Scientific Reports
·
2025
·Vol. 15
·期 1
·1-12
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IF 3.9
Cheng Chunfang,Zhang Shasha,Chen Chong,Gong Yanchun,Ding Kaizhi,Li Guoyin,Jiang Wei,Zhang Zhenyu,He Bin,Hu Zhihong,Li Yuhua,Yao Lihua
Excessive exercise can lead to physical fatigue and disruption of the antioxidant system, resulting in neurological damage and cognitive decline. Cordycepin, the main component of Cordyceps militaris , has anti-inflammatory, antioxidant and neuroprotective effects. In this study, the anti-fatigue effect and potential mechanism of action of cordycepin were investigated using a forced exercise mouse model. The results showed that oral administration of cordycepin enhanced exercise endurance, increased liver and muscle glycogen content, and simultaneously decreased serum levels of lactic acid, lactate dehydrogenase, creatine kinase, and blood urea nitrogen ( p < 0.05). In addition, cordycepin had antioxidant effects, increasing superoxide dismutase activity and decreasing serum malondialdehyde (MDA) levels ( p < 0.01). In vitro experiments further demonstrated the antioxidant and anti-fatigue effects of cordycepin. Behavioral tests showed that the learning and memory ability of mice in the excessive exercise model group decreased to 40% compared with the control group. Cordycepin alleviated the learning and memory deficits in the over-exercised mice, significantly reduced the levels of fatigue metabolites and oxidative stress in vivo ( p < 0.05), and altered the levels of neurotransmitters levels ( p < 0.05). Furthermore, cordycepin modulated Keap1/Nrf2/HO-1-mediated oxidative stress and enhanced BDNF levels ( p < 0.05). These findings suggest that cordycepin can alleviate excessive exercise-induced fatigue by modulating the Keap1/Nrf2/HO-1 signaling pathway and BDNF expression, providing strong supporting evidence for the development of cordycepin-functional foods or anti-fatigue drugs.
研究领域:
运动生理学
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药理学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2024
·
IF 2.8
Yang Chen,Shujun Bao,Zhongzhao Wang,Zheng Fang,Hao Tang
Background Cisplatin (DDP) chemotherapy is commonly used in therapy for non-small cell lung cancer (NSCLC), but increased drug resistance has become a huge obstacle. Baicalin (BA) contributed to the sensitivity of NSCLC to DDP. Here, we aimed to further probe the pathophysiological mechanisms of BA in NSCLC. Methods A549 and A549/DDP cells and xenograft mice were treated with BA and DDP. Xenograft mice were treated additionally with the NRF2 inducer (Bardoxolone methyl, BM) and KEAP1 knockdown. The levels of ferritinophagy-related proteins and biomarkers were determined. The autophagosomes were observed. M1 macrophage polarization and the contents of related indicators were analyzed. The involvement of KEAP1/NRF2/HO-1 was determined. Results BA inhibited cell development, and the effect of BA and DDP on cell development was additive. The abundance of ferritinophagy-related proteins and the number of autophagosomes were induced by BA. BA also promoted the transition of GSH to GSSH. BA favored M1 macrophage polarization and affected the expression of related proteins. When BA and DDP combined, these molecular phenomena were further exacerbated. BA induced accumulation of KEAP1 and reduction of NRF2 and HO-1. However, BM and KEAP1 knockdown disrupted the synergistic effects of BA and DDP on inhibiting NSCLC growth. BM and KEAP1 knockdown reversed DDP and BA-promoted protein expression activity and M1 macrophage polarization. Conclusion Our findings suggest that BA is involved in ferritinophagy and macrophage immunity through the KEAP1-NRF2/HO-1 axis, thereby improving the DDP sensitivity in NSCLC, which could provide new candidates for treatment strategies.
研究领域:
肿瘤学
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药理学
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免疫学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Yulu Wang,Minghao Yuan,Sihui Li,Jiamei Tang,Yan Wan,Xue Liang,Yiping Guo,Li Guo
Alcohol liver disease (ALD) is a chronic liver disorder resulting from long-term heavy alcohol consumption. The pathogenesis of ALD is multifactorial, and existing therapeutic agents primarily target specific aspects of the disease while presenting significant side effects, including drug-induced liver injury and hepatobiliary disease. Silibinin (SLB) has attracted widespread attention for its hepatoprotective effects and favorable safety profile. However, inherent limitations associated with SLB, such as poor solubility and bioavailability, have significantly limited its clinical application. Drug delivery systems, including liposomes, offer promising potential for the delivery of hydrophobic drugs. However, the selection of an appropriate delivery vehicle requires optimization. Ursodeoxycholic acid sodium (UAS) serves as a promising alternative to cholesterol in liposomal formulations, offering a potential strategy to mitigate the health risks associated with cholesterol. In this study, UAS was employed as the liposomal membrane material to prepare a UAS liposome loaded with SLB (SUL), and its efficacy and mechanism of action in alcoholic-induced liver injury were subsequently evaluated. The experimental results demonstrated that SUL exhibited a uniform particle size distribution, good stability, and an effective release profile in vitro. Following oral administration, SUL effectively inhibited alcohol-induced liver damage, oxidative stress, and fat accumulation. In addition, SUL regulated the expression of the kelch-1ike ECH- associated protein l (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) proteins, thereby exerting antioxidative stress effects. Furthermore, it also modulated apoptosis-related factors, including B-cell lymphoma-2 (Bcl-2), BCL-2-associated X (Bax), cysteinyl aspartate specific proteinase-3 (Caspase-3), and cleaved caspase-3, to mitigate hepatocyte apoptosis. In summary, SUL demonstrates enhanced therapeutic efficacy against ALD, offering a novel approach for the clinical application of SLB in the prevention and treatment of ALD.
研究领域:
药理学
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肝病学
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药物递送系统
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
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
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毒理学
✓ 已验证
产品关联
DOI
高影响因子
BIOMETALS
·
2018
·Vol. 31
·期 6
·1051-1059
·
IF 2.478
Luo Junchong,Li Xiaowen,Li Xinran,He Yongming,Zhang Mengdan,Cao Changyu,Wang Kai
To investigate the effect of Selenium Rich Yeast ( SeY ) on hepatotoxicity of Aluminium (Al), SeY (0.1 mg/kg) was orally administrated to aluminium-exposed mice (10 mg/kg) for 28 days. The risk of oxidative stress was assessed by detecting the total antioxidant capacity (T-AOC), catalase activity, H 2 O 2 content, and mRNA levels of the Keap1/Nrf-2/HO-1 pathway. Inflammatory reactions were assessed by detecting the mRNA levels of inflammatory biomarkers. Our results showed that SeY protected against the liver histological changes induce by Al. The body weight gain of mice treated with SeY + Al restore to normal compare with mice exposed to Al alone. Al treatment significantly decreased the activities of antioxidant enzymes, reduced T-AOC levels, and up-regulated the mRNA level of Nrf2 and HO-1, thereby ultimately leading to peroxidation. SeY shown a significant protective effect against oxidative stress caused by Al. In addition, Al exposure induced inflammatory responses in rat liver by promoting the release of inflammatory cytokines (TNF-a, NF-kB, TNF-R1, IL-1, IL-6, and COX-2). SeY protected against changes in liver by regulating the mRNA expression levels of inflammatory factors. These results suggested that Se protected the liver from the Al-induced hepatotoxicity by regulating the mRNA level of Keap1/Nrf2/HO-1, and inhibited inflammatory responses by down-regulating the expression level of inflammatory cytokine.
研究领域:
毒理学
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药理学
·
分子生物学
·
营养科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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