Multiple components of Mahuang Shengma Decoction on prevention and treatment of acute lung injury based on RAGE/NF-κB signaling pathway.
10.19540/j.cnki.cjcmm.20210802.401
- Author:
Yan-Miao MA
1
;
Li-Jun ZHAO
1
;
Ming-Ran LIU
1
;
Kai LIANG
1
;
Bo SONG
1
;
Shu-Xia BAI
2
;
Zhen-Yu LI
3
;
Zhi CHAI
1
;
Tao PENG
4
Author Information
1. Shanxi University of Chinese Medicine Taiyuan 030619, China.
2. the Hospital of Shanxi University of Chinese Medicine Taiyuan 03 0024, China.
3. Modern Research Center for Traditional Chinese Medicine, Shanxi University Taiyuan 030006,China.
4. Shanxi Hospital of Integrated Traditional and Western Medicine Taiyuan 030013, China.
- Publication Type:Journal Article
- Keywords:
Mahuang Shengma Decoction;
RAGE/NF-κB;
acute lung injury(ALI);
bioinformatics;
mechanism
- MeSH:
Acute Lung Injury/genetics*;
Animals;
Drugs, Chinese Herbal/pharmacology*;
Lipopolysaccharides;
Lung/metabolism*;
Mice;
NF-kappa B/metabolism*;
Network Pharmacology;
Receptor for Advanced Glycation End Products/metabolism*;
Signal Transduction
- From:
China Journal of Chinese Materia Medica
2021;46(21):5693-5700
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the potential molecular markers and drug-compound-target mechanism of Mahuang Shengma Decoction(MHSM) in the intervention of acute lung injury(ALI) by network pharmacology and experimental verification. Databases such as TCMSP, TCMIO, and STITCH were used to predict the possible targets of MHSM components and OMIM and Gene Cards were employed to obtain ALI targets. The common differentially expressed genes(DEGs) were therefore obtained. The network diagram of DEGs of MHSM intervention in ALI was constructed by Cytoscape 3. 8. 0, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of target genes. The ALI model was induced by abdominal injection of lipopolysaccharide(LPS) in mice. Bronchoalveolar lavage fluid(BALF) was collected for the detection of inflammatory factors. Pathological sectioning and RT-PCR experiments were performed to verify the therapeutic efficacy of MHSM on ALI. A total of 494 common targets of MHSM and ALI were obtained. Among the top 20 key active compounds of MHSM, 14 from Ephedrae Herba were found to be reacted with pivotal genes of ALI [such as tumor necrosis factor(TNF), tumor protein 53(TP53), interleukin 6(IL6), Toll-like receptor 4(TLR4), and nuclear factor-κB(NF-κB)/p65(RELA)], causing an uncontrolled inflammatory response with activated cascade amplification. Pathway analysis revealed that the mechanism of MHSM in the treatment of ALI mainly involved AGE-RAGE, cancer pathways, PI3 K-AKT signaling pathway, and NF-κB signaling pathway. The findings demonstrated that MHSM could dwindle the content of s RAGE, IL-6, and TNF-α in the BALF of ALI mice, relieve the infiltration of inflammatory cells in the lungs, inhibit alveolar wall thickening, reduce the acute inflammation-induced pulmonary congestion and hemorrhage, and counteract transcriptional activities of Ager-RAGE and NF-κB p65. MHSM could also synergically act on the target DEGs of ALI and alleviate pulmonary pathological injury and inflammatory response, which might be achieved by inhibiting the expression of the key gene Ager-RAGE in RAGE/NF-κB signaling pathway and downstream signal NF-κB p65.
