Abstract
Oral ulcers are the most prevalent oral mucosal diseases globally, and no specific treatment schemes are currently available due to the complexity of oral ulcer diseases. Sleep deprivation increases the risk of a deterioration in oral health. Kouyanqing Granule (KYQG) has been used for decades in China to treat inflammatory diseases of the mouth and throat associated with the hyperactivity of fire due to yin deficiency syndrome. However, the mechanisms underlying the effects of KYQG in the treatment of oral ulcers are still unclear. The aims of this study were to investigate whether KYQG treatment could attenuate the symptoms of oral ulcers worsened by sleep deprivation and identify the involved metabolic pathways. First, we conducted chemical profiling of KYQG via UPLC–MS analysis. We then combined pharmacological and metabolomics approaches in a phenol-induced rat model of oral ulcers worsened by sleep deprivation. A total of 79 compounds were initially identified. Our observations showed that KYQG treatment induced a significantly higher healing rate in oral ulcers worsened by sleep deprivation. KYQG significantly reduced the levels of 5-HT and GABA in serum, and only decreased the 5-HT level in brain tissue after phenol injury followed by sleep deprivation. Moreover, KYQG administration significantly suppressed systemic inflammation by inhibiting TNF-α, IL-1β, IL-6, IL-18, and MCP-1. Immunohistochemical analysis further revealed that KYQG inhibited IL-6 expression in buccal mucosa tissues. KYQG treatment also significantly decreased the serum levels of ACTH, CORT, IgM, and 8-OHdG. Serum metabolomics analysis showed that a total of 30 metabolites showed significant differential abundances under KYQG intervention, while metabolic pathway analysis suggested that the altered metabolites were associated with the dysregulation of eight metabolic pathways. Taken together, our results indicated that KYQG attenuates the symptoms of oral ulcers worsened by sleep deprivation probably through the regulation of the neuroimmunoendocrine system, oxidative stress levels, and tryptophan metabolism. This study also provides a novel approach for addressing the increased health risks resulting from sleep deficiency using an herbal medicine formula.
Highlights
Oral ulcers are among the most painful and common mucosal diseases
The total ion chromatograms of KYQG in the positive and negative modes are shown in Supplementary Figure S1
We have combined data obtained by different experimental methods, and explored the associations between oral ulcer progression, metabolomics, inflammation, oxidative stress, neurotransmitter levels, and HPA activity in a rat model of oral ulcers
Summary
Oral ulcers are among the most painful and common mucosal diseases. These conditions have uncertain and complex etiology, including mechanical injuries, immunologic dysregulation, genetic predisposition, hormonal level fluctuations, systemic diseases, microelement deficiencies, nutritional imbalances, microbial infections, allergic factors, adverse drug reactions, and psychological stress (Scully and Shotts, 2000; Guimaraes et al, 2007; Akintoye and Greenberg, 2014). Oral ulcers usually expose nerve endings in the underlying lamina propria and can severely affect patients’ quality of life. Due to their complexity, no specific or ideal treatment approach is currently available for the treatment of these diseases
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