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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01288

Inter-module Coupling Analysis of Huang-Lian-Jie-Du-Decoction on stroke

 Pengqian Wang1*, Weiwei Zhou1, Jing Meng1, Hairu Huo1 and Feng Sui1
  • 1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, China

Huang-Lian-Jie-Du Decotion (HLJDD) is a “Fangji” made up of well-designed Chinese herb array and widely used to treat ischemic stroke. Here we aimed to investigate pharmacological mechanism by introducing an inter-module analysis to identify an overarching view of target profile and action mode of HLJDD. Stroke-related genes were obtained from OMIM (Online Mendelian Inheritance in Man). And the potential target proteins of HLJDD were identified according to TCMsp (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform). The two sets of molecules related to stroke and HLJDD were respectively imported into STRING database to construct the stroke network and HLJDD network, which were dissected into modules through MCODE, respectively. We analyzed the inter-module connectivity by quantify “coupling score” (CS) between HLJDD-modules (H-modules) and stroke-modules (S-module) to explore the pharmacological acting pattern of HLJDD on stroke. A total of 267 stroke-related proteins and 15 S-modules, 335 HLJDD putative targeting proteins and 13 H-modules were identified, respectively. HLJDD directly targeted 28 proteins in stroke network, majority (16, 57.14%) of which were in S-module 1 and 4. According to the modular map based on inter-module CS analysis, H-module 1, 2, 8 densely connected with S-module 1, 3 and 4, to constitute a module-to-module bridgeness, and the enriched pathways of this bridgeness with top significance were TNF signaling pathway, HIF signaling pathway, PI3K-Akt signaling pathway. Furthermore, through this bridgeness, H-module 2 and 4 cooperatively work together to regulate mitochondrial apoptosis against the ischemia injury. Finally, the core protein in H-module 4 account for mitochondrial apoptosis was validated by in vivo experiment. This study has developed an integrative approach by inter-modular analysis for elucidating the “shotgun-like” pharmacological mechanism of HLJDD for stoke.

Keywords: Huang-Lian-Jie-Du Decotion, Stroke, Pharmacological mechanism, Network Pharmacology, Inter-module analysis

Received: 04 Jan 2019; Accepted: 08 Oct 2019.

Copyright: © 2019 Wang, Zhou, Meng, Huo and Sui. 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.

* Correspondence: Dr. Pengqian Wang, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China, pengqian.wang@163.com