Inokosterone Is A Potential Drug Target of Estrogen Receptor 1 in Rheumatoid Arthritis Patients: Analysis from Active Ingredient of Cyathula Officinalis / 中国结合医学杂志

OBJECTIVE@#To elucidate the active compounds and the molecular mechanism of Cyathula Officinalis as a drug treatment for rheumatoid arthritis (RA).@*METHODS@#The target genes of active ingredients from Cyathula Officinalis were obtained from bioinformatics analysis tool for the molecular mechanism of traditional Chinese medicine. The protein-protein interaction between the target genes were analyzed using STRING and Genemania. The transcriptome of RA patients compared to healthy people (GSE121894) were analyzed using R program package Limma. The relative expression of the target genes was obtained from the RNA-seq datasets. The molecular docking analyses were processed based on the molecular model of estrogen receptor 1 (ESR1) binding with estradiol (PDB ID:1A52). The binding details were analyzed by SYBYL.@*RESULTS@#Inokosterone, ecdysterone, and cyaterone were the 3 active ingredients from Cyathula Officinalis that bind to target genes. Of all the significantly changed genes from RA patients, ESR1, ADORA1, and ANXA1 were significantly increased in mRNA samples of RA patients.@*CONCLUSION@#ESR1, the transcription factor that binds inokosterone in the molecular binding analysis, is the target protein of Cyathula Officinalis.

A combination of four effective components derived from Sheng-mai san attenuates hydrogen peroxide-induced injury in PC12 cells through inhibiting Akt and MAPK signaling pathways / 中国天然药物

The present study was designed to investigate whether a combination of four effective components derived from Sheng-mai san (SMXZF; ginsenoside Rb1: ginsenoside Rg1: DT-13: Schizandrol A as 6 : 9 : 4 : 5) could attenuate hydrogen peroxide (H2O2)-induced injury in PC12 cells, focusing on the Akt and MAPK pathways . The PC12 cells were exposed to H2O2 (400 μmol·L(-1)) for 1 h in the presence or absence of SMXZF pre-treatment for 24 h. Cell viability was measured by MTT assay. The efflux of lactate dehydrogenase (LDH), the intracellular content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), and caspase-3 were also determined. Cell apoptosis was measured by Hoechst 33342 staining and Annexin V-FITC/PI staining method. The expression of Bcl-2, Bax, cleaved caspase-3, Akt, and MAPKs were detected by Western blotting analyses. SMXZF pretreatment significantly increased the cell viability and SOD activity and improved the cell morphological changes, while reduced the levels of LDH and MDA at the concentrations of 0.1, 1 and 10 μg·mL(-1). SMXZF also inhibited H2O2-induced apoptosis in PC12 cells. Moreover, SMXZF reduced the activity of caspase-3, up-regulated the protein ratio of Bcl-2 and Bax and inhibited the expression of cleaved caspase-3, p-Akt, p-p38, p-JNK and p-ERK1/2 in H2O2-induced PC12 cells. Co-incubation of Akt inhibitor or p38 inhibitor partly attenuated the protection of SMXZF against H2O2-injured PC12 cells. In conclusion, our findings suggested that SMXZF attenuated H2O2-induced injury in PC12 cells by inhibiting Akt and MAPKs signaling pathways, which might shed insights on its neuroprotective mechanism.

Network pharmacology-based prediction and verification of the molecular targets and pathways for schisandrin against cerebrovascular disease / 中国天然药物

AIM@#To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification.@*METHOD@#A protein database was established through constructing the drug-protein network from literature mining data. The protein-protein network was built through an in-depth exploration of the relationships between the proteins. The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network. Then the key targets and pathways were identified from the sensitive sub-network. The most related targets and pathways were also confirmed in hydrogen peroxide (H2O2)-induced PC12 cells by Western blotting.@*RESULTS@#Twelve differentially expressed proteins (gene names: NFKB1, RELA, TNFSF10, MAPK1, CHUK, CASP8, PIGS2, MAPK14, CREB1, IFNG, APP, and BCL2) were confirmed as the central nodes of the interaction network (45 nodes, 93 edges). The NF-κB signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease. Furthermore, schisandrin was found to suppress the expression and phosphorylation of IKKα, as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting.@*CONCLUSION@#The computational platform that integrates literature mining data, protein-protein interactions, sensitive sub-network, and pathway results in identification of the NF-κB signaling pathway as the key targets and pathways for schisandrin.