Abstract

Herbal pairs are used as a bridge between single herb and polyherbal formulas in Traditional Chinese Medicine (TCM) to provide rationale for complicated TCM formulas. The effectiveness and rationality of TCM herbal pairs have been widely applied as a strategy for dietary supplements. However, due to the complexity of the phytochemistry of individual and combinations of herbal materials, it is difficult to reveal their effective and synergistic mechanisms from a molecular or systematic point of view. In order to address this question, UPLC-Q-TOF/MS analysis and System Pharmacology tools were applied to explore the mechanism of action, using a White Peony (Paeoniae Radix Alba) and Licorice (Glycyrrhizae Radix et Rhizoma)-based dietary supplement. A total of sixteen chemical constituents of White Peony and Licorice were isolated and identified, which interact with 73 liver protection-related targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then performed along with network analysis. Results showed that the synergistic mechanism of the White Peony and Licorice herbal pair was associated with their coregulation of bile secretion and ABC transporter pathways. In addition, Licorice exhibits a specific response to drug and xenobiotic metabolism pathways, whereas White Peony responds to Toll-like receptor signaling, C-type lectin receptor signaling, IL-17 signaling, and TNF signaling pathways, resulting in the prevention of hepatocyte apoptosis and the reduction of immune and inflammation-mediated liver damage. These findings suggest that a White Peony and Licorice herbal pair supplement would have a liver-protecting benefit through complimentary and synergistic mechanisms. This approach provides a new path to explore herbal compatibility in dietary supplements derived from TCM theory.

Highlights

  • Traditional Chinese Medicine (TCM) has been practiced in China for thousands of years

  • These results suggest that regulation of bile secretion and membrane transporters associated with drug/chemical metabolism and elimination may be the important mechanism of White Peony and Licorice to alleviate chemical-induced liver injury

  • SLCO1B1, ABCB1, ABCB11, and ATPIA1 are coregulated by phytochemicals from White Peony and Licorice, while ABCC1, ABCC2, HMGCR, and CFTR are only regulated by phytochemicals from Licorice, and ABCB4 is only regulated by phytochemicals from White Peony

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Summary

Introduction

Traditional Chinese Medicine (TCM) has been practiced in China for thousands of years. Certain herbal blends emerged as classic formulas to treat aliments, improve quality of life, or nourish body function Though these TCM formulas have been effectively used, the complexity of phytochemistry in individual herb or herbal combinations makes it very difficult to understand the root cause of the formulas’ effectiveness at the molecular or systemic level. A dietary supplement (White Peony and Licorice Tablets (WLT)) was developed based on this herbal pair and successfully registered as a functional food in China (Approval Number G20141040) with claim of “Auxiliary Function of Protecting against Chemical-Induced Liver Injury”. We intend to integrate the UPLC-Q-TOF/MS method and advanced System Pharmacology to explore the potential synergy between White Peony and Licorice in this dietary supplement

Results and Discussion
F10 Galloylpaeoniflorin
F10 CYP2C9 CYP2C8 UGT1A1 ICAM1
Material and Method
Conclusion
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