High-throughput metabolomics reveals the perturbed metabolic pathways and biomarkers of Yang Huang syndrome as potential targets for evaluating the therapeutic effects and mechanism of geniposide
Authors: Jingbo Yu
Aihua Zhang
Heng Fang
Xiaohang Zhou
Qi Song
Xijun Wang
Journal: Frontiers of medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: liquid chromatography-mass spectrometry; metabolic pathways; metabolites; metabolomics.
Affiliations: Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, National Chinmedomics Research Center, Harbin, 150040, China., Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, National Chinmedomics Research Center, Harbin, 150040, China. ., State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, 519020, China. .

Abstract:  High-throughput metabolomics can clarify the underlying molecular mechanism of diseases via the qualitative and quantitative analysis of metabolites. This study used the established Yang Huang syndrome (YHS) mouse model to evaluate the efficacy of geniposide (GEN). Urine metabolic data were quantified by ultraperformance liquid chromatography-tandem mass spectrometry. The non-target screening of the massive biological information dataset was performed, and a total of 33 metabolites, including tyramine glucuronide, aurine, and L-cysteine, were identified relating to YHS. These differential metabolites directly participated in the disturbance of phase I reaction and hydrophilic transformation of bilirubin. Interestingly, they were completely reversed by GEN. While, as the auxiliary technical means, we also focused on the molecular prediction and docking results in network pharmacological and integrated analysis part. We used integrated analysis to communicate the multiple results of metabolomics and network pharmacology. This study is the first to report that GEN indirectly regulates the metabolite "tyramine glucuronide" through its direct effect on the target heme oxygenase 1 in vivo. Meanwhile, heme oxygenase-1, a prediction of network pharmacology, was the confirmed metabolic enzyme of phase I reaction in hepatocytes. Our study indicated that the combination of high-throughput metabolomics and network pharmacology is a robust combination for deciphering the pathogenesis of the traditional Chinese medicine (TCM) syndrome. 

Retracted: No

PubPeer comments:
 The authors describe a mouse model of Yang Huang Syndrome (YHS), which appears to be a rebranding of the existing u03b1-naphthylisothiocyanate-poisoning mouse model of biliary injury and hepatic fibrosis (with the rationale that jaundice is a late rediscovery of Yang Huang symptoms). They describe this as  the established Yang Huang syndrome (YHS) mouse model , where  established here means  mentioned only in the same authors previous paper , [Liu et al (2018)] . Here they compare a group of YHS-model mice (poisoned with ANIT) against a group of **unpoisoned** mice dosed with geniposide *instead*, to see how geniposide cures YHS. ![file] Am I missing something? ,