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. 2024 Sep 4:15:1451553.
doi: 10.3389/fphar.2024.1451553. eCollection 2024.

Mechanistic study of leukopenia treatment by Qijiao shengbai Capsule via the Bcl2/Bax/CASAPSE3 pathway

Siyue Jiang #  1   2 , Pengjiao Wang #  1   2 , Xiaodong Sun  1   2 , Min Zhang  1   2 , Shuo Zhang  1   3 , Yu Cao  1   2 , Yuben Wang  1   2 , Li Liu  1   2 , Xiuli Gao  1   2
Affiliations

Mechanistic study of leukopenia treatment by Qijiao shengbai Capsule via the Bcl2/Bax/CASAPSE3 pathway

Siyue Jiang et al. Front Pharmacol. .

Abstract

Background: Leukopenia can be caused by chemotherapy, which suppresses bone marrow function and can impact the effectiveness of cancer treatment. Qijiao Shengbai Capsule (QJSB) is commonly used to treat leukopenia, but the specific bioactive components and mechanisms of action are not well understood.

Objectives and results: This study aimed to analyze the active ingredients of QJSB and its potential targets for treating leukopenia using network pharmacology and molecular docking. Through a combination of serum pharmacochemistry, multi-omics, network pharmacology, and validation experiments in a murine leukopenia model, the researchers sought to understand how QJSB improves leukopenia. The study identified 16 key components of QJSB that act in vivo to increase the number of white blood cells in leukopenic mice. Multi-omics analysis and network pharmacology revealed that the PI3K-Akt and MAPK signaling pathways are important in the treatment of leukopenia with QJSB. Five specific targets (JUN, FOS, BCl-2, CASPAS-3) were identified as key targets.

Conclusion: Validation experiments confirmed that QJSB regulates genes related to cell growth and inhibits apoptosis, suggesting that apoptosis may play a crucial role in leukopenia development and that QJSB may improve immune function by regulating apoptotic proteins and increasing CD4+ T cell count in leukopenic mice.

Keywords: Leukopenia; Qijiao Shengbai Capsule; apoptosis; mitochondrial apoptosis; multi-omics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The target information of QJSB in the treatment of leukopenia. (A) Venn diagram of component targets-disease targets. (B) PPIs. (C) Results of KEGG enrichment analysis of the potential targets.
FIGURE 2
FIGURE 2
The effect of QJSB on the peripheral WBC (A) in leucopenia mice induced by CTX. After 2 weeks of treatment, QJSB increased peripheral WBCs (B) The effect of QJSB on the spleen index (C) The effect of QJSB on the thymus index (E) Data on lymphocyte subpopulations in the spleens of control mice; (F) Data on lymphocyte subpopulations in the spleens of Model mice; (G) Data on lymphocyte subpopulations in the spleens of QJSB mice. Data are presented as means ± SD. ### Represent p < 0.001 vs. normal group and ∗, ∗∗, and ∗∗∗ represent p < 0.05, 0.01, and 0.001 vs. model group, respectively.
FIGURE 3
FIGURE 3
Effect of QJSB on spleen tissue in mice (H&E control, model, QJSB magnification ×100 and ×200).
FIGURE 4
FIGURE 4
QJSB regulates metabolites in serum of CTX-induced leukopenia mice. (A) PLS-DA score plot in ESI ± mode. (B) Venn diagram of metabolites (C) Clustering heat map of potential differential metabolites in serum. (D) Key metabolic pathways of differential metabolites.
FIGURE 5
FIGURE 5
Transcriptomics analysis of QJSB on CTX-induced leukopenia mice. (A) Relative volcano plot in Model and Control groups. (B) Relative volcano plot in Model and QJSB groups. (C) GO enrichment analysis of differently expressed genes. (D) KEGG enrichment analysis of differently expressed genes. (E) Enriched chord diagram of pathways.
FIGURE 6
FIGURE 6
Molecular models of 16 QJSB core active components binding to the four most promising target proteins on leukopenia. (A) Heat map of minimum binding energy (B–F) Visualization of molecular docking with minimum binding energy less than −7 kJ/mol.
FIGURE 7
FIGURE 7
Effect of QJSB on protein expression of apoptosis in spleen tissue of leukopenia. Data are presented as means ± SD. ### Represent p < 0.001 vs. normal group and ∗, ∗∗, and ∗∗∗ represent p < 0.05, 0.01, and 0.001 vs. model group, respectively. Quantification of Bax, Bcl-2, Caspase-3, Cyt-C protein expression (A–D).
FIGURE 8
FIGURE 8
Correlation analysis between key proteins concentration, DEGs and DMs performed by Mantel test in RStudio. The orange color curve indicated significant correlation, the green color curve in-dicated statistical difference, and the purple curve indicated no significant correlation. (A) Correlation analysis between DMs and DEMs. (B) Correlation analysis between Path-way-related genes and DMs. (C) Correlation analysis between key proteins concentration and DMs. (D) Correlation analysis between key proteins concentration and Pathway-related genes.
FIGURE 9
FIGURE 9
QJSB improvement mechanism of leukopenia diagram.
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Grants and funding

The author(s) declare that the financial support was received for the research, authorship, and/or publication of this article. This study was reviewed and approved by [The Animal Care and Use Committee of Guizhou Medical University], with the approval number: [License number: SYXK (Qian) 2018-0001; No. 2303443].

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