Wei Shizhang, Qian Liqi, Niu Ming, Liu Honghong, Yang Yuxue, Wang Yingying, Zhang Lu, Zhou Xuelin, Li Haotian, Wang Ruilin, Li Kun, Zhao Yanling
Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, China.
Department of Traditional Chinese Medicine, First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
Front Pharmacol. 2018 Jun 19;9:651. doi: 10.3389/fphar.2018.00651. eCollection 2018.
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. : 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. : 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 , , , and . 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. : 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.
乳汝康（LRK）已用于治疗乳腺增生（HMG）数十年，且能有效改善临床症状。本研究旨在基于代谢组学和网络药理学分析相结合的综合方法，探讨LRK干预HMG的机制。：通过分析乳腺组织的形态学和病理学特征，评估LRK对大鼠雌激素 - 孕酮诱导的HMG的影响。此外，采用超高效液相色谱 - 四极杆飞行时间质谱（UPLC - QTOF/MS）来探索可能影响HMG病理过程的特定代谢物以及LRK的作用。结合代谢组学和网络药理学分析进行通路分析，以阐明LRK治疗HMG的通路和网络。：乳汝康显著改善了乳腺组织的形态学和病理学特征。代谢组学分析表明，LRK的治疗作用主要与10种代谢物的调节有关，包括 ， ， ，和 。通路分析表明，这些代谢物与花生四烯酸代谢、甘油磷脂代谢和亚油酸代谢有关。此外，主成分分析表明，模型组中的代谢物明显聚类，而LRK组中的代谢物介于正常组和模型组之间，但更接近正常组。这一发现表明这些代谢物可能是LRK发挥作用的原因。LRK对HMG的治疗作用可能与10种特定代谢物的调节有关。此外，我们进一步验证了网络药理学分析预测的关键靶点蛋白激酶Cα（PKCα）的表达，并表明LRK可显著提高PKCα的表达。：我们的研究成功地利用代谢组学和网络药理学分析解释了LRK治疗对HMG的调节特性。这种系统方法可为进一步理解HMG的复杂机制以及治疗HMG的可能中药活性成分提供方法学支持。
