High-throughput metabolomics used to identify potential therapeutic targets of Guizhi Fuling Wan against endometriosis of cold coagulation and blood stasis

Wu, Xiuhong; Zhao, Chuang; Zhang, Aihua; Zhang, Jinqi; Wang, Xu; Xiaolan, Sun; Ze, Sun; Wang, Xijun

doi:10.1039/c8ra00978c

Cited by 21 publications

(10 citation statements)

References 45 publications

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“…This manifests that the CNS is inhibited when KYDS occurs, YGP; however, can regulate and reinforce the development of the CNS by affecting the production of creatine and glycine amidinotransferase. Phenylalanine, a metabolite used in the synthesis of important neurotransmitters and hormones, such as dopamine, epinephrine, and norepinephrine, showed a significant decrease in the MOD group and a significant increase in the YGP group, which also confirmed this conclusion [45].…”

Section: Discussionmentioning

confidence: 63%

“…The biological derivative compound of fatty acids (e.g., acetylcarnitine) may be closely related to KYDS, because it possesses a neuroprotective role on ischemic brain damage and can improve the neurological symptoms, reduce the free radical-mediated protein oxidation, and restore the brain energy metabolites [12,59,60]. Tryptophan, an essential amino acid of protein biosynthesis, is primarily involved in two metabolic pathways: The kynurenine pathways and serotonin (5-HT) formation, which affects the function of neurotransmitters, neural circuits, and neuromodulator in the body [19,45]. It was evident that tryptophan decreased in the MOD group and increased in the YGP group.…”

Section: Discussionmentioning

confidence: 99%

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Integrated Systems Pharmacology, Urinary Metabonomics, and Quantitative Real-Time PCR Analysis to Uncover Targets and Metabolic Pathways of the You-Gui Pill in Treating Kidney-Yang Deficiency Syndrome

Chen

Wang

Zhan

et al. 2019

IJMS

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Kidney-yang deficiency syndrome (KYDS) is a metabolic disease caused by a neuro-endocrine disorder. The You-gui pill (YGP) is a classic traditional Chinese medicine (TCM) formula for the treatment of KYDS and has been widely used to warm and recuperate KYDS clinically for hundreds of years in China. However, it is unknown whetherthe corresponding targets and metabolic pathways can also be found via using metabonomics based on one platform (e.g., 1H NMR) to study different biological samples of KYDS. At the same time, relevant reports on further molecular verification (e.g., RT-qPCR analysis) of these targets associated with biomarkers and metabolic pathways have not yet, to our knowledge, been seen in KYDS’s research. In the present study, a comprehensive strategy integrating systems pharmacology and 1H NMR-based urinary metabonomics analysis was proposed to identify the target proteins and metabolic pathways that YGP acts on KYDS. Thereafter, further validation of target proteins in kidney tissue was performed through quantitative real-time PCR analysis (RT-qPCR). Furthermore, biochemical parameters and histopathological analysis were studied. As a result, seven target proteins (L-serine dehydratase; phosphoenolpyruvate carboxykinase; spermidine synthase; tyrosyl-tRNA synthetase, glutamine synthetase; 3-hydroxyacyl-CoA dehydrogenase; glycine amidinotransferase) in YGP were discovered to play a therapeutic role in KYDS via affecting eight metabolic pathways (glycine, serine and threonine metabolism; butanoate metabolism; TCA cycle, etc.). Importantly, three target proteins (i.e., 3-hydroxyacyl-CoA dehydrogenase; glutamine synthetase; and glycine amidinotransferase) and two metabolic pathways (butanoate metabolism and dicarboxylate metabolism) related to KYDS, to our knowledge, had been newly discovered in our study. The mechanism of action mainly involved energy metabolism, oxidative stress, ammonia metabolism, amino acid metabolism, and fatty acid metabolism. In short, our study demonstrated that targets and metabolic pathways for the treatment of KYDS by YGP can be effectively found via combining with systems pharmacology and urinary metabonomics. In addition to this, common and specific targets and metabolic pathways of KYDS treated by YGP can be found effectively by integration with the analysis of different biological samples (e.g., serum, urine, feces, and tissue). It is; therefore, important that this laid the foundation for deeper mechanism research and drug-targeted therapy of KYDS in future.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Integrated Systems Pharmacology, Urinary Metabonomics, and Quantitative Real-Time PCR Analysis to Uncover Targets and Metabolic Pathways of the You-Gui Pill in Treating Kidney-Yang Deficiency Syndrome

Chen

Wang

Zhan

et al. 2019

IJMS

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“…Metabolomics is a newly developed discipline that mainly studies small molecular metabolites (MW < 1000) as substrates and products of various metabolic pathways, it is a branch of system biology based on group index analysis, high-throughput detection and data processing, and aiming at information modeling and system integration (Wu et al, 2018). Metabolomics plays an important role in exploring metabolic disorder metabolism-related diseases (Zhang et al, 2013b, 2014b,c,d, 2018a; Wang et al, 2014; Liu et al, 2018; Sun et al, 2018), biomarkers identification (Wang et al, 2015a; Zhang et al, 2015b,c; Zhao et al, 2016; Song et al, 2017; Ren et al, 2018) and response to treatment (Wu et al, 2011; Dong et al, 2012; Sun et al, 2013; Wang et al, 2013a, 2016; Zhang et al, 2013a, 2018b).…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Metabolomics Evaluate the Efficacy of Total Lignans From Acanthophanax Senticosus Stem Against Ovariectomized Osteoporosis Rat

Zhang

Sun

et al. 2019

Front. Pharmacol.

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Postmenopausal osteoporosis (PMOP) is a common clinical illness in postmenopausal women, but there is no effective drug at present. Metabolomics approach was used to explore the potential biomarkers of PMOP and evaluate the efficacy and therapeutic targets of total lignans in the stem of Acanthophanax senticosus (ASSL) on the ovariectomized osteoporosis model rats. UPLC/MS and pattern recognition methods were used for serum metabolites discovery to illustrate the pathological mechanism of PMOP model rats, and then revealing the intervention effect of ASSL. The pattern recognition result showed that serum metabolic profiles of the sham operation group and the model group were clustered clearly, and 16 potential biomarkers were finally identified (7 in positive ion mode and 9 in negative ion mode), and they are involved in 15 related metabolic pathways. After oral administration of ASSL, 10 biomarkers were found to be significantly up-regulated and mainly regulated metabolic pathways include unsaturated fatty acid biosynthesis, linoleic acid metabolism, and arachidonic acid metabolism, primary bile acid synthesis, tyrosine metabolism, etc. Our study demonstrated that the ASSL could affect the endogenous metabolites related metabolic mechanism, provides a pharmacological basis of the ASSL for PMOP treatment.

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“…The pathogenesis of blood stasis was thought to be related to inflammatory factors and immune response in recent studies [57, 58]. Arachidonic acid and its metabolites (eicosanoids) could promote the production of proinflammatory cytokines and inflammatory response [59].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effect and Mechanism Study of Rhodiola wallichiana var. cholaensis Injection to Acute Blood Stasis Using Metabolomics Based on UPLC-Q/TOF-MS

Ran

Pang

Guan

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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In traditional Chinese medicine theory, blood stasis syndrome (BSS), characterized by blood flow retardation and blood stagnation, is one of the main pathologic mechanisms and clinical syndromes of cardiovascular diseases (CVDs). Rhodiola wallichiana var. cholaensis injection (RWCI) is made from dry roots and stems of RWC via the processes of decoction, alcohol precipitation, filtration, and dilution. Studies indicated the extracts of RWC could alleviate CVDs; however, the mechanism had not been illustrated. In the present study, the acute blood stasis rat model was established to investigate the pathogenesis of BSS and the therapeutic mechanism of RWCI against BSS. Hemorheological parameters (whole blood viscosity and plasma viscosity) and inflammatory factors (TNF-α and IL-6) were used to evaluate the success of the BSS rat model and RWCI efficacy. 14 and 33 differential metabolites were identified from plasma and urine samples using the metabolomics approach based on ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The results of multivariate analysis displayed that there were significant separations among model, control, and treatment groups, but the high-dose RWCI treatment group was closer to the control group. 9 perturbed metabolic pathways were related to BSS's development and RWCI intervention. 5 metabolic pathways (arachidonic acid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, retinol metabolism, and steroid hormone biosynthesis) showed apparent correlations. These differential metabolites and perturbed metabolic pathways might provide a novel view to understand the pathogenesis of BSS and the pharmacological mechanism of RWCI.

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High-throughput metabolomics used to identify potential therapeutic targets of Guizhi Fuling Wan against endometriosis of cold coagulation and blood stasis

Abstract: Metabolomics is an emerging and robust discipline and involves the comprehensive evaluation of small molecule endogenous metabolites and enables the exploration of the pathogenesis of diseases.

Cited by 21 publications

References 45 publications

Integrated Systems Pharmacology, Urinary Metabonomics, and Quantitative Real-Time PCR Analysis to Uncover Targets and Metabolic Pathways of the You-Gui Pill in Treating Kidney-Yang Deficiency Syndrome

Integrated Systems Pharmacology, Urinary Metabonomics, and Quantitative Real-Time PCR Analysis to Uncover Targets and Metabolic Pathways of the You-Gui Pill in Treating Kidney-Yang Deficiency Syndrome

High-Throughput Metabolomics Evaluate the Efficacy of Total Lignans From Acanthophanax Senticosus Stem Against Ovariectomized Osteoporosis Rat

Therapeutic Effect and Mechanism Study of Rhodiola wallichiana var. cholaensis Injection to Acute Blood Stasis Using Metabolomics Based on UPLC-Q/TOF-MS

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