Revealing the mechanisms and the material basis of Rubia cordifolia L. on abnormal uterine bleeding with uniting simultaneous determination of four components and systematic pharmacology approach-experimental validation

Kan Wang; Lan Gao; Qiao Zhang; Yi Zhang; Weifeng Yao; Min Zhang; Yuping Tang; Anwei Ding; Li Zhang

doi:10.1016/j.jpba.2020.113475

Revealing the mechanisms and the material basis of Rubia cordifolia L. on abnormal uterine bleeding with uniting simultaneous determination of four components and systematic pharmacology approach-experimental validation

J Pharm Biomed Anal. 2020 Sep 10:189:113475. doi: 10.1016/j.jpba.2020.113475. Epub 2020 Jul 15.

Authors

Kan Wang¹, Lan Gao², Qiao Zhang¹, Yi Zhang¹, Weifeng Yao¹, Min Zhang¹, Yuping Tang³, Anwei Ding¹, Li Zhang⁴

Affiliations

¹ Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
² Nanjing Jiangning Hospital of Chinese Medicine, Teaching Hospital of Nanjing University of Chinese Medicine, Nanjing, 211100, China.
³ Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China.
⁴ Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: zhangli@njucm.edu.cn.

PMID: 32688212
DOI: 10.1016/j.jpba.2020.113475

Abstract

The roots of Rubia cordifolia L. (RCL) have become an important medicine for abnormal uterine bleeding (AUB) and hemorrhage syndrome in Traditional Asian medicine. However, the underlying mechanism and the material basis of RCL for treating AUB has not been fully elucidated. In this study, quantitative evaluation of quinones, systematic pharmacology and experimental verification were adopted. Firstly, the Disease-Ingredient-Target network was established by Cytoscape, which was consistent with 23 compounds and 47 target genes. The hub targets were discovered by Maximal Clique Centrality (MCC) method with Cytohubba plugins of Cytoscape, and top 20 nodes were ranked by MCC. It was assumed that mollugin is the main ingredient of RCL for treating AUB. Pathways on which RCL acted were obtained from observation of its biological functions, KEGG pathways and Reactome pathway enrichment analysis. The possible mechanism of RCL for treating AUB was revealed for improvment of the blood clotting system, blood circulation, arachidonic acid metabolism and inflammation. Then, a novel method for evaluating the quality of RCL was established, and the content of mollugin in RCL was the higher than others. Finally, pharmacologic experiments confirmed that RCL could improve the inflammation by inhibiting the activity of COX-2 and cPLA₂ enzyme, ameliorate blood hypercoagulability by affecting coagulation cascade and fibrinolytic system. It was found that RCL inhibited the expression COX-2 and PAI-1 by reducing HIF-1α expression. The trend of each index of mollugin was consistent with that of RCL, indicating that it played an important role in RCL for treating AUB. The above results could provide a novel method for the quality evaluation of RCL and was expected to give us more important information regarding the use of RCL as a promising drug candidate for AUB, offering a fertility preserving medical, non-hormonal treatment choose for women with AUB.

Keywords: Abnormal uterine bleeding; Mollugin; Rubia cordifolia L.; Systematic pharmacology.

MeSH terms

Female
Humans
Medicine, East Asian Traditional*
Rubia*
Uterine Hemorrhage