Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic ...Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.展开更多
Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in ...Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in vitro and in vivo studies revealed that cordycepin inhibited proliferation and migration in HepG-2 cells and inhibited the growth of HepG-2 xenograft-bearing nude mice by inducing apoptosis.Transcriptome sequencing analysis revealed a total of 403 differential genes,which revealed that cordycepin may play an anti-HCC role by regulating Hippo signaling pathway.The regulatory effects of cordycepin on the Hippo signaling pathway was further investigated using a YAP1 inhibitor.The results demonstrated that cordycepin upregulated the expression of MST1 and LAST1,and subsequently inhibited YAP1,which activated the Hippo signaling pathway.This in turn downregulated the expression of GBP3 and ETV5,and subsequently inhibited cell proliferation and migration.Additionally,YAP1 regulated the expression of Bax and Bcl-2,regulated the mitochondrial apoptotic pathway,and induced apoptosis by upregulating the expression of the caspase-3 protein.In summary,this study reveals that cordycepin exerts its anti-hepatocarcinoma effect through regulating Hippo signaling pathway,and GBP3 and ETV5 may be potential therapeutic targets for hepatocarcinoma.展开更多
Cordyceps sinensis, a parasitic fungus on the larva of Lapidoptera, has been used as a traditional Chinese medicine. We previously reported that the growth of B16-BL6 mouse melanoma (B16-BL6) cells and mouse Lewis lun...Cordyceps sinensis, a parasitic fungus on the larva of Lapidoptera, has been used as a traditional Chinese medicine. We previously reported that the growth of B16-BL6 mouse melanoma (B16-BL6) cells and mouse Lewis lung carcinoma (LLC) cells was inhibited by cordycepin (3’-deoxyadenosine), an ingredient of Cordyceps sinensis, and its effect was antagonized by MRS1191, a selective adenosine A3 receptor (A3-R) antagonist although adenosine (up to 100 μM) had no effect on the growth of B16-BL6 and LLC cells. In this study, we investigated whether water extracts of Cordyceps sinensis (WECS) inhibit the growth of B16-BL6 cells, LLC cells, HT1080 human fibrosarcoma (HT1080) cells and CW-2 human colon carcinoma (CW-2) cells via their A3-R. As a result, the growth of all cell lines were potently inhibited by WECS (10 μg/mL) and the inhibitory effect of WECS was significantly antagonized by MRS1191 (1 μM). Furthermore, WECS included 2.34% w/w cordycepin and 0.12% w/w adenosine as components according to the HPLC- ECD system. In conclusion, WECS inhibited the proliferation of four cancer cell lines by stimulation of A3-R and the main component in WECS with anticancer action might be cordycepin instead of adenosine.展开更多
Objective： To evaluate apoptotic effects of cisplatin and cordycepin as single agent or in combination with cytotoxicity in oral cancer cells. Methods： The influences of cisplatin （2.5 μg/mL） and/or cordycapin tr...Objective： To evaluate apoptotic effects of cisplatin and cordycepin as single agent or in combination with cytotoxicity in oral cancer cells. Methods： The influences of cisplatin （2.5 μg/mL） and/or cordycapin treatment （10 or 100 μmol/L） to human OC3 oral cancer cell line were investigated by morphological observation for cell death appearance, methylthiazoletetrazolium （MTT） assay for cell viability, flow cytometry assay for cell apoptosis, and Western blotting for apoptotic protein expressions. Results： Data demonstrated that co-administration of cisplatin （2.5 μg/mL） and cordycepin （10 or 100μmol/L） resulted in the enhancement of OC3 cell apoptosis compared to cisplatin or cordycapin alone treatment （24 h）, respectively （P〈0.05）. In flow cytometry assay, percentage of cells arrested at subG1 phase with co-treatment of cordycepin and cisplatin （30%） was significantly higher than cisplatin （5%） or cordycepin （12%） alone group （P〈0.05）, confirming a synergistically apoptotic effect of cordycepin and cisplatin. In cellular mechanism study, co-treatment of cordycepin and cisplatin induced more stress-activated protein kinase/dun terminal kinase （JNK）, the expressions of caspase-7, and the cleavage of poly ADP-ribose polymerase （PARP） as compared to cisplatin or cordycepin alone treatment （P〈0.05）. Conclusion： Cisplatin and cordycepin possess synergistically apoptotic effect through the activation of JNK/caspase-7/PARP pathway in human OC3 oral cancer cell line.展开更多
基金supported by the National Natural Science Foundation of China,No.81971246 (to TM)Opening Foundation of Jiangsu Key Laboratory of Neurodegeneration,Nanjing Medical University,No.KF202204 (to LZ and SF)。
文摘Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.
基金supported by the National Natural Science Foundation of China(81503187)。
文摘Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in vitro and in vivo studies revealed that cordycepin inhibited proliferation and migration in HepG-2 cells and inhibited the growth of HepG-2 xenograft-bearing nude mice by inducing apoptosis.Transcriptome sequencing analysis revealed a total of 403 differential genes,which revealed that cordycepin may play an anti-HCC role by regulating Hippo signaling pathway.The regulatory effects of cordycepin on the Hippo signaling pathway was further investigated using a YAP1 inhibitor.The results demonstrated that cordycepin upregulated the expression of MST1 and LAST1,and subsequently inhibited YAP1,which activated the Hippo signaling pathway.This in turn downregulated the expression of GBP3 and ETV5,and subsequently inhibited cell proliferation and migration.Additionally,YAP1 regulated the expression of Bax and Bcl-2,regulated the mitochondrial apoptotic pathway,and induced apoptosis by upregulating the expression of the caspase-3 protein.In summary,this study reveals that cordycepin exerts its anti-hepatocarcinoma effect through regulating Hippo signaling pathway,and GBP3 and ETV5 may be potential therapeutic targets for hepatocarcinoma.
文摘Cordyceps sinensis, a parasitic fungus on the larva of Lapidoptera, has been used as a traditional Chinese medicine. We previously reported that the growth of B16-BL6 mouse melanoma (B16-BL6) cells and mouse Lewis lung carcinoma (LLC) cells was inhibited by cordycepin (3’-deoxyadenosine), an ingredient of Cordyceps sinensis, and its effect was antagonized by MRS1191, a selective adenosine A3 receptor (A3-R) antagonist although adenosine (up to 100 μM) had no effect on the growth of B16-BL6 and LLC cells. In this study, we investigated whether water extracts of Cordyceps sinensis (WECS) inhibit the growth of B16-BL6 cells, LLC cells, HT1080 human fibrosarcoma (HT1080) cells and CW-2 human colon carcinoma (CW-2) cells via their A3-R. As a result, the growth of all cell lines were potently inhibited by WECS (10 μg/mL) and the inhibitory effect of WECS was significantly antagonized by MRS1191 (1 μM). Furthermore, WECS included 2.34% w/w cordycepin and 0.12% w/w adenosine as components according to the HPLC- ECD system. In conclusion, WECS inhibited the proliferation of four cancer cell lines by stimulation of A3-R and the main component in WECS with anticancer action might be cordycepin instead of adenosine.
基金Supported by National Science Council Grant(No.982320-B-006-016),Taiwan,China
文摘Objective： To evaluate apoptotic effects of cisplatin and cordycepin as single agent or in combination with cytotoxicity in oral cancer cells. Methods： The influences of cisplatin （2.5 μg/mL） and/or cordycapin treatment （10 or 100 μmol/L） to human OC3 oral cancer cell line were investigated by morphological observation for cell death appearance, methylthiazoletetrazolium （MTT） assay for cell viability, flow cytometry assay for cell apoptosis, and Western blotting for apoptotic protein expressions. Results： Data demonstrated that co-administration of cisplatin （2.5 μg/mL） and cordycepin （10 or 100μmol/L） resulted in the enhancement of OC3 cell apoptosis compared to cisplatin or cordycapin alone treatment （24 h）, respectively （P〈0.05）. In flow cytometry assay, percentage of cells arrested at subG1 phase with co-treatment of cordycepin and cisplatin （30%） was significantly higher than cisplatin （5%） or cordycepin （12%） alone group （P〈0.05）, confirming a synergistically apoptotic effect of cordycepin and cisplatin. In cellular mechanism study, co-treatment of cordycepin and cisplatin induced more stress-activated protein kinase/dun terminal kinase （JNK）, the expressions of caspase-7, and the cleavage of poly ADP-ribose polymerase （PARP） as compared to cisplatin or cordycepin alone treatment （P〈0.05）. Conclusion： Cisplatin and cordycepin possess synergistically apoptotic effect through the activation of JNK/caspase-7/PARP pathway in human OC3 oral cancer cell line.
