Objective. To explore the mechanisms of the volatiles of Wendan granule (WDG) for the treatment of Alzheimer’s disease, network pharmacology method integrating absorption, distribution, metabolism, and excretion (ADME) screening, target fishing, network constructing, pathway analysing, and correlated diseases prediction was applied. Methods. Twelve small molecular compounds of WDG were selected as the objects from 74 volatiles with the relative abundances above 2 %, and their ADME parameters were collected from Traditional Chinese Medicine Systems Pharmacology platform (TCMSP), and the corresponding targets, genes, pathways, and diseases were predicted according to the data provided by TCMSP, DrugBank, Uniport, and the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Then the related pathways and correlation analysis were explored by the Kyoto Encyclopedia and Genomes (KEGG) database. Finally, the networks of compound target, target pathway, and pathway disease of WDG were constructed by Cytoscape software. Results. Twelve compounds interacted with 49 targets, of which top three targets were gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), prostaglandin G/H synthase 2 (PGHS-2), and sodium-dependent noradrenaline transporter. Interestingly, these targets were highly associated with depression, insomnia, and Alzheimer’s disease that mainly corresponded to mental and emotional illnesses. Conclusion. The integrated network pharmacology method provides precise probe to illuminate the molecular mechanisms of the main volatiles of WDG for relieving senile dementia related syndromes, which will also facilitate the application of traditional Chinese medicine as an alternative or supplementary to conventional treatments of AD, as well as follow-up studies such as upgrading the quality standard of clinically applied herbal medicine and novel drug development.

Introduction Drug delivery systems (DDSs) based on liposomes are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve biosafe, accurate, and efficient cancer therapy of liposomes with single function or single mechanism. To solve this problem, we designed a multifunctional and multimechanism nanoplatform based on polydopamine (PDA)-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT. Methods ICG and DOX were co-incorporated in polyethylene glycol modified liposomes, which were further coated with PDA by a facile two-step method to construct PDA-liposome nanoparticles (PDA@Lipo/DOX/ICG). The safety of nanocarriers was investigated on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, and combinatorial treatment effect of the nanoparticles were assessed on human breast cancer cells MDA-MB-231. In vivo biodistribution, thermal imaging, biosafety assessment, and combination therapy effects were estimated based on MDA-MB-231 subcutaneous tumor model. Results Compared with DOX·HCl and Lipo/DOX/ICG, PDA@Lipo/DOX/ICG showed higher toxicity on MDA-MB-231 cells. After endocytosis by target cells, PDA@Lipo/DOX/ICG produced a large amount of ROS for PDT by 808 nm laser irradiation, and the cell inhibition rate of combination therapy reached up to 80.4%. After the tail vein injection (DOX equivalent of 2.5 mg/kg) in mice bearing MDA-MB-231 tumors, PDA@Lipo/DOX/ICG significantly accumulated at the tumor site at 24 h post injection. After 808 nm laser irradiation (1.0 W/cm 2 , 2 min) at this timepoint, PDA@Lipo/DOX/ICG efficiently suppressed the proliferation of MDA-MB-231 cell and even thoroughly ablated tumors. Negligible cardiotoxicity and no treatment-induced side effects were observed. Conclusion PDA@Lipo/DOX/ICG is a multifunctional nanoplatform based on PDA-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT.

Yiqi Sanjie formula (YQSJF) is mainly applied clinically for the treatment of lung neoplasms. The purpose of this study was to explore the pharmacodynamics of the active components of YQSJF and the mechanism of therapeutic effects in the treatment of lung neoplasm diseases based on network pharmacology. The network of component-target, target-pathway, and pathway-disease of YQSJF was constructed by using Cytoscape software. According to the screening result, 37 key components, 57 important targets, and 866 candidate pathways were obtained. The enrichment analysis results indicated that YQSJF might play a therapeutic role in lung cancer by regulating several signaling pathways, such as the PI3K-AKT, non-small cell lung cancer, small cell lung cancer, and apoptosis pathways. There were 53 intersection genes between YQSJF and the lung cancer gene, 52 common genes, and 11 key targets, including CASP8, CASP9, AR, ESR1, PTGS2, NOS3, PGR, TGFB1, PPARG, RELA, and NOS2, screened by using Protein-Protein Interaction (PPI) analysis. These could be the potential therapeutic targets of YQSJF against lung cancer. Enrichment analysis of the intersection gene pathways revealed 10 major functional pathways, including the VEGF, apoptosis, and IL-17 signaling pathways. The molecular docking results showed the potential regulating activity of kaempferol against AR, pelargonidin against PGR, and baicalein against both PTGS2 and AR. In conclusion, combinational network pharmacology analysis results indicated that YQSJF might present its efficacy of alleviating lung neoplasm symptoms through multiple targets in a synergetic way.