Mechanism Assay of Honeysuckle for Heat-Clearing Based on Metabolites and Metabolomics.

Hechen Wang,Yuanyau Hou,Yiman Han,Lu Tian,Gang Bai,Xiaoyao Ma

doi:10.3390/metabo12020121

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as cyclooxygenase (Cox)-1/2 inhibitor, have emerged as potent antipyretics and analgesics. However, few herbs with Cox-1/2 inhibitory activity are commonly used for heat-clearing in China. Although these are known to have antipyretic activity, there is a lack of molecular data supporting their activity. Using the traditional Chinese medicine herb honeysuckle (Hon) as an example, we explored key antipyretic active compounds and their mechanisms of action by assessing their metabolites and metabolomics. Mitogen-activated protein kinase (MAPK) 3 and protein kinase B (AKT) 1 were suggested as key targets regulated primarily by chlorogenic acid (CA) and swertiamarin (SWE). CA and SWE synergistically inhibited the production of interleukin (IL)-1 and IL-6, alleviated generation of prostaglandin E2, and played an antipyretic role equivalent to honeysuckle extract at the same dose contents within 3 h. Collectively, these findings indicated that lipopolysaccharide-induced fever can be countered by CA with SWE synergistically, allowing the substitution of a crude extract of complex composition with active compounds. Our findings demonstrated that, unlike the traditional NSAIDs, the Hon extract showed a remote and indirect mechanism for alleviating fever that depended on the phosphatidylinositol-3-kinase–AKT and MAPK pathways by regulating the principal mediator of inflammation.

Highlights

Starting with aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), which target cyclooxygenase (COX)-1/2, have emerged as potent antipyretics and analgesics [1]
Global metabolite profiling based on negative and positive ion modes was performed to identify key metabolites in plasma derived from honeysuckle extractive preparation (HEP), a honeysuckle oral liquid freezedried powder
The MS data of different groups were integrated into the Global Natural Product Social Molecular Networking (GNPS) platform

Summary

Introduction

Nonsteroidal anti-inflammatory drugs (NSAIDs), which target cyclooxygenase (COX)-1/2, have emerged as potent antipyretics and analgesics [1]. Almost no heat-clearing herbal medicines containing COX-1/2 inhibitors based on traditional Chinese medicine are being used for alleviating fever. One of the few examples of plants that are being used is honeysuckle (Hon), which refers to the flower buds of Lonicera japonica Thunb., possessing as it does potential anti-pyretic and antiinflammatory activities, and which is widely used clinically after extraction [2]. More than 140 phytoconstituents have been identified from honeysuckle extracts. The key component responsible for its antipyretic activity and its corresponding target remain unknown. It is important to investigate the complex mechanism behind antipyretic activity exerted by these active compounds, as this will provide the knowledge required to precisely tailor therapies for various conditions, such as exopathogenic diseases, sores, carbuncles, and some infectious diseases

Methods

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Conclusion