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Anti-Inflammatory Effect of a TCM Formula Li-Ru-Kang in Rats With Hyperplasia of Mammary Gland and the Underlying Biological Mechanisms

Li-Ru-Kang (LRK), a formula of eight traditional Chinese medicines (TCM), has been used to treat hyperplasia of mammary gland (HMG) in TCM clinics. However, how LRK works in HMG patients is unclear. To explore the possible mechanisms of LRK against HMG, the network pharmacology was used to screen th...

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Autores principales: Wang, Yingying, Wei, Shizhang, Gao, Tian, Yang, Yuxue, Lu, Xiaohua, Zhou, Xuelin, Li, Haotian, Wang, Tao, Qian, Liqi, Zhao, Yanling, Zou, Wenjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262177/
https://www.ncbi.nlm.nih.gov/pubmed/30524280
http://dx.doi.org/10.3389/fphar.2018.01318
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author Wang, Yingying
Wei, Shizhang
Gao, Tian
Yang, Yuxue
Lu, Xiaohua
Zhou, Xuelin
Li, Haotian
Wang, Tao
Qian, Liqi
Zhao, Yanling
Zou, Wenjun
author_facet Wang, Yingying
Wei, Shizhang
Gao, Tian
Yang, Yuxue
Lu, Xiaohua
Zhou, Xuelin
Li, Haotian
Wang, Tao
Qian, Liqi
Zhao, Yanling
Zou, Wenjun
author_sort Wang, Yingying
collection PubMed
description Li-Ru-Kang (LRK), a formula of eight traditional Chinese medicines (TCM), has been used to treat hyperplasia of mammary gland (HMG) in TCM clinics. However, how LRK works in HMG patients is unclear. To explore the possible mechanisms of LRK against HMG, the network pharmacology was used to screen the potential targets and possible pathways that involved in LRK treated HMG. Rat HMG model induced by estrogen and progesterone was used to further verify the effects of the key molecules of LRK selected from the enriched pathways on HMG. Nipple heights and diameters were measured and uterus index was calculated. The histopathological changes of mammary gland tissue were detected by hematoxylin-eosin (H&E) staining. Western blot was used to detect the phosphorylation of ERK, JNK, and P38. And immunohistochemistry staining was performed to evaluate the levels of estrogen receptor α (ERα), progesterone receptor (PR), nuclear factor-(NF-)κB (p65), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), cyclooxygenases 2 (COX-2), inducible nitric oxide synthase (iNOS), 8-hydroxy-2′deoxyguanosine (8-OHdG), and nitrotyrosine (NT). Our results indicate that LRK treatment rescues significantly nipples height and diameter, decreases uterus index and ameliorates HMG. LRK treatment also markedly attenuates the over-expression of IL-1β, TNF-α, COX-2, and iNOS, and suppressed the formation of 8-OHdG and NT. Furthermore, LRK treatment significantly inhibits the phosphorylation of JNK, ERK, and p38 and expression of NF-κB (p65), interestingly, LRK treatment has no effect on the expression of ERα and PR. Our data suggest that the LRK treatment protects the mammary glands from the damage of oxidative stress and inflammation induced by estrogen and progesterone, via suppresses of MAPK/NF-κB signaling pathways without affecting on the expression of ERα and PR.
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spelling pubmed-62621772018-12-06 Anti-Inflammatory Effect of a TCM Formula Li-Ru-Kang in Rats With Hyperplasia of Mammary Gland and the Underlying Biological Mechanisms Wang, Yingying Wei, Shizhang Gao, Tian Yang, Yuxue Lu, Xiaohua Zhou, Xuelin Li, Haotian Wang, Tao Qian, Liqi Zhao, Yanling Zou, Wenjun Front Pharmacol Pharmacology Li-Ru-Kang (LRK), a formula of eight traditional Chinese medicines (TCM), has been used to treat hyperplasia of mammary gland (HMG) in TCM clinics. However, how LRK works in HMG patients is unclear. To explore the possible mechanisms of LRK against HMG, the network pharmacology was used to screen the potential targets and possible pathways that involved in LRK treated HMG. Rat HMG model induced by estrogen and progesterone was used to further verify the effects of the key molecules of LRK selected from the enriched pathways on HMG. Nipple heights and diameters were measured and uterus index was calculated. The histopathological changes of mammary gland tissue were detected by hematoxylin-eosin (H&E) staining. Western blot was used to detect the phosphorylation of ERK, JNK, and P38. And immunohistochemistry staining was performed to evaluate the levels of estrogen receptor α (ERα), progesterone receptor (PR), nuclear factor-(NF-)κB (p65), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), cyclooxygenases 2 (COX-2), inducible nitric oxide synthase (iNOS), 8-hydroxy-2′deoxyguanosine (8-OHdG), and nitrotyrosine (NT). Our results indicate that LRK treatment rescues significantly nipples height and diameter, decreases uterus index and ameliorates HMG. LRK treatment also markedly attenuates the over-expression of IL-1β, TNF-α, COX-2, and iNOS, and suppressed the formation of 8-OHdG and NT. Furthermore, LRK treatment significantly inhibits the phosphorylation of JNK, ERK, and p38 and expression of NF-κB (p65), interestingly, LRK treatment has no effect on the expression of ERα and PR. Our data suggest that the LRK treatment protects the mammary glands from the damage of oxidative stress and inflammation induced by estrogen and progesterone, via suppresses of MAPK/NF-κB signaling pathways without affecting on the expression of ERα and PR. Frontiers Media S.A. 2018-11-20 /pmc/articles/PMC6262177/ /pubmed/30524280 http://dx.doi.org/10.3389/fphar.2018.01318 Text en Copyright © 2018 Wang, Wei, Gao, Yang, Lu, Zhou, Li, Wang, Qian, Zhao and Zou. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wang, Yingying
Wei, Shizhang
Gao, Tian
Yang, Yuxue
Lu, Xiaohua
Zhou, Xuelin
Li, Haotian
Wang, Tao
Qian, Liqi
Zhao, Yanling
Zou, Wenjun
Anti-Inflammatory Effect of a TCM Formula Li-Ru-Kang in Rats With Hyperplasia of Mammary Gland and the Underlying Biological Mechanisms
title Anti-Inflammatory Effect of a TCM Formula Li-Ru-Kang in Rats With Hyperplasia of Mammary Gland and the Underlying Biological Mechanisms
title_full Anti-Inflammatory Effect of a TCM Formula Li-Ru-Kang in Rats With Hyperplasia of Mammary Gland and the Underlying Biological Mechanisms
title_fullStr Anti-Inflammatory Effect of a TCM Formula Li-Ru-Kang in Rats With Hyperplasia of Mammary Gland and the Underlying Biological Mechanisms
title_full_unstemmed Anti-Inflammatory Effect of a TCM Formula Li-Ru-Kang in Rats With Hyperplasia of Mammary Gland and the Underlying Biological Mechanisms
title_short Anti-Inflammatory Effect of a TCM Formula Li-Ru-Kang in Rats With Hyperplasia of Mammary Gland and the Underlying Biological Mechanisms
title_sort anti-inflammatory effect of a tcm formula li-ru-kang in rats with hyperplasia of mammary gland and the underlying biological mechanisms
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262177/
https://www.ncbi.nlm.nih.gov/pubmed/30524280
http://dx.doi.org/10.3389/fphar.2018.01318
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