Abstract

Objective To analyze the potential active ingredients and related crucial targets of the ShengDiHuang Decoction (SDHD) formula in the treatment of dysfunctional uterine bleeding (DUB) by using network pharmacology and verification experiment. Methods In this study, we determined the potential active ingredients from the traditional SDHD formula and their targets with the network pharmacology method. The network of “compound-disease-target” was constructed by the software of Cytoscape. Software of DAVID was used to enrich pathways for these 87 targets of SDHD. Further, the therapeutic effect of SDHD on DUB was verified by observing the morphological changes of the uterus and ovaries and determining the expression of ERS2 and progesterone in the plasma. Results 52 compounds of Rheum and 5 compounds of Rehmannia were selected, and 87 potential targets were screened by network pharmacology. Furthermore, 7 main active ingredients were acquired by the ADME process. In addition, enrichment analysis of drug-target networks indicated that SDHD may play a role in overall coordination through “multicomponent and multitarget” in different organ patterns by regulating multiple pathways directly or indirectly. Finally, in the verification experiment of SDHD on DUB, it was found that SDHD can effectively repair the uterus and ovaries and also have an upregulation effect on the target ESR2 and increase the content of progesterone. Conclusion Overall, this study revealed potential mechanisms of multitarget and multicomponent about SDHD in the treatment of DUB and provided a scientific foundation for further studying the mechanism.

Highlights

  • Dysfunctional uterine bleeding (DUB) is defined as a state of abnormal uterine bleeding [1], which is a symptom of a serious disorder of the menstrual cycle, menstrual period, and menstrual flow [2, 3]. e broad spectrum of causes of abnormal uterine bleeding includes both genital and extra genital lesions

  • A total of 65 constituent compounds of the 2 herbs contained in ShengDiHuang Decoction (SDHD) were collected, including 57 of Rheum and 8 of Rehmannia. 1085 proteins were predicted for Rheum ingredients, and 319 proteins of Rehmannia ingredients were fished. 415 related targets for dysfunctional uterine bleeding were collected

  • All these results suggested that multiple targets were associated with a variety of compounds in different herbs, which might exhibit synergistic effects or additive effects of SDHD in the treatment of dysfunctional uterine bleeding

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Summary

Objective

To analyze the potential active ingredients and related crucial targets of the ShengDiHuang Decoction (SDHD) formula in the treatment of dysfunctional uterine bleeding (DUB) by using network pharmacology and verification experiment. We determined the potential active ingredients from the traditional SDHD formula and their targets with the network pharmacology method. Software of DAVID was used to enrich pathways for these 87 targets of SDHD. Enrichment analysis of drug-target networks indicated that SDHD may play a role in overall coordination through “multicomponent and multitarget” in different organ patterns by regulating multiple pathways directly or indirectly. In the verification experiment of SDHD on DUB, it was found that SDHD can effectively repair the uterus and ovaries and have an upregulation effect on the target ESR2 and increase the content of progesterone. This study revealed potential mechanisms of multitarget and multicomponent about SDHD in the treatment of DUB and provided a scientific foundation for further studying the mechanism

Introduction
Materials and Methods
Network Construction
Conclusion
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