Luo Keke, Zhao Haiyu, Bian Baolin, Wei Xiaolu, Si Nan, Brantner Adelheid, Fan Xiaorui, Gu Xinru, Zhou Yanyan, Wang Hongjie
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria.
Front Pharmacol. 2021 Apr 30;12:616318. doi: 10.3389/fphar.2021.616318. eCollection 2021.
"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 ( < 0.001); tumor necrosis factor-alpha, adenosine triphosphate, citric acid ( < 0.01); interleukin-8 (IL-8), 4-hydroxynonenal, pyruvic acid, lactate dehydrogenase ( < 0.05). The levels of glucocorticoid, adrenocorticotropic hormone ( < 0.01); lactic acid, IL-4, IL-10 ( < 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".
“上火”是由内生火热过盛引起的，目前尚无全面系统的中医理论。在之前的研究中，我们评估了黄连解毒汤（颗粒）对“上火”患者的治疗效果，然而，具体机制尚不清楚，有待进一步探索。为解释其干预机制，我们选取57例由“上火”引起口腔疾病的患者和20名健康志愿者，分为口腔疾病组、黄连解毒汤干预组和健康对照组。首先，检测黄连解毒汤干预前后的生化指标，如炎症因子、氧化应激因子和能量代谢因子。结果显示，黄连解毒汤可显著降低琥珀酸（<0.001）、肿瘤坏死因子-α、三磷酸腺苷、柠檬酸（<0.01）、白细胞介素-8（IL-8）、4-羟基壬烯醛、丙酮酸、乳酸脱氢酶（<0.05）的指标水平。黄连解毒汤干预后，糖皮质激素、促肾上腺皮质激素（<0.01）、乳酸、IL-4、IL-10（<0.05）的水平显著升高。此外，我们采用多组学分析方法来研究潜在的生物标志物。非靶向代谢组学表明，黄连解毒汤干预后7种差异代谢物的水平接近健康对照组，通过代谢途径分析，这些代谢物与组氨酸代谢、β-丙氨酸代谢和鞘脂代谢相关。靶向脂质组学结果和受试者工作特征曲线分析表明，三组中鉴定出13种差异脂质，主要集中在溶血磷脂酰胆碱、溶血磷脂酰乙醇胺。最后，这些差异生物标志物的网络关联揭示了三磷酸腺苷和三羧酸循环的调节在黄连解毒汤治疗“上火”的作用机制中起重要作用。该研究为进一步揭示其机制和寻找与“上火”相关的临床生物标志物奠定了基础。
