed that modified Ti can inhibit the ferroptosis of MSCs in the pathological environment of PMOP and promote osseointegration in two main ways. Firstly, DFO was released under high oxidative stress, chelating with excess iron and decreasing the labile iron pool in MSCs. Meanwhile, CA and DFO activated the KEAP1/NRF2/HMOX1 pathway in MSCs and reduced the level of intracellular lipid peroxidation. So, the ferroptosis of MSCs is inhibited by promoting the SLC7A11/GSH/GPX4 pathway. Furthermore, the remained CA coating on the Ti surface could reduce the extracellular oxidative stress and glutathione level. This study offers a novel inspiration for the specific design of Ti implants in the treatment of PMOP.

CAS / MDL: 937-14-4
研究领域: 生物材料 · 骨科 · 材料科学 · 细胞生物学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2024 · IF 5.3

Prediction and verification of targets for α-hederin/oxaliplatin dual-loaded rHDL modified liposomes: Reversing effector T-cells dysfunction and improving anti-COAD efficiency in vitro and in vivo

Gang Wang,Xiao-Na Xu,Zhu Zhi-Min,Kun Wang,Fei Li

This study tried to develop the α-Hederin/Oxaliplatin (OXA) dual-loaded rHDL (α-Hederin-OXA-rHDL) modified liposomes to improve the therapeutic index on colon adenocarcinoma (COAD). The α-Hederin-OXA-rHDL were prepared and evaluated for characterizations, accumulate to tumor tissues, and antitumor activity. A thorough investigation into oxaliplatin resistant and KRAS-mutant related hub keg genes were identified and performed to assess the prognosis role of the genetic signature in COAD. The potential immune signatures and molecular docking for verifing the predicted targets of α-Hederin-OXA-rHDL in tumor-bearing mice. Results suggested that α-Hederin-OXA-rHDL could enhance the sensitivity of oxaliplatin in HCT116/L-OHP cells via the regulation of KEAP1/NRF2 -mediated signaling and HO1 or GPX4 proteins. Furthermore, α-Hederin-OXA-rHDL regulated the predicted targets of PRDM1 interaction with miR-140-5p, efficient activing CD8 T cell to improve therapeutic response in vivo . Collectively, this work provides drug delivery with rHDL dual-loaded α-Hederin and oxaliplatin synergistically targets cancer cells and effectory T cells combating COAD.

CAS / MDL: 7783-20-2 57-88-5
研究领域: 药学 · 癌症生物学 · 分子生物学 · 免疫学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Nano Materials · 2023 · IF 5.9

Antioxidation and Anti-Inflammatory Activity of Prussian Blue Nanozymes to Alleviate Acetaminophen-Induced Acute Liver Injury

Qiang Feng,Hongting Xu,Xiaoyu Pan,Siqi Geng,Huifeng Qian,Chujie Wang,Ying Li,Jiaying Qin,Yiting Wu,Bangyi Zhou,Xiaoyu Liu,Zhiqiu Ye,Yingchun Xu,Zhangsen Yu

Acetaminophen (APAP), a common antipyretic and analgesic drug, is considered the most common cause of drug-induced liver injury (DILI). The mechanism of liver injury induced by APAP is mainly related to oxidative stress and inflammatory reaction. Herein, we report a simple and efficient one-step synthesis of Prussian blue (PB) nanozymes with multiple antioxidant enzymatic activities that effectively treat APAP-induced DILI. At the cellular level, reaching 10 μg/mL PB nanozymes can effectively scavenge intracellular reactive oxygen species (ROS), reduce mitochondrial membrane potential drop, and inhibit hepatocyte apoptosis. According to in vivo experimental studies, the levels of serum biochemical indicators and histopathological examination of DILI mice livers showed that 12.5 mg/kg PB nanozymes could effectively inhibit liver necrosis and 25 mg/kg PB nanozymes achieved the same therapeutic effect as 300 mg/kg NAC. More importantly, compared with NAC, PB nanozymes can still attenuate APAP-induced acute liver injury in mice after APAP-induced acute liver injury in mice for 3 h. Therefore, PB nanozymes can effectively prolong the therapeutic time window, revealing the potential of PB nanozymes in clinical applications for advanced DILI treatment. Furthermore, the therapeutic mechanism studies have shown that PB nanozymes with abundant and variable valence states could not only directly scavenge ROS but also through the Keap1-Nrf2/HO-1 pathway to reduce oxidative stress. Moreover, the decreased expression levels of myeloperoxidase and F4/80 in the liver, which are markers of neutrophil and macrophage infiltration, indicated that the Prussian blue nanozymes modulates inflammation to protect against APAP-induced acute liver injury. Consequently, our findings suggested that PB nanozymes have excellent clinical application prospects for acetaminophen-induced acute liver injury.

研究领域: 药理学 · 纳米医学 · 肝病学 · 生物化学 · 毒理学
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Food Bioscience · 2021 · IF 4.24

Apios americana Medik leaf extracts attenuate H2O2-induced hepatotoxicity

Qiang Chu,Ruoyi Jia,Chaowei Chen,Yaxuan Wang,Xin Yu,Yiru Zhang,Tao Wu,Xiaodong Zheng

Apios americana Medik leaves are rich in polyphenols and prevent glucose-induced damage in organisms. Polyphenols are a group of natural antioxidants. Therefore, a H 2 O 2 induced oxidative stress model of HepG2 cells was used to explore the protective effects of the Apios americana Medik leaves water extract (ALWE) against oxidative stress. Nine compounds were identified in ALWE using HPLC-TOF-MS including C 18 H 24 O 13 , which had not previously been reported. Fluorescence staining assays showed that the ALWE significantly decreased apoptosis, intracellular ROS generation, mitochondrial membrane potential (MMP) dissipation and mitochondrial membrane lipid peroxidation after ALWE pretreatment. Data from western blots showed that Keap1-Nrf2 and Sirt1-FoxO1 signaling pathways were involved in preventing H 2 O 2 induced oxidative stress. Transmission electron microscope and Western blot analyses indicated that autophagy contributed to the regulation of the oxidative balance. These results together indicated that ALWE is a potential antioxidant and autophagy activator, and it protects HepG2 cells against H 2 O 2 damage through activation of autophagy.

研究领域: 药理学 · 细胞生物学 · 分子生物学
✓ 已验证 DOI 高影响因子
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INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY · 2024 · IF 2.6

Identification and molecular mechanisms of novel antioxidant peptides in black soldier fly larvae protein: simulated gastrointestinal digestion, molecular docking and in vitro/in vivo studies

Wangxiang Huang,Chen Wang,Qianzi Chen,Feng Chen,Haohan Hu,Jianfei Li,Jingling Kang,Qiyi He,Xiaodong Yu

Summary This study aims to identify novel antioxidant peptides within black soldier fly larvae protein (BSFLP) using simulated gastrointestinal processes, LC–MS/MS analysis, and virtual screening. Two peptides, PFCPK and ADFW, exhibited significant antioxidant properties in both in vitro radical scavenging experiments and in vivo evaluations using zebrafish embryos induced with 2,2′-azobis(2-methylpropionamidine) dihydrochloride. Treatment with 25 μg mL −1 of PFCPK or ADFW significantly ( P < 0.05) enhanced zebrafish embryo survival, reduced abnormal heartbeats and lowered ROS generation rate by 62.98% and 83.44%, lipid peroxidation by 52.54% and 68.35%, and cell death rate by 86.92% and 97.54%, respectively. Moreover, they restored antioxidant enzyme activities and MDA levels to near-normal values, demonstrating significant therapeutic effects. The observed antioxidant effects may potentially be linked to the modulation of the Keap1/Nrf2 pathway. This study provides valuable insights for developing novel natural antioxidants and maximising the high-value applications of BSFLP.

研究领域: 食品科学 · 生物化学 · 分子生物学 · 药理学
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TOXICOLOGY · 2016 · IF 3.817

Genomic and proteomic analysis of the inhibition of synthesis and secretion of aldosterone hormone induced by quinocetone in NCI-H295R cells

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 · 药理学 · 内分泌学 · 分子生物学 · 细胞生物学
✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY · 2022 ·Vol. 58 ·期 4 ·2115-2129 · IF 3.612

The structural characteristic of bamboo shoot shell polysaccharides extracted using ultrasound-assisted phosphotungstic acid hydrolysis and its protection against cell oxidative injury

Jing Dai,Zhuqian Xiao,Jiajie Li,Qing Ge,Hongpeng Wang,Ruyi Sha,Jianwei Mao

Summary In this study, crude polysaccharide (BSSP) was extracted from bamboo ( Phyllostachys edulis ) shoot shell using the ultrasonic-assisted phosphotungstic acid hydrolysis method. Then, BSSP was further fractionated by DEAE Sepharose fast flow column and serial NaCl solution elutions to obtain two fractions, BSSP-A and BSSP-B. The results showed that the maximum yield of BSSP was 195.2 mg g −1 (19.52%) under optimised conditions. Structural analysis indicated that both BSSP-A and BSSP-B were heteropolysaccharides with α-pyranoside bond structure and mainly consisted of xylose by scanning electronic microscopy, Fourier transform infrared spectroscopy, ultraviolet–visible spectroscopy, thermal characterisation and nuclear magnetic resonance spectroscopy. BSSP-B showed a better protective effect than BSSP-A against H 2 O 2 -induced oxidative injury in WRL-68 cells by protecting the cell membrane structure, maintaining mitochondrial membrane potential and increasing intracellular antioxidant enzymes activities. Immunoblotting indicated that polysaccharides might up-regulate the expression of antioxidant enzymes through the Keap1/Nrf2 signalling pathway and thus alleviate H 2 O 2 -induced cell injury. The findings of this study suggested that polysaccharides from bamboo shoot shell may act as potent antioxidants in functional food industries.

研究领域: 食品科学 · 生物化学 · 药理学 · 细胞生物学
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Bioactive Materials · 2023 · IF 18.9

Smart antioxidant function enhancing (SAFE) nucleic acid therapy for ROS-related chronic diseases and comorbidities

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.

CAS / MDL: 78-67-1 7722-84-1
研究领域: 药理学 · 纳米技术 · 神经科学 · 分子生物学 · 治疗学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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