Network pharmacology to explore the molecular mechanisms of Prunella vulgaris for treating thyroid cancer.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy that has rapidly increased in global incidence. Prunella vulgaris (PV) has manifested therapeutic effects in patients with TC. We aimed to investigate its molecular mechanisms against TC and provide potential drug targets by using network pharmacology and molecular docking. METHODS: The ingredients of PV were retrieved from Traditional Chinese Medicine Systematic Pharmacology Database. TC-related gene sets were established using the GeneCard and OMIM databases. The establishment of the TC-PV target gene interaction network was accomplished using the STRING database. Cytoscape constructed networks for visualization. Protein-protein interaction, gene ontology and the biological pathway Kyoto encyclopedia of genes and genomes enrichment analyses were performed to discover the potential mechanism. Molecular docking technology was used to analyze the effective compounds from PV for treating TC. RESULTS: 11 active compounds and 192 target genes were screened from PV. 177 potential targets were obtained by intersecting PV and TC gene sets. Network pharmacological analysis showed that the PV active ingredients including Vulgaxanthin-I, quercetin, Morin, Stigmasterol, poriferasterol monoglucoside, Spinasterol, kaempferol, delphinidin, stigmast-7-enol, beta-sitosterol and luteolin showed better correlation with TC target genes such as JUN, AKT1, mitogen-activated protein kinase 1, IL-6 and RELA. The gene ontology and Kyoto encyclopedia of genes and genomes indicated that PV can act by regulating the host defense and response to oxidative stress immune response and several signaling pathways are closely associated with TC, such as the TNF and IL-17. Protein-protein interaction network identified 8 hub genes. The molecular docking was conducted on the most significant gene MYC. Eleven active compounds of PV can enter the active pocket of MYC, namely poriferasterol monoglucoside, stigmasterol, beta-sitosterol, vulgaxanthin-I, spinasterol, stigmast-7-enol, luteolin, delphinidin, morin, quercetin and kaempferol. Further analysis showed that oriferasterol monoglucoside, followed by tigmasterol, were the potential therapeutic compound identified in PV for the treatment of TC. CONCLUSION: The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism of PV. MYC is a promising drug target to reduce oxidative stress damage and potential anti-tumor effect. Oriferasterol monoglucoside and kaempferol were 2 bioactive compounds of PV to treat TC. This provides a basis to understand the mechanism of the anti-TC activity of PV.

Ultrasound-Targeted Microbubble Destruction-Mediated Cell-Mimetic Nanodrugs for Treating Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease that mainly affects joints, and it can lead to disability and damage to vital organs if not diagnosed and treated in time. However, all current therapeutic agents for RA have limitations such as high dose, severe side effects, long-term use, and unsatisfactory therapeutic effects. The long-term use and dose escalation of methotrexate (MTX) may cause mild and severe side effects. To overcome the limitations, it is critical to target drug delivery to the inflamed joints. In this work, we constructed a folic acid-targeted and cell-mimetic nanodrug, MTX-loaded mesoporous silica composite nanoplatform (MMPRF), which can regulate drug release under ultrasound (US) and microbubble (MB) mediation. The targeted delivery and drug therapy were investigated through in vitro RAW264.7 cell experiments and in vivo collagen-induced arthritis animal experiments. The result showed that the targeting ability to the joints of MMPRF was strong and was more significant after US and MB mediation, which can potently reduce joint swelling, bone erosion, and inflammation in joints. This work indicated that the US- and MB-mediated MMPRF not only would be a promising method for synergistic targeted treatment of RA but also may show high potential for serving as a nanomedicine for many other biomedical fields.