TY - JOUR
T1 - A novel network pharmacology strategy to decode mechanism of Wuling Powder in treating liver cirrhosis
AU - Liu, Qinwen
AU - Li, Xiaowei
AU - Li, Yi
AU - Luo, Qian
AU - Fan, Qiling
AU - Lu, Aiping
AU - Guan, Daogang
AU - Li, Jiahui
N1 - This study was supported by the Startup Fund from the Southern Medical University (grant no. G820282016), Natural Science Foundation Council of China (grant nos. 31501080 and 32070676), Natural Science Foundation of Guangdong Province (grant no. 2021A1515010737 and 2023A1515012902), Hong Kong Baptist University Strategic Development Fund (grant no. SDF13-1209-P01, SDF15-0324-P02(b), SDF19-0402-P02), and Hong Kong Baptist University Interdisciplinary Research Matching Scheme (Grant No. RC/IRCs/17–18/04), and 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund (Guangdong-Hong Kong-Macau Joint Lab, grant No. 2020B1212030006).
Publisher Copyright:
© The Author(s) 2024.
PY - 2024/3/1
Y1 - 2024/3/1
N2 - Background: Liver cirrhosis is a chronic liver disease with hepatocyte necrosis and lesion. As one of the TCM formulas Wuling Powder (WLP) is widely used in the treatment of liver cirrhosis. However, it’s key functional components and action mechanism still remain unclear. We attempted to explore the Key Group of Effective Components (KGEC) of WLP in the treatment of Liver cirrhosis through integrative pharmacology combined with experiments. Methods: The components and potential target genes of WLP were extracted from published databases. A novel node importance calculation model considering both node control force and node bridging force is designed to construct the Function Response Space (FRS) and obtain key effector proteins. The genetic knapsack algorithm was employed to select KGEC. The effectiveness and reliability of KGEC were evaluated at the functional level by using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, the effectiveness and potential mechanism of KGEC were confirmed by CCK-8, qPCR and Western blot. Results: 940 effective proteins were obtained in FRS. KEGG pathways and GO terms enrichments analysis suggested that effective proteins well reflect liver cirrhosis characteristics at the functional level. 29 components of WLP were defined as KGEC, which covered 100% of the targets of the effective proteins. Additionally, the pathways enriched for the KGEC targets accounted for 83.33% of the shared genes between the targets and the pathogenic genes enrichment pathways. Three components scopoletin, caryophyllene oxide, and hydroxyzinamic acid from KGEC were selected for in vivo verification. The qPCR results demonstrated that all three components significantly reduced the mRNA levels of COL1A1 in TGF-β1-induced liver cirrhosis model. Furthermore, the Western blot assay indicated that these components acted synergistically to target the NF-κB, AMPK/p38, cAMP, and PI3K/AKT pathways, thus inhibiting the progression of liver cirrhosis. Conclusion: In summary, we have developed a new model that reveals the key components and potential mechanisms of WLP for the treatment of liver cirrhosis. This model provides a reference for the secondary development of WLP and offers a methodological strategy for studying TCM formulas.
AB - Background: Liver cirrhosis is a chronic liver disease with hepatocyte necrosis and lesion. As one of the TCM formulas Wuling Powder (WLP) is widely used in the treatment of liver cirrhosis. However, it’s key functional components and action mechanism still remain unclear. We attempted to explore the Key Group of Effective Components (KGEC) of WLP in the treatment of Liver cirrhosis through integrative pharmacology combined with experiments. Methods: The components and potential target genes of WLP were extracted from published databases. A novel node importance calculation model considering both node control force and node bridging force is designed to construct the Function Response Space (FRS) and obtain key effector proteins. The genetic knapsack algorithm was employed to select KGEC. The effectiveness and reliability of KGEC were evaluated at the functional level by using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, the effectiveness and potential mechanism of KGEC were confirmed by CCK-8, qPCR and Western blot. Results: 940 effective proteins were obtained in FRS. KEGG pathways and GO terms enrichments analysis suggested that effective proteins well reflect liver cirrhosis characteristics at the functional level. 29 components of WLP were defined as KGEC, which covered 100% of the targets of the effective proteins. Additionally, the pathways enriched for the KGEC targets accounted for 83.33% of the shared genes between the targets and the pathogenic genes enrichment pathways. Three components scopoletin, caryophyllene oxide, and hydroxyzinamic acid from KGEC were selected for in vivo verification. The qPCR results demonstrated that all three components significantly reduced the mRNA levels of COL1A1 in TGF-β1-induced liver cirrhosis model. Furthermore, the Western blot assay indicated that these components acted synergistically to target the NF-κB, AMPK/p38, cAMP, and PI3K/AKT pathways, thus inhibiting the progression of liver cirrhosis. Conclusion: In summary, we have developed a new model that reveals the key components and potential mechanisms of WLP for the treatment of liver cirrhosis. This model provides a reference for the secondary development of WLP and offers a methodological strategy for studying TCM formulas.
KW - Liver cirrhosis
KW - Network pharmacology
KW - Traditional Chinese Medicine
KW - Wuling Powder
UR - http://www.scopus.com/inward/record.url?scp=85186544817&partnerID=8YFLogxK
U2 - 10.1186/s13020-024-00896-z
DO - 10.1186/s13020-024-00896-z
M3 - Journal article
C2 - 38429802
AN - SCOPUS:85186544817
SN - 1749-8546
VL - 19
JO - Chinese Medicine (United Kingdom)
JF - Chinese Medicine (United Kingdom)
IS - 1
M1 - 36
ER -
