Identification of Fangji Huangqi Tang as a potential herbal formula for Sjogren syndrome treatment via network pharmacology and experimental validation

Article

作者: Shao, Yanxiong ; Jiang, Hua ; Xu, Yubo ; Li, Chaoran ; Zhang, Jie ; Miao, Guojun ; Hu, Jun ; Wang, Shaohai

AbstractFangji Huangqi Tang (FHT) is a well‐known Chinese herbal formula that is prescribed as treatment for rheumatoid diseases. In this study, we aimed to investigate the potential therapeutic targets, efficacy, and safety of FHT in the treatment of Sjogren's syndrome (SS). The Gene Expression Omnibus (GEO) database was used to screen differentially expressed genes (DEGs) in SS. Further, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the potential biological functions of the DEGs. Subsequently, an FHT‐herb‐active compound‐target network was constructed to identify the relationship between the active compounds in FHT and the related targets. Then, enrichment analysis involving the DEGs and protein–protein interaction (PPI) network analysis were performed to analyze the biological functions of potential targets and screen hub genes. Further, molecular docking was employed to verify the binding affinity between the active compounds and the hub targets, and in vivo experiments involving NOD/LtJ mice were conducted to verify the therapeutic effects of FHT on SS‐like symptoms. Finally, inhibition of PIK3CK/Akt pathway by FHT was validated by WB and rt‐qPCR. A total of 1836 DEGs were identified in SS based on the GSE159574 dataset, and 114 targets of the active compounds in FHT were screened. Further, via network pharmacology analysis and molecular docking, six active compounds and five hub targets were obtained, and enrichment analysis showed that the anti‐SS effect of FHT was predominantly associated with immune cells, such as T cells and neutrophils. In vivo, FHT effectively reduced lymphocyte infiltration foci, increased saliva flow rate, and inhibited increases in the levels of SS‐related autoantibodies (anti‐SSA and anti‐SSB). Furthermore, the biosafety of FHT was verified via the serological examination of liver and kidney function. WB and rt‐qPCR analysis confirmed that FHT could inhibit the expression of PIK3CG and the activation of PIK3CG/Akt pathway. Via network pharmacological analysis, molecular docking, and in vivo verification, we demonstrated the multicomponent and multitarget characteristics of FHT in SS treatment, thereby providing novel insights into the pathogenesis of SS and the therapeutic targets of FHT for SS.

2023-08-01·Journal of Chromatography B

Comparison of two different integrated method of pharmacokinetics by the integrated pharmacokinetic research of fangji huangqi decoction

Article

作者: Li, Aiping ; Zhang, Lichao ; Liu, Yuetao ; Cui, Wenbo ; Wei, Jie ; Li, Ke ; Qin, Xuemei ; Zhao, Yirui

Traditional Chinese medicine (TCM) is characterized by its multiple components. The utilization of mathematical statistical methods to integrate the pharmacokinetics of monomer components can provide a comprehensive understanding of the holistic pharmacokinetic process of TCM. Two distinct integrated methods, namely the correlation coefficient method and the AUC-based weight coefficient method, were employed in this study to elucidate and compare their differences in the integrated pharmacokinetic research of Fangji Huangqi decoction (FHD). FHD is commonly used in clinical practice to treat the nephrotic syndrome. Firstly, one-dose FHD was given to doxorubicin-induced nephropathy (DN) rats, and the prototype compounds of FHD and their metabolites in plasma were qualitatively and semi-quantitatively analyzed by UHPLC-MS/MS. Secondly, the efficacy of FHD was quantitatively characterized by the relative distance method based on metabolomics. The correlation coefficients were obtained by analyzing the correlation between efficacy (relative distance values) and the content of compound, and they were subsequently used for the model integration (correlation coefficient method). Thirdly, the effective compounds of FHD treating DN were screened by integrating network pharmacology and molecular docking, and they were used for another integrated pharmacokinetic model by AUD-based weight coefficient method. Finally, the 2 integrated methods and the 2 integrated pharmacokinetic models were compared. In this study, 30 prototype compounds and 41 metabolites of FHD in plasma were identified, and the pharmacokinetic curve of 18 prototype compounds were built. The efficacy of FHD in the treatment of DN has been relatively quantitation. The 2 established integrated pharmacokinetic models of FHD indicated that the correlation coefficient method was the optimal approach for conducting the integrated pharmacokinetic research on the TCM with unknown effective compounds, whereas the AUC-based coefficient method was suitable for the TCM with the clear effective compounds. The integrated pharmacokinetic models indicated that FHD had high bioavailability and an absorption peak at about 6 h after administration, indicating that the 6 h after administration was the critical period of FHD treating DN. This research would be helpful for the pharmacological and pharmacokinetic research of FHD, and provide a method reference for the integrated pharmacokinetic research of TCM.

2020-04-01·Biomedical Chromatography4区 · 医学

Comprehensive investigation of mechanism and effective ingredients of Fangji Huangqi Tang by serum pharmacochemistry and network pharmacology

4区 · 医学

Article

作者: Li, Ke ; Qin, Xuemei ; Chen, Meng ; Li, Aiping ; Yang, Liu ; Yan, Yan ; Liu, Yuetao ; Jia, Jinping

AbstractFangji Huangqi Tang (FHT), has been reported to show effects on nephrotic syndrome, but its mechanism of action and bioactive components have not yet been determined. In this study, a method using UPLC–HRMS/MS was established for the detection and identification of the chemical constituents and metabolites absorbed into the blood. Absorbed components in serum were then used for the network pharmacology analysis to deduce the mechanism and effective components. A total of 86 compounds were identified or tentatively characterized. Based on the same instrumental conditions, 85 compounds were found in rat serum after oral administration of FHT, including 22 prototypes and 63 metabolites. Network pharmacology analysis showed that absorbed components, such as (3R)‐2′,3′,4′,7‐tetrahydroxyisoflavan, astrapterocarpan, cycloastragenol, 7,2′‐dihydroxy‐3′,4′‐dimethoxyisoflavan, astragaloside IV, astrapterocarpan glucoside and glycyrrhetinic acid, could be responsible for the pharmacological activity of nephrotic syndrome by regulating the VEGF signaling pathway, focal adhesion and MAPK signaling pathway. Furthermore, the pathway‐target network showed that the MAPK1, AKT2 and CDC42 were involved in the signal pathways above. This study provides a scientific basis for the mechanism and effective ingredients of FHT.

100 项与防己黄芪汤相关的药物交易

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