Safety evaluation of Tibetan medicine Qishiwei Zhenzhu Pills based on serum pharmacochemistry and network pharmacology / 中国中药杂志

To explore the mechanism of the active ingredients of Qishiwei Zhenzhu Pills in inhibiting the hepatorenal toxicity of the zogta component based on serum pharmacochemistry and network pharmacology, thereby providing references for the clinical safety application of Qishiwei Zhenzhu Pills. The small molecular compounds in the serum containing Qishiwei Zhenzhu Pills of mice were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Then, by comprehensively using Traditional Chinese Medicines Systems Pharmacology(TCMSP), High-throughput Experiment-and Reference-guided Database(HERB), PubChem, GeneCards, SuperPred, and other databases, the active compounds in the serum containing Qishiwei Zhenzhu Pills were retrieved and their action targets were predicted. The predicted targets were compared with the targets of liver and kidney injury related to mercury toxicity retrieved from the database, and the action targets of Qishiwei Zhenzhu Pills to inhibit the potential mercury toxicity of zogta were screened out. Cytoscape was used to construct the active ingredient in Qishiwei Zhenzhu Pills-containing serum-action target network, and STRING database was used to construct the protein-protein interaction(PPI) network of intersection targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out on the target genes by the DAVID database. The active ingredient-target-pathway network was constructed, and the key ingredients and targets were screened out for molecular docking verification. The results showed that 44 active compounds were identified from the serum containing Qishiwei Zhenzhu Pills, including 13 possible prototype drug ingredients, and 70 potential targets for mercury toxicity in liver and kidney were identified. Through PPI network topology analysis, 12 key target genes(HSP90AA1, MAPK3, STAT3, EGFR, MAPK1, APP, MMP9, NOS3, PRKCA, TLR4, PTGS2, and PARP1) and 6 subnetworks were obtained. Through GO and KEGG analysis of 4 subnetworks containing key target genes, the interaction network diagram of active ingredient-action target-key pathway was constructed and verified by molecular docking. It was found that taurodeoxycholic acid, N-acetyl-L-leucine, D-pantothenic acid hemicalcium, and other active ingredients may regulate biological functions and pathways related to metabolism, immunity, inflammation, and oxidative stress by acting on major targets such as MAPK1, STAT3, and TLR4, so as to inhibit the potential mercury toxicity of zogta in Qishiwei Zhenzhu Pills. In conclusion, the active ingredients of Qishiwei Zhenzhu Pills may have a certain detoxification effect, thus inhibiting the potential mercury toxicity of zogta and playing a role of reducing toxicity and enhancing effect.

Simultaneous determination of six constituents in Qishiwei Zhenzhu Pills by HPLC / 中成药

AIM To establish an HPLC method for the simultaneous content determination of six constituents in Tibetan medicine Qishiwei Zhenzhu Pills (Croci Stigma,Dalbergiae odoriferae Lignum,Glycyrrhizae Radix et Rhizoma,etc.).METHODS The analysis of 50％ methanol extract of this drug was carried out on a 30 ℃ thermostatic Inertsil(C)ODS-3 column (250 mm ×4.6 mm,5 μm),with the mobile phase comprising of 0.2％ phosphoric acid-acetonitrile flowing at 0.8 mL/min in a gradient elution manner,and the detection wavelength was set at 254 nm.RESULTS Gallic acid,corilagin,agarotetrol,ellagic acid,crocin Ⅰ and crocin Ⅱ showed good linear relationships within the ranges of 1.41-42.24,0.61-18.24,0.30-9.12,0.47-14.04,0.62-18.48 and 0.32-9.45 μg/mL (R2 ≥0.999 4),whose average recoveries (RSDs) were 93.41％ (1.75％),96.84％ (1.75％),97.45％ (0.58％),93.22％ (0.56％),97.01％ (1.39％) and 97.22％ (1.11％),respectively.The contents of various constituents in different batches of samples from two manufactures showed some differences,especially for those of corilagin and agarotetrol.CONCLUSION We should pay attention to the unstable quality of Qishiwei Zhenzhu Pills.

Simultaneous determination of six constituents in Qishiwei Zhenzhu Pills by HPLC / 中成药

AIM To establish an HPLC method for the simultaneous content determination of six constituents in Tibetan medicine Qishiwei Zhenzhu Pills (Croci Stigma,Dalbergiae odoriferae Lignum,Glycyrrhizae Radix et Rhizoma,etc.).METHODS The analysis of 50％ methanol extract of this drug was carried out on a 30 ℃ thermostatic Inertsil(C)ODS-3 column (250 mm ×4.6 mm,5 μm),with the mobile phase comprising of 0.2％ phosphoric acid-acetonitrile flowing at 0.8 mL/min in a gradient elution manner,and the detection wavelength was set at 254 nm.RESULTS Gallic acid,corilagin,agarotetrol,ellagic acid,crocin Ⅰ and crocin Ⅱ showed good linear relationships within the ranges of 1.41-42.24,0.61-18.24,0.30-9.12,0.47-14.04,0.62-18.48 and 0.32-9.45 μg/mL (R2 ≥0.999 4),whose average recoveries (RSDs) were 93.41％ (1.75％),96.84％ (1.75％),97.45％ (0.58％),93.22％ (0.56％),97.01％ (1.39％) and 97.22％ (1.11％),respectively.The contents of various constituents in different batches of samples from two manufactures showed some differences,especially for those of corilagin and agarotetrol.CONCLUSION We should pay attention to the unstable quality of Qishiwei Zhenzhu Pills.