Abstract
“Shanghuo” (“excessive internal heat”) is caused by exuberant endogenous fire, which does not have a comprehensive and systematic traditional Chinese medicine theory. In previous study, we had evaluated the therapeutic effect of Huanglian Jiedu Decoction (HLJDD) (granule) on patients with “Shanghuo”, however, the specific mechanism was not clear, which need further exploration. To explain its intervention mechanism, we select 57 patients with oral diseases caused by “Shanghuo” and 20 health volunteers to divide into oral disease group, HLJDD intervention group and healthy control group. Firstly, biochemical indicators before and after HLJDD intervention are detected, such as inflammatory factors, oxidative stress factors and energy metabolism factors. The results exhibit that HLJDD significantly decreases indicators succinic acid (p < 0.001); tumor necrosis factor-alpha, adenosine triphosphate, citric acid (p < 0.01); interleukin-8 (IL-8), 4-hydroxynonenal, pyruvic acid, lactate dehydrogenase (p < 0.05). The levels of glucocorticoid, adrenocorticotropic hormone (p < 0.01); lactic acid, IL-4, IL-10 (p < 0.05) significantly increase after HLJDD intervention. In addition, we adopt multi-omics analysis approach to investigate the potential biomarkers. Nontargeted metabolomics demonstrate that the levels of 7 differential metabolites approach that in the healthy control group after HLJDD intervention, which are correlated with histidine metabolism, beta-alanine metabolism and sphingolipid metabolism through metabolic pathway analysis. Targeted lipidomics results and receiver operating characteristic curve analysis show that 13 differential lipids are identified in the three groups mainly focuse on lysophosphatidylcholines, lysophosphatidylethanolamines. Finally, the network associations of those differential biomarkers reveal the regulation of adenosine triphosphate and tricarboxylic acid cycle play essential role in the therapeutic effect mechanism of HLJDD in “Shanghuo”. The study has laid the foundation for further revealing the mechanism and finding clinical biomarkers related to “Shanghuo”.
Highlights
Some studies have emphasized the importance of traditional Chinese medicine (TCM) treatment of “Shanghuo” in maintaining normal physiological functions, such as immunity, lipid metabolism and reactive oxygen species (ROS) clearance (Pan et al, 2020)
Our research focus on the influence of Huanglian Jiedu Decoction (HLJDD) on inflammation, oxidative stress factors and energy metabolism aspects in “Shanghuo”, and explore its intervention in other endogenous components through nontargeted and targeted lipid metabonomics analysis to find the differential metabolites in HLJDD to interfere with “Shanghuo”, and to lay the foundation for finding biomarkers in the future
High Resolution-mass spectrum (MS)/MS technology was used comprehensively for nontargeted metabolomics and target lipidomics to elucidate the potential biomarkers closely related to the essence of “Shanghuo” and the treatment mechanism of HLJDD from the perspectives of the healthy control group, oral disease group and HLJDD intervention group
Summary
Some studies have emphasized the importance of TCM treatment of “Shanghuo” in maintaining normal physiological functions, such as immunity, lipid metabolism and reactive oxygen species (ROS) clearance (Pan et al, 2020). Combined with the research on the original form of HLJDD and its metabolites in rat plasma (Zuo et al, 2014), these results clarified the possible material basis of the in vivo effects exerted by HLJDD and provided basic chemical information for our study. Scholars evaluated the effects of HLJDD by simulating rat “Shanghuo” gingivitis, and the results showed that HLJDD inhibited energy metabolism and oxidative stress through tuberous sclerosis complex signaling pathway and glycolysisrelated molecules (Zhang et al, 2017). The occurrence of “Shanghuo” is closely related to inflammatory immunity, oxidative stress, energy metabolism and their interactions. We investigated the intervention mechanism and potential biomarkers of HLJDD (granule) in the treatment of “Shanghuo”. Our study provides a new experimental basis to understand the treatment mechanism of HLJDD in “Shanghuo” and proposes potential biomarkers and metabolic pathways for “Shanghuo” diagnosis. This study might lay the foundation for further understanding the pathogenesis of “Shanghuo” and the intervention mechanism of HLJDD in “Shanghuo”
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