BIOMEDICAL AND ENVIRONMENTAL SCIENCES
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2025
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IF 4.1
Jia Lin Liu,Min Wang,Rui Zhang,Ji Fang Zheng,Xi Xiu Jiang,Qiao Ni Hu
Objective: To explore the protective effects and underlying mechanisms of H 2 S against lipid peroxidation-mediated carbonyl stress in the uranium-treated NRK-52E cells. Methods: Cell viability was evaluated using CCK-8 assay. Apoptosis was measured using flow cytometry. Reagent kits were used to detect carbonyl stress markers malondialdehyde, 4-hydroxynonenal, thiobarbituric acid reactive substances, and protein carbonylation. Aldehyde-protein adduct formation and alcohol dehydrogenase, aldehyde dehydrogenase 2, aldo-keto reductase, nuclear factor E2-related factor 2 (Nrf2), and cystathionine β-synthase (CBS) expression were determined using western blotting or real-time PCR. Sulforaphane (SFP) was used to activate Nrf2. RNA interference was used to inhibit CBS expression. Results: GYY4137 (an H 2 S donor) pretreatment significantly reversed the uranium-induced increase in carbonyl stress markers and aldehyde-protein adducts. GYY4137 effectively restored the uranium-decreased Nrf2 expression, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2, accompanied by a reversal of the uranium-decreased expression of CBS and aldehyde-metabolizing enzymes. The application of CBS siRNA efficiently abrogated the SFP-enhanced effects on the expression of CBS, Nrf2 activation, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2 and concomitantly reversed the SFP-enhanced effects of the uranium-induced mRNA expression of aldehyde-metabolizing enzymes. Simultaneously, CBS siRNA reversed the SFP-mediated alleviation of the uranium-induced increase in reactive aldehyde levels, apoptosis rates, and uranium-induced cell viability. Conclusion: H 2 S induces Nrf2 activation and nuclear translocation, which modulates the expression of aldehyde-metabolizing enzymes and the CBS/H 2 S axis. Simultaneously, the Nrf2-controlled CBS/H 2 S axis may at least partially promote Nrf2 activation and nuclear translocation. These events form a cycle-regulating mode through which H 2 S attenuates the carbonyl stress-mediated NRK-52E cytotoxicity triggered by uranium.
研究领域:
毒理学
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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
FOOD RESEARCH INTERNATIONAL
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2022
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IF 7.425
Jinxin Li,Hao Zhang,Xijuan Yang,Ling Zhu,Gangcheng Wu,Xiguang Qi,Hui Zhang
The carbonyl trapping activity of bound-polyphenol rich insoluble dietary fiber (BP-IDF) from different whole grains and underlying mechanism of these BP-IDF actions were studied under simulated physiological conditions. We found that the black highland barley BP-IDF exhibited the most pronounced effect in scavenging carbonyls by trapping 88.7%, 72.2%, 95.7%, and 31.4% for methylglyoxal, glyoxal, acrolein, and malondialdehyde within 24 h, respectively. After vitro gastrointestinal digestion, the black highland barley BP-IDF still retained considerable trapping activity for carbonyls. The carbonyl scavenging capacity was reduced by up to 93% after removing bound polyphenols from the black highland barley BP-IDF, which was consistent with the reduction in its total phenolic content. Moreover, the formation of adducts between reactive carbonyl species (RCS) and polyphenols bound to insoluble dietary fiber (IDF) was also detected. Overall, these findings confirmed that IDF-bound polyphenols were still active to trap RCS, indicating the potential benefits of BP-IDF from whole grains as functional ingredients to limit carbonyl stress across the gastrointestinal tract.
研究领域:
食品科学
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营养学
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生物化学
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
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2023
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IF 7.2
Zhi-Tong Zhang,Si-Min Deng,Chong Chen,Qing-Hui He,Xian-Wu Peng,Qing-Feng Liang,Guo-Dong Zhuang,Shu-Mei Wang,Dan Tang
Diabetic cognitive impairment (DCI) is a serious neurodegenerative disorder caused by diabetes, with chronic inflammation being a crucial factor in its pathogenesis. Pterostilbene is a well-known natural stilbene derivative that has excellent anti-inflammatory activity, suggesting its potential medicinal advantages for treating DCI. Therefore, this study is to explore the beneficial effects of pterostilbene for improving cognitive dysfunction in DCI mice. A diabetic model was induced by a high-fat diet plus streptozotocin (40 mg·kg −1 ) for consecutive 5 days. After the animals were confirmed to be in a diabetic state, they were treated with pterostilbene (20 or 60 mg·kg −1 , i.g.) for 10 weeks. Pharmacological evaluation showed pterostilbene could ameliorate cognitive dysfunction, regulate glycolipid metabolism disorders, improve neuronal damage, and reduce the accumulation of β-amyloid in DCI mice. Pterostilbene alleviated neuroinflammation by suppressing oxidative stress and carbonyl stress damage, astrocyte and microglia activation, and dopaminergic neuronal loss. Further investigations showed that pterostilbene reduced the level of lipopolysaccharide, modulated colon and brain TLR4/NF-κB signaling pathways, and decreased the release of inflammatory factors, which in turn inhibited intestinal inflammation and neuroinflammation. Furthermore, pterostilbene could also improve the homeostasis of intestinal microbiota, increase the levels of short-chain fatty acids and their receptors, and suppress the loss of intestinal tight junction proteins. In addition, the results of plasma non-targeted metabolomics revealed that pterostilbene could modulate differential metabolites and metabolic pathways associated with inflammation, thereby suppressing systemic inflammation in DCI mice. Collectively, our study found for the first time that pterostilbene could alleviate diabetic cognitive dysfunction by inhibiting the TLR4/NF-κB pathway through the microbiota-gut-brain axis, which may be one of the potential mechanisms for its neuroprotective effects.
研究领域:
药理学
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神经科学
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免疫学
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代谢组学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
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