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. 2019 Jul 24;9(1):10713.
doi: 10.1038/s41598-019-47300-7.

Precise and systematic survey of the efficacy of multicomponent drugs against functional dyspepsia

Junying Wei  1 , Qiong Man  2 , Feifei Guo  3 , Minghua Xian  3 , Tingting Wang  3 , Chunyu Tang  4 , Yi Zhang  3 , Defeng Li  3 , Daifeng Tang  4 , Hongjun Yang  5 , Luqi Huang  6
Affiliations

Precise and systematic survey of the efficacy of multicomponent drugs against functional dyspepsia

Junying Wei et al. Sci Rep. .

Abstract

Functional dyspepsia (FD) is one of the most prevalent functional gastrointestinal disorders, and more and more multicomponent drugs represented by traditional Chinese medicines have provided a favorable therapeutic effect in its treatment. However, their precise localization in the clinic, as well as corresponding mechanism, is ambiguous, thus hindering their widespread use. To meet this requirement, a precise and systematic approach based on a restriction of special disease-related molecules and the following network pharmacology analysis was developed and applied to a multicomponent conventional drug, XiaoErFuPi (XEFP) granules. Experimental verification of the results indicates that this approach can facilitate the prediction, and the precise and systematic efficacy of XEFP could be easily revealed, which shows that XEFP has an advantage over the positive control drug on lactate, gastrin, interleukin 4 and calcitonin gene-related peptide. Moreover, by the proteomics analysis, its superposition of multi-_target effects was revealed and a new candidate _target for the treatment of FD, striatin, was obtained and verified. This study provides a practicable precise approach for the investigation of the efficacy of multicomponent drugs against FD and offers a promising alternative for the systematical management of FD.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Network pharmacology prediction result of the efficacy of XiaoErFuPi (XEFP) granules.
Figure 2
Figure 2
Effects of XEFP on the blood levels of amylase (AMS), lactate, gastrin and nitric oxide synthase (NOS) in FD rats. XEFP-H, high-dosage XEFP. XEFP-M, medium-dosage XEFP. XEFP-L, low-dosage XEFP.
Figure 3
Figure 3
Effects of XEFP on the blood levels of calcitonin gene-related peptide (CGRP), somatostatin (SS), vasoactive intestinal polypeptide (VIP), interferon-γ (IFN-γ) and interleukin 4 (IL-4) levels in FD rats. XEFP-H, high-dosage XEFP. XEFP-M, medium-dosage XEFP. XEFP-L, low-dosage XEFP.
Figure 4
Figure 4
Network of interactions among the chemical components of XEFP, predicted and identified protein _targets, and effector molecules regulated by XEFP against FD. (A) Effector molecule: amylase (B) effector molecule: motilin (C) effector molecule: CGRP.
Figure 5
Figure 5
Network of interactions among the chemical components of XEFP, effector molecules regulated by XEFP against FD, potential protein _targets, and related pathways in which these genes are involved.
Figure 6
Figure 6
Proteomic investigation of the dynamic changes of proteins in FD and XEFP-treated rats, and discovery and verification of a new candidate _target for the treatment of FD. (A) Volcano plot of dynamic changes of proteins in FD rats (model). (B) Biological process or molecular function of the proteins in model group with upregulated expression levels (p < 0.05) compared to the control. (C). Volcano plot of dynamic changes of proteins in FD rats after XEFP treatment. (D) Biological process or molecular function of the proteins of XEFP-treated FD rats with downregulated expression levels (p < 0.05) compared to model. (E) Proteomic quantitative analysis of the candidate _target regulated by XEFP against FD in rats. (F) Western-blot verification of the new candidate _target (striatin, STRN) for the treatment of FD. Blots were cropped from the same gel, but with different exposures (first striatin, then β-actin), and their full-length gels and blots are included in the Supporting Information file. XEFP-H, high-dosage XEFP. XEFP-M, medium-dosage XEFP. XEFP-L, low-dosage XEFP.
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