Inhibitory effect of saffron on head and neck squamous cell carcinoma via targeting of ESR1 and CCND1 by its active compound crocetin

Background:Traditional Chinese medicine is promising for managing challenging and complex disorders,including cancer,and in particular,saffron is applied in treating various cancer types.However,its potential therapeutic efficacy and active components in managing squamous cell carcinoma of the head and neck(HNSCC)remain unclear yet.Methods:Using network pharmacology approaches,active ingredients of saffron,their target genes,and HNSCC-related genes were identified.Enrichment analyses were conducted for determining molecular functions and pathways enriched by genes that overlapped between the saffron target gene set and the HNSCC gene set.Among the four known active ingredients of saffron,crocetin was found to have the strongest inhibitory impact on HNSCC,based on the findings of cell viability and migration assays.Therefore,the potential target genes of crocetin in HNSCC cells were examined using molecular docking experiments and were confirmed by qPCR.Result s:Four active ingredients of saffron and 184 of their target genes were identified.Further,a total of 34 overlapping saffron-/HNSCC-associated targets related to the four active ingredients were screened,and crocetin was chosen for further investigation because it had the strongest inhibitory effect on HNSCC cells.Molecular docking experiments indicated that ESR1 and CCND1 were the target genes of crocetin.These results were confirmed through qPCR analysis,in which crocetin was found to lower the expression of the ESR1 and CCND1 genes in AMC-HN-8 and FaDu cells.Conclusion:According to our results,crocetin is a primary active anti-cancer component of saffron that may have potential in the development of novel HNSCC-treating medications.However,more thorough molecular research is necessary for confirming these results and elucidating the anti-cancer mechanism underlying saffron.

Comparing the mechanism of four classic Gualou-Xiebai prescriptions for cardiovascular diseases with phlegm and blood stasis syndrome based on molecular network modeling

Background:Four classical Traditional Chinese Medicine prescriptions,namely Gualou Xiebai Baijiu decoction,Gualou Xiebai Banxia decoction(GLXBBX),Zhishi Xiebai Guizhi decoction(ZSXBGZ)and Danlou prescription(DL),have been frequently used for treatment of phlegm and blood stasis syndrome(PBSS)-related cardiovascular diseases.However,its therapeutic mechanism has not been clearly elucidated.This study aimed to explore PBSS and its molecular mechanism,clarify and compare the mechanisms of four prescriptions in treating PBSS-related diseases.Method:In this study,we collected four prescriptions’compounds,predicted therapeutic targets,and enriched pathways which were based on network pharmacology.Then,we analysed the commen and different mechanisms by combing the network of components,targets and pathways.Finally,molecular docking was engaged to assess the binding potential of key compounds and hub targets.Results:We showed that four prescriptions’intersection genes(VEGFA,SRC,EGFR,etc.)were commonly enriched in PI3K-AKT signaling pathway,HIF-1 signaling pathway,etc.In addition,platelet activation and cAMP signaling pathway were singly enriched from the GLXBBX through unique compounds 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid and Cyclo(L-tyrosyl-L-phenylalanyl).These bioactive compounds may exert GLXBBX’s unique pharmacological pathways via involving in mediating PPARA,PTGER3,etc.Sphingolipid signaling pathway was singly enriched from the ZSXBGZ through unique compounds tetramethoxyluteolin,ergosterol peroxide,etc.These bioactive compounds could mediate ADORA1,ADORA3 and TNFRSF1A to regulate ZSXBGZ’s unique pharmacological pathways.AMPK signaling pathway was singly enriched from the DL through unique compounds kaempferol,evofolinb,ethyl acid and aureusidin.These bioactive compounds were involved in mediating the main targets of AMPK signaling pathway,such as TNF,TNFRSF1A,etc.Conclusions:Our research demonstrated that GLXB-prescriptions involved in almost all pathological stages of PBSS-related cardiovascular diseases by modulating high-frequency shared pathways and targets mainly through key compounds(quercetin,mandenol,sitosteryl acetate and luteolin,etc.),for example,participate in the process of atherosclerosis,lipid metabolism,inflammation,immune response,thrombosis,inhibit inflammatory factors and platelet aggregation,regulate immune function,vascular function,oxidative stress.In addition to common pharmacological efficacies,there could also be specificities among GLXB prescriptions due to different compounds.For example,GLXBBX tends to regulate the function of vascular and endothelial barrier,prevent thrombosis.ZSXBGZ tends to regulate lipid metabolism and protect the heart from lipid accumulation.DL tends to maintain energy homeostasis and improve inflammation.