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Network pharmacology exploration reveals the bioactive compounds and molecular mechanisms of Li-Ru-Kang against hyperplasia of mammary gland

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Abstract

Li-Ru-Kang (LRK) has been commonly used in the treatment of hyperplasia of mammary gland (HMG) as a cipher prescription and achieved obvious therapeutic effects. However, the bioactive compounds and underlying pharmacological mechanisms remain unclear. This study aims to decipher the bioactive compounds and potential action mechanisms of LRK in the treatment of HMG using an integrated pharmacology approach. The ingredients of LRK and the corresponding drug targets were retrieved through drug target databases and were used to construct the “compound–target–disease” network and function–pathway network. Ultimately, 89 compounds and 2150 drug targets were collected. Gene ontology enrichment analysis revealed that mammary gland alveolus development and mammary gland lobule development were the key biological processes and were regulated simultaneously by three direct targets, including androgen receptor (AR), estrogen receptor (ER) and cyclin-D1. Moreover, 14 compounds of LRK were directly involved in the regulation of the three aforementioned targets. KEGG pathway enrichment analysis found that five signaling pathways and seven direct targets were closely related with HMG treatment by LRK. The results of animal experiments showed that LRK significantly improved the histopathological status of HMG in rats. Additionally, LRK markedly regulated the protein expressions of AR, cyclin-D1, MMP2, MMP3 and MMP9. But interestingly, the effect of LRK on ER was not obvious. This study demonstrated that LRK exerted its therapeutic efficacy based on multi-components, multi-targets and multi-pathways. This research confirms the advantages of network pharmacology analyses and the necessity for experimental verification.

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Funding

This work was financially supported by Project of the Project of Chinese Medicine Education Association (no. 2016SKT-M035), Chinese Medicine Education Association (no. 2016SKT-Z003) and Beijing Municipal Science & Technology Commission (no. Z171100001717013), and State Natural Science Foundation (no. 81573631).

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Authors and Affiliations

  1. Department of Pharmacy, the Fifth Medical Center of PLA General Hospital, 100 Western 4th Ring Road, Beijing, 100039, China

    Shizhang Wei, Xuelin Zhou, Haotian Li, Huadan Cai & Yanling Zhao

  2. China Military Institute of Chinese Medicine, the Fifth Medical Center of PLA General Hospital, Beijing, 100039, China

    Ming Niu, Xiaoyi Liu & Pengyan Li

  3. College of Pharmacy and Chemistry, Dali University, Dali, 671000, China

    Haizhu Zhang

  4. Department of Integrative Medical Center, the Fifth Medical Center of PLA General Hospital, Beijing, 100039, China

    Ruilin Wang

Authors
  1. Shizhang Wei
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  2. Xuelin Zhou
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  3. Ming Niu
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  4. Haizhu Zhang
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  5. Xiaoyi Liu
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  6. Ruilin Wang
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  7. Pengyan Li
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  8. Haotian Li
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  9. Huadan Cai
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  10. Yanling Zhao
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Correspondence to Yanling Zhao.

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Human/animal rights statement

This article does not contain any studies with human participants performed by any of the authors. All the above experimental operations were performed in accordance with the Guiding Principles for the Care and Use of Laboratory Animals of China. All animal studies were approved by the Ethical Committee of the fifth medical center of PLA general hospital.

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Communicated by S. Hohmann.

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Wei, S., Zhou, X., Niu, M. et al. Network pharmacology exploration reveals the bioactive compounds and molecular mechanisms of Li-Ru-Kang against hyperplasia of mammary gland. Mol Genet Genomics 294, 1159–1171 (2019). https://doi.org/10.1007/s00438-019-01569-5

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