Abstract
Background: Li-Ru-Kang (LRK) has been used in the treatment of hyperplasia of mammary glands (HMG) for several decades and can effectively improve clinical symptoms. This study aims to investigate the mechanism by which LRK intervenes in HMG based on an integrated approach that combines metabolomics and network pharmacology analyses.Methods: The effects of LRK on HMG induced by estrogen-progesterone in rats were evaluated by analyzing the morphological and pathological characteristics of breast tissues. Moreover, UPLC-QTOF/MS was performed to explore specific metabolites potentially affecting the pathological process of HMG and the effects of LRK. Pathway analysis was conducted with a combination of metabolomics and network pharmacology analyses to illustrate the pathways and network of LRK-treated HMG.Results: Li-Ru-Kang significantly improved the morphological and pathological characteristics of breast tissues. Metabolomics analyses showed that the therapeutic effect of LRK was mainly associated with the regulation of 10 metabolites, including prostaglandin E2, phosphatidylcholine, leukotriene B4, and phosphatidylserine. Pathway analysis indicated that the metabolites were related to arachidonic acid metabolism, glycerophospholipid metabolism and linoleic acid metabolism. Moreover, principal component analysis showed that the metabolites in the model group were clearly classified, whereas the metabolites in the LRK group were between those in the normal and model groups but closer to those in the normal group. This finding indicated that these metabolites may be responsible for the effects of LRK. The therapeutic effect of LRK on HMG was possibly related to the regulation of 10 specific metabolites. In addition, we further verified the expression of protein kinase C alpha (PKCα), a key target predicted by network pharmacology analysis, and showed that LRK could significantly improve the expression of PKCα.Conclusion: Our study successfully explained the modulatory properties of LRK treatment on HMG using metabolomics and network pharmacology analyses. This systematic method can provide methodological support for further understanding the complex mechanism underlying HMG and possible traditional Chinese medicine (TCM) active ingredients for the treatment of HMG.
Highlights
Hyperplasia of mammary glands is one of the most common breast diseases in middle-aged women and accounts for more than 70% of all breast disease (Chen et al, 2015)
hyperplasia of mammary glands (HMG) is classified in the “Rupi” category according to traditional Chinese medicine (TCM) theory (Fan et al, 2013)
By combining metabolomics and network pharmacology, we were able to gain a deeper understanding of the molecular mechanisms underlying TCM treatment
Summary
Hyperplasia of mammary glands is one of the most common breast diseases in middle-aged women and accounts for more than 70% of all breast disease (Chen et al, 2015). HMG is overlooked because of its clinical characteristics until the generation of mammary carcinoma. There is still not a sufficient understanding of the etiology of HMG, and pertinent therapeutic strategies are limited. Hormone or endocrine therapy is one of the most commonly used methods to mitigate the clinical symptoms of HMG. The side effects decrease the quality of life for patients who receive long-term treatment. Surgical treatment as a form of therapy is hardly accepted by most patients with recurring symptoms (Henry, 2014). Finding a more appropriate treatment with fewer side effects and more therapeutic advantages is the current goal standard for treating HMG. Li-Ru-Kang (LRK) has been used in the treatment of hyperplasia of mammary glands (HMG) for several decades and can effectively improve clinical symptoms. This study aims to investigate the mechanism by which LRK intervenes in HMG based on an integrated approach that combines metabolomics and network pharmacology analyses
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