Abstract

BackgroundOral ulcer diseases are complex inflammatory diseases caused by multi-factors, which severely impact patient quality of life. Kouyanqing Granule (KYQG) has been used to treat inflammatory diseases of the mouth and throat, including recurrent aphthous stomatitis (RAS), traumatic ulcers, oral leukoplakia and so on. However, the underlying molecular mechanisms of KYQG in treating these diseases are still unclear. We aimed to explore the possible mechanisms in KYQG for the treatment of oral ulcers.MethodsAn innovative network pharmacology method was established by incorporating targets searching and fishing, network analysis, and silico validation to discover the pharmacological mechanisms of action of KYQG for the treatment of oral ulcers. Then, we verified the reliability of this method by an animal experiment.ResultsOur data indicated that a total of 47 key targets were screened, which mainly involved in three function modules including the inhibition of inflammation, the regulation of immunological response, and the suppression of oxidative stress. The implementation of these functions relies on the complex multi-pathways network, especially TNF signaling pathway and HIF-1 signaling pathway. The results of the experimental verification indicated that KYQG significantly inhibited the serum levels of cyclooxygenase-2 (COX2), matrix metalloproteinase 9 (MMP9) and tumor necrosis factor-alpha (TNF-α) in rats with oral ulcer.ConclusionKYQG exhibited the therapeutic effects on oral ulcers probably by inhibiting inflammation, regulating immunological response, and suppressing oxidative stress through a complex multi-pathways network. Particularly, TNF signaling pathway and HIF-1 signaling pathway may play crucial roles in the protection of KYQG against oral ulcers. This work not only offers a method for understanding the functional mechanisms of KYQG for treating oral ulcer diseases from a multi-scale perspective but also may provide an efficient way for research and development of complex composition formula.

Highlights

  • Oral ulcer diseases are complex inflammatory diseases caused by multi-factors, which severely impact patient quality of life

  • Compound target-oral ulcers target network construction and analysis A total of 274 potential targets were obtained for sixteen active components

  • Kouyanqing Granule (KYQG) (4.7 g/kg/d) significantly inhibited the COX2, matrix metalloproteinase 9 (MMP9) and Tumor necrosis factor-alpha (TNF-α) (P < 0.01) levels in serum. These results suggest that the therapeutic effects of KYQG were related to the decreases of COX2, MMP9, and TNF-α, which are consistent with our network pharmacology study

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Summary

Introduction

Oral ulcer diseases are complex inflammatory diseases caused by multi-factors, which severely impact patient quality of life. Kouyanqing Granule (KYQG) has been used to treat inflammatory diseases of the mouth and throat, including recurrent aphthous stomatitis (RAS), traumatic ulcers, oral leukoplakia and so on. We aimed to explore the possible mechanisms in KYQG for the treatment of oral ulcers. Oral ulcers include conditions such as local trauma, recurrent aphthous stomatitis (RAS), viral and bacterial infections, allergic reactions, adverse drug reactions, or systemic disease [1, 2]. KYQG is recorded in the Chinese Pharmacopoeia 2015 edition to treat mouth and throat inflammatory diseases, such as RAS, oral leukoplakia, and oral lichen planus [5]. The active mechanisms by which KYQG contributing to therapeutic effects on oral ulcers remain poorly understood due to the large number of ingredients in this formulation

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