MOLECULES
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2020
·Vol. 25
·期 20
·4789
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IF 3.267
Xiang-rong Cheng,Wei Zhao,Wen-le Dong,Guo-wei Le
The edible and medicinal part ofInula nervosaWall. (Xiaoheiyao) is confined to its root without sufficient phytochemical and biological investigation. In this study, the secondary metabolites of root, stem, leaf, and flower ofI. nervosaWall. were visualized using Global Natural Products Social Molecular Networking (GNPS), MolNetEnhancer, XCMS(xcmsonline.scripps.edu) analysis, and `ili mapping based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) data to reveal their chemical differences. Among the 11 kinds of chemical repertoires annotated by MolNetEnhancer and 16 hits against the GNPS library, 10-isobutyryloxy-8,9-epoxythymol isobutyrate (1) was revealed as the most dominant and responsible marker between the roots and the other parts. Moreover, a battery of unique MS features as well as differential markers were discovered from different parts of the plant. The chemical differences contribute to the bioactivity differences, which presented in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH)assay and H2O2-insulted HepG2 cells and were in significant correlations with the contents of1. real-time reverse transcription polymerase chain reaction (RT-PCR)results demonstrated thatI. nervosaWall. extracts upregulated the mRNA expression of nuclear factor E2-related factor 2(Nrf2), heme oxygenase 1(HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), manganese superoxide dismutase (MnSOD), and glutamate-cysteine ligase catalytic subunit (GCLC) actors involved in antioxidative response in H2O2-challenged HepG2 cells. These findings support the roots ofI. nervosaWall. as active parts ofXiaoheiyao, and also indicate the potential antioxidant activities of other parts.Keywords:Xiaoheiyao;GNPS molecular networking;MolNetEnhancer;XCMS online;Nrf2
研究领域:
植物化学
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药理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Yunjia Wang,Zhongjing Jiang,Linhua Deng,Gengming Zhang,Xia Xu,Emmanuel Alonge,Hongqi Zhang,Chaofeng Guo
Glucocorticoid-induced osteoporosis (GIOP) represents the foremost cause of secondary osteoporosis and fragility fractures. Novel therapeutic strategies for GIOP are needed, with improved safety profiles and reduced costs compared to current options. Dendrobium officinale ( D. officinale ) is a traditional Chinese medicine that has been reported to have beneficial effects on bone metabolism. Here, we sought to investigate the impacts of D. officinale polysaccharides (DOP), the main active constituents of D. officinale , on GIOP in vivo models and dexamethasone (DEX)-treated osteoblast lineage cells. We found that low concentrations of DOP are relatively safe in vitro and in vivo , respectively. Importantly, we found that DOP treatment significantly inhibited DEX-induced osteoporosis in two in vivo models, zebrafish and mice, while boosting osteogenic differentiation of hBMSCs exposed to DEX. Futhermore, our data reveal that DOP elevates nuclear Nrf2 levels under DEX treatment, by suppressing of Nrf2 ubiquitination. Leveraging Keap1b knockout zebrafish and RNAi approach, we demonstrated that DOP disrupts the association of Nrf2/Keap1, resulting in the inhibition of Nrf2 ubiquitination. Taken together, these results illuminate that DOP stimulates osteogenesis in the presence of DEX by destabilizing the Nrf2/Keap1 interaction. These findings suggest that DOP may serve as a novel drug against osteoporosis caused by glucocorticoids.
研究领域:
药理学
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骨骼生物学
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传统中药
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分子生物学
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2019
·
IF 3.571
Yi Zhao,Mu-Zi Li,Yue Shen,Jia Lin,Hao-Ran Wang,Milton Talukder,Jin-Long Li
As a plasticizer, di(2-ethylhexyl) phthalate (DEHP) is the most usually used phthalate. Leydig cell is a male-specific cell, which plays a principal role in spermatogenesis and masculinization by the androgens of synthesis and secretion. Numerous researchers have indicated that DEHP can result in testicular toxicity by inducing oxidative stress. Lycopene (LYC) is a possible treatment option for male infertility due to its natural antioxidant properties. Our study was aimed to investigate whether LYC could rescue DEHP-induced Leydig cell damage. The mice were treated with DEHP (500 mg/kg BW/day or 1000 mg/kg BW/day) and/or LYC (5 mg/kg BW/day) for 28 days. We found that LYC attenuated DEHP-induced Leydig cell damage. Moreover, the protective role of LYC was verified by the histopathological and ultrastructural analysis of the Leydig cell. LYC suppressed oxidative stress that was induced by DEHP. In the Leydig cell, the expressions of the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes were improved through LYC-mediated protection in DEHP-induced Leydig cell damage. Our findings indicated that LYC could increase the antioxidant capacity via mediating Nrf2 signaling pathway, thereby attenuating DEHP-induced Leydig cell damage.
研究领域:
毒理学
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生殖生物学
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药理学
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PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
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2024
·Vol. 19
·期 1
·1-13
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IF 2.8
Huang Fenglan,Wang Yiteng,Liu Jinzhu,Cheng Ye,Zhang Xiaonan,Jiang Haoli
Background Osteoporosis is a metabolic bone disease that has a common occurrence in postmenopausal women. Asperuloside (ASP) has been reported to exert anti-inflammatory and anti-oxidative effects in numerous diseases, such as rheumatoid arthritis and acute lung injury. However, whether ASP plays a role in osteoporosis has not been addressed.Methods In vivo, ovariectomy (OVX) was used to induce mouse osteoporosis. Then, the mice were treated with 20 and 40 mg/kg ASP. In vitro, MC3T3-E1 cells were treated with 0, 1, 10, 20, 40 and 80 µM ASP. We chose 20 and 40 µM for further experiments due to no significant effects on cell viability.Results The data indicated that ASP reduced osteoporosis in OVX mice and promoted osteogenic differentiation and mineralization in MC3T3-E1 cells. In addition, we explored that ASP protected against osteoporosis via inducing autophagy and activating Nrf2.Conclusion ASP alleviates OVX-induced osteoporosis by promoting autophagy and regulating Nrf2 activation.
研究领域:
药理学
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骨骼生物学
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医学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
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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
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分子生物学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
Communications Biology
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2024
·Vol. 7
·期 1
·1-17
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IF 5.2
Wang Yi,Fu Xiaolong,Zeng Li,Hu Yan,Gao Rongyang,Xian Siting,Liao Songjie,Huang Jianxiang,Yang Yonggang,Liu Jilong,Jin Hai,Klaunig James,Lu Yuanfu,Zhou Shaoyu
Nuclear factor erythroid 2-related factor-2 (Nrf2) antioxidant signaling is involved in liver protection, but this generalization overlooks conflicting studies indicating that Nrf2 effects are not necessarily hepatoprotective. The role of Nrf2/heme oxygenase-1 (HO-1) in cholestatic liver injury (CLI) remains poorly defined. Here, we report that Nrf2/HO-1 activation exacerbates liver injury rather than exerting a protective effect in CLI. Inhibiting HO-1 or ameliorating bilirubin transport alleviates liver injury in CLI models. Nrf2 knockout confers hepatoprotection in CLI mice, whereas in non-CLI mice, Nrf2 knockout aggravates liver damage. In the CLI setting, oxidative stress activates Nrf2/HO-1, leads to bilirubin accumulation, and impairs mitochondrial function. High levels of bilirubin reciprocally upregulate the activation of Nrf2 and HO-1, while antioxidant and mitochondrial-targeted SOD2 overexpression attenuate bilirubin toxicity. The expression of Nrf2 and HO-1 is elevated in serum of patients with CLI. These results reveal an unrecognized function of Nrf2 signaling in exacerbating liver injury in cholestatic disease.
研究领域:
肝病学
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分子生物学
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病理学
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PubMed
高影响因子
NEUROMOLECULAR MEDICINE
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2025
·Vol. 27
·期 1
·1-14
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IF 3.9
Wang Yiming,Chen Yifei,Yang Jianbo,Sun Wei,Zhang Xiaoning
Post-stroke insomnia (PSI) is a common complication following stroke, which seriously affects patients’ life quality. Electro-acupuncture (EA) is an innovative form of traditional Chinese acupuncture that combines electricity with needles to achieve the prevention and treatment of diseases. However, there is limited understanding regarding the treatment mechanism of EA in PSI. In our study, we aimed to investigate the role of EA on PSI development. Our study findings indicated that the quality of sleep, levels of neurotransmitters 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (γ-GABA), and antioxidant levels showed significant improvement following EA treatment in PSI clinical samples and rat models, while the levels of pro-inflammatory factor interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and astrocyte damage were notably reduced. Furthermore, it was discovered that the levels of sirtuin 1 (Sirt1) were reduced in PSI, a condition that was significantly ameliorated by EA treatment. Additionally, the inhibition of Sirt1 caused a marked elevation in astrocyte apoptosis, inflammatory response, and oxidative stress. Besides, the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway was deactivated in the PSI rat model and Sirt1-silenced cells. However, the suppressive impact was successfully counteracted by EA or estazolam (ES), and the overexpression of Nrf2 partially alleviated the increase in apoptosis, inflammation, and oxidative stress caused by Sirt1 knockdown. Taken together, these findings indicated that EA improved sleep quality and silenced Sirt1-induced apoptosis, inflammation, and oxidative stress in PSI by activating the Nrf2-ARE pathway.
研究领域:
神经科学
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中医学
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分子生物学
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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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DOI
PubMed
高影响因子
Food Science & Nutrition
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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
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DOI
PubMed
高影响因子
TOXICOLOGY
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2024
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IF 4.8
Jianan Zhai,Zhengguo Chen,Qi zhu,Zhifang Guo,Xiance Sun,Liping Jiang,Jing Li,Ningning Wang,Xiaofeng Yao,Cong Zhang,Haoyuan Deng,Shaopeng Wang,Guang Yang
Patulin (PAT), the most common mycotoxin, is widespread in foods and beverages which poses a serious food safety issue to human health. Our previous research confirmed that exposure to PAT can lead to acute kidney injury (AKI). Curcumin is the most abundant active ingredient in turmeric rhizome with various biological activities. The aim of this study is to investigate whether curcumin can prevent the renal injury caused by PAT, and to explore potential mechanisms. In vivo , supplementation with curcumin attenuated PAT-induced ferroptosis. Mechanically, curcumin inhibited autophagy, led to the accumulation of p62 and its interaction with Keap1, promoted the nuclear translocation of nuclear factor E2 related factor 2 (Nrf2), and increased the expression of antioxidant stress factors in the process of ferroptosis. These results have also been confirmed in HKC cell experiments. Furthermore, knockdown of Nrf2 in HKC cells abrogated the protective effect of curcumin on ferroptosis. In conclusion, we confirmed that curcumin mitigated PAT-induced AKI by inhibiting ferroptosis via activation of the p62/Keap1/Nrf2 pathway. This study provides new potential targets and ideas for the prevention and treatment of PAT.
研究领域:
毒理学
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药理学
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分子生物学
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食品安全
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产品关联
DOI
PubMed
高影响因子
Discovery Medicine
·
2024
·Vol. 36
·期 181
·266-277
·
IF 2
Luo X,Liao H,Peng J,Jiang X
Background Osteoarthritis (OA) is a common disease that causes pain to many older adults. Because the pathogenesis is not fully elucidated, effective drug therapies are currently lacking. This study aimed to determine how salidroside (Sal)-mediated reduction of osteoarthritis development in mice worked and to identify the underlying mechanism. Methods Using in vitro experiments, ATDC5 cells were treated with various concentrations of Sal and interleukin (IL)-1β for 24 hours to mimic OA. An enzyme-linked immunosorbent assay (ELISA) was conducted to detect the production of pro-inflammatory cytokines and reactive oxygen species (ROS). Western blotting was performed to observe the nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. In in vivo experiments, pathological examination was used to assess the effects of Sal on alleviating OA progression in mice. Nrf2 signaling and its downstream proteins were further tested by immunofluorescence analysis. Results The results showed that both pro-inflammatory cytokines and ROS were significantly reduced following Sal treatment in a concentration-dependent manner. Western blotting revealed that Sal could inhibit the expression of the NF-κB/hypoxia-inducible factor-2α pathway and activate the Nrf2/heme oxygenase-1 pathway. In vivo experiments showed that the cartilage surface in the saline-treated group eroded to a greater extent than the Sal-treated groups ( p < 0.001). Immunohistochemistry analysis revealed that matrix metallopeptidase (MMP) 9, MMP13, and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) decreased expression level. In contrast, collagen-II and aggrecan increased in the Sal-treated groups compared to the saline-treated group. Conclusions Our findings indicate that Sal can alleviate OA progression by promoting anti-oxidant expression and inhibiting degradation enzyme expression. These findings suggest that Sal inhibits the NF-κB pathway and its downstream targets through up-regulating the Nrf2 pathway.
研究领域:
医学
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药理学
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DOI
PubMed
高影响因子
Food Frontiers
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2025
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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
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）