Integrating pharmacokinetics and network pharmacology to identify and validate targets of Guben Xiaozhen prescription for the treatment of chronic urticaria. (15th November 2022)

• Record Type: Journal Article
• Authors: Wu, Yayun; Ren, Yuanxin; Liu, Lijuan; Zhao, Ya; Wang, Yang; Zhao, Ruizhi; Lu, Chuanjian
• Is Part Of: Journal of ethnopharmacology. Volume 298(2022)
• Publication Date: 2022-11-15
• Subjects: Integrative screening method -- Fraxinellone -- Chronic urticaria; CU Chronic urticaria -- GXP Guben Xiaozhen prescription -- CTD The Comparative Toxicogenomics Database -- TCMSP TCM System Pharmacology -- GO Gene Ontology -- KEGG Kyoto encyclopedia of genes and genomes -- ELANE Neutrophil elastase -- ADRB2 β2 adrenergic receptor -- CTSC Cathepsin C -- ALOX5 Arachidonate 5-lipoxygenase -- HPLC/MS High-Performance Liquid Chromatography/Mass spectrometry -- LLOQ Lowest limit of quantification -- AUC Area under the curve -- TLR9 Toll-like receptor 9 -- CASP8 Caspase 8; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.115628
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Guben Xiaozhen prescription (GXP), a prescription of traditional Chinese medicine, has been used to treat skin diseases for a long history and achieved satisfactory therapeutic effects. However, its active ingredients and targets remain to be further elucidated. Aim of this study: Identify activity ingredients of GXP for the treatment of chronic urticaria (CU) and further validate the efficacy and targets of the selected component. Materials and methods: Firstly, the pharmacokinetics of different disassemble groups of GXP was investigated to screen for active ingredients with improved bioavailability. Then, shared targets between active ingredients and CU were performed by network pharmacology. Finally, the ovalbumin (OVA) induced CU model was used to verify the efficacy and targets of the screened active ingredient. Results: Pharmacokinetic results showed that, compared with sub-division groups, the maximum concentration (Cmax ) and blood concentration-time curve (AUC0-t ) of eight ingredients, including 6-shogaol, 6-gingerol, calycosin, dictamnine, fraxinellone, schizandrin, cimifugin, and sec-o-glucosylhamaudol were increased in the GXP group. Then, 218 CU-related targets and 20 shared targets with six potential active compounds were screened by network pharmacology. Further analysis found that fraxinellone was not reported to be associated with CU in the literature. Therefore, the present study employed an OVA-induced CU model and found that fraxinellone could dose-dependently inhibit the locus coeruleus reaction, mast cell degranulation, and pathological skin damage. Moreover, we further verified the ADRB2 and its downstream target caspase3 predicted by network pharmacology, and fraxinellone inhibited the expression of ADRB2 and caspase3 in high dose group, suggesting that fraxinellone may play an anti-CU role by inhibiting inflammation and cell apoptosis. Conclusion: In this study, integrated pharmacokinetics and network pharmacology methods were established to screen out six effective active ingredients in GXP for the treatment of CU. This study provides a new idea for screening active substances in traditional Chinese medicine. Graphical abstract: Image 1 Highlights: An integrated method for screening active ingredients and targets of GXP was established. Six active ingredients in GXP with therapeutic effects on chronic urticaria were screened out. Discovered and reported the therapeutic effect of fraxinellone and its targets in treating chronic urticaria.