Liver cancer is the fourth cause of cancer-related deaths and the primary cause of death in patients with compensated cirrhosis.In recent years,the role of traditional Chinese medicine in the treatment of liver cancer...Liver cancer is the fourth cause of cancer-related deaths and the primary cause of death in patients with compensated cirrhosis.In recent years,the role of traditional Chinese medicine in the treatment of liver cancer has attracted more and more attention and recognition.Luteolin(LUT)and glycyrrhetinic(GA)are natural compounds extracted from Chinese herbal medicine.LUT exhibits various biological activity including anti-inflammatory,antibacterial,antiviral,anti-tumor,and neuroprotective effects.GA significantly inhibits the growth and metastasis of cancer cells.However,the low water solubility of both compounds hinders their clinical applications.In this study,rod-shaped nanoparticles(NPs)self-assembled from LUT and GA were designed to enhance drug solubility and tumor-targeting capability.We verified that the assembly mechanism of the NPs was π-π stacking.These NPs significantly inhibited the proliferation of liver cancer cells while had no significant effect on normal liver cells.In a mouse model of liver cancer,these NPs demonstrated superior tumor-targeting ability due to the enhanced permeability and retention effect,and the affinity of GA for liver cancer cells,resulting in better therapeutic efficacy with lower systemic toxicity.Results of network pharmacology analysis showed that LUT and GA respectively targeted estrogen receptor 1(ESR1)protein and cyclin-dependent kinase 1(CDK1)protein to corporately induce tumor cell cycle arrest,which induced the inhibition of tumor cell proliferation.In conclusion,this study provides a novel reference for the treatment of liver cancer.展开更多
Salvianolic acids,including salvianolic acid A(SAA)and salvianolic acid B(SAB),are.the main water-soluble bioactive compounds isolated from the Chinese medicinal herb Danshen and have been shown to exert in vitro and ...Salvianolic acids,including salvianolic acid A(SAA)and salvianolic acid B(SAB),are.the main water-soluble bioactive compounds isolated from the Chinese medicinal herb Danshen and have been shown to exert in vitro and in vivo cardiovascular protection.Recent studies suggest that epoxyeicosatrienoic acids(EETs),the primary cytochrome P4502J(CYP2J)epoxygenase metabolites of arachidonic acid,are involved in the progression of ischemic injury in diverse organs.Here,we investigated the relation between the protective effects of salvianolic acids and EETs/sEH as well as MAPK signaling pathway.In the present study,the rat acute myocardial infarction(AMI)model was established by the left anterior descending coronary artery occlusion.Our results showed that salvianolic acids significantly reduced ST-segment elevation and serum levels of CK-MB,LDH,and ALT in AMI rats,and significantly attenuated the caspase 3 expression and reduced the ratio of Bax/Bcl-2.ELISA measurement showed that salvianolic acids significantly increased the 14,15-EET levels in blood and heart,and attenuated hydrolase activity of sEH in heart of AMI rat.Western blotting analysis suggested that salvianolic acids significantly attenuated the phosphorylation of JNK and p38,and increased phosphorylation of ERK in heart.In conclusion,these results indicate that EETs/sEH and MAPK signaling pathways are important processes in cardioprotection of salvianolic acids.展开更多
基金the financial support from Henan Province Natural Science Foundation(No.252300420583)Henan Provincial Science and Technology Research Project(Nos.242102310455,242102310473,242102310517)the Key Project of Science and Technology Research funded by the Henan Provincial Department of Education(No.24A350002)。
文摘Liver cancer is the fourth cause of cancer-related deaths and the primary cause of death in patients with compensated cirrhosis.In recent years,the role of traditional Chinese medicine in the treatment of liver cancer has attracted more and more attention and recognition.Luteolin(LUT)and glycyrrhetinic(GA)are natural compounds extracted from Chinese herbal medicine.LUT exhibits various biological activity including anti-inflammatory,antibacterial,antiviral,anti-tumor,and neuroprotective effects.GA significantly inhibits the growth and metastasis of cancer cells.However,the low water solubility of both compounds hinders their clinical applications.In this study,rod-shaped nanoparticles(NPs)self-assembled from LUT and GA were designed to enhance drug solubility and tumor-targeting capability.We verified that the assembly mechanism of the NPs was π-π stacking.These NPs significantly inhibited the proliferation of liver cancer cells while had no significant effect on normal liver cells.In a mouse model of liver cancer,these NPs demonstrated superior tumor-targeting ability due to the enhanced permeability and retention effect,and the affinity of GA for liver cancer cells,resulting in better therapeutic efficacy with lower systemic toxicity.Results of network pharmacology analysis showed that LUT and GA respectively targeted estrogen receptor 1(ESR1)protein and cyclin-dependent kinase 1(CDK1)protein to corporately induce tumor cell cycle arrest,which induced the inhibition of tumor cell proliferation.In conclusion,this study provides a novel reference for the treatment of liver cancer.
基金The study was supported by the National Science Foundation for Young Scholars of China(Grant No.81202538).
文摘Salvianolic acids,including salvianolic acid A(SAA)and salvianolic acid B(SAB),are.the main water-soluble bioactive compounds isolated from the Chinese medicinal herb Danshen and have been shown to exert in vitro and in vivo cardiovascular protection.Recent studies suggest that epoxyeicosatrienoic acids(EETs),the primary cytochrome P4502J(CYP2J)epoxygenase metabolites of arachidonic acid,are involved in the progression of ischemic injury in diverse organs.Here,we investigated the relation between the protective effects of salvianolic acids and EETs/sEH as well as MAPK signaling pathway.In the present study,the rat acute myocardial infarction(AMI)model was established by the left anterior descending coronary artery occlusion.Our results showed that salvianolic acids significantly reduced ST-segment elevation and serum levels of CK-MB,LDH,and ALT in AMI rats,and significantly attenuated the caspase 3 expression and reduced the ratio of Bax/Bcl-2.ELISA measurement showed that salvianolic acids significantly increased the 14,15-EET levels in blood and heart,and attenuated hydrolase activity of sEH in heart of AMI rat.Western blotting analysis suggested that salvianolic acids significantly attenuated the phosphorylation of JNK and p38,and increased phosphorylation of ERK in heart.In conclusion,these results indicate that EETs/sEH and MAPK signaling pathways are important processes in cardioprotection of salvianolic acids.
