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Purpose To study the effects of Lu-tong Granules (LTG) in ICH etermine the underlying mechanism of molecular network Methods Modern bioinformatics and network pharmacology methods were used to predict molecular network mechanisms between ICH and LTG. Animal experiments were carried out to verify the effect of LTG for the treatment of ICH, combined with behavior test and morphologic detection. Results Forty-three active components in LTG and involved 192 gene targets were identified successfully. Moreoner, they were intersected with 1132 genes of ICH,88 intersection targets were obtained. subsequently, Cytoscape was used to screen Hub genes, in which,6 core molecules, including AKT1, IL6, VEGFA, CASP3, JUN and MMP9 were recognized. Furthermore, we constructed Six core compounds by " disease-drug-active ingredient-target-KEGG " (D-D-A-T-K) network, showed including quercetin, luteolin, β sitosterol, stigmasterol, kaempferol and formononetin, and PPI protein network interaction showed that AKT1:OS3 and CNA2:DKN1A had the highest correlation. Whereas the enrichment of GO and KEGG indicated that LTG was most likely to play a therapeutic role in ICH through AGE-RAGE signaling pathway in diabetic complications. Integrated analysis also showed that the first 10 pathways of KEGG are integrated into 59 genes, among which 6 core genes are closely involved. Lastly, molecular docking showed that there was a good binding activity between the core components and the core genes, and animal experiments confirmed effect of LTG in the treatment of ICH, by using TTC staining and behavior test. Conclusion LTG are effective for the treatment of ICH, the underlying mechanism could be involved in gene network including anti-inflammatory response, nerve repair, analgesia, anti-epilepsy and other aspects.

Objectives Triple negative breast cancer (TNBC) lacks specific drug targets and remains challenging. Palbociclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor is approved for metastatic estrogen receptor (ER)-positive and human epithermal growth factor 2 (HER2)-negative breast cancer. The nature of cell cycle inhibition by palbociclib suggests its potential in TNBC cells. Retinoblastoma (RB, a known substrate of CDK4/6) pathway deregulation is a frequent occurrence in TNBC and studies have revealed that pharmacological CDK4/6 inhibition induces a cooperative cytostatic effect with doxorubicin in RB-proficient TNBC models. In addition, recent studies reported that anti-androgen therapy shows preclinical efficacy in androgen-receptor (AR)-positive TNBC cells. Here we examined the effect of palbociclib in combination with an anti-androgen enzalutamide in TNBC cells. Method MDA-MB-453, BT-549, MDA-MB-231 and MDA-MB-468 TNBC cell lines were used for in vitro studies. Protein expressions were assessed by Western blot analysis. Cytostatic effect was examined by MTT assay. Cell cycle and apoptosis were examined by flow cytometry. Results Palbociclib showed inhibitory effect in RB-proficient TNBC cells, and enzalutamide inhibited cell viability in AR-positive TNBC cells. Enzalutamide treatment could enhance the palbociclib-induced cytostatic effect in AR-positive/RB-proficient TNBC cells. In addition, palbociclib-mediated G1 arrest in AR-positive/RB-proficient TNBC cells was attenuated by RB knockdown. Conclusion Our study provided a preclinical rationale in selecting patients who might have therapeutic benefit from combining CDK4/6 inhibitors with AR antagonists.