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Abstract
Background
Annao Pingchong decoction (ANPCD) is a traditional Chinese decoction which has definite effects on treating intracerebral hemorrhage (ICH) validated through clinical and experimental studies. However, the impact of ANPCD on oxidative stress (OS) after ICH remains unclear and is worth further investigating.
Aim
To investigate whether the therapeutic effects of ANPCD on ICH are related to alleviating OS damage and seek potential targets for its antioxidant effects.
Materials and Methods
The therapeutic candidate genes of ANPCD on ICH were identified through a comparison of the target genes of ANPCD, target genes of ICH and differentially expressed genes (DEGs). Protein–protein interaction (PPI) network analysis and functional enrichment analysis were combined with targets-related literature to select suitable antioxidant targets. The affinity between ANPCD and the selected target was verified using macromolecular docking. Subsequently, the effects of ANPCD on OS and the selected target were further investigated through in vivo experiments.
Results
Forty-eight candidate genes were screened, in which silent information regulator sirtuin 1 (SIRT1) is one of the core genes that has antioxidant effects and ICH significantly affected its expression. The good affinity between 6 compounds of ANPCD and SIRT1 was also demonstrated by macromolecular docking. The results of in vivo experiments demonstrated that ANPCD significantly decreased modified neurological severity scoring (mNSS) scores and serum MDA and 8-OHdG content in ICH rats, while significantly increasing serum SOD and CAT activity, complicated with the up-regulation of ANPCD on SIRT1, FOXO1, PGC-1α and Nrf2. Furthermore, ANPCD significantly decreased the apoptosis rate and the expression of apoptosis-related proteins (P53, cytochrome c and caspase-3).
Conclusion
ANPCD alleviates OS damage and apoptosis after ICH in rats. As a potential therapeutic target, SIRT1 can be effectively regulated by ANPCD, as are its downstream proteins.
Graphical Abstract
Abbreviation
ANPCD, Annao Pingchong decoction; CAT, catalase; DEGs, differentially expressed genes; FOXO1, forkhead box O transcription factor 1; ICH, intracerebral hemorrhage; MDA, malondialdehyde; mPTP, mitochondrial permeability transition pore; NP, network pharmacology; Nrf2, nuclear factor-erythroid-2-related factor 2; OS, oxidative stress; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator-1α; PPI, protein–protein interaction networks; ROS, reactive oxygen species; SIRT1, silent information regulator sirtuin 1; SOD, superoxide dismutase; TCM, traditional Chinese medicine; 8-OHdG, 8-hydroxy-2-deoxyguanosine.
Data Sharing Statement
The original contributions presented in this study are included in the article/Supplementary Material, and further inquiries can be directed to the corresponding authors.
Ethics Statement
The animal study was reviewed and approved by the Ethics Committee for Experimental Animals of the First Hospital of Hunan University of Chinese Medicine.
Acknowledgments
We thank the Experimental Center of Medical Innovation of The First Hospital of Hunan University of Chinese Medicine for providing the experimental conditions.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.