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Bu Miin Huang - One of the best experts on this subject based on the ideXlab platform.
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The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin
'MDPI AG', 2021Co-Authors: Yu-ying Chen, Bu Miin Huang, Chun-hsien Chen, Wei-chen Lin, Chih-wei Tung, Yung-chia Chen, Shang-hsun Yang, Rong-jane ChenAbstract:Cordycepin is an adenosine derivative isolated from Cordyceps sinensis, which has been used as an herbal complementary and alternative medicine with various biological activities. The general anti-cancer mechanisms of Cordycepin are regulated by the adenosine A3 receptor, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), and glycogen synthase kinase (GSK)-3β, leading to cell cycle arrest or apoptosis. Notably, Cordycepin also induces autophagy to trigger cell death, inhibits tumor metastasis, and modulates the immune system. Since the dysregulation of autophagy is associated with cancers and neuron, immune, and kidney diseases, Cordycepin is considered an alternative treatment because of the involvement of Cordycepin in autophagic signaling. However, the profound mechanism of autophagy induction by Cordycepin has never been reviewed in detail. Therefore, in this article, we reviewed the anti-cancer and health-promoting effects of Cordycepin in the neurons, kidneys, and the immune system through diverse mechanisms, including autophagy induction. We also suggest that formulation changes for Cordycepin could enhance its bioactivity and bioavailability and lower its toxicity for future applications. A comprehensive understanding of the autophagy mechanism would provide novel mechanistic insight into the anti-cancer and health-promoting effects of Cordycepin
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anti cancer effect of Cordycepin on fgf9 induced testicular tumorigenesis
International Journal of Molecular Sciences, 2020Co-Authors: Ming Min Chang, Bu Miin Huang, Shang-hsun Yang, Siou Ying Hong, Chia Yih WangAbstract:Cordycepin, a bioactive constituent from the fungus Cordyceps sinensis, could inhibit cancer cell proliferation and promote cell death via induction of cell cycle arrest, apoptosis and autophagy. Our novel finding from microarray analysis of Cordycepin-treated MA-10 mouse Leydig tumor cells is that Cordycepin down-regulated the mRNA levels of FGF9, FGF18, FGFR2 and FGFR3 genes in MA-10 cells. Meanwhile, the IPA-MAP pathway prediction result showed that Cordycepin inhibited MA-10 cell proliferation by suppressing FGFs/FGFRs pathways. The in vitro study further revealed that Cordycepin decreased FGF9-induced MA-10 cell proliferation by inhibiting the expressions of p-ERK1/2, p-Rb and E2F1, and subsequently reducing the expressions of cyclins and CDKs. In addition, a mouse allograft model was performed by intratumoral injection of FGF9 and/or intraperitoneal injection of Cordycepin to MA-10-tumor bearing C57BL/6J mice. Results showed that FGF9-induced tumor growth in Cordycepin-treated mice was significantly smaller than that in a PBS-treated control group. Furthermore, Cordycepin decreased FGF9-induced FGFR1-4 protein expressions in vitro and in vivo. In summary, Cordycepin inhibited FGF9-induced testicular tumor growth by suppressing the ERK1/2, Rb/E2F1, cell cycle pathways, and the expressions of FGFR1-4 proteins, suggesting that Cordycepin can be used as a novel anticancer drug for testicular cancers.
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Cordycepin induced ma 10 mouse leydig tumor cell apoptosis by regulating p38 mapks and pi3k akt signaling pathways
Scientific Reports, 2015Co-Authors: Bo Syong Pan, Yang Kao Wang, Meng Shao Lai, Bu Miin HuangAbstract:The p38 MAPKs play important roles in the regulation of balance between cell survival and cell death on the development of various cancers. However, the roles of p38 MAPKs regulating apoptotic effects on Leydig tumor cells remain unclear. In the present study, we showed that Cordycepin (3'-deoxyadenosine) selectively induced apoptosis in MA-10 mouse Leydig tumor cells through regulating the p38 MAPK and PI3K/AKT signaling pathways. Cordycepin reduced viability in MA-10, TM4, and NT2/D1 cells, but not cause cell death of primary mouse Leydig cells on moderate concentration. Cordycepin increased reactive oxygen species (ROS) levels, which is associated with the induction of apoptosis as characterized by positive Annexin V binding, activation of caspase-3, and cleavage of PARP. Inhibition of p38 MAPKs activity by SB203580 significantly prevented Cordycepin-induced apoptosis in MA-10 cells. Co-treatment with wortmannin or the autophagy inhibitor 3-methyladenine (3-MA) elevated levels of apoptosis in Cordycepin-treated MA-10 cells. Moreover, Cordycepin activated p53, p21 and TGFs; and downregulated CDK2. The antitumour activity of Cordycepin-treated MA-10 cells was significantly distinct in severe combined immunodeficiency (SCID) mice in vivo. These results suggested that cordycein is a highly selective treatment to induce MA-10 cells apoptosis via p38 MAPKs signaling.
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Cordycepin induced ma 10 mouse leydig tumor cell apoptosis through caspase 9 pathway
Evidence-based Complementary and Alternative Medicine, 2011Co-Authors: Chunyi Jen, Bu Miin Huang, Chunyu Lin, Sewfen LeuAbstract:In the present study, the apoptotic effect of Cordycepin on MA-10 cells, a mouse Leydig tumor cell line, was investigated. Results demonstrated that the number of rounding-up cell increased by Cordycepin (10 μM to 5 mM for 24 h), and cells with plasma membrane blebbing could be observed by 100 μM Cordycepin. In viability test, MA-10 cell surviving rate significantly decreased as the dosage (10 μM to 5 mM) and duration (3–24 h) of Cordycepin treatment increased (P < 0.05). Cordycepin at 100 μM and 1 mM for 24 h treatment induced significant DNA fragmentation (P < 0.05). In addition, the percentage of G1 and G2/M phase cell significantly declined by Cordycepin (100 μM and 1 mM) for 24 h treatment, while the percentages of subG1 phase cell increased by 100 μM and/or 1 mM Cordycepin in 6, 12 and 24 h treatments (P < 0.05), respectively, which highly suggested that Cordycepin induced MA-10 cell apoptosis. In mechanism study with the treatments of caspases, c-Jun NH2 terminal kinase (JNK) or reactive oxygen species (ROS) inhibitors plus Cordycepin for 24 h, only caspases inhibitor suppressed subG1 phase in MA-10 cells. Moreover, western blotting results showed that Cordycepin induced caspase-9, -3 and -7 protein expressions, but not caspase-8, in time- and dose-dependent manners. In conclusion, Cordycepin induced apoptosis in MA-10 mouse Leydig tumor cells through a caspase-9 and -3 and -7 dependent pathway.
Jianjiang Zhong - One of the best experts on this subject based on the ideXlab platform.
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significant effect of nh4 on Cordycepin production by submerged cultivation of medicinal mushroom cordyceps militaris
Enzyme and Microbial Technology, 2006Co-Authors: Xianbing Mao, Jianjiang ZhongAbstract:Abstract Effects of nitrogen sources on cell growth and Cordycepin production by submerged cultivation of Cordyceps militaris, a traditional Chinese medicinal mushroom, were investigated. In complex medium, peptone was identified as the best nitrogen source for Cordycepin biosynthesis. A study using chemically defined medium indicated that NH4+ played an important role in Cordycepin biosynthesis. To enhance Cordycepin production, fed-batch culture with NH4+ feeding was conducted in complex medium with peptone. By optimizing the feeding time and feeding amount of NH4+, a maximal Cordycepin concentration of 420.5 ± 15.1 mg/l was obtained, which was 70% higher than that in batch cultivation. The fed-batch cultivation process was also demonstrated in a 3.5 l stirred tank bioreactor and the Cordycepin production was increased from 208.8 ± 7.6 mg/l in batch culture to 346.1 ± 3.6 mg/l in fed-batch culture. The information is useful for large-scale efficient production of Cordycepin by the mushroom cultures.
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optimization of carbon source and carbon nitrogen ratio for Cordycepin production by submerged cultivation of medicinal mushroom cordyceps militaris
Process Biochemistry, 2005Co-Authors: Xianbing Mao, Titiporn Eksriwong, Somchai Chauvatcharin, Jianjiang ZhongAbstract:Abstract Effects of various carbon sources and carbon/nitrogen ratios on production of a useful bioactive metabolite, Cordycepin (3′-deoxyadenosine), by submerged cultivation of a Chinese traditional medicinal mushroom Cordyceps militaris were investigated in shake flasks. The carbon sources examined were lactose, sucrose, glucose, fructose, galactose, maltose and xylose, and glucose was found to be most favourable to Cordycepin production, whereas cells grew best in galactose medium. The dry cell weight (DW) was increased with an increase in initial glucose concentration within the range of 25–70 g/l as investigated. The highest Cordycepin production, i.e. 245.7 ± 4.4 mg/l on day 18, was obtained in medium containing 40 g glucose/l. To enhance further the Cordycepin production, the effect of carbon/nitrogen ratios was studied using central composite design and response surface analysis. The maximum Cordycepin production and productivity of 345.4 ± 8.5 mg/l and 19.2 ± 0.5 mg/l per day were achieved in medium with optimized carbon and nitrogen sources, i.e. 42.0 g glucose/l and 15.8 g peptone/l. The information obtained is helpful for the hyperproduction of Cordycepin by submerged cultivation of C. militaris on a large scale.
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hyperproduction of Cordycepin by two stage dissolved oxygen control in submerged cultivation of medicinal mushroom cordyceps militaris in bioreactors
Biotechnology Progress, 2004Co-Authors: Xianbing Mao, Jianjiang ZhongAbstract:Effect of oxygen supply on Cordycepin production was investigated in submerged cultivation of Cordyceps militaris, a famous traditional Chinese medicinal mushroom, in a 5-L turbine-agitated bioreactor (TAB). Initial volumetric oxygen transfer coefficient (kLa) within the range of 11.5-113.8 h(-1) had significant influence on Cordycepin production. The highest Cordycepin concentration of 167.5 mg/L was obtained at an initial kLa value of 54.5 h(-1), where a moderate dissolved oxygen (DO) pattern was observed throughout cultivation. The possible correlation between Cordycepin production and DO level was explored by DO control experiments, and the results showed that DO within the range of 10-80% of air saturation greatly affected the cultivation process. To obtain a high specific Cordycepin formation rate (rho) throughout cultivation, a two-stage DO control strategy was developed based on the analysis of the relationship of rho and DO. That is, DO was controlled at 60% from the beginning of cultivation and then shifted to a lower control level of 30% when rho started to decrease. As a result, a high Cordycepin production of 201.1 mg/L and a high productivity of 15.5 mg/(L.d) were achieved, which was enhanced by about 15% and 30% compared to the highest titers obtained in conventional DO control experiments, respectively. The proposed DO control strategy was also applied to a recently developed 5-L centrifugal impeller bioreactor (CIB) with Cordycepin production and productivity titers of 188.3 mg/L and 14.5 mg/(L.d). Furthermore, the scale-up of the two-stage DO control process from 5-L CIB to 30-L CIB was successfully demonstrated. The work is useful for the efficient large-scale production of bioactive metabolites by mushroom cultures.
Xianbing Mao - One of the best experts on this subject based on the ideXlab platform.
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significant effect of nh4 on Cordycepin production by submerged cultivation of medicinal mushroom cordyceps militaris
Enzyme and Microbial Technology, 2006Co-Authors: Xianbing Mao, Jianjiang ZhongAbstract:Abstract Effects of nitrogen sources on cell growth and Cordycepin production by submerged cultivation of Cordyceps militaris, a traditional Chinese medicinal mushroom, were investigated. In complex medium, peptone was identified as the best nitrogen source for Cordycepin biosynthesis. A study using chemically defined medium indicated that NH4+ played an important role in Cordycepin biosynthesis. To enhance Cordycepin production, fed-batch culture with NH4+ feeding was conducted in complex medium with peptone. By optimizing the feeding time and feeding amount of NH4+, a maximal Cordycepin concentration of 420.5 ± 15.1 mg/l was obtained, which was 70% higher than that in batch cultivation. The fed-batch cultivation process was also demonstrated in a 3.5 l stirred tank bioreactor and the Cordycepin production was increased from 208.8 ± 7.6 mg/l in batch culture to 346.1 ± 3.6 mg/l in fed-batch culture. The information is useful for large-scale efficient production of Cordycepin by the mushroom cultures.
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optimization of carbon source and carbon nitrogen ratio for Cordycepin production by submerged cultivation of medicinal mushroom cordyceps militaris
Process Biochemistry, 2005Co-Authors: Xianbing Mao, Titiporn Eksriwong, Somchai Chauvatcharin, Jianjiang ZhongAbstract:Abstract Effects of various carbon sources and carbon/nitrogen ratios on production of a useful bioactive metabolite, Cordycepin (3′-deoxyadenosine), by submerged cultivation of a Chinese traditional medicinal mushroom Cordyceps militaris were investigated in shake flasks. The carbon sources examined were lactose, sucrose, glucose, fructose, galactose, maltose and xylose, and glucose was found to be most favourable to Cordycepin production, whereas cells grew best in galactose medium. The dry cell weight (DW) was increased with an increase in initial glucose concentration within the range of 25–70 g/l as investigated. The highest Cordycepin production, i.e. 245.7 ± 4.4 mg/l on day 18, was obtained in medium containing 40 g glucose/l. To enhance further the Cordycepin production, the effect of carbon/nitrogen ratios was studied using central composite design and response surface analysis. The maximum Cordycepin production and productivity of 345.4 ± 8.5 mg/l and 19.2 ± 0.5 mg/l per day were achieved in medium with optimized carbon and nitrogen sources, i.e. 42.0 g glucose/l and 15.8 g peptone/l. The information obtained is helpful for the hyperproduction of Cordycepin by submerged cultivation of C. militaris on a large scale.
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hyperproduction of Cordycepin by two stage dissolved oxygen control in submerged cultivation of medicinal mushroom cordyceps militaris in bioreactors
Biotechnology Progress, 2004Co-Authors: Xianbing Mao, Jianjiang ZhongAbstract:Effect of oxygen supply on Cordycepin production was investigated in submerged cultivation of Cordyceps militaris, a famous traditional Chinese medicinal mushroom, in a 5-L turbine-agitated bioreactor (TAB). Initial volumetric oxygen transfer coefficient (kLa) within the range of 11.5-113.8 h(-1) had significant influence on Cordycepin production. The highest Cordycepin concentration of 167.5 mg/L was obtained at an initial kLa value of 54.5 h(-1), where a moderate dissolved oxygen (DO) pattern was observed throughout cultivation. The possible correlation between Cordycepin production and DO level was explored by DO control experiments, and the results showed that DO within the range of 10-80% of air saturation greatly affected the cultivation process. To obtain a high specific Cordycepin formation rate (rho) throughout cultivation, a two-stage DO control strategy was developed based on the analysis of the relationship of rho and DO. That is, DO was controlled at 60% from the beginning of cultivation and then shifted to a lower control level of 30% when rho started to decrease. As a result, a high Cordycepin production of 201.1 mg/L and a high productivity of 15.5 mg/(L.d) were achieved, which was enhanced by about 15% and 30% compared to the highest titers obtained in conventional DO control experiments, respectively. The proposed DO control strategy was also applied to a recently developed 5-L centrifugal impeller bioreactor (CIB) with Cordycepin production and productivity titers of 188.3 mg/L and 14.5 mg/(L.d). Furthermore, the scale-up of the two-stage DO control process from 5-L CIB to 30-L CIB was successfully demonstrated. The work is useful for the efficient large-scale production of bioactive metabolites by mushroom cultures.
Bo Syong Pan - One of the best experts on this subject based on the ideXlab platform.
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Cordycepin induced ma 10 mouse leydig tumor cell apoptosis by regulating p38 mapks and pi3k akt signaling pathways
Scientific Reports, 2015Co-Authors: Bo Syong Pan, Yang Kao Wang, Meng Shao Lai, Bu Miin HuangAbstract:The p38 MAPKs play important roles in the regulation of balance between cell survival and cell death on the development of various cancers. However, the roles of p38 MAPKs regulating apoptotic effects on Leydig tumor cells remain unclear. In the present study, we showed that Cordycepin (3'-deoxyadenosine) selectively induced apoptosis in MA-10 mouse Leydig tumor cells through regulating the p38 MAPK and PI3K/AKT signaling pathways. Cordycepin reduced viability in MA-10, TM4, and NT2/D1 cells, but not cause cell death of primary mouse Leydig cells on moderate concentration. Cordycepin increased reactive oxygen species (ROS) levels, which is associated with the induction of apoptosis as characterized by positive Annexin V binding, activation of caspase-3, and cleavage of PARP. Inhibition of p38 MAPKs activity by SB203580 significantly prevented Cordycepin-induced apoptosis in MA-10 cells. Co-treatment with wortmannin or the autophagy inhibitor 3-methyladenine (3-MA) elevated levels of apoptosis in Cordycepin-treated MA-10 cells. Moreover, Cordycepin activated p53, p21 and TGFs; and downregulated CDK2. The antitumour activity of Cordycepin-treated MA-10 cells was significantly distinct in severe combined immunodeficiency (SCID) mice in vivo. These results suggested that cordycein is a highly selective treatment to induce MA-10 cells apoptosis via p38 MAPKs signaling.
Li-hua Yao - One of the best experts on this subject based on the ideXlab platform.
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Modulation Effects of Cordycepin on Voltage-Gated Sodium Channels in Rat Hippocampal CA1 Pyramidal Neurons in the Presence/Absence of Oxygen
Hindawi Limited, 2017Co-Authors: Zhi-bin Liu, Bin Zeng, Li-ping Huang, Chao Liu, Li-hua YaoAbstract:Our previous study revealed that Cordycepin features important neuroprotective effects against hypoxic insult by improvement of neuronal electrophysiological function. Modulation on voltage-gated sodium channel (VGSC) in CA1 neurons is the initial event during hypoxia/ischemia. However, no study comprehensively investigated Cordycepin on VGSC. Hence, this study investigated modulation effects of Cordycepin on VGSC not only in oxygen physiological conditions but also in acute oxygen deprivation injury conditions. Results revealed that Cordycepin (80 μM) reduced the amplitude of VGSC currents (INa) (77.6% of control, p
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Anti-effects of Cordycepin to hypoxia-induced membrane depolarization on hippocampal CA1 pyramidal neuron
European journal of pharmacology, 2016Co-Authors: Chong Chen, Xin-ping Liu, Jiang Wei, Bin Zeng, Wei Meng, Li-ping Huang, Wei Sun, Chun-hua Yuan, Li-hua YaoAbstract:Cordycepin has important neuroprotective effects in hypoxic or ischemic insult. However, the direct electrophysiological evidence of Cordycepin's neuroprotection from hypoxic or ischemic insult remains unknown. Hence, in this study, the electrophysiological mechanism by which Cordycepin protects against ischemic and hypoxic damages has been studied using an energy-deprivation injury model through whole-cell patch clamp techniques. Results revealed that Cordycepin (80µM) significantly delayed hypoxia-induced membrane depolarization, including Cordycepin reduced slope, and extended the duration of slow depolarization, prolonged the ability to generate spontaneous action potential (AP) firing, delayed the onset of rapid depolarization, and maintained the more hyperpolarized membrane potential after rapid depolarization. Additionally, Cordycepin also delayed the hypoxia-induced decrease in the evoked AP amplitude. Furthermore, Cordycepin can rescue the neuronal electrophysiological function after the 5min hypoxia pretreatment insult as seen the recovery on the evoked spike amplitude, membrane potential, and evoked AP latency during reoxygenation of hippocampal slices with Cordycepin. Collectively, the results in this study provide direct evidence demonstrating the important neuroprotective effects of Cordycepin against the hypoxic insult via improvement of the neuronal electrophysiological function, and the mechanism underlying the anti hypoxia-induced membrane depolarization is strongly recommended.
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Cordycepin decreases activity of hippocampal ca1 pyramidal neuron through membrane hyperpolarization
Neuroscience Letters, 2011Co-Authors: Li-hua Yao, Wenwen Yan, Junni Huang, Wenxiao Liu, Peng XiaoAbstract:a b s t r a c t Cordycepin (3 � -deoxyadenosine) is the main functional component of Cordycepins militaris, a renowned traditional Chinese medicine, which has been shown to possess anti-tumor, anti-inflammatory, antidiabetic and neuro-protective effects. However, the effect of Cordycepin on the central nervous system (CNS) remains unclear. In this study, the effects of Cordycepin on neuronal activity were investigated on the CA1 pyramidal neurons in rat hippocampal brain slices using a whole-cell patch clamp technique. Our results revealed that Cordycepin significantly decreased the frequency of both the spontaneous and evoked action potential (AP) firing. While AP spike width, the amplitude of fast after hyperpolarization (fAHP), and membrane input resistance were not altered by Cordycepin, the neuronal membrane potential was hyperpolarized by Cordycepin. Collectively, these results demonstrate that Cordycepin reduces neuronal activity by inducing membrane hyperpolarization, indicating that Cordycepin may be a potential therapeutic strategy for ischemic and other excitotoxic disorders. © 2011 Elsevier Ireland Ltd. All rights reserved.