FREE RADICAL BIOLOGY AND MEDICINE
·
2025
·
IF 8.2
Ying-ying Gu,Ming-xuan Liu,Xin-ru Zhao,Ying Yi,Jia-yi Wang,Yi-lin Lin,Xiao-le Xu,Xiao-ling Zhang
Olfactory dysfunction is one of the earliest non-motor symptoms of Parkinson's disease (PD), accompanied by abnormal α-synuclein aggregation in the olfactory bulb (OB). We previously reported that Cordycepin (Cor), a potential anti-inflammatory and anti-oxidative adenosine derivative, has emerged as an attractive candidate for PD treatment. However, existing investigations have predominantly focused on the amelioration of motor symptoms rather than modulating the disease course from prodromal stage. This study aimed to evaluate if Cor exerts a disease-modifying effect at the prodromal stage prior to the onset of motor deficits in eight-week-old male C57BL/6 mice exposed to rotenone. Our results showed that Cor administration significantly attenuated olfactory dysfunction and delayed the onset of motor impairments. This therapeutic effect was concomitant with pathological α-synuclein aggregates degradation in OB. RNA sequencing analyses revealed that Autophagy-lysosomal pathway (ALP) in OB may be associated with the neuroprotective actions of Cor in PD. Furthermore, Cor significantly stabilized Calcyclin-binding protein/Siah1-interacting protein (CacyBP/SIP) via inhibiting its ubiquitin-proteasome degradation in rotenone-treated SH-SY5Y cells. This stabilization suppressed NLRP3 inflammasome activation and subsequently enhanced autophagosome-lysosome fusion, culminating in the autophagic degradation of α-synuclein. Notably, blockade of CacyBP/SIP abrogated the neuroprotective effects of Cor against rotenone-induced olfactory impairment. Collectively, these findings suggest CacyBP/SIP-NLRP3-α-synuclein axis may serve as a key target of Cor in the early treatment of PD, which provides novel insights into the mechanisms for the anti-PD effect of Cor.
研究领域:
神经科学
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药理学
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生物化学
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细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Cheng Jingliang,Fu Jiewen,Tan Qi,Liu Zhiying,Guo Kan,Zhang Lianmei,He Jiayue,Zhou Baixu,Liu Xiaoyan,Li Dabing,Fu Junjiang
ISG20 inhibits viruses such as SARS-CoV-2 invasion; however, details of its expression and regulation with viral susceptibility remain to be elucidated. The present study analyzed ISG20 expression, isoform information, survival rate, methylation patterns, immune cell infiltration, and COVID-19 outcomes in healthy and cancerous individuals. Cordycepin (CD) and N6, N6-dimethyladenosine (m62A) were used to treat cancer cells for ISG20 expression. We revealed that ISG20 mRNA expression was primarily located in the bone marrow and lymphoid tissues. Interestingly, its expression was significantly increased in 11 different types of cancer, indicating that cancer patients may be less vulnerable to SARS-CoV-2 infection. Among them, higher expression of ISG20 was associated with a long OS in CESC and SKCM, suggesting that ISG20 may be a good marker for both viral prevention and cancer progress. ISG20 promoter methylation was significantly lower in BLCA, READ, and THCA tumor tissues than in the matched normal tissues, while higher in BRCA, LUSC, KIRC, and PAAD. Hypermethylation of ISG20 in KIRC and PAAD tumor tissues was correlated with higher expression of ISG20, suggesting that methylation of ISG20 may not underlie its overexpression. Furthermore, ISG20 expression was significantly correlated with immune infiltration levels, including immune lymphocytes, chemokine, receptors, immunoinhibitors, immunostimulators, and MHC molecules in pan-cancer. STAD exhibited the highest degree of ISG20 mutations; the median progression-free survival time in months for the unaltered group was 61.84, while it was 81.01 in the mutant group. Isoforms ISG20-001 and ISG20−009 showed the same RNase_T domain structure, demonstrating the functional roles in tumorigenesis and SARS-CoV-2 invasion inhibition in cancer patients. Moreover, CD and m62A increase ISG20 expression in various cancer cell lines, implying the antiviral/anti-SARS-CoV-2 therapeutic potential. Altogether, this study highlighted the value of combating cancer by targeting ISG20 during the COVID-19 pandemic, and small molecules extracted from traditional Chinese medicines, such as CD, may have potential as anti-SARS-CoV-2 and anticancer agents by promoting ISG20 expression.
研究领域:
医学
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分子生物学
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肿瘤学
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病毒学
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DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2016
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IF 2.529
Yueqian Zhang,Junfen Wan,Xuejun Cao
Cordycepin is an antibiotic with excellent biological and pharmacological activities. In this work, surface imprinting technology was used for cordycepin purification. Gaussian 09 simulation software was used to screen out methacrylic acid and acrylamide as the functional monomers of molecularly imprinted polymers (MIPs). The synthesis was accomplished with modified silica gel as a matrix, cordycepin as a template, methacrylic acid and acrylamide as functional monomers, ethyleneglycol dimethacrylate as a crosslinking agent and azodiisobutyronitrile as an initiator. MIPs for cordycepin separation were characterized by scanning electron microscope, Fourier transform infrared spectroscopy, elemental analysis and the pore size distribution analysis method. Adsorption isotherms for cordycepin show that the adsorption capacity using an initial cordycepin concentration of 16 mg/mL was 91.78 mg/g. According to the adsorption kinetic curve, MIPs obtained the maximum adsorption amount at 95.37 mg/g. In the adsorption kinetic experiments, adsorption reached equilibrium at 14 h with a rapid increase up to 4–6 h. The selectivity coefficients of MIPs were 3.14 (cordycepin versus inosine) and 3.74 (cordycepin versus adenosine). Experimental results indicated that the adsorption capacity and selectivity of MIPs were sufficient for the separation of cordycepin. MIPs were used to separate cordycepin from Cordyceps militaris . Cordycepin with 98% purity was obtained with the recovery of 25.67%. This result showed that MIPs prepared in this method have a good application prospect in the separation of cordycepin.
研究领域:
生物化学
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药物分离工程
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DOI
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 2
·483
·
IF 4.2
Linlin Cui,Li Zhao,Guanghuan Shen,Dahai Yu,Tian Yuan,Yingyu Zhang,Bo Yang
Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipolysis group was introduced at the cordycepin N6 to improve the problem, cordycepin derivatives (3a–4c) were synthesized, and biological evaluation of compounds was studied. In this study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound4ashowed the most obvious inhibitory effect on MCF7 cells with an IC50value of 27.57 ± 0.52 μM, which was much lower than cordycepin. Compound4ashowed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound4apromoted apoptosis and blocked the cell cycle in the G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound4acould down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3 and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound4ainduced the apoptosis of MCF7 cells through the mitochondrial pathway.Keywords:cordycepin derivatives;antitumor;structural modification
研究领域:
药理学
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肿瘤学
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分子生物学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·Vol. 33
·期 18
·2214059
·
IF 19
Xinyue Li,Yuanyuan Fan,Zhengbao Zha,Deyan Gong,Jiajia Yu,Qianhui Li,Ruoyao Li,Hua Wang,Fei Wang
Cordycepin (3′-deoxyadenosine) has a demonstrated value in ameliorating nonalcoholic steatohepatitis (NASH); however, its short in vivo metabolism time and high dose-induced cytotoxicity are challenges limiting its clinical application. Herein, a cordycepin-loaded macrophage vesicle (C-MV) is developed for targeted cordycepin delivery to achieve stable and durable mitigation of NASH. The C-MV is obtained using cytochalasin B-stimulated RAW 264.7 cells to produce MV, followed by repeated freeze-thawing and extrusion of MV and cordycepin. C-MV selectively delivers cordycepin to macrophages at the site of liver injury, slowly releases cordycepin, reduces the toxicity associated with high cordycepin doses, and increases the mice's survival rate from 40% to 90%. Moreover, C-MV reduces liver apoptosis and attenuated NASH liver injury by activating AMP-activated protein kinase and inhibiting caspase 6 activity. Overall, C-MV exhibits better anti-inflammatory, lipid-lowering, and anti-apoptosis properties than free cordycepin, making it a promising delivery system for the potential clinical application of cordycepin. MV combined with cordycepin provides an inspiring bionic strategy for NASH treatment that can achieve effective therapeutic effects in vivo.
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
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产品关联
DOI
高影响因子
CHEMISTRY & BIODIVERSITY
·
2025
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IF 2.5
Linlin Cui,Zheng Xu,Yu Zhu,Xuan Liu,Shihao Li,Li Zhao,Zhihua Xing,Guanghuan Shen
This study aimed to design and synthesize a series of novel cordycepin derivatives featuring urea groups to explore the antitumor efficacy of natural product derivatives with enhanced potency. The structures of the target compounds were characterized using infrared spectroscopy (IR), proton/carbon nuclear magnetic resonance spectroscopy ( 1 H and 13 C NMR), high-performance liquid chromatography (HPLC), and high-resolution mass spectrometry (HRMS). In vitro activity against MCF-7, HepG-2, SGC-7901, and HK-2 cells was evaluated using the standard methyl thiazolyltetrazolium assay (MTT), revealing that compound 4l exhibited significant inhibitory effects on HepG-2 cells (IC 50 = 14.86 ± 2.37 µM), outperforming cordycepin. Mechanistic studies indicated that 4l induced dose-dependent apoptosis, arrested the cell cycle at the G 0 /G 1 phase, and activated the intrinsic mitochondrial pathway. Molecular docking simulations further elucidated its binding mode with target proteins. Collectively, compound 4l shows promise as a candidate drug for liver cancer therapy. Graphical Synthesis of a Series of Cordycepin Derivatives and Their Antitumor Activity Study.
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PubMed
高影响因子
Infection and Drug Resistance
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2022
·
IF 4.177
Yu Wang,Zejun Pei,Zaixiang Lou,Hongxin Wang
Introduction The opportunistic pathogen Candida albicans can form biofilms, resulting in drug resistance with great risk to medical treatment.Methodology We investigated the ability of C. albicans to form biofilms on different materials, as well as the inhibitory and eradicating effects of cordycepin on biofilm. The action mechanism of cordycepin against biofilm was studied by crystal violet staining, XTT [2, 3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction method, phenol-sulfuric acid method, cellular superficial hydrophobicity (CSH) assay, and confocal laser scanning microscope observation. We also evaluated the acute toxicity of cordycepin in vivo.Results The results showed facile formation of biofilms by C. albicans on polypropylene. The 50% minimum inhibitory concentration (MIC50) of cordycepin was 0.062 mg/mL. A concentration of 0.125 mg/mL significantly decreased biofilm formation, metabolic activity, secretion of extracellular polysaccharides, and relative CSH. Cordycepin could inhibit biofilm formation at low concentration without affecting fungal growth. In addition, cordycepin effectively eradicated 59.14% of mature biofilms of C. albicans at a concentration of 0.5 mg/mL. For acute toxicity, the LD50 (50% of lethal dose) of cordycepin was determined as higher than 500 mg/kg for mice.Conclusion The results of this study show that cordycepin significantly inhibited and eradicated biofilms by decreasing metabolic activity, the ratio of living cells, the hydrophobicity, and damaging the extracellular polysaccharides of biofilm. These findings should facilitate more effective application of cordycepin and suggest a new direction for the treatment of fungal infections.
研究领域:
微生物学
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药理学
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医学真菌学
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DOI
PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-12
·
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
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神经科学
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DOI
PubMed
高影响因子
CELL STRESS & CHAPERONES
·
2024
·
IF 3.3
Huizhen Sun,Shanshan Wei,Yanchun Gong,Kaizhi Ding,Shan Tang,Wei Sun,Chunhua Yuan,Liping Huang,Zhibing Liu,Chong Chen,Lihua Yao
ABSTRACT Glutamate is a neurotransmitter that can cause excitatory neurotoxicity when its extracellular concentration is too high, leading to disrupted calcium balance and increased production of reactive oxygen species (ROS). Cordycepin, a nucleoside adenosine derivative, has been shown to protect against excitatory neurotoxicity induced by glutamate. To investigate its potential neuroprotective effects, the present study employed fluorescence detection and spectrophotometry techniques to analyze primary hippocampal-cultured neurons. The results showed that glutamate toxicity reduced hippocampal neuron viability, increased ROS production, and increased intracellular calcium levels. Additionally, glutamate-induced cytotoxicity activated acetylcholinesterase (AChE) and decreased glutathione (GSH) levels. However, cordycepin inhibited glutamate-induced cell death, improved cell viability, reduced ROS production, and lowered Ca 2+ levels. It also inhibited AChE activation and increased GSH levels. This study suggests that cordycepin can protect against glutamate-induced neuronal injury in cell models, and this effect was inhibited by adenosine A 1 receptor blockers, indicating that its neuroprotective effect is achieved through activation of the adenosine A 1 receptor.
研究领域:
神经科学
·
药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE SCIENCE
·
2026
·
IF 8.8
Chen Wang,Chenxuan Shao,Houyi Peng,Yanchen Liu,Qi Zhang,Xiaohui Ju,Weixing Li
Precise control over the pore size of polyamide nanofiltration membranes is critical for achieving efficient separation between small-molecule biological substances and inorganic salts. However, general polyamide membranes of negatively charged exhibit limited pore-size tunability due to the rapid kinetics of interfacial polymerization, which severely compromises the separation efficiency between small molecules and inorganic salt ions. Herein, a pore-size engineering strategy for interfacial polymerization was proposed by introducing a zwitterionic triamine monomer, tris(2-aminoethyl)amine N-oxide (TRENO) into the piperazine (PIP) aqueous phase to react with trimesoyl chloride (TMC). The strong hydrophilicity of TRENO retards the diffusion of monomers to organic phase, thereby yielding a thinner polyamide layer. Meanwhile, its triamine structure renders the polyamide layer denser and decreases pore radius from 0.35 nm to 0.28 nm. Furthermore, the multi-amine structure of TRENO increases the crosslinking density of the polyamide layer by consuming more acyl chloride groups, thereby reducing the formation of hydrolyzed carboxyl groups on membrane surface. It lowers the surface negative charge and weakens Donnan exclusion effects, allowing small charged solutes such as inorganic salts and amino acids to permeate more readily. As a result, the optimal membrane achieves a pure water flux of 86.0 L m −2 h −1 (nearly three times that of the pristine membrane), and when tested with a ternary mixture of cordycepin, KH 2 PO 4 and FeCl 2 , it exhibits a high cordycepin rejection of 83.6%, low salt rejection, and a cordycepin/KH 2 PO 4 selectivity of 5.65. It also exhibits excellent stability and high flux recovery ratio (FRR) of 93%. This work proves that zwitterion-modulated interfacial polymerization offers a viable route to address the trade-off between selectivity and permeability in biomolecule purification.
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高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
·
2021
·
IF 3.636
Wei Liu,Ling Zhang,Shuo Sun,Long-sheng Tang,Shi-min He,An-qi Chen,Li-na Yao,Da-Long Ren
As a natural extract, cordycepin has been shown to play important regulatory roles in many life activities. In the study, the effects of cordycepin on inflammatory responses and the underlying mechanisms was explored using a zebrafish model. In the model of LPS-induced inflammation, cordycepin was found to significantly inhibited the expression of pro-inflammatory cytokines such as tnf-α, il-1β, il-6, and il-8 . Using in vivo imaging model, cordycepin significantly inhibited fluorescent-labeled neutrophils migrating towards injury sites. Furthermore, results showed that the phosphorylation level of ERK protein dramatically decreased after cordycepin treatment. Meanwhile, the ERK inhibitor, PD0325901, significantly inhibited the expression of pro-inflammatory cytokines in LPS-induced inflammatory model and neutrophils migration in the caudal fin injury model. This study indicated the important roles of cordycepin in inhibiting LPS and injury-induced inflammation and preliminarily explained the role of ERK protein in this process.
研究领域:
免疫学
·
药理学
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分子生物学
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DOI
PubMed
高影响因子
NEUROTOXICOLOGY
·
2018
·
IF 3.076
Hao Song,Li-Ping Huang,Yuping Li,Chao Liu,Songhua Wang,Wei Meng,Shanshan Wei,Xin-Ping Liu,Yanchun Gong,Li-Hua Yao
In Alzheimer’s disease (AD), β-amyloid (Aβ) protein toxicity increases the formation of reactive oxygen species (ROS) and intracellular calcium levels, resulting in neuronal dysfunction, neurodegenerative disorders, and cell death. Cordycepin is a derivative of the nucleoside adenosine; also, it is speculated to exert neuroprotective effects against Aβ-induced oxidative toxicity in hippocampal neurons. In the present study, the fluorescence detection method and whole-cell patch-clamp recordings were used to study the neuroprotective effects against Aβ-induced toxicity in the primary hippocampal cultured neurons. The results revealed that Aβ 25–35 toxicity causes increased cellular ROS production and abnormal calcium homeostasis in hippocampal neurons. Moreover, Aβ 25–35 -induced cytotoxicity led to a series of downstream events, including the activation of acetylcholinesterase, increased p-Tau expression, and increased apoptosis. Cordycepin inhibits ROS production, elevated levels of Ca 2+ induced by Aβ 25–35 , and the activation of acetylcholinesterase; all these are involved in oxidative-induced apoptosis. In addition, it decreases the increased p-Tau expression that plays a key role in the initiation of the AD. Results showed that the anti-apoptotic effects of cordycepin are partially dependent on the activation of adenosine A 1 receptor, whereas an antagonist selectively attenuated the neuroprotective effects of cordycepin. Collectively, these results suggest that cordycepin could be a potential future therapeutic agent for neuronal disorders, such as AD.
研究领域:
神经科学
·
药理学
·
分子生物学
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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）