PMID- 31210713
OWN - NLM
STAT- MEDLINE
DCOM- 20191216
LR  - 20200225
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Print)
IS  - 1007-9327 (Linking)
VI  - 25
IP  - 21
DP  - 2019 Jun 7
TI  - Systems pharmacology approach reveals protective mechanisms of Jian-Pi Qing-Chang 
      decoction on ulcerative colitis.
PG  - 2603-2622
LID - 10.3748/wjg.v25.i21.2603 [doi]
AB  - BACKGROUND: Given the complex pathogenesis of ulcerative colitis (UC), the 
      conventional therapeutic methods are not fully curative. As a sort of systematic 
      complementary and alternative medicine, traditional Chinese medicine (TCM) 
      provides new options for the standard therapy. Nevertheless, there are still 
      numerous problems with the promotion of TCM attributed to its complexity, and 
      consequently, new research approaches are urgently needed. Thus, we explored the 
      protective effects of Jian-Pi Qing-Chang (JPQC) decoction on UC based on systems 
      pharmacology approach, which might fill the current innovation gap in drug 
      discovery and clinical practice pertaining to TCM. AIM: To investigate the 
      protective mechanisms of JPQC decoction on UC based on systems pharmacology 
      approach. METHODS: We performed systems pharmacology to predict the active 
      ingredients, the matched targets, and the potential pharmacological mechanism of 
      JPQC on UC. In vivo, we explored the effects of JPQC in a colitis model induced 
      by dextran sulfate sodium. In vitro, we adopted the bone marrow-derived 
      macrophages (BMDMs) as well as BMDMs co-cultured with Caco2 cells to verify the 
      underlying mechanisms and effects of JPQC on UC under TNF-alpha stimulation. RESULTS: 
      Systems pharmacology revealed 170 targets for the 107 active ingredients of JPQC 
      and 112 candidate targets of UC. Protein-protein interaction networks were 
      established to identify the underlying therapeutic targets of JPQC on UC. Based 
      on enrichment analyses, we proposed our hypothesis that JPQC might have a 
      protective effect on UC via the NF-kappaB/HIF-1alpha signalling pathway. Subsequent 
      experimental validation revealed that treatment with TNFalpha activated the 
      NF-kappaB/HIF-1alpha signalling pathway in BMDMs, thereby damaging the epithelial barrier 
      permeability in co-cultured Caco2 cells, while JPQC rescued this situation. The 
      findings were also confirmed in a dextran sulfate sodium-induced colitis model. 
      CONCLUSION: JPQC could improve the mucosal inflammatory response and intestinal 
      epithelial barrier function via the NF-kappaB/HIF-1alpha signalling pathway, which 
      provides new perspectives on the pharmaceutical development and clinical practice 
      of TCM.
FAU - Chen, You-Lan
AU  - Chen YL
AD  - Institute of Digestive Disease, Longhua Hospital, Shanghai University of 
      Traditional Chinese Medicine, Shanghai 200032, China.
FAU - Zheng, Yi-Yuan
AU  - Zheng YY
AD  - Institute of Digestive Disease, Longhua Hospital, Shanghai University of 
      Traditional Chinese Medicine, Shanghai 200032, China.
FAU - Dai, Yan-Cheng
AU  - Dai YC
AD  - Institute of Digestive Disease, Longhua Hospital, Shanghai University of 
      Traditional Chinese Medicine, Shanghai 200032, China.
FAU - Zhang, Ya-Li
AU  - Zhang YL
AD  - Institute of Digestive Disease, Longhua Hospital, Shanghai University of 
      Traditional Chinese Medicine, Shanghai 200032, China.
FAU - Tang, Zhi-Peng
AU  - Tang ZP
AD  - Institute of Digestive Disease, Longhua Hospital, Shanghai University of 
      Traditional Chinese Medicine, Shanghai 200032, China. zhipengtang@sohu.com.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (NF-kappa B)
RN  - 0 (Tnf protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (jianpi qingchang decoction)
RN  - 9042-14-2 (Dextran Sulfate)
SB  - IM
MH  - Animals
MH  - Caco-2 Cells
MH  - Coculture Techniques
MH  - Colitis, Ulcerative/chemically induced/*drug therapy/immunology
MH  - Colon/drug effects/immunology/pathology
MH  - Dextran Sulfate/toxicity
MH  - Disease Models, Animal
MH  - Drug Discovery
MH  - Drugs, Chinese Herbal/*pharmacology/therapeutic use
MH  - Humans
MH  - Intestinal Mucosa/drug effects/immunology/pathology
MH  - Macrophages
MH  - Mice
MH  - NF-kappa B/immunology/metabolism
MH  - Primary Cell Culture
MH  - Signal Transduction/*drug effects/immunology
MH  - *Systems Biology
MH  - Tumor Necrosis Factor-alpha/immunology/metabolism
PMC - PMC6558442
OTO - NOTNLM
OT  - Inflammation
OT  - Intestinal epithelial barrier function
OT  - Jian-Pi Qing-Chang decoction
OT  - Systems pharmacology
OT  - Ulcerative colitis
COIS- Conflict-of-interest statement: The authors declare that there are no conflicts 
      of interest related to this study.
EDAT- 2019/06/19 06:00
MHDA- 2019/12/18 06:00
PMCR- 2019/06/07
CRDT- 2019/06/19 06:00
PHST- 2019/03/02 00:00 [received]
PHST- 2019/03/27 00:00 [revised]
PHST- 2019/04/19 00:00 [accepted]
PHST- 2019/06/19 06:00 [entrez]
PHST- 2019/06/19 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/06/07 00:00 [pmc-release]
AID - 10.3748/wjg.v25.i21.2603 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2019 Jun 7;25(21):2603-2622. doi: 
      10.3748/wjg.v25.i21.2603.