TY - JOUR
T1 - Detecting Critical Functional Ingredients Group and Mechanism of Xuebijing Injection in Treating Sepsis
AU - Wu, Qi
AU - Yin, Chuan Hui
AU - Li, Yi
AU - Cai, Jie Qi
AU - Yang, Han Yun
AU - Huang, Ying Ying
AU - Zheng, Yi Xu
AU - Xiong, Ke
AU - Yu, Hai Lang
AU - Lu, Ai Ping
AU - Wang, Ke Xin
AU - Guan, Dao Gang
AU - Chen, Yu Peng
N1 - Funding Information:
This study is financially supported by the Startup fund from Southern Medical University (grant No. G619280010), the Natural Science Foundation Council of China (grant No. 32070676, 31501080), the National Key R&D Program of China (2018YFC1705205), Natural Science Foundation of Guangdong Province (grant No. 2021A1515010737), Hong Kong Baptist University Strategic Development Fund (grant No. SDF13-1209-P01, SDF15-0324-P02(b) and SDF19-0402-P02), Hong Kong Baptist University Interdisciplinary Research Matching Scheme (grant No. RC/IRCs/17-18/04).
Publisher Copyright:
Copyright © 2021 Wu, Yin, Li, Cai, Yang, Huang, Zheng, Xiong, Yu, Lu, Wang, Guan and Chen.
PY - 2021/12/6
Y1 - 2021/12/6
N2 - Sepsis is a systemic inflammatory reaction caused by various infectious or noninfectious factors, which can lead to shock, multiple organ dysfunction syndrome, and death. It is one of the common complications and a main cause of death in critically ill patients. At present, the treatments of sepsis are mainly focused on the controlling of inflammatory response and reduction of various organ function damage, including anti-infection, hormones, mechanical ventilation, nutritional support, and traditional Chinese medicine (TCM). Among them, Xuebijing injection (XBJI) is an important derivative of TCM, which is widely used in clinical research. However, the molecular mechanism of XBJI on sepsis is still not clear. The mechanism of treatment of “bacteria, poison and inflammation” and the effects of multi-ingredient, multi-target, and multi-pathway have still not been clarified. For solving this issue, we designed a new systems pharmacology strategy which combines target genes of XBJI and the pathogenetic genes of sepsis to construct functional response space (FRS). The key response proteins in the FRS were determined by using a novel node importance calculation method and were condensed by a dynamic programming strategy to conduct the critical functional ingredients group (CFIG). The results showed that enriched pathways of key response proteins selected from FRS could cover 95.83% of the enriched pathways of reference targets, which were defined as the intersections of ingredient targets and pathogenetic genes. The targets of the optimized CFIG with 60 ingredients could be enriched into 182 pathways which covered 81.58% of 152 pathways of 1,606 pathogenetic genes. The prediction of CFIG targets showed that the CFIG of XBJI could affect sepsis synergistically through genes such as TAK1, TNF-α, IL-1β, and MEK1 in the pathways of MAPK, NF-κB, PI3K-AKT, Toll-like receptor, and tumor necrosis factor signaling. Finally, the effects of apigenin, baicalein, and luteolin were evaluated by in vitro experiments and were proved to be effective in reducing the production of intracellular reactive oxygen species in lipopolysaccharide-stimulated RAW264.7 cells, significantly. These results indicate that the novel integrative model can promote reliability and accuracy on depicting the CFIGs in XBJI and figure out a methodological coordinate for simplicity, mechanism analysis, and secondary development of formulas in TCM.
AB - Sepsis is a systemic inflammatory reaction caused by various infectious or noninfectious factors, which can lead to shock, multiple organ dysfunction syndrome, and death. It is one of the common complications and a main cause of death in critically ill patients. At present, the treatments of sepsis are mainly focused on the controlling of inflammatory response and reduction of various organ function damage, including anti-infection, hormones, mechanical ventilation, nutritional support, and traditional Chinese medicine (TCM). Among them, Xuebijing injection (XBJI) is an important derivative of TCM, which is widely used in clinical research. However, the molecular mechanism of XBJI on sepsis is still not clear. The mechanism of treatment of “bacteria, poison and inflammation” and the effects of multi-ingredient, multi-target, and multi-pathway have still not been clarified. For solving this issue, we designed a new systems pharmacology strategy which combines target genes of XBJI and the pathogenetic genes of sepsis to construct functional response space (FRS). The key response proteins in the FRS were determined by using a novel node importance calculation method and were condensed by a dynamic programming strategy to conduct the critical functional ingredients group (CFIG). The results showed that enriched pathways of key response proteins selected from FRS could cover 95.83% of the enriched pathways of reference targets, which were defined as the intersections of ingredient targets and pathogenetic genes. The targets of the optimized CFIG with 60 ingredients could be enriched into 182 pathways which covered 81.58% of 152 pathways of 1,606 pathogenetic genes. The prediction of CFIG targets showed that the CFIG of XBJI could affect sepsis synergistically through genes such as TAK1, TNF-α, IL-1β, and MEK1 in the pathways of MAPK, NF-κB, PI3K-AKT, Toll-like receptor, and tumor necrosis factor signaling. Finally, the effects of apigenin, baicalein, and luteolin were evaluated by in vitro experiments and were proved to be effective in reducing the production of intracellular reactive oxygen species in lipopolysaccharide-stimulated RAW264.7 cells, significantly. These results indicate that the novel integrative model can promote reliability and accuracy on depicting the CFIGs in XBJI and figure out a methodological coordinate for simplicity, mechanism analysis, and secondary development of formulas in TCM.
KW - critical functional ingredients group
KW - functional response space
KW - key response proteins
KW - network pharmacology
KW - sepsis
KW - Xuebijing injection (XBJI)
UR - http://www.scopus.com/inward/record.url?scp=85121979081&partnerID=8YFLogxK
U2 - 10.3389/fphar.2021.769190
DO - 10.3389/fphar.2021.769190
M3 - Journal article
AN - SCOPUS:85121979081
SN - 1663-9812
VL - 12
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 769190
ER -