TY - JOUR
T1 - Uncovering the mechanisms of Chinese herbal medicine (MaZiRenWan) for functional constipation by focused network pharmacology approach
AU - Huang, Tao
AU - Ning, Ziwan
AU - Hu, Dongdong
AU - Zhang, Man
AU - Zhao, Ling
AU - Lin, Chengyuan
AU - Zhong, Linda L. D.
AU - Yang, Zhijun
AU - Xu, Hongxi
AU - Bian, Zhaoxiang
AU - MZRW Research Group
N1 - Funding information:
This study was supported by Health and Health Services Fund, Hong Kong SAR, China (project no. 09101501) and Shenzhen Science and Technology Innovation Committee (No. JCYJ20140419130444178).
Publisher copyright:
© 2018 Huang, Ning, Hu, Zhang, Zhao, Lin, Zhong, Yang, Xu and Bian.
PY - 2018/3/26
Y1 - 2018/3/26
N2 - MaZiRenWan (MZRW, also known as Hemp Seed Pill) is a Chinese Herbal Medicine which has been demonstrated to safely and effectively alleviate functional constipation (FC) in a randomized, placebo-controlled clinical study with 120 subjects. However, the underlying pharmacological actions of MZRW for FC, are still largely unknown. We systematically analyzed the bioactive compounds of MZRW and mechanism-of-action biological targets through a novel approach called "focused network pharmacology." Among the 97 compounds identified by UPLC-QTOF-MS/MS in MZRW extract, 34 were found in rat plasma, while 10 were found in rat feces. Hierarchical clustering analysis suggest that these compounds can be classified into component groups, in which compounds are highly similar to each other and most of them are from the same herb. Emodin, amygdalin, albiflorin, honokiol, and naringin were selected as representative compounds of corresponding component groups. All of them were shown to induce spontaneous contractions of rat colonic smooth muscle in vitro. Network analysis revealed that biological targets in acetylcholine-, estrogen-, prostaglandin-, cannabinoid-, and purine signaling pathways are able to explain the prokinetic effects of representative compounds and corresponding component groups. In conclusion, MZRW active components enhance colonic motility, possibly by acting on multiple targets and pathways.
AB - MaZiRenWan (MZRW, also known as Hemp Seed Pill) is a Chinese Herbal Medicine which has been demonstrated to safely and effectively alleviate functional constipation (FC) in a randomized, placebo-controlled clinical study with 120 subjects. However, the underlying pharmacological actions of MZRW for FC, are still largely unknown. We systematically analyzed the bioactive compounds of MZRW and mechanism-of-action biological targets through a novel approach called "focused network pharmacology." Among the 97 compounds identified by UPLC-QTOF-MS/MS in MZRW extract, 34 were found in rat plasma, while 10 were found in rat feces. Hierarchical clustering analysis suggest that these compounds can be classified into component groups, in which compounds are highly similar to each other and most of them are from the same herb. Emodin, amygdalin, albiflorin, honokiol, and naringin were selected as representative compounds of corresponding component groups. All of them were shown to induce spontaneous contractions of rat colonic smooth muscle in vitro. Network analysis revealed that biological targets in acetylcholine-, estrogen-, prostaglandin-, cannabinoid-, and purine signaling pathways are able to explain the prokinetic effects of representative compounds and corresponding component groups. In conclusion, MZRW active components enhance colonic motility, possibly by acting on multiple targets and pathways.
KW - Chinese Herbal Medicine
KW - Component group
KW - Focused network pharmacology
KW - Functional constipation
KW - MaZiRenWan
KW - Representative compound
UR - http://www.scopus.com/inward/record.url?scp=85044306983&partnerID=8YFLogxK
U2 - 10.3389/fphar.2018.00270
DO - 10.3389/fphar.2018.00270
M3 - Journal article
AN - SCOPUS:85044306983
SN - 1663-9812
VL - 9
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 270
ER -