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IMCC-Based Elucidation on Divergent and Convergent of Inter-Module Coordination Maps the Pharmacological Puzzle of Natural Products on Cerebral Ischemia

122 Pages Posted: 21 Dec 2018

See all articles by Pengqian Wang

Pengqian Wang

Chinese Academy of Medical Sciences - Institute of Materia Medica

Jun Liu

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Yanan Yu

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Yingying Zhang

Beijing University of Chinese Medicine - Dongzhimen Hospital

Bing Li

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Dongfeng Li

Peking University - School of Mathematical Sciences

Wenjuan Xu

Beijing University of Chinese Medicine

Haixia Li

China Academy of Chinese Medical Sciences

Qiong Liu

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Zhong Wang

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

More...

Abstract

Detecting the strength of inter-module coordination and modular rewiring is essential to characterize the reactive bio-systematical variation of different related drugs, especially for multiple-target compounds from traditional Chinese medicine (TCM). However, the quantitative method for inter-module connections is far from perfect. Here, an evaluation approach (named as IMCC) for inter-module coordination and its transition was developed. Applying IMCC to mouse ischemia-related genes micro-array, we investigated modular map and its rewiring from disease to drugs perturbation states: transition of IMCC distribution from vehicle to negative-phenotype group (CM) was minor than that to other positive-phenotype groups (BA, JA, or UA). Furthermore, the architecture in cerebral ischemia exhibited a characteristic "core-periphery structure", highlighting "core" as nervous injury related pathways bridged by MAPK signaling pathway. Notably, this architecture was rewired by the positive-phenotype compounds heterogeneously: BA and UA converged modules into an intensively connected integrity; whereas JA diverged partial modules and widened the remaining inter-module paths. Combination of compounds with divergent directions showed a merging or fusing mode. The conclusion was validated by in vivo experiments. This strategy may lead to systematically explore detailed variation of inter-module pharmacological action mode of multiple-target drugs and combination therapies.

Funding Statement: This work was supported by National Science and Technology Major Projects “Major New Drug Development Project”. [grant number 2017ZX09301-059].

Declaration of Interests: The authors declare that they have no competing interests.

Ethics Approval Statement: All of the animal experiments were conducted in accordance with the Prevention of Cruelty to Animals Act 1986 and NIH Guidelines for the Care and Use of Laboratory Animals for Experimental Procedures [Council, 1996], and also approved by Ethics Committee of China Academy of Chinese Medicine.

Keywords: IMCC, inter-module coordination, multiple-target compounds, cerebral ischemia

Suggested Citation

Wang, Pengqian and Liu, Jun and Yu, Yanan and Zhang, Yingying and Li, Bing and Li, Dongfeng and Xu, Wenjuan and Li, Haixia and Liu, Qiong and Wang, Zhong, IMCC-Based Elucidation on Divergent and Convergent of Inter-Module Coordination Maps the Pharmacological Puzzle of Natural Products on Cerebral Ischemia (December 18, 2018). Available at SSRN: https://ssrn.com/abstract=3304269 or http://dx.doi.org/10.2139/ssrn.3304269

Pengqian Wang (Contact Author)

Chinese Academy of Medical Sciences - Institute of Materia Medica

China

Jun Liu

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Yanan Yu

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Yingying Zhang

Beijing University of Chinese Medicine - Dongzhimen Hospital

Beijing, 100029
China

Bing Li

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Dongfeng Li

Peking University - School of Mathematical Sciences

Peking
China

Wenjuan Xu

Beijing University of Chinese Medicine

Beijing, 100029
China

Haixia Li

China Academy of Chinese Medical Sciences

Dongcheng District
Beijing 100700
China

Qiong Liu

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Zhong Wang

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine ( email )

Beijing 100700
China

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