An integrated metabolomics strategy to reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats

Chen, Jiaqian; Chen, Yanyan; Tao, Hui-Juan; Pu, Zong-Jin; Shi, Xu-Qin; Zhang, Jing; Tan, Yunlong; Yue, Shi‐Jun; Zhou, Guisheng; Shang, Erxin; Tang, Yuping; Duan, Jin‐Ao

doi:10.1016/j.jpba.2019.112837

Cited by 26 publications

(16 citation statements)

References 20 publications

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“…16,17 Metabolomics is an important analysis method for studying the therapeutic effect and toxicity of drug. [18][19][20] Therefore, nontargeted metabolomics technology in the study is used to analyze the changes in endogenous metabolic markers after rhubarbinduced liver injury. Network pharmacology is a discipline that explains the process of disease development based on the principles of systems biology, and it uses the overall view of network databases to study the interaction between drugs and the body.…”

Section: Introductionmentioning

confidence: 99%

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology

Li¹,

Wang²,

Li³

et al. 2021

DDDT

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Background Rhubarb, as a traditional Chinese medicine, is the preferred drug for the treatment of stagnation and constipation in clinical practice. It has been reported that rhubarb possesses hepatotoxicity, but its mechanism in vivo is still unclear. Methods In this study, the chemical components in rhubarb were identified based on UPLC-Q-TOF/MS combined with data postprocessing technology. The metabolic biomarkers obtained through metabolomics technology were related to rhubarb-induced hepatotoxicity. Furthermore, the potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology involving the above components and metabolites. Meanwhile, GO gene enrichment analysis and KEGG pathway analysis were performed on the common targets. Results Twenty-eight components in rhubarb were identified based on UPLC-Q-TOF/MS, and 242 targets related to rhubarb ingredients were predicted. Nine metabolic biomarkers obtained through metabolomics technology were closely related to rhubarb-induced hepatotoxicity, and 282 targets of metabolites were predicted. Among them, the levels of 4 metabolites, namely dynorphin B (10–13), cervonoyl ethanolamide, lysoPE (18:2), and 3-hydroxyphenyl 2-hydroxybenzoate, significantly increased, while the levels of 5 metabolites, namely dopamine, biopterin, choline, coenzyme Q9 and P1, P4-bis (5ʹ-uridyl) tetraphosphate significantly decreased. In addition, 166 potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology. The KEGG pathway analysis was performed on the common targets to obtain 46 associated signaling pathways. Conclusion These data suggested that rhubarb may cause liver toxicity due to its action on dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), phosphodiesterase 4B (PDE4B), vanilloid receptor (TRPV1); transient receptor potential cation channel subfamily M member 8 (TRPM8), prostanoid EP2 receptor (PTGER2), acetylcholinesterase (ACHE), muscarinic acetylcholine receptor M3 (CHRM3) through the cAMP signaling pathway, cholinergic synapses, and inflammatory mediators to regulate TRP channels. Metabolomics technology and network pharmacology were integrated to explore rhubarb hepatotoxicity to promote the reasonable clinical application of rhubarb.

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Section: Introductionmentioning

confidence: 99%

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology

Li¹,

Wang²,

Li³

et al. 2021

DDDT

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“…So far, it is unclear how these pathways interacted with CPC. Recently, the study identified the arachidonic acid metabolism as biomarkers for constipation rats [ 19 ]. Researchers also found arachidonic acid metabolites were induced during chronic intestinal inflammation [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Acupoint Massage Therapy Alters the Composition of Gut Microbiome in Functional Constipation Patients

Chen

Tan

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Objective and Background. Constipation is under high incidence globally. Current drug treatment on constipation, especially chronic functional constipation (CFC), lacks of efficiency and has an adverse reaction. Acupoint Massage Therapy (AMT) is traditionally applied to CFC with a good success rate and without unfavorable reaction in China. The underline mechanism of AMT remains unclear. Recent studies revealed that gut microbiome is involved in constipation development and treatment. Our aim is to evaluate the composition of gut microbiome of CFC patients after AMT. Patients and Methods. 104 CFC patients were enrolled in the study, including 49 males and 55 females. We investigated the gut microbiome of CFC patients after AMT through 16SrDNA sequencing. Results. Results showed the overall structure of gut microbiome has no significant difference between experimental and control groups. In the genus level, the abundance of Pseudobutyrivibrio and Ruminiclostridium is higher in the experiment group than in the control, whereas that of Fusicatenibacter is less. The 16S KEGG function prediction suggested that Parkinson disease, retinol metabolism, and arachidonic acid metabolism could explain the biological function of different gut microbiome. Furthermore, cytokines in the serum showed a correlation with the abundance of Pseudobutyrivibrio in CFC. Conclusion. AMT could change the composition of gut microbiome which is associated with cytokines in CFC patients.

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“…We optimized the gradient elution program: 0 ~ 2 min, 3 ~ 10% B; 2 ~ 5 min, 10 ~ 15% B; 5 ~ 8 min, 15% B; 8 ~ 11 min, 15 ~ 23% B; 11 ~ 16 min, 23 ~ 30% B; 16 ~ 20 min, 30 ~ 60% B; 20 ~ 24 min, 60 ~ 80% B; 24 ~ 25 min, 80 ~ 3% B. Remaining device parameters were the same as we described previously [ 34 ]. At the beginning of the analytical batch, QC sample was continuously injected 5 times to balance the system.…”

Section: Methodsmentioning

confidence: 99%

Fuzzy identification of bioactive components for different efficacies of rhubarb by the back propagation neural network association analysis of UPLC-Q-TOF/MSE and integrated effects

Chen

et al. 2022

Chin Med

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Background Rhei Radix et Rhizoma (rhubarb), as one of the typical representatives of multi-effect traditional Chinese medicines (TCMs), has been utilized in the treatment of various diseases due to its multicomponent nature. However, there are few systematic investigations for the corresponding effect of individual components in rhubarb. Hence, we aimed to develop a novel strategy to fuzzily identify bioactive components for different efficacies of rhubarb by the back propagation (BP) neural network association analysis of ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry for every data (UPLC-Q-TOF/MSE) and integrated effects. Methods Through applying the fuzzy chemical identification, most components of rhubarb were classified into different chemical groups. Meanwhile the integration effect values of different efficacies can be determined by animal experiment evaluation and multi-attribute comprehensive indexes. Then the BP neural network was employed for association analysis of components and different efficacies by correlating the component contents determined from UPLC-Q-TOF/MSE profiling and the integration effect values. Finally, the effect contribution of one type of components may be totaled to demonstrate the universal and individual characters for different efficacies of rhubarb. Results It suggested that combined anthraquinones, flavanols and their polymers may be the universal character to the multi-functional properties of rhubarb. Other components contributed to the individuality of rhubarb efficacies, including stilbene glycosides, anthranones and their dimers, free anthraquinones, chromones, gallic acid and gallotannins, butyrylbenzenes and their glycosides. Conclusions Our findings demonstrated that the bioactive components for different efficacies of rhubarb were not exactly the same and can be systematically differentiated by the network-oriented strategy. These efforts will advance our knowledge and understanding of the bioactive components in rhubarb and provide scientific evidence to support the expansion of its use in clinical applications and the further development of some products based on this medicinal herb.

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An integrated metabolomics strategy to reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats

Cited by 26 publications

References 20 publications

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology

Acupoint Massage Therapy Alters the Composition of Gut Microbiome in Functional Constipation Patients

Fuzzy identification of bioactive components for different efficacies of rhubarb by the back propagation neural network association analysis of UPLC-Q-TOF/MSE and integrated effects

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