Molecular mechanism of ginsenoside Rg_1 against radiation enteritis: based on network pharmacology and in vitro experiment / 中国中药杂志

Via network pharmacology, molecular docking, and cellular experiment, this study explored and validated the potential molecular mechanism of ginsenoside Rg_1(Rg_1) against radiation enteritis. Targets of Rg_1 and radiation enteritis were retrieved from BATMAN-TCM, SwissTargetPrediction, and GeneCards. Cytoscape 3.7.2 and STRING were employed for the construction of protein-protein interaction(PPI) network for the common targets, and screening of core targets. DAVID was used for Gene Ontology(GO) term and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict the possible mechanism, followed by molecular docking of Rg_1 with core targets and cellular experiment. For the cellular experiment, ~(60)Co-γ irradiation was performed for mo-deling of IEC-6 cells, which were then treated with Rg_1, protein kinase B(AKT) inhibitor LY294002, and other drugs to verify the effect and mechanism of Rg_1. The results showed that 29 potential targets of Rg_1, 4 941 disease targets, and 25 common targets were screened out. According to the PPI network, the core targets were AKT1, vascular endothelial growth factor A(VEGFA), heat shock protein 90 alpha family class A member 1(HSP90AA1), Bcl-2-like protein 1(BCL2L1), estrogen receptor 1(ESR1), etc. The common targets were mainly involved in the GO terms such as positive regulation of RNA polymerase Ⅱ promoter transcription, signal transduction, positive regulation of cell proliferation, and other biological processes. The top 10 KEGG pathways included phosphoinositide 3-kinase(PI3K)/AKT pathway, RAS pathway, mitogen-activated protein kinase(MAPK) pathway, Ras-proximate-1(RAP1) pathway, and calcium pathway, etc. Molecular docking showed that Rg_1 had high binding affinity to AKT1, VEGFA, HSP90AA1, and other core targets. Cellular experiment indicated that Rg_1 can effectively improve cell viability and survival, decrease apoptosis after irradiation, promote the expression of AKT1 and B-cell lymphoma-extra large(BCL-XL), and inhibit the expression of the pro-apoptotic protein Bcl-2-associated X protein(BAX). In conclusion, through network pharmacology, molecular docking, and cellular experiment, this study verified the ability of Rg_1 to reduce radiation enteritis injury. The mechanism was that it regulated PI3K/AKT pathway, thereby suppressing apoptosis.

Effect of Modified Xijiao Dihuang Decoction () on Intestinal Flora and Th17/Treg in Rats with Radiation Enteritis / 中国结合医学杂志

OBJECTIVE@#To observe the effect of Modified Xijiao Dihuang Decoction (, MXDD) on rats with radiation enteritis, and explore its action mechanism.@*METHODS@#Thirty female Sprague Dawley rats were divided into the control, model, dexamethasone (DXM), golden bifid (GB) and MXDD groups using random number table, 6 rats in each group. Except the control group, the other rats were developed into radiation enteritis model by exposing to a single @*RESULTS@#On day 1 to 3 after radiation, compared with the control group, the body weight in model group was decreased (P<0.05 or P<0.01). Compared with the model group, MXDD could alleviate weight loss and diarrhea caused by irradiation. At the phylum level, MXDD cause a significant increase in Firmicutes, and a decrease in Proteobacteria (P<0.05 or P<0.01). At the genus level, MXDD reduced the proportion of Escherichia Shigella (P<0.01). In addition, IL-17 and FoxP3 mRNA and protein expression levels were down-regulated and ROR-γt was up-regulated by MXDD treatment (P<0.05). Besides, Firmicutes and Lactobacillus were positively correlated with FoxP3 (r=0.73, 0.79, respectively; P<0.01), negatively correlated with IL-17 (r=0.66, 0.64, respectively; P<0.01 or P<0.05) and ROR-γt (r0.73, 0.81, respectively; P<0.01). Proteobacteria and Escherichia Shigella both had positive correlation with IL-17 (r 0.77, 0.57, respectively; P<0.01 or P<0.05 ) and ROR-γt (r=0.94, 0.79, respectively; P<0.01) and negative correlation with FoxP3 (r0.74, 0.65; P<0.01).@*CONCLUSION@#MXDD could improve the survival status of irradiated rats by regulating the richness, diversity and composition of intestinal flora, and restoring the balance of Th17/Treg.

Pharmacokinetics of tectorigenin in rabbit / 中成药

AIM To develop a HPLC method for determining tectorigenin content in rabbit plasma for pharmacokinetics.METHODS As self crossover control,the rabbits,six Japanese giant ear rabbits were subject to a singledose intragastric administration of 60 mg/kg (tectorigenin 40 mg/kg) pueraria isoflavone.The free and enzymatic tectorigenin contents in plasma were measured by HPLC,and then pharmacokinetic parameters were calculated by PKsolver 2.0 pharmacokinetic program.RESULTS The AUC0-t,Tmax,Cmax after intragastric administration of pueraria isoflavone were (46.78 ±5.12) μg · min/mL,(5.39 ±0.54) min,(0.84 ±0.21) μg/mL for free tectorigenin,respectively;(485.48 ±23.53) μg · min/mL,(20.12 ±2.84) min,(2.95 ±0.67) μg/mL for total tectorigenin,respectively.CONCLUSION HPLC method is suitable for tectorigenin pharmacokinetic study.Tectorigenin is present mainly as glucuronide conjugates in plasma after intragastric administration pueraria isoflavone.

Pharmacokinetics of tectorigenin in rabbit / 中成药

AIM To develop a HPLC method for determining tectorigenin content in rabbit plasma for pharmacokinetics.METHODS As self crossover control,the rabbits,six Japanese giant ear rabbits were subject to a singledose intragastric administration of 60 mg/kg (tectorigenin 40 mg/kg) pueraria isoflavone.The free and enzymatic tectorigenin contents in plasma were measured by HPLC,and then pharmacokinetic parameters were calculated by PKsolver 2.0 pharmacokinetic program.RESULTS The AUC0-t,Tmax,Cmax after intragastric administration of pueraria isoflavone were (46.78 ±5.12) μg · min/mL,(5.39 ±0.54) min,(0.84 ±0.21) μg/mL for free tectorigenin,respectively;(485.48 ±23.53) μg · min/mL,(20.12 ±2.84) min,(2.95 ±0.67) μg/mL for total tectorigenin,respectively.CONCLUSION HPLC method is suitable for tectorigenin pharmacokinetic study.Tectorigenin is present mainly as glucuronide conjugates in plasma after intragastric administration pueraria isoflavone.